pituitrin and Diabetes-Insipidus

Vasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon.. We retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not.. Out of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium.. Temporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

Topics: COVID-19; Critical Illness; Diabetes Insipidus; Humans; Polyuria; Retrospective Studies; Sodium; Vasopressins

Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.

Topics: Animals; Antidiuretic Agents; COVID-19; COVID-19 Drug Treatment; Deamino Arginine Vasopressin; Diabetes Insipidus; Hemostatics; Humans; Lypressin; Molecular Structure; Ornipressin; Pandemics; SARS-CoV-2; Terlipressin; Vasopressins

Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day [1,2]. Central DI results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland. Besides central DI further underlying etiologies of DI can be due to other primary forms (renal origin) or secondary forms of polyuria (resulting from primary polydipsia). All these forms belong to the Polyuria Polydipsia Syndrom (PPS). In most cases central and nephrogenic DI are acquired, but there are also congenital forms caused by genetic mutations of the AVP gene (central DI) [3] or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) [4]. Primary polydipsia (PP) as secondary form of polyuria includes an excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response. Differentiation between the three mentioned entities is difficult [5], especially in patients with Primary polydipsia or partial, mild forms of DI [1,6], but different tests for differential diagnosis, most recently based on measurement of copeptin, and a thorough medical history mostly lead to the correct diagnosis. This is important since treatment strategies vary and application of the wrong treatment can be dangerous [7]. Treatment of central DI consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP), that is used as nasal or oral preparation in most cases. Main side effect can be dilutional hyponatremia [8]. In this review we will focus on central diabetes insipidus and describe the prevalence, the clinical manifestations, the etiology as well as the differential diagnosis and management of central diabetes insipidus in the out- and inpatient setting.

Topics: Adult; Antidiuretic Agents; Aquaporin 2; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Glycopeptides; Humans; Mutation; Neurophysins; Pituitary Gland; Polydipsia; Polyuria; Protein Precursors; Vasopressins

Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations.. This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI.. The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis.. To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) < 1.005, and at least one of the following symptoms: excessive thirst, serum osmolality > 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.

Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms; Postoperative Period; Vasopressins

Arginine vasopressin (AVP)-mediated osmoregulatory disorders, such as diabetes insipidus (DI) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are common in the differential diagnosis for children with hypo- and hypernatremia and require timely recognition and treatment. DI is caused by a failure to concentrate urine secondary to impaired production of or response to AVP, resulting in hypernatremia. Newer methods of diagnosing DI include measuring copeptin levels; copeptin is AVP's chaperone protein and serves as a surrogate biomarker of AVP secretion. Intraoperative copeptin levels may also help predict the risk for developing DI after neurosurgical procedures. Copeptin levels hold diagnostic promise in other pediatric conditions, too. Recently, expanded genotype and phenotype correlations in inherited DI disorders have been described and may better predict the clinical course in affected children and infants. Similarly, newer formulations of synthetic AVP may improve pediatric DI treatment. In contrast to DI, SIADH, characterized by inappropriate AVP secretion, commonly leads to severe hyponatremia. Contemporary methods aid clinicians in distinguishing SIADH from other hyponatremic conditions, particularly cerebral salt wasting. Further research on the efficacy of therapies for pediatric SIADH is needed, although some adult treatments hold promise for pediatrics. Lastly, expansion of home point-of-care sodium testing may transform management of SIADH and DI in children. In this article, we review recent developments in the understanding of pathophysiology, diagnostic workup, and treatment of better outcomes and quality of life for children with these challenging disorders.

Topics: Child; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Neurophysins; Protein Precursors; Vasopressins

The treatment of central diabetes insipidus has not changed significantly in recent decades, and dDAVP and replacement of free water deficit remain the cornerstones of treatment. Oral dDAVP has replaced nasal dDAVP as a more reliable mode of treatment for chronic central diabetes insipidus. Hyponatraemia is a common side effect, occurring in one in four patients, and should be avoided by allowing a regular break from dDAVP to allow a resultant aquaresis. Hypernatraemia is less common, and typically occurs during hospitalization, when access to water is restricted, and in cases of adipsic DI. Management of adipsic DI can be challenging, and requires initial inpatient assessment to establish dose of dDAVP, daily fluid prescription, and eunatraemic weight which can guide day-to-day fluid targets in the long-term.

Topics: Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Hypernatremia; Hyponatremia; Neurophysins; Protein Precursors; Vasopressins

In the pregnant patient, hypotonic polyuria in the setting of elevated serum osmolality and polydipsia should narrow the differential to causes related to diabetes insipidus (DI). Gestational DI, also called transient DI of pregnancy, is a distinct entity, unique from central DI or nephrogenic DI which may both become exacerbated during pregnancy. These three different processes relate to vasopressin, where increased metabolism, decreased production or altered renal sensitivity to this neuropeptide should be considered. Gestational DI involves progressively rising levels of placental vasopressinase throughout pregnancy, resulting in decreased endogenous vasopressin and resulting hypotonic polyuria worsening through the pregnancy. Gestational DI should be distinguished from central and nephrogenic DI that may be seen during pregnancy through use of clinical history, urine and serum osmolality measurements, response to desmopressin and potentially, the newer, emerging copeptin measurement. This review focuses on a brief overview of osmoregulatory and vasopressin physiology in pregnancy and how this relates to the clinical presentation, pathophysiology, diagnosis and management of gestational DI, with comparisons to the other forms of DI during pregnancy. Differentiating the subtypes of DI during pregnancy is critical in order to provide optimal management of DI in pregnancy and avoid dehydration and hypernatremia in this vulnerable population.

Topics: Dehydration; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Female; Humans; Hypernatremia; Neurophysins; Osmoregulation; Polydipsia; Polyuria; Pregnancy; Pregnancy Complications; Protein Precursors; Vasopressins; Water-Electrolyte Balance

The two main differential diagnoses of central diabetes insipidus are nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between those entities is essential as treatment differs substantially with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the indirect water deprivation test had several pitfalls, resulting in a low diagnostic accuracy. With the introduction of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of diabetes insipidus was new evaluated. While unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, a stimulation test is needed to differentiate patients with central diabetes insipidus from patients with primary polydipsia. Stimulation can either be achieved through hypertonic saline infusion or arginine infusion. While the former showed high diagnostic accuracy and superiority over the indirect water deprivation test in a recent validation study, the diagnostic accuracy for arginine-stimulated copeptin was slightly lower, but superior in test tolerance. In summary of the recent findings, a new copeptin based diagnostic algorithm is proposed for the reliable diagnosis of diabetes insipidus.

Topics: Biomarkers; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Diagnostic Techniques, Endocrine; Humans; Neurophysins; Polyuria; Protein Precursors; Vasopressins

In the majority of cases, hereditary neurohypophyseal diabetes insipidus (DI) is a monogenic disorder caused by mutations in the AVP gene. Dominant transmission is by far the most common form. In these patients, symptoms develop gradually at various ages during childhood, progressing with complete penetrance to polyuria and polydipsia that is usually severe. In autosomal dominant neurohypophyseal DI (ADNDI), the mutant prohormone is folding deficient and consequently retained in the ER, where it forms amyloid-like fibrillar aggregates. Degradation by proteasomes occurs, but their clearance capacity appears to be insufficient. Postmortem studies in affected individuals suggest a neurodegenerative process confined to vasopressinergic neurons. Other forms of genetic neurohypophyseal DI include the very rare autosomal recessive type, also caused by mutations in the AVP gene, and complex multiorgan disorders, such as Wolfram syndrome. In all individuals where a congenital form of DI is suspected, including nephrogenic types, genetic analysis should be performed.

Topics: Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Mutation; Neurophysins; Protein Precursors; Vasopressins

Diabetes insipidus (DI) is a disorder characterized by excretion of large amounts of hypotonic urine. Central DI results from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, whereas nephrogenic DI results from resistance to AVP in the kidneys. Central and nephrogenic DI are usually acquired, but genetic causes must be evaluated, especially if symptoms occur in early childhood. Central or nephrogenic DI must be differentiated from primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Primary polydipsia is most common in psychiatric patients and health enthusiasts but the polydipsia in a small subgroup of patients seems to be due to an abnormally low thirst threshold, a condition termed dipsogenic DI. Distinguishing between the different types of DI can be challenging and is done either by a water deprivation test or by hypertonic saline stimulation together with copeptin (or AVP) measurement. Furthermore, a detailed medical history, physical examination and imaging studies are needed to ensure an accurate DI diagnosis. Treatment of DI or primary polydipsia depends on the underlying aetiology and differs in central DI, nephrogenic DI and primary polydipsia.

Topics: Diabetes Insipidus; Humans; Neurophysins; Pituitary Gland, Posterior; Protein Precursors; Vasopressins

Arginine Vasopressin (AVP) and copeptin derive from the same precursor molecule. Due to the equimolar secretion, copeptin responds as rapidly as AVP to osmotic, hemodynamic and unspecific stress-related stimuli and both peptides show a very strong correlation. The physiological functions of AVP are homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response. In contrast, the exact function of copeptin remains unknown. Since copeptin, in contrast to AVP, can easily be measured with a sandwich immunoassay, its main function so far that it indirectly indicates the amount of AVP in the circulation. Copeptin has emerged as a useful measure in different diseases. On one hand, through its characteristics as a marker of stress, it provides a unique measure of the individual stress burden. As such, it is a prognostic marker in different acute diseases such as ischemic stroke or myocardial infarction. On the other side, it has emerged as a promising marker in the diagnosis of AVP-dependent fluid disorders. Copeptin reliably differentiates various entities of the polyuria polydipsia syndrome; baseline levels >20 pmol/L without prior fluid deprivation identify patients with nephrogenic diabetes insipidus, whereas levels measured upon osmotic stimulation with hypertonic saline or upon non-osmotic stimulation with arginine differentiate primary polydipsia from central diabetes insipidus. In patients with hyponatremia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, but copeptin levels overlap in all other causes of hyponatremia, limiting its diagnostic use in hyponatremia. Copeptin has also been put forward as predictive marker for autosomal dominant polycystic kidney disease and for diabetes mellitus, but more studies are needed to confirm these findings.

Topics: Arginine Vasopressin; Diabetes Insipidus; Female; Glycopeptides; Humans; Male; Vasopressins

The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI). A lack of VP production precipitates central diabetes insipidus (CDI), which can be managed effectively by VP supplementation. A majority of cases of nephrogenic diabetes insipidus (NDI) result from V2R mutations that impair receptor sensitivity. No specific therapy is currently available for management of NDI. Evidence is evolving that (pro)renin receptor (PRR), a newly identified member of the renin-angiotensin system, is capable of regulating VP production and action. As such, PRR should be considered strongly as a therapeutic target for treating CDI and NDI. The current review will summarize recent advances in understanding the physiology of renal and central PRR as it relates to the two types of DI.

Topics: Animals; Antidiuretic Agents; Diabetes Insipidus; Diuresis; Genetic Predisposition to Disease; Humans; Kidney; Mutation; Phenotype; Prorenin Receptor; Receptors, Cell Surface; Receptors, Vasopressin; Renin-Angiotensin System; Vasopressins

Arginine vasopressin (AVP) is a common second-line or third-line vasopressor used in critically ill neurosurgical patients. Neurosurgical indications include hyperdynamic therapy for vasospasm, maintenance of cerebral perfusion pressure in patients with intracranial hypertension, and prevention of hypotension in patients with sepsis.. A series of 6 neurosurgical patients receiving AVP infusions developed severe but transient diabetes insipidus (tDI) after cessation of AVP. To our knowledge, no previous reports of this phenomenon in neurosurgical patients have been published. We reviewed the clinical histories, intensive care unit treatment, medication administration records, and laboratory values of these patients, and we found recurrent elevated serum sodium and urine output and decreased urine specific gravity after discontinuation of AVP. Resolution of tDI occurred upon resumption of AVP or administration of desmopressin. Elevated serum sodium levels were often severe, resulting in worsened clinical outcomes. When AVP was resumed, tDI typically recurred if AVP was again tapered and discontinued. Routine administration of desmopressin was useful in controlling sodium levels until the tDI resolved.. Recognition of this phenomenon has caused us to change our clinical management of neurosurgical patients receiving AVP. We hypothesize that tDI is caused by downregulation of the V2 receptor mass in the renal distal convoluted tubule and collecting duct cells. When AVP is discontinued, patients develop nephrogenic tDI secondary to decreased V2 receptor binding, which explains why desmopressin is effective in correcting tDI. Future research includes a large prospective study to determine risk factors for tDI, its incidence, and its pathophysiology.

Topics: Adult; Critical Care; Diabetes Insipidus; Drug Administration Schedule; Female; Humans; Hypotension; Male; Middle Aged; Neurosurgical Procedures; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Young Adult

Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI.. A literature search was performed to review the background, etiology, management and associated complications of this rare condition.. ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI.. The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.

Topics: Animals; Arginine Vasopressin; Complement Factor D; Diabetes Insipidus; Humans; Hypernatremia; Vasopressins

Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) . This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R ) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antidiuretic Agents; Aquaporin 2; Deamino Arginine Vasopressin; Diabetes Insipidus; Disease Models, Animal; Gene Expression Regulation; Humans; Kidney; Phosphodiesterase Inhibitors; Protein Isoforms; Receptors, Vasopressin; Vasopressins; Water; Water-Electrolyte Balance

The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

Topics: Animals; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Models, Animal; Oxytocin; Vasopressins

Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates circulating vasopressin. Gestational, transient DI occurs late in pregnancy and disappears few days after delivery. Acquired central DI can also occur during pregnancy, for example in a patient with hypophysitis or neuroinfundibulitis during late pregnancy or postpartum. Finally, pre-existing central or nephrogenic DI may occasionally be unmasked by pregnancy. Treatment with dDAVP (desmopressin, Minirin(®)) is very effective on transient DI of pregnancy and also on pre-existing or acquired central DI. Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Female; Humans; Pregnancy; Pregnancy Complications; Vasopressins

Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal "osmoreceptors" that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance.

Topics: Brain; Cell Size; Diabetes Insipidus; Homeostasis; Humans; Hyponatremia; Kidney Medulla; Kidney Tubules, Collecting; Osmotic Pressure; Sensory Receptor Cells; Thirst; Vasopressins; Water; Water-Electrolyte Balance

Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

Topics: Antidiuretic Agents; Diabetes Insipidus; Endocrinology; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Vasopressins

Disorders of body fluids are among the most commonly encountered problems in the practice of clinical medicine. This is in large part because many different disease states can potentially disrupt the finely balanced mechanisms that control the intake and output of water and solute. It therefore behooves clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. Since body water is the primary determinant of the osmolality of the extracellular fluid (ECF), disorders of body water homeostasis can be divided into hypoosmolar disorders, in which there is an excess of body water relative to body solute, and hyperosmolar disorders, in which there is a deficiency of body water relative to body solute. The classical hyperosmolar disorder is diabetes insipidus (DI), and the classical hypoosmolar disorder is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This chapter first reviews the regulatory mechanisms underlying water and sodium metabolism, the two major determinants of body fluid homeostasis. The major disorders of water metabolism causing hyperosmolality and hypoosmolality, DI and SIADH, are then discussed in detail, including the pathogenesis, differential diagnosis and treatment of these disorders.

Topics: Animals; Diabetes Insipidus; Diagnosis, Differential; Humans; Hypernatremia; Inappropriate ADH Syndrome; Vasopressins; Water; Water-Electrolyte Imbalance

The therapies of mood and anxiety disorders are not solved, because current antidepressants have delayed onset of therapeutic action and a significant number of patients are non-responsive. Research on the field was leaning towards neuropeptides as therapeutic targets. Vasopressin (VP) is a hot candidate, as beyond its peripheral actions VP is implicated in interneuronal communication and modulates the hypothalamo-pituitary-adrenal (HPA), the key stress axis, as well as behavioural functions. Affective disorders are stress related disorders and the most frequently occurring abnormality in depressed subjects is hyperactivity of the HPA. VP with nucleus paraventricularis hypothalami origin is a direct adrenocorticotrophin secretagogue through its V1b receptor. VP seems to have special importance under prolonged stress conditions, which are known to be strong predictive factor of depressive disorder and can induce depressive-like symptoms. Preclinical and clinical data summarized in this review underline the importance of VP in the development of anxiety- and depressive-like symptoms. Orally active nonpeptiderg V1b antagonists were developed and seemed to have effective anxiolytic and antidepressant profile in preclinical studies, which was not fully confirmed by clinical observations. It seems that V1a receptors on special brain areas could have same importance. Taken together current knowledge strongly implies an importance of vasopressinergic regulation in affective disorders and consider VP as endogenous anxiogenic/depressogenic substance. However, wide range of side effects could develop as a result of an intervention on the VP system; therefore there is a need for area-specific targeting of VP receptors (e.g. with modified nanoparticles).

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Antidiuretic Hormone Receptor Antagonists; Anxiety; Anxiety Disorders; Depression; Depressive Disorder; Diabetes Insipidus; Disease Models, Animal; Humans; Hypothalamo-Hypophyseal System; Inappropriate ADH Syndrome; Mice; Mice, Inbred BALB C; Mice, Knockout; Molecular Targeted Therapy; Mood Disorders; Pituitary-Adrenal System; Rats; Rats, Brattleboro; Rats, Mutant Strains; Receptors, Vasopressin; Stress, Psychological; Vasopressins

Diabetes insipidus (DI) is a rare disorder of horses characterized by profound polyuria and polydipsia (PU/PD), which can be caused by loss of production of arginine vasopressin (AVP). This condition is termed neurogenic or central DI. DI may also develop with absence or loss of AVP receptors or activity on the basolateral membrane of collecting-duct epithelial cells. This condition is termed nephrogenic DI. Equine clinicians may differentiate true DI from more common causes of PU/PD by a systematic diagnostic approach. DI may not be a correctable disorder, and supportive care of affected horses requires an adequate water source.

Topics: Animals; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Female; Homeostasis; Horse Diseases; Horses; Male; Vasopressins; Water; Water-Electrolyte Imbalance

Over the past two decades, the genetic and molecular basis of familial forms of diabetes insipidus has been elucidated. Diabetes insipidus is a clinical syndrome characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The most common type of diabetes insipidus is caused by lack of the antidiuretic hormone arginine vasopressin (vasopressin), which is produced in the hypothalamus and secreted by the neurohypophysis. This type of diabetes insipidus is referred to here as neurohypophyseal diabetes insipidus. The syndrome can also result from resistance to the antidiuretic effects of vasopressin on the kidney, either at the level of the vasopressin 2 receptor or the aquaporin 2 water channel (which mediates the re-absorption of water from urine), and is referred to as renal or nephrogenic diabetes insipidus. Differentiation between these two types of diabetes insipidus and primary polydipsia can be difficult owing to the existence of partial as well as complete forms of vasopressin deficiency or resistance. Seven different familial forms of diabetes insipidus are known to exist. The clinical presentation, genetic basis and cellular mechanisms responsible for them vary considerably. This information has led to improved methods of differential diagnosis and could provide the basis of new forms of therapy.

Topics: Animals; Aquaporin 2; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Female; Humans; Male; Mutation; Phenotype; Polydipsia; Polyuria; Receptors, Vasopressin; Vasopressins

To review the etiology, diagnosis, and management of diabetes insipidus during pregnancy.. A search of the literature was performed in PubMed using key word searching and citation snowballing to identify articles published in English between January 1, 1980, and December 31, 2008, on the subject of diabetes insipidus during pregnancy. Once the articles were identified, a thorough review of all results was conducted. Results and conclusions were compiled and summarized.. We reviewed 50 studies selected using the following key words: diabetes insipidus, pregnancy, arginine vasopressin, vasopressinase.. Gestational diabetes insipidus is underdiagnosed because polyuria is often considered normal during pregnancy. Clinicians caring for pregnant women should consider screening for gestational diabetes insipidus, because it could be associated with serious underlying pathology.

Topics: Antidiuretic Agents; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes, Gestational; Diuretics; Female; Humans; Hydrochlorothiazide; Magnetic Resonance Imaging; Pituitary Gland, Posterior; Pregnancy; Puerperal Disorders; Ultrasonography, Prenatal; Vasopressins

Intensive care patients often suffer from hypo- or hypernatremia. These dysnatremias reflect an antidiuretic-hormone (ADH)-related water imbalance and are the result of the underlying disease. However, they are often triggered by drug side effects and exacerbated by an intentional or unintentional sodium imbalance. Dysnatremias are also caused by artificial ventilation; however, the mechanisms behind this are beyond the scope of this article. Considerations regarding etiology, water and sodium balance and, in particular, the variable in urine dilution or concentration, take priority over a brisk normalization of sodium concentration. Therefore, the 3 most important factors are: 1) delivery of water and sodium to the collecting duct; 2) generation and maintenance of an osmotic pressure gradient exerted by solutes present in the renal medullary interstitium; 3) the regulated water permeability of collecting duct cells under the control of antidiuretic hormone. With these, most disorders can already be identified from patient history and simple factors such as body weight and serum and urine osmolality.

Topics: Critical Care; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Sodium; Vasopressins; Water-Electrolyte Imbalance

Copeptin denominates the C-terminal fragment of the vasopressin (AVP) precursor hormone. Circulating copeptin levels reflect the activity of the AVP system and correlate closely with plasma osmolality. The measurement of stimulated plasma AVP levels is crucial in the differential diagnosis of diabetes insipidus, particularly the characterization of partial forms, and is used to diagnose primary polydipsia. However, determination of AVP levels is technically demanding, and validated assays are not readily available for clinical routine. Recently, a reliable sandwich immunoassay for measurement of serum or plasma copeptin levels has been introduced. Assaying stimulated copeptin levels will be helpful in the differential diagnosis of diabetes insipidus. Recent studies suggest that measurement of copeptin, once the assay is commercially available, might prove useful in the workup of hyponatremic disorders. Moreover, copeptin has been found to be a prognostically relevant biomarker in a variety of illnesses such as sepsis, shock, pneumonia, acute exacerbation of COPD, heart failure, and myocardial infarction.

Topics: Biomarkers; Diabetes Insipidus; Glycopeptides; Humans; Hyponatremia; Immunoassay; Prognosis; Protein Precursors; Vasopressins; Water-Electrolyte Imbalance

Vasopressin is a neuropeptide with multiple functions. In addition to its predominantly antidiuretic action after peripheral secretion from the posterior pituitary, it seems to fulfill--together with its receptor subtype--all requirements for a neuropeptide system critically involved in higher brain functions, including cognitive abilities and emotionality. Following somatodendritic and axonal release in distinct brain areas, vasopressin acts as a neuromodulator and neurotransmitter in multiple and varying modes of interneuronal communication. Accordingly, changes in vasopressin expression and release patterns may have wide-spread consequences. As shown in mice, rats, voles, and humans, central vasopressin release along a continuum may be beneficial to the individual, serving to adjust physiology and behavior in stressful scenarios, possibly at the potential expense of increasing susceptibility to disease. Indeed, if over-expressed and over-released, it may contribute to hyper-anxiety and depression-like behaviors. A vasopressin deficit, in turn, may cause signs of both diabetes insipidus and total hypo-anxiety. The identification of genetic polymorphisms underlying these phenomena does not only explain individual variation in social memory and emotionality, but also help to characterize potential targets for therapeutic interventions. The capability of both responding to stressful stimuli and mediating genetic polymorphisms makes the vasopressin system a key mediator for converging (i.e., environmentally and genetically driven) behavioral regulation.

Topics: Animals; Autistic Disorder; Brain; Diabetes Insipidus; Emotions; Humans; Mental Disorders; Polymorphism, Genetic; Schizophrenia; Social Behavior; Vasopressins

Topics: Aquaporin 2; Body Water; Dehydration; Diabetes Insipidus; Edema; Humans; Inappropriate ADH Syndrome; Kidney Concentrating Ability; Mutation; Osmolar Concentration; Sodium; Vasopressins

Disorders of water balance are a common feature of clinical practice. An understanding of the physiology and pathophysiology of the key endocrine regulator of water balance vasopressin (VP) is key to diagnosis and management of these disorders. Diabetes insipidus is the result of a lack of VP or (less commonly) resistance to the renal effects of the hormone. Diagnostic testing can clarify aetiology and direct appropriate management. VP production can be associated with hyponatraemia. A comprehensive assessment of cardiovascular status and pharmacological influences are needed in these circumstances to differentiate between primary (inappropriate) and secondary (appropriate) physiological VP production. As with diabetes insipidus, diagnostic testing can help define the aetiology of hyponatraemia and direct appropriate management. Patients with disorders of water balance benefit from a joint clinical and laboratory medicine approach to diagnosis and management.

Topics: Aquaporins; Body Water; Diabetes Insipidus; Diuresis; Humans; Hypernatremia; Hyponatremia; Kidney; Molecular Structure; Polyuria; Receptors, Vasopressin; Sodium; Thirst; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

Pre-operative central diabetes insipidus has been reported in 8-35% of patients affected with craniopharyngioma, and in 70-90% after surgery. The management of postoperative polyuria and polydipsia can be challenging and fluid balance needs to be closely monitored. The classical triphasic pattern of endogenous vasopressin secretion--an initial phase of symptomatic diabetes insipidus occurring 24 hours after surgery; a second phase of inappropriate vasopressin secretion potentially causing hyponatraemia; and a third phase with a return to diabetes insipidus occurring up to 2 weeks later--is often complicated by cerebral salt wasting and thirst disorders. Inadequate adrenal replacement therapy and anticonvulsant agent treatment may increase the risk of life-threatening hyponatraemia in the course of desmopressin (DDAVP) treatment. Appropriate management, in order to avoid life-threatening or disabling electrolyte disturbances, requires a good grasp of the relevant pathophysiology. We review here the pathophysiology and management of the multiple fluid disorders encountered following surgery for craniopharyngiomas.

Topics: Child; Craniopharyngioma; Diabetes Insipidus; Humans; Hyponatremia; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications; Thirst; Vasopressins; Water-Electrolyte Imbalance

Topics: Body Water; Diabetes Insipidus; Electrolytes; Humans; Hyperaldosteronism; Hypertension; Hypoaldosteronism; Inappropriate ADH Syndrome; Natriuretic Peptides; Renin-Angiotensin System; Vasopressins; Water-Electrolyte Imbalance

Water homeostasis in the body is finely balanced by the release of the antidiuretic hormone vasopressin and the stimulation of thirst. Vasopressin acts in the kidneys to concentrate urine and reduce plasma osmolality. Diabetes insipidus is a disorder of water balance characterized by a failure to concentrate urine. There are two types of diabetes insipidus: central and nephrogenic. Central diabetes insipidus is caused by insufficient production of vasopressin, while nephrogenic diabetes insipidus is caused by an impaired response of the kidneys to vasopressin. Patients with central diabetes insipidus respond to treatment with vasopressin or its synthetic analogue, desmopressin; however, caution should be utilized in treating infants with vasopressin or analogues-infants can be treated successfully with fluids alone. Treatment of nephrogenic diabetes insipidus involves removing the underlying cause, if possible, reducing solute load or therapy with a diuretic agent.

Topics: Animals; Antidiuretic Agents; Body Water; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Homeostasis; Humans; Infant; Vasopressins

Topics: Animals; Diabetes Insipidus; Humans; Radioimmunoassay; Vasopressins

Aquaporins are channels that facilitate movement of water across lipid bilayers. They are expressed in multiple tissues and are essential for regulation of body water homeostasis. The kidney is the main organ responsible for this regulation, and at least seven aquaporins are expressed at distinct sites in the kidney. Aquaporin expression correlates with observed water permeability of each nephron segment: proximal tubule and descending thin limb of Henle have constitutive high water permeability due to expression of AQP1, whereas collecting duct water permeability is tightly regulated by the antidiuretic hormone vasopressin via regulation of AQP2. This review aims at providing insight into renal aquaporins, with special focus on AQP2.

Topics: Animals; Aquaporin 2; Aquaporins; Body Water; Diabetes Insipidus; Humans; Kidney; Mice; Vasopressins

The widespread physiologic changes that follow brain stem death lead to a high incidence of complications in the donor and jeopardize vital organ function. Strategies for the management of organ donors exist whereby the rapid physiologic decline seen after brain stem death can be stabilized by active donor resuscitation so that the functional integrity of potentially transplantable organs is maintained. Understanding the complex physiologic changes that occur after brain stem death is crucial to the development of effective donor management strategies. This article reviews the pathophysiologic changes that occur after brain stem death and discusses controversies in donor management.

Topics: Brain Death; Brain Stem; Diabetes Insipidus; Disseminated Intravascular Coagulation; Endocrine System; Hormones; Humans; Hypotension; Insulin; Lung; Thyroid Gland; Tissue Donors; Vasopressins

Diabetes insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. In many patients, it is caused by the destruction or degeneration of the neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. Known causes of these lesions include: germinoma or craniopharyngioma; Langerhans cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma following surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Magnetic resonance imaging (MRI) allows identification of the posterior pituitary hyperintensity and of hypothalamic-pituitary abnormalities. Thickening of the pituitary stalk is the second most common finding on MRI scans in several local inflammatory pathologies and autoimmune diseases or germinoma, but it is not specific to any single subtype. A progressive increase in the size of the anterior pituitary gland should alert physicians to the possibility that a germinoma is present, whereas a decrease can suggest the presence of an inflammatory or autoimmune process. Most children with acquired central diabetes insipidus and a thickened pituitary stalk have anterior pituitary hormone deficiencies during follow-up. Biopsy of enlarged pituitary stalk should be reserved for patients with a hypothalamic-pituitary mass and progressive thickening of the pituitary stalk, since spontaneous recovery may occur.

Topics: Body Water; Diabetes Insipidus; Histiocytosis, Langerhans-Cell; Homeostasis; Humans; Magnetic Resonance Imaging; Pituitary Gland, Posterior; Vasopressins

Diabetes insipidus is a disorder of the water retaining ability of the organism. It is a polydipsic-polyuric syndrome caused by partial or complete vasopressin deficiency (central diabetes insipidus) or vasopressin resistance of the kidney tubules (nephrogenic diabetes insipidus) or increased water intake due to oversensitivity of the thirst centre (dipsogenic diabetes insipidus = primary polydipsia). The pathogenetic factors may affect the osmoreceptors, the vasopressinergic magnocellular nuclei of the hypothalamus, the median eminence, the pituitary stalk, the vasopressin release from the neurohypophysis, the vasopressin inactivating mechanisms and the renal structures mediating the antidiuretic effect of vasopressin. In the evaluation of the results of the diagnostic procedures, it is to be considered that long-term overhydration of any origin suppresses the vasopressin secretion and the "washout" effect of the long-term water-diuresis decreases the concentration gradient of the renal medulla leading to blunted sensitivity towards vasopressin. This is, why the differential diagnostics of central, nephrogenic and dipsogenic diabetes insipidus seems sometimes to be enigmatic. Central diabetes insipidus can be excluded only on the basis of proportional parallel increase of plasma osmolality and plasma vasopressin level. Similarly, nephrogenic diabetes insipidus will be excluded when plasma vasopressin increases proportionately with the increase of urinary osmolality. In equivocal cases T1-weighted MRI of the pituitary may be of help in the establishment of an exact diagnosis. As far as possible, the therapy is to be focused on the diabetes insipidus evoking basal diseases. In central diabetes insipidus, diuresis can be decreased by vasopressin substitution. The first choice compound for this purpose is 1-desamino-8-D-arginine-vasopressin. The non-vasopressin containing oral antidiuretics have become outdated in the treatment of central diabetes insipidus. There is no specific treatment for nephrogenic and dipsogenic diabetes insipidus, so far. Nephrogenic diabetes insipidus can be influenced by non-steroidal antiinflammatory agents or diuretics. Their combined administration is even more effective, however, still does not exceed a 50-percent mitigation in diuresis.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Magnetic Resonance Imaging; Osmolar Concentration; Pituitary Gland, Posterior; Renal Agents; Vasopressins

Topics: Diabetes Insipidus; Diagnosis, Differential; Diuretics; Humans; Inappropriate ADH Syndrome; Vasopressins; Water-Electrolyte Imbalance

Animal models of genetic hormone deficiency are useful as models for physiological studies of hormone deficiency and hormone action. Structure-function studies of the specific underlying gene defect may help in understanding mechanisms regulating gene expression and secretion of the peptide product. Spontaneous genetic models of vasopressin deficiency, such as the Brattleboro rat and human familial diabetes insipidus, have facilitated many studies of vasopressin. However, the Brattleboro rat may not be an ideal model of genetic vasopressin deficiency and therefore could be less useful for studies of the central nervous system or as a background strain for the introduction of new vasopressin gene constructs. The human model is appropriately limited by the constraints of human studies, so that engineered animal models of specific diseases, such as familial neurohypophysial diabetes insipidus, are required. The recent development of a vasopressin-null mouse may provide insights into the various roles of vasopressin in the stress response, cardiovascular regulation and behaviour. Additionally, animals with a complete genetic deficiency of vasopressin can serve as a background strain for introduction of novel vasopressin gene constructs to enable sophisticated studies of the regulation of vasopressin expression and the intracellular processes required for appropriate secretion of vasopressin peptide. As advanced techniques of genetic manipulation become more reliable, conditional expression of vasopressin, regulated by time or body site will permit even more detailed studies in this field.

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Humans; Mice; Mice, Transgenic; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Vasopressins

After the story of success of hormone blockers for catecholamines, aldosterone and angiotensin II and their successful implementation into clinical practice another endocrine cardiovascular system has come into focus. It has long been known, that the hormone vasopressin plays an important role in peripheral vasoconstriction, hypertension and in several disease conditions with dilutional hyponatremia in edematous disorders, like congestive heart failure, liver cirrhosis, SIADH and nephrotic syndrome. A series of orally active nonpeptide antagonists against the vasopressin receptor subtypes has recently been synthesized and is now under intensive examination. Nonpeptide V1a-receptor specific antagonists, OPC 21268 and SR 49059, nonpeptide V2-receptor specific antagonists, SR 121463 A and VPA 985, and combined V1a-/V2-receptor antagonists, OPC 31260 and YM 087, have become available for clinical research. AVP-V2-receptor antagonists lead to a dose-dependent diabetes insipidus in animals and man. The term aquaretic drugs (aquaretics) has been coined for these drugs to highlight their different mechanism compared to the saluretic diuretic furosemide. V1a-receptor antagonists might offer new therapeutic advantages in the treatment of vasoconstriction and hypertension. Combined V1a-/V2-receptor antagonists might be beneficial in the treatment of congestive heart failure. Early results are promising and now need to be confirmed in large clinical studies.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Antihypertensive Agents; Diabetes Insipidus; Hormone Antagonists; Humans; Vasodilator Agents; Vasopressins

Topics: Algorithms; Critical Care; Decision Trees; Diabetes Insipidus; Diagnosis, Differential; Humans; Patient Discharge; Patient Education as Topic; Prognosis; Vasopressins

Topics: Arginine Vasopressin; Diabetes Insipidus; Humans; Mutation; Protein Precursors; Vasopressins

Topics: Adolescent; Adult; Body Water; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Homeostasis; Humans; Infant; Magnetic Resonance Imaging; Polyuria; Renal Agents; Vasopressins

Thirst and drinking are essential components of normal osmoregulation in healthy man. Abnormalities of thirst appreciation, in particular hypodipsia, have profound implications for water homeostasis. The combination of cranial diabetes insipidus and hypodipsia can have particularly serious consequences, with the potential for life-threatening hyponatraemia. Although the tools for measuring thirst are subjective and lack true specificity, their use in clinical research has contributed greatly to our understanding of the physiology of thirst appreciation and the abnormal control of thirst in osmoregulatory disorders. The precise neural control of thirst appreciation remains unknown, and perhaps as a result of this, satisfactory therapies for the treatment of disorders of thirst have not yet been developed; behavioural modification and retraining of drinking habits remain the rather limited cornerstones of management.

Topics: Adult; Aged; Aging; Brain Neoplasms; Diabetes Insipidus; Diabetes Mellitus; Drinking; Humans; Inappropriate ADH Syndrome; Middle Aged; Schizophrenia; Thirst; Vasopressins; Water-Electrolyte Balance

Vasopressin, released from the posterior pituitary and from the vascular endothelium, can cause vasoconstriction and provoke platelet aggregation, leading to an impaired tissue blood supply. In humans with pituitary diabetes insipidus the central release of vasopressin is diminished, and in the Brattleboro homozygous rat there is congenitally no synthesis of this hormone. The gastroduodenal intramucosal vasopressin level is elevated in normal rats following various acute ulcerogenic challenges (after ethanol, reserpine, indomethacin, cold-restraint stress, endotoxin shock and hemorrhagic shock), and vasopressin-deficient rats are less sensitive to these stimuli. In a hospital- and population-based case-control, age-matched retrospective study, the incidence of human gastroduodenal ulceration is significantly higher in the normal population (in whom the release of vasopressin is presumed to be intact) than in the vasopressin-deficient one (central diabetes insipidus patients). In conclusion, endogenous vasopressin plays an aggressive role in development of gastroduodenal ulceration, especially that related to stress.

Topics: Adult; Aged; Animals; Case-Control Studies; Diabetes Insipidus; Humans; Incidence; Middle Aged; Peptic Ulcer; Rats; Rats, Brattleboro; Stress, Physiological; Vasoconstrictor Agents; Vasopressins

Topics: Diabetes Insipidus; Diagnosis, Differential; Humans; Inappropriate ADH Syndrome; Pituitary Function Tests; Pituitary Gland, Posterior; Polyuria; Vasopressins; Water; Water Deprivation

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Humans; Pituitary Function Tests; Pituitary Gland, Anterior; Vasoconstrictor Agents; Vasopressins

The aquaporins are a recently recognized family of water channels that mediate water transport in kidney and in other organs. Aquaporin-2, 'vasopressin-regulated water channel', is regulated by vasopressin in two ways to account for overall control of collecting duct water permeability. First, vasopressin has a short-term effect in triggering translocation of aquaporin-2-containing intracytoplasmic vesicles to the apical plasma membrane, thus increasing principal cell water permeability. Second, vasopressin has a long-term effect in increasing the abundance of aquaporin-2 in collecting duct principal cells, increasing the maximal attainable water permeability. Using animal models, defects in these control mechanisms have been shown to be associated with several disorders of water balance, including central diabetes insipidus, congenital nephrogenic diabetes insipidus, acquired diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, and several extracellular fluid volume expanded states.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Drinking; Extracellular Space; Humans; Inappropriate ADH Syndrome; Ion Channels; Kidney Tubules, Collecting; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Mutation; Vasopressins

Topics: Animals; Body Water; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Vasopressins

Topics: Animals; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Benzeneacetamides; Body Water; Demeclocycline; Diabetes Insipidus; Dogs; Humans; Kidney; Liver Cirrhosis; Liver Cirrhosis, Experimental; Loop of Henle; Pyrrolidines; Rats; Receptors, Opioid; Vasopressins; Water-Electrolyte Balance

Topics: Aging; Animals; Child; Diabetes Insipidus; Female; Humans; Male; Mutation; Pituitary Gland, Posterior; Receptors, Vasopressin; Vasopressins; Water-Electrolyte Imbalance

Diabetes insipidus, characterized by the excretion of copious volumes of unconcentrated urine, results from a deficiency in the action of the antidiuretic hormone arginine vasopressin and can be caused by any of four fundamentally different defects, including impaired secretion (neurohypophyseal diabetes insipidus), impaired renal response (nephrogenic diabetes insipidus), excessive fluid intake (primary polydipsia), or increased metabolism of the hormone (gestational diabetes insipidus). Differentiation between their causes, pathophysiology, and treatment methods is essential for effective management and is best achieved by a combination of hormonal, clinical, and neuroradiologic observations. Understanding of the genetic forms has advanced greatly and may soon lead to improved methods of prevention, diagnosis, and treatment.

Topics: Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diagnosis, Differential; Female; Humans; Male; Osmolar Concentration; Polyuria; Pregnancy; Vasopressins

Differential diagnosis of diabetes insipidus has been discussed in this paper in terms of pathophysiological aspects. Three points are emphasized: (1) we should include dipsogenic D.I. as one form of diabetes insipidus; (2) the water deprivation test is inconclusive in approximately 25% of patients, where the main difficulty is to distinguish between partial neurogenic D.I. and dipsogenic D.I.; and (3) this difficulty cannot be solved by a single determination of plasma vasopressin. Pathophysiology of inherited neurogenic D.I. and nephrogenic D.I. are also discussed.

Topics: Animals; Diabetes Insipidus; Diagnosis, Differential; Humans; Lithium; Mutation; Receptors, Vasopressin; Vasopressins; Water Deprivation

The hypothalamic paraventricular nucleus (PVN) plays a pivotal role in the regulation of endocrine processes and the modulation of autonomic functions. The multi-channel outputs of the nucleus are directed toward the anterior and posterior lobes of the pituitary, autonomic centers, and limbic structures. Counterbalancing the wide spectrum of efferent projections, the nucleus receives humoral signals from endocrine glands and neuronal afferents from several loci of the brain. The multiple functions of the nucleus are executed by neurons that are organized in distinct subnuclei and display complex chemotypes. The review demonstrates and discusses the organization, architecture, chemical composition, plasticity, and pathology of paraventricular neurons of the rat hypothalamus from the perspective of ultrastructural analysis. Electron microscopy--by its high resolution--offers a powerful tool that is suitable for revealing the structural background of physiological processes that modulate and govern the operation of paraventricular neurons.

Topics: Afferent Pathways; Animals; Brain Tissue Transplantation; Diabetes Insipidus; Efferent Pathways; Feedback; Humans; Hypothalamic Hormones; Hypothalamo-Hypophyseal System; Hypothalamus; Lactation; Microscopy, Electron; Nerve Regeneration; Neurons; Neurotransmitter Agents; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Receptors, Cell Surface; Vasopressins

The authors describe several useful surgical techniques from our experiences in transsphenoidal microsurgery for pituitary adenomas. Intentional two-staged transsphenoidal removal with open sella floor and intrasellar drainage is available for most of giant adenomas with suprasellar extension. The open sella floor method and intrasellar drainage after first transsphenoidal adenomectomy accelerate to decrease the suprasellar tumor extension. In four of six patients in our series, macroscopically total selective adenomectomy was achieved by a second transsphenoidal operation without complications. As for extremely small microadenomas, represented in patients with Cushing's disease, stepwise systemic search is required to identify a subcortical microadenoma, preserving postoperative pituitary function. Edge resection around the microadenoma is also necessary for normalization of hormonal hypersecretion and permanent cure.

Topics: Adenoma; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hydrocortisone; Hypophysectomy; Pituitary Neoplasms; Postoperative Care; Vasopressins

Although the majority of patients with pituitary tumor, undergoing transsphenoidal microsurgery, have a low incidence of hormonal deficiency after surgery, the endocrinological evaluations should be carefully done before and after surgery. Glucocorticoid replacement is necessary in patients with Cushing's disease during and after surgery as well as those with adrenal insufficiency. Repeated CRF test is useful to assess the secondary adrenal insufficiency of Cushing's disease after surgery. Patients with impaired secretion of both ACTH and TSH should receive glucocorticoid replacement before thyroid hormone replacement in order to avoid adrenal crisis. A combination of CRF, GRF, TRH and GnRH is a safer and more reliable test to evaluate pituitary function than the conventional triple test consisting of insulin, TRH and GnRH, especially in patients predicted to have pituitary-adrenal insufficiency. Diabetes insipidus(DI), immediately after pituitary surgery, should be treated with subcutaneous injection of Pitressin. Even if patients seem to have recovered from DI several days after surgery, they must be monitored closely because of the incidence of triphasic DI. Less attention has been given to replacement for GH deficiency in adults. Recent reports revealed that GH replacement in adults with GH deficiency decreases visceral fat tissue and increases plasma calcium, phosphorus, osteocalcin and procollagen III levels. GH replacement will become more popular even in adults. Many options and technological advantages in the diagnosis and treatment of pituitary tumors have developed in a decade. In the near future, post-operative patients with pituitary tumors must be cared for in view of the "quality of life".

Topics: Adenoma; Diabetes Insipidus; Female; Follow-Up Studies; Humans; Hydrocortisone; Hypophysectomy; Male; Pituitary Neoplasms; Postoperative Care; Vasopressins

Topics: Diabetes Insipidus; Gene Expression; Humans; Molecular Biology; Molecular Conformation; Protein Precursors; Vasopressins

Topics: Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Hypothalamus; Protein Precursors; Rats; Rats, Brattleboro; Sodium Chloride; Vasopressins

Cranial diabetes insipidus (DI) arises when release of arginine vasopressin (AVP, antidiuretic hormone) in response to osmotic stimuli is inadequate. The correct diagnosis and management of cranial DI is particularly important when it arises as an acute complication of surgery, trauma or in subjects who lack thirst sensation. Desmopressin (1-desamino-8-D-arginine-vasopressin, DDAVP) provides an effective and convenient replacement therapy when given by the intranasal route. However, nasal administration is difficult for some patients, and in the future oral or transcutaneous desmopressin formulations may prove to be satisfactory alternatives. By contrast, treatments for nephrogenic DI, where there is failure of the antidiuretic response to endogenous or exogenous vasopressin, have been disappointing and water replacement remains the mainstay of therapy. An understanding of the physiology and pathophysiology of water homeostasis and correct interpretation of water balance and electrolyte data are essential for correct diagnosis and management of all cases of DI.

Topics: Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypernatremia; Kidney Diseases; Male; Pregnancy; Pregnancy Complications; Thirst; Vasopressins

Topics: Autoantibodies; Autoimmune Diseases; Child; Diabetes Insipidus; Fetus; Humans; Hypothalamus; Vasopressins

To review the pathophysiology, diagnosis, and treatment of the syndromes of diabetes insipidus with an emphasis on those situations likely to be encountered in the critical care setting.. Extensive clinical experience and relevant publications from the English literature identified via MEDLINE search, citation in reviews, publications of original data, and endocrine texts.. Landmark papers pertaining to all aspects of diabetes insipidus were selected. Reviews, primary articles, and case reports pertaining to diabetes insipidus in the critical care setting were identified and selected according to their content of clinically useful information.. Diabetes insipidus may result from impaired synthesis and release of vasopressin from the hypothalamic-pituitary unit (neurogenic) or renal insensitivity to circulating vasopressin (nephrogenic). A number of interventions, diseases, and drugs commonly encountered in the critical care setting may result in the development or exacerbation of diabetes insipidus. The diagnosis of diabetes insipidus requires the exclusion of other causes of polyuria and a systematic demonstration of the response of homeostatic mechanisms to controlled dehydration. The treatment of diabetes insipidus depends on many factors, including the clinical setting, degree and pathophysiologic classification, ability of the patient to compensate for free water losses, and expected duration of the abnormality. Underlying disorders should be treated appropriately whenever possible.

Topics: Blood Volume; Critical Care; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Hemodynamics; Humans; Hydrochlorothiazide; Osmolar Concentration; Plasma; Urinalysis; Vasopressins; Water Deprivation

In a strain of mice called DI +/+ Severe, nephrogenic (or vasopressin-resistant) diabetes insipidus is caused by an inability of the antidiuretic hormone (ADH, or vasopressin) to increase the water permeability of the renal collecting system. That inability, in turn, arises from abnormally high activity of the enzyme cAMP-phosphodiesterase, specifically of the isozyme type III (PDE-III), which hydrolyzes cAMP and prevents the intracellular buildup of this second messenger. Two rather specific inhibitors of PDE-III, rolipram and cilostamide, used either in vitro or in vivo, reverse the deficiencies in DI +/+ Severe mice by increasing intracellular cAMP and water permeability toward or to their normal values. These results have implications for the treatment of nephrogenic diabetes insipidus in human patients.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Body Water; Cyclic AMP; Diabetes Insipidus; Kidney Concentrating Ability; Mice; Permeability; Phosphodiesterase Inhibitors; Pyrrolidinones; Quinolones; Rolipram; Vasopressins

The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism, in 6 with Addison's disease, and in 21 with central diabetes insipidus (CDI). In the latter disease the effect of histamine stimulus was also evaluated. Plasma AVP was measured by radioimmunoassay (RIA). Patients with primary hypothyroidism were classified into subgroups with elevated or normal basal levels of plasma AVP. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels. Patients with Addison's disease exhibited an increased basal level of plasma AVP and a decreased osmotic threshold. CDI patients according to their AVP responses on osmotic stimulus fell into two groups: CDI I gave no response at all, while CDI II responded subnormally. CDI II exhibited blunted AVP release to histamine. The AVP reactions of the CDI I patients fell into two subgroups: CDI I/A had undetectable plasma AVP, whereas histamine evoked AVP release in CDI I/B. Patients with CDI II suffer from a partial CDI, while those with CDI I/A represent a complete form of the disease and CDI I/B presumably have an osmoreceptor failure.

Topics: Addison Disease; Adult; Arginine; Diabetes Insipidus; Female; Humans; Hypothyroidism; Male; Middle Aged; Saline Solution, Hypertonic; Vasopressins; Water-Electrolyte Balance

Arginine vasopressin preparations have been used in the treatment of diabetes insipidus for many years. Compared with older antidiuretic agents, the synthetic analog desmopressin is more potent, longer acting and easier to use. It is available for intravenous, subcutaneous and intranasal administration. Desmopressin may be useful in the treatment of hemostatic disorders such as von Willebrand's disease and hemophilia A. It has also been used for nocturnal enuresis. The vasopressor effects of arginine vasopressin preparations have been exploited for use as a temporizing measure in controlling acute gastrointestinal bleeding. Side effects such as hyponatremia and water intoxication are uncommon when these drugs are used with proper precautions.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Enuresis; Gastrointestinal Hemorrhage; Hemorrhagic Disorders; Humans; Vasopressins

Topics: Animals; Brain; Cardiovascular System; Diabetes Insipidus; Humans; Oropharynx; Osmolar Concentration; Postoperative Complications; Vasopressins; Water-Electrolyte Imbalance

Topics: Adrenocorticotropic Hormone; Animals; Arachidonic Acids; Cattle; Diabetes Insipidus; Glycolysis; Humans; Inappropriate ADH Syndrome; Liver; Pituitary Diseases; Pituitary Gland, Posterior; Rats; Second Messenger Systems; Signal Transduction; Vasopressins

Topics: Animals; Base Sequence; Brain; Diabetes Insipidus; DNA; Gene Expression Regulation; Neurophysins; Vasopressins

Topics: Animals; Base Sequence; Cloning, Molecular; Diabetes Insipidus; Oxytocin; Protein Biosynthesis; Rats; RNA, Messenger; Tissue Distribution; Vasopressins

Topics: Benzothiadiazines; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuretics; Humans; Hypothalamo-Hypophyseal System; Pituitary Diseases; Postoperative Complications; Prognosis; Prostaglandin Antagonists; Sodium Chloride Symporter Inhibitors; Vasopressins

Topics: Adolescent; Adult; Child; Child, Preschool; Cyclic AMP; Diabetes Insipidus; Dinoprostone; Female; Genes, Recessive; Humans; Hydrochlorothiazide; Indomethacin; Infant; Infant, Newborn; Kidney Tubules; Kidney Tubules, Collecting; Male; Prostaglandins E; Sodium; Vasopressins

Topics: Animals; Blood; Blood Pressure; Blood Volume; Diabetes Insipidus; Diuresis; Female; Humans; Hyperaldosteronism; Hypernatremia; Hyponatremia; Hypothalamus; Lung Neoplasms; Nausea; Osmolar Concentration; Pituitary Gland, Posterior; Pregnancy; Pressoreceptors; Sodium; Thirst; Urine; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

Topics: Animals; Antibodies; Avoidance Learning; Behavior, Animal; Brain; Diabetes Insipidus; Humans; Injections, Intraventricular; Memory; Structure-Activity Relationship; Vasopressins

Topics: Action Potentials; Animals; Diabetes Insipidus; Electric Conductivity; Electrophysiology; Evoked Potentials; Hippocampus; Hypothalamus; Injections, Intraventricular; Iontophoresis; Neurons; Neurotransmitter Agents; Oxytocin; Perfusion; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Amino Acid Sequence; Animals; Axonal Transport; Cytoplasmic Granules; Diabetes Insipidus; Glycopeptides; Hypothalamus; Molecular Weight; Neurons; Neurophysins; Oxytocin; Peptide Hydrolases; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Protein Precursors; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Animals; Brain; Corticotropin-Releasing Hormone; Diabetes Insipidus; Follicle Stimulating Hormone; Growth Hormone; Hormones; Hypothalamus; Luteinizing Hormone; Neurophysins; Oxytocin; Pituitary Hormones, Posterior; Prolactin; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Thyrotropin; Vasopressins

Topics: Adrenal Glands; Animals; Dehydration; Diabetes Insipidus; Diet; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Hemodynamics; Kidney; Osmolar Concentration; Potassium; Prostaglandins; Rats; Rats, Brattleboro; Rats, Mutant Strains; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Arginine Vasopressin; Blood Pressure; Blood Volume; Cardiac Output; Catecholamines; Desoxycorticosterone; Diabetes Insipidus; Drug Interactions; Hemodynamics; Hemorrhage; Homeostasis; Humans; Hypertension; Immune Sera; Pressoreceptors; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vascular Resistance; Vasopressins

It has been demonstrated through the use of new techniques that the action of vasopressin on the kidneys is not limited to changing the water permeability of distal tubules and collecting ducts. However, it has yet to be established whether these additional actions, such as lowering Kf (possibly by contracting mesangial cells), or increasing postglomerular vascular resistance, are important factors in the control of GFR and renal blood flow. The use of animals with diabetes insipidus, particularly the Brattleboro homozygous (DI) rat, may help to circumvent a number of methodological problems and provide a useful model for assessing the role of vasopressin in the control of renal hemodynamics. Although that role may be exerted through a direct effect on the vascular tone, it may be an indirect effect in which the antidiuretic action of vasopressin alters fluid balance and elicits secondary changes in other vasoactive hormones. The complexity of this latter possibility suggests that other methodological problems (in the measurement and/or control of the related variables) may complicate the final resolution of this issue for some time to come.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Disease Models, Animal; Diuresis; Glomerular Filtration Rate; Hemodynamics; Kidney; Oxytocin; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renal Circulation; Vascular Resistance; Vasopressins

Topics: Angiotensin II; Animals; Aorta; Arterioles; Blood Pressure; Catecholamines; Diabetes Insipidus; Female; Homeostasis; Male; Microcirculation; Mononuclear Phagocyte System; Muscle Contraction; Muscle, Smooth, Vascular; Oxytocin; Phagocytosis; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Shock; Vasopressins; Wounds and Injuries

Topics: Animals; Avoidance Learning; Behavior, Animal; Diabetes Insipidus; Discrimination Learning; Extinction, Psychological; Learning; Memory; Oxytocin; Rats; Rats, Brattleboro; Rats, Mutant Strains; Retention, Psychology; Vasopressins

Topics: Animals; Axons; Cytoplasmic Granules; Diabetes Insipidus; Endoplasmic Reticulum; Golgi Apparatus; Hypothalamus; Microtubules; Models, Biological; Nerve Endings; Neurons; Neurophysins; Neurosecretory Systems; Oxytocin; Peptides; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

The total restoration of urinary concentrating ability of the DI rat given daily injections of vasopressin takes several weeks, although complete osmotic equilibrium across the collecting duct is manifest within hours. This suggests that there may be other deficiencies of the renal concentrating mechanism that, if corrected by vasopressin treatment, are corrected more slowly. I have focussed on just three possibilities. First, the morphology of the medullary interstitium is different from normal rats. Perhaps associated with this finding are alterations in the levels of medullary glycosaminoglycans which may have a role to play in water balance. Functional and morphological changes in the juxtamedullary nephrons are also evident. Second, the possibility exists that the countercurrent multiplier of the DI rat operates less efficiently than in the normal animal. Finally, reduced synthesis of PGs in the renal medulla of DI rats may also influence the concentrating mechanism, although in a favorable direction. While most (if not all) of these differences are secondary to the lack of vasopressin, in some instances it appears that it is the high water turnover (possibly the altered chemical composition of the medullary interstitium) that is the primary culprit. While the DI rat remains an excellent model for the study of water balance and the action of vasopressin, the presence of multiple defects within the system should be borne in mind. This is particularly true when comparing data obtained following acute treatment with vasopressin versus that following chronic treatment.

Topics: Adenylyl Cyclases; Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Disease Models, Animal; Glomerular Filtration Rate; Glycosaminoglycans; Kidney; Kidney Concentrating Ability; Kidney Medulla; Loop of Henle; Nephrons; Osmolar Concentration; Prostaglandins; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Drinking Behavior; Electroshock; Hypothalamus, Anterior; Kinetics; Male; Osmolar Concentration; Rats; Rats, Brattleboro; Rats, Mutant Strains; Reflex, Startle; Vasopressins

Topics: Aging; Animals; Animals, Newborn; Arginine Vasopressin; Body Water; Brain; Cell Count; Cerebellum; Cerebral Cortex; Diabetes Insipidus; DNA; Female; Male; Olfactory Bulb; Organ Size; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

A new approach to the classification of disorders of urinary concentration and dilution is recommended based on recent studies of how the kidney elaborates a urine of widely varying osmolality. The capacity to concentrate urine depends on ft, the fractional reabsorption of solute delivered to the loop of Henle; fu, the excretion of solute relative to the sum of solute excretion and solute delivery to Henle's loop; fw, the fraction of solute loss by vascular outflow from the medulla relative to that reabsorbed by the loop; and finally, collecting duct response to antidiuretic hormone (ADH). A decrease in ft or in increased fu or fw will diminish urinary concentrating ability, as will resistance of the tubule to ADH. Conversely, urinary dilution depends on the delivery of sodium and water to the ascending limb; NaCl reabsorption by the ascending limb; and the absence of ADH. A decrease in sodium and water delivery to the ascending limb or in NaCl reabsorption by the ascending limb will impair urinary diluting ability, as will the presence of ADH. The consequences of disorders in urinary concentrating and diluting ability vary widely. In an alert patient with an intact thirst center, there may be no consequence; in a patient unable to communicate thirst or whose thirst center is deranged, the results may be catastrophic. Keeping in mind the kidney's few basic requirements for formation of concentrated or dilute urine may help the physician avoid these potentially serious dislocations of water balance.

Topics: Absorption; Animals; Body Water; Diabetes Insipidus; Humans; Kidney Concentrating Ability; Kidney Diseases; Kidney Medulla; Loop of Henle; Osmolar Concentration; Potassium; Sodium; Vasopressins

Topics: Anti-Inflammatory Agents; Chlorpropamide; Diabetes Insipidus; Female; Furosemide; Humans; Inappropriate ADH Syndrome; Male; Polyuria; Vasopressins

Topics: Adenylyl Cyclases; Animals; Cyclic AMP; Diabetes Insipidus; Diuresis; Dogs; Guinea Pigs; Humans; Kidney; Kidney Medulla; Kidney Tubules, Collecting; Potassium; Prostaglandins; Prostaglandins E; Rats; Regional Blood Flow; Thirst; Vasopressins; Water

Topics: Aged; Benzothiadiazines; Carbamazepine; Clofibrate; Diabetes Insipidus; Diagnosis, Differential; Diuretics; Humans; Hypoglycemic Agents; Hypothalamic Diseases; Hypothalamic Neoplasms; Hypothalamus; Sodium Chloride Symporter Inhibitors; Vasopressins

Topics: Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Osmolar Concentration; Pituitary Function Tests; Vasopressins

Topics: Animals; Arginine Vasopressin; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Lypressin; Vasopressins; Water-Electrolyte Imbalance

Topics: Anesthesia; Brain Neoplasms; Diabetes Insipidus; Humans; Surgical Procedures, Operative; Vasopressins

The clinical features, genetics, pathophysiology, and management of endocrine diseases in which primary hormone resistance is the fundamental defect have been reviewed. Primary hormone resistance has been documented for nearly all hormones--vasopressin, parathyroid hormone, growth hormone, adrenocroticotropin, thyrotropin, gonadotropins, insulin, androgens, cortisol, aldosterone, progesterone, thyroid hormones, and vitamin D. A striking exception is estradiol, a steroid that may be vital for early embryonic development. Most of the hormone unresponsiveness syndromes represent only partial defects, and it is likely that most such patients go unrecognized. Therefore, hormone resistance should be suspected not only when a patient presents with hypofunction of particular endocrine system combined with high endogenous hormone levels but also whenever apparently normal function of an endocrine system is associated with inappropriately elevated levels of the corresponding hormone. The value of these defects in hormone responsiveness as a natural laboratory for the study of the normal mechanisms of hormone action is discussed.

Topics: Adrenocorticotropic Hormone; Diabetes Insipidus; Endocrine System Diseases; Gonadal Steroid Hormones; Growth Hormone; Hormones; Humans; Insulin; Insulin Resistance; Parathyroid Hormone; Thyrotropin; Vasopressins

Arginine vasotocin, arginine vasopressin, and oxytocin play a critical role in the stimulation of labor and delivery and in salt and water homeostasis in the newborn infant. The authors present information on their chemistry, secretion, and metabolism, and discuss the clinical effects upon target organs of their presence or absence.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Female; Fetus; Humans; Inappropriate ADH Syndrome; Infant, Newborn; Infant, Newborn, Diseases; Oxytocin; Pituitary Gland; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Pregnancy; Vasopressins; Vasotocin

Water balance is tightly regulated within a tolerance of less than 1 percent by a physiologic control system located in the hypothalamus. Body water homeostasis is achieved by balancing renal and nonrenal water losses with appropriate water intake. The major stimulus to thirst is increased osmolality of body fluids as perceived by osmoreceptors in the anteroventral hypothalamus. Hypovolemia also has an important effect on thirst which is mediated by arterial baroreceptors and by the renin-angiotensin system. Renal water loss is determined by the circulating level of the antidiuretic hormone, arginine vasopressin (AVP). AVP is synthesized in specialized neurosecretory cells located in the supraoptic and paraventricular nuclei in the hypothalamus and is transported in neurosecretory granules down elongated axons to the posterior pituitary. Depolarization of the neurosecretory neurons results in the exocytosis of the granules and the release of AVP and its carrier protein (neurophysin) into the circulation. AVP is secreted in response to a wide variety of stimuli. Change in body fluid osmolality is the most potent factor affecting AVP secretion, but hypovolemia, the renin-angiotensin system, hypoxia, hypercapnia, hyperthermia and pain also have important effects. Many drugs have been shown to stimulate the release of AVP as well. Small changes in plasma AVP concentration of from 0.5 to 4 muU per ml have major effects on urine osmolality and renal water handling.

Topics: Adolescent; Adult; Aged; Animals; Arginine Vasopressin; Blood Volume; Body Fluids; Body Water; Child; Child, Preschool; Dehydration; Diabetes Insipidus; Dogs; Female; Homeostasis; Humans; Hyperaldosteronism; Hypothalamus; Infant; Infant, Newborn; Kidney; Male; Middle Aged; Osmosis; Rats; Sheep; Thirst; Vasopressins; Water-Electrolyte Balance

Topics: Diabetes Insipidus; Endocrine System Diseases; Female; Humans; Kidney Diseases; Male; Neurophysins; Osmolar Concentration; Oxytocin; Pituitary Function Tests; Polyuria; Radioimmunoassay; Vasopressins

Topics: Adolescent; Adult; Child; Child, Preschool; Diabetes Insipidus; Follow-Up Studies; Humans; Hydronephrosis; Hypothalamo-Hypophyseal System; Infant; Kidney Concentrating Ability; Pituitary Gland, Posterior; Vasopressins

Topics: Brain Diseases; Diabetes Insipidus; Electrolytes; Humans; Hypernatremia; Hyponatremia; Postoperative Complications; Vasopressins; Water; Water Intoxication; Water-Electrolyte Imbalance

Topics: Adrenocorticotropic Hormone; Animals; Benzothiadiazines; Chlorpropamide; Corticotropin-Releasing Hormone; Diabetes Insipidus; Disease Models, Animal; Diuresis; Diuretics; Female; Hypothalamus; Male; Pituitary Gland, Anterior; Rats; Sodium Chloride Symporter Inhibitors; Thyroid Gland; Vasopressins; Water-Electrolyte Imbalance

Topics: Contraceptives, Oral; Diabetes Insipidus; Diethylstilbestrol; Estrogens; Female; Humans; Kinetics; Male; Neurophysins; Nicotine; Osmolar Concentration; Oxytocin; Posture; Smoking; Surgical Procedures, Operative; Syndrome; Vasopressins

Topics: Arginine Vasopressin; Biological Assay; Diabetes Insipidus; Humans; Oxytocin; Pituitary Gland, Posterior; Radioimmunoassay; Syndrome; Vasopressins; Water Deprivation

Topics: Animals; Blood Volume; Diabetes Insipidus; Dog Diseases; Dogs; Humans; Kidney Concentrating Ability; Polyuria; Rats; Specific Gravity; Thirst; Vasopressins; Water Deprivation

Topics: Animals; Anura; Chlorpropamide; Diabetes Insipidus; Diabetes Mellitus; Dogs; Humans; Prostaglandins E; Rabbits; Rats; Urinary Bladder; Vasopressins

Topics: Adult; Animals; Body Fluid Compartments; Body Fluids; Body Water; Brain; Dehydration; Diabetes Insipidus; Extracellular Space; Glucose; Homeostasis; Humans; Hyperglycemia; Infant, Newborn; Intracellular Fluid; Male; Osmolar Concentration; Plasma; Sodium; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

A synthetic vasopressin analog, 1-desamino-8D-arginine vasopressin (DDAVP also known as desmopressin), was found to be highly effective in the treatment of seven children and one adult with vasopressin-sensitive diabetes insipidus. The average duration of action of DDAVP was 10 to 11 hours, and with proper adjustment of dose, the subjects were able to control their symptoms satisfactorily with one or two inhalations daily. The youngest child in whom adequate control was achieved was 2 years of age. All subjects found the use of intranasal DDAVP superior to other forms of therapy, and none experienced any known side-effects after six months of treatment. All subjects in this study are currently using 2.5 mug to 10 mug of DDAVP once or twice daily.

Topics: Adolescent; Adult; Arginine Vasopressin; Child; Child, Preschool; Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Infant; Osmolar Concentration; Vasopressins

This chapter has sought to gather together the background information on systems controlling homoeostasis of salt and water and their clinical derangement. The temptation to adopt an all-embracing approach to the management of these problems is strong but such an approach is difficult to achieve and indeed dangerous. The circumstances of each sick infant are unique and plans for treatment must be individually tailored and flexible, dependent upon clinical and biochemical progress. Future developments in this field are likely to involve further understanding of renal and hormonal control of fluid and electrolyte and it might be expected that as new methods of management emerge they will be accompanied by their own peculiar risks of inducing secondary homoeostatic disturbances. With regard to infant feeding each advance appears to underline the desirability of breast feeding and support current moves toward provision of low solute feeds for those who are artificially fed. Paediatricians should be vocal in their advocation of breast feeding and ensure that the major principles of salt and water handling are understood by all who work with small infants. An extra scoop of powdered milk can be more of a poison than a food.

Topics: Aldosterone; Angiotensin II; Blood Volume; Diabetes Insipidus; Humans; Infant, Newborn; Infant, Newborn, Diseases; Kidney; Metabolism; Natriuresis; Nutritional Requirements; Osmolar Concentration; Potassium; Prolactin; Renin; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Benzothiadiazines; Body Water; Diabetes Insipidus; Diuretics; Humans; Hypernatremia; Hypertension, Renal; Hyponatremia; Hypothalamus; Infusions, Parenteral; Kidney Concentrating Ability; Osmotic Pressure; Pituitary Gland; Sodium; Sodium Chloride; Sodium Chloride Symporter Inhibitors; Vasopressins

Topics: Adrenal Glands; Animals; Aorta; Blood Volume; Carotid Arteries; Diabetes Insipidus; Heart Atria; Humans; Hypothalamo-Hypophyseal System; Neurons; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Portal System; Saline Solution, Hypertonic; Secretory Rate; Sensory Receptor Cells; Stimulation, Chemical; Stress, Physiological; Supraoptic Nucleus; Thirst; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Chlorpropamide; Diabetes Insipidus; Disease Models, Animal; Diuresis; Kidney; Osmolar Concentration; Rats; Rodent Diseases; Sodium; Urine; Vasopressins

Topics: Arginine Vasopressin; Blood Pressure; Blood Volume; Carbamazepine; Chlorpropamide; Chromatography, Gel; Diabetes Insipidus; Diuresis; Humans; Osmolar Concentration; Radioimmunoassay; Stress, Physiological; Stress, Psychological; Vasopressins; Vomiting; Water-Electrolyte Balance

The authors present a brief review of the problem of diabetes insipidus in neurosurgical patients, with particular emphasis on the differential diagnosis of postoperative and posttraumatic polyuria and the management of diabetes insipidus in these periods. A listing of drugs currently used in its treatment is given.

Topics: Administration, Intranasal; Benzothiadiazines; Brain Injuries; Carbamazepine; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Mellitus; Diagnosis, Differential; Diuretics; Humans; Hypothalamo-Hypophyseal System; Lypressin; Methods; Polyuria; Postoperative Complications; Sodium Chloride Symporter Inhibitors; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Blood Volume; Diabetes Insipidus; Feedback; Hormones, Ectopic; Humans; Hyponatremia; Kidney; Osmolar Concentration; Pancreas; Paraneoplastic Endocrine Syndromes; Stress, Physiological; Sweat Glands; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Cyclic AMP; Diabetes Insipidus; Humans; Kidney Diseases; Kidney Medulla; Lithium; Polyuria; Serous Membrane; Sodium; Thirst; Vasopressins; Water-Electrolyte Balance

Topics: Amino Acids; Animals; Biological Transport; Cattle; Cysteine; Cytoplasmic Granules; Diabetes Insipidus; Electrophoresis, Polyacrylamide Gel; Homozygote; Microscopy, Electron; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Gland, Posterior; Protein Binding; Rats; Ribosomes; Species Specificity; Swine; Time Factors; Vasopressins

Topics: Chemical Phenomena; Chemistry; Diabetes Insipidus; Exocytosis; Hormones, Ectopic; Humans; Molecular Weight; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Pituitary Diseases; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Radioimmunoassay; Sodium; Vasopressins

Topics: Adenylyl Cyclases; Adrenal Glands; Adult; Animals; Body Water; Chlorpropamide; Dehydration; Diabetes Insipidus; Genes; Growth Hormone; Heterozygote; Humans; Hyponatremia; Hypothalamus; Oxytocin; Pituitary Gland; Pituitary Gland, Posterior; Rats; Sodium; Vasopressins

Topics: Adrenal Glands; Animals; Antineoplastic Agents; Anura; Biological Transport; Calcium; Cell Membrane Permeability; Chlorpropamide; Clofibrate; Cyclic AMP; Diabetes Insipidus; Dogs; Humans; Models, Biological; Molecular Conformation; Osmolar Concentration; Oxytocin; Pituitary Hormones, Posterior; Prostaglandins; Radioimmunoassay; Receptors, Cell Surface; Sodium; Thiazines; Vasopressins; Water

Topics: Animals; Arginine; Carbamazepine; Chlorpropamide; Clofibrate; Cyclic AMP; Diabetes Insipidus; Hypothalamus; Kidney Diseases; Lithium; Methoxyflurane; Peptide Biosynthesis; Protein Biosynthesis; Rats; Rodent Diseases; Tetracycline; Vasopressins; Vermont

Topics: Adenylyl Cyclases; Animals; Chlorpropamide; Crosses, Genetic; Diabetes Insipidus; Disease Models, Animal; Drug Synergism; Genes; Genetic Diseases, Inborn; Humans; Hybridization, Genetic; Hypertrophy; Hypothalamus; Kidney Concentrating Ability; Kidney Diseases; Kidney Medulla; Loop of Henle; Mice; Pituitary Gland; Rats; Vasopressins

Topics: Adult; Biological Assay; Blood; Blood Pressure; Blood Volume; Dehydration; Diabetes Insipidus; Humans; Kidney Concentrating Ability; Osmolar Concentration; Polyuria; Posture; Radioimmunoassay; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Acetaminophen; Amitriptyline; Animals; Anura; Body Fluids; Carbamazepine; Chlorpropamide; Clofibrate; Cyclophosphamide; Diabetes Insipidus; Diabetes Mellitus; Diazoxide; Drug-Related Side Effects and Adverse Reactions; Humans; Hypoglycemic Agents; Hyponatremia; Kidney; Rats; Sodium; Sulfonylurea Compounds; Tolbutamide; Urinary Bladder; Vasopressins; Vincristine; Water Intoxication; Water-Electrolyte Balance

Topics: Adrenal Cortex Hormones; Biological Transport; Brain; Carbohydrate Metabolism; Catecholamines; Circadian Rhythm; Cyclic AMP; Diabetes Insipidus; Digestive System; Electrolytes; Heart; Humans; Hyperthyroidism; Intestinal Absorption; Kidney; Lipid Metabolism; Lithium; Nervous System; Neural Conduction; Synaptic Transmission; Thyrotropin; Thyroxine; Vasopressins; Water

Topics: Chromatography, Ion Exchange; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Extracellular Space; Glucagon; Humans; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Immune Sera; Inosine Nucleotides; Iodine Radioisotopes; Methods; Nucleotides, Cyclic; Phosphorus Radioisotopes; Protein Kinases; Tritium; Vasopressins

Topics: Affective Symptoms; Animals; Asthma; Caffeine; Calcitonin; Calcium; Catecholamines; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Diabetes Insipidus; Glucagon; Growth Hormone; Humans; Hypercalcemia; Hyperparathyroidism; Hypocalcemia; Hypoparathyroidism; Insulin; Organ Specificity; Parathyroid Hormone; Psoriasis; Vasopressins

Topics: Adrenal Gland Diseases; Diabetes Insipidus; Diabetic Nephropathies; Diagnosis, Differential; Diuresis; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyponatremia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Natriuresis; Osmolar Concentration; Urologic Diseases; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Axons; Catecholamines; Circadian Rhythm; Diabetes Insipidus; Histocytochemistry; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Microscopy, Electron; Nerve Degeneration; Nerve Regeneration; Neuroglia; Neurons; Testis; Time Factors; Vasopressins; Water

Topics: Carbamazepine; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuretics; Humans; Vasopressins

Topics: Adult; Animals; Antibody Formation; Cattle; Chlorpropamide; Diabetes Insipidus; Female; Fetus; Goats; Humans; Infant, Newborn; Male; Neurophysins; Oxytocin; Pregnancy; Radioimmunoassay; Rats; Swine; Vasopressins

Topics: Animals; Cyclic AMP; Diabetes Insipidus; Glucagon; Humans; Kidney; Parathyroid Hormone; Pseudohypoparathyroidism; Rabbits; Rats; Vasopressins

Topics: Adolescent; Blood Glucose; Child; Diabetes Insipidus; Dwarfism, Pituitary; Growth Hormone; Humans; Infant, Newborn; Insulin; Kidney Tubules; Osmolar Concentration; Radioimmunoassay; RNA; RNA Nucleotidyltransferases; Thyroid Function Tests; Vasopressins

Topics: Body Weight; Dehydration; Diabetes Insipidus; Diagnosis, Differential; Humans; Hypertonic Solutions; Injections, Intramuscular; Injections, Intravenous; Isotonic Solutions; Nicotine; Polyuria; Smoking; Sodium Chloride; Sulfonylurea Compounds; Thirst; Vasopressins

Topics: Adult; Diabetes Insipidus; Female; Humans; Vasopressins

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Cushing Syndrome; Diabetes Insipidus; Diagnosis, Differential; Growth Hormone; Hormones, Ectopic; Humans; Hyperpituitarism; Hypopituitarism; Pituitary Diseases; Pituitary Function Tests; Pituitary Gland; Pituitary Gland, Posterior; Vasopressins

Topics: Animals; Child; Child, Preschool; Chlorpropamide; Clofibrate; Diabetes Insipidus; Dibenzazepines; Diuretics; Humans; Infant; Injections, Intramuscular; Injections, Subcutaneous; Osmolar Concentration; Pituitary Hormones, Posterior; Rats; Vasopressins

Topics: Adult; Animals; Anura; Biological Assay; Chlorpropamide; Diabetes Insipidus; Dibenzazepines; Female; Humans; Hydrogen; Kidney Concentrating Ability; Potassium; Rats; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Acromegaly; Cushing Syndrome; Diabetes Insipidus; Gigantism; Humans; Hypopituitarism; Hypothalamo-Hypophyseal System; Pituitary Diseases; Pituitary Gland, Posterior; Vasopressins

Topics: Adult; Blood Pressure; Diabetes Insipidus; Female; Humans; Lung Neoplasms; Vasopressins

Topics: Circadian Rhythm; Diabetes Insipidus; Humans; Methods; Vasopressins; Water

Topics: Animals; Biological Assay; Chemical Phenomena; Chemistry; Diabetes Insipidus; Diagnosis, Differential; Diuretics; Humans; Hypothalamo-Hypophyseal System; Infant, Newborn; Neurosecretion; Osmolar Concentration; Oxytocin; Pituitary Gland, Posterior; Radioimmunoassay; Sensory Receptor Cells; Thirst; Vasopressins

Topics: Anencephaly; Cavernous Sinus; Cerebral Angiography; Diabetes Insipidus; Diabetic Retinopathy; Endocrine System Diseases; Feedback; Hemianopsia; Humans; Hypothalamo-Hypophyseal System; Nervous System Diseases; Neurosecretion; Phlebography; Pituitary Hormones, Posterior; Pituitary Neoplasms; Pneumoencephalography; Sella Turcica; Vasopressins; Water Deprivation

Topics: Animals; Biological Assay; Blood Volume; Diabetes Insipidus; Hormones, Ectopic; Humans; Hypothalamo-Hypophyseal System; Kidney Tubules; Neurosecretion; Pituitary Gland, Posterior; Radioimmunoassay; Sensory Receptor Cells; Vasopressins

Topics: Adolescent; Adult; Aged; Animals; Arginine; Child; Dehydration; Diabetes Insipidus; Female; Humans; Hyperaldosteronism; Hypertonic Solutions; Hypocalcemia; Kidney Failure, Chronic; Kidney Transplantation; Kidney Tubules; Male; Middle Aged; Nicotine; Osmolar Concentration; Polyuria; Sex Factors; Sodium Chloride; Thirst; Time Factors; Urine; Urologic Diseases; Vasopressins; Water-Electrolyte Balance

Topics: Acid-Base Equilibrium; Aldosterone; Amino Acids; Angiotensin II; Animals; Diabetes Insipidus; Glomerular Filtration Rate; Glucose; Humans; Inulin; Juxtaglomerular Apparatus; Kidney; Kidney Tubules; Oxygen Consumption; Potassium Deficiency; Proteins; Sodium; Urea; Uric Acid; Vasoconstrictor Agents; Vasopressins

Topics: Arginine; Diabetes Insipidus; Diuresis; Humans; Hyponatremia; Lung Neoplasms; Pituitary Diseases; Pituitary Gland, Posterior; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Insufficiency; Animals; Congenital Hypothyroidism; Diabetes Insipidus; Heart Failure; Humans; Liver Cirrhosis; Osmolar Concentration; Pituitary Diseases; Vasopressins

Topics: Acromegaly; Addison Disease; Adult; Central Nervous System Diseases; Diabetes Insipidus; Humans; Hyperthyroidism; Hypothyroidism; Kidney; Lung Diseases; Male; Neoplasms; Pituitary Diseases; Thyroid Diseases; Vasopressins

Topics: Acromegaly; Addison Disease; Adrenocortical Hyperfunction; Cushing Syndrome; Diabetes Insipidus; Endocrine System Diseases; Humans; Hyperaldosteronism; Hyperparathyroidism; Hypopituitarism; Hypothyroidism; Kidney; Vasopressins; Water-Electrolyte Balance

Topics: Diabetes Insipidus; Humans; Vasopressins

Topics: Alcohols; Body Water; Central Nervous System Diseases; Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diuresis; Edema; Ethanol; Histiocytosis, Langerhans-Cell; Homeostasis; Humans; Hyponatremia; Infant; Infant, Newborn; Kidney Diseases; Nicotine; Physiology; Pituitary Gland; Pituitary Gland, Posterior; Potassium Deficiency; Prednisone; Pyloric Stenosis; Vasopressins; Water

Topics: Blood; Chlorothiazide; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Humans; Permeability; Thirst; Urine; Vasopressins

A synthetic vasopressin analog, 1-desamino-8D-arginine vasopressin (DDAVP also known as desmopressin), was found to be highly effective in the treatment of seven children and one adult with vasopressin-sensitive diabetes insipidus. The average duration of action of DDAVP was 10 to 11 hours, and with proper adjustment of dose, the subjects were able to control their symptoms satisfactorily with one or two inhalations daily. The youngest child in whom adequate control was achieved was 2 years of age. All subjects found the use of intranasal DDAVP superior to other forms of therapy, and none experienced any known side-effects after six months of treatment. All subjects in this study are currently using 2.5 mug to 10 mug of DDAVP once or twice daily.

Topics: Adolescent; Adult; Arginine Vasopressin; Child; Child, Preschool; Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Infant; Osmolar Concentration; Vasopressins

Topics: Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Evaluation; Humans; Vasopressins

Topics: Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Kidney Function Tests; Vasopressins

The antidiuretic effects of graded intravenous and intranasal doses of a new vasopressin analogue (DDAVP) were investigated in two groups of patients with pituitary diabetes insipidus. In the first group, three patients with a high requirement of maintenance doses of peroral anti-diuretic drugs were included; and in the second group, ten patients with a normal (usual) requirement were included. Comparing the antidiuretic responses during 24-hour collection periods, DDAVP, on a microgram basis, was less effective in the "high peroral-dose requirement" patients. The duration of action of single intravenous doses (0.04-24 micrograms) of DDAVP was significantly shortened in the "high peroral-dose requirement" group. However, comparing the peak responses induced by increasing doses of DDAVP in the two groups, there was no demonstrable diminution in the anti-diuretic ability of DDAVP in the "high peroral-dose requirement" patients. Although the possibility of a smaller remnant reserve of ADH was also considered, shortened duration of action ot DDAVP suggests more probably enhanced metabolic breakdown of vasopressin in "high peroral-dose requirement" patients.

Topics: Adult; Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Osmolar Concentration; Time Factors; Vasopressins

Topics: Adolescent; Child; Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Evaluation; Female; Humans; Male; Vasopressins

Topics: Clinical Trials as Topic; Diabetes Insipidus; Diabetes Mellitus; Diuresis; Diuretics; Glomerular Filtration Rate; Glyburide; Humans; Lysine; Vasopressins

A study was performed on the effects of carbamazepine and of clofibrate in 7 cases of diabetes insipidus of high origin. In 4 cases the action of the two substances used in association was studied. Carbamazepine, in a dose of 0.60 g/day was effective in all cases with negativisation of free water clearance in 5 out of 7. Clofibrate, in a dose of 1.50 g/day was effective in 4 cases out of 7 with negativation of free water clearance in 2. Both medications act by provoking the secretion of anti-diuretic hormone by the hypothalamic/posterior pituitary centres and are thus only active if a minimal secretion of ADH is still possible. There is no apparent potentialisation of the two substances, which both require a minimal possibility of ADH secretion to be active. There is no diminution in the ADH secretor effect, since both products remain active for as long as they are given, making it possible to observe in 3 out of 7 cases spontaneous cure of the diabetes insipidus, allowing suppression of the treatment.

Topics: Adolescent; Adult; Carbamazepine; Clinical Trials as Topic; Clofibrate; Diabetes Insipidus; Drug Therapy, Combination; Female; Humans; Hypothalamus; Long-Term Care; Male; Middle Aged; Osmolar Concentration; Pituitary Gland, Posterior; Secretory Rate; Stimulation, Chemical; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Clinical Trials as Topic; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Evaluation; Female; Humans; Vasopressins

Topics: Administration, Intranasal; Adolescent; Child; Clinical Trials as Topic; Diabetes Insipidus; Drug Tolerance; Female; Humans; Male; Vasopressins

Topics: Adolescent; Arginine; Child; Clinical Trials as Topic; Diabetes Insipidus; Drug Evaluation; Female; Humans; Male; Solutions; Vasopressins

Topics: Adolescent; Adult; Arginine; Blood Pressure; Body Weight; Child; Clinical Trials as Topic; Diabetes Insipidus; Diuresis; Drug Evaluation; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Lysine; Male; Middle Aged; Osmolar Concentration; Pulse; Vasopressins

In 11 patients with vasopressin-sensitive diabetes insipidus the effectiveness of the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) for controlling diabetes insipidus has been compared with that of lysine vasopressin. DDAVP in equivalent intravenous dosage has been found to be at least as potent and to have a more prolonged action, lasting 13-22 hours instead of 1-2 hours. Twice-daily intranasal DDAVP effected satisfactory control in all these patients, without side effects, and all the patients preferred this to their previous treatment. Single daily intramuscular injections of DDAVP were found to offer excellent control for any subject unable to manage intranasal administration.

Topics: Administration, Intranasal; Adult; Arginine; Child; Diabetes Insipidus; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Lysine; Male; Middle Aged; Prednisolone; Rhinitis; Vasoconstrictor Agents; Vasopressins

Topics: Acne Vulgaris; Animals; Anura; Cyclic AMP; Demeclocycline; Diabetes Insipidus; Dose-Response Relationship, Drug; Humans; In Vitro Techniques; Osmosis; Urinary Bladder; Vasopressins

Topics: Adult; Benzothiadiazines; Carbamazepine; Chlorpropamide; Clinical Trials as Topic; Clofibrate; Delayed-Action Preparations; Diabetes Insipidus; Diuretics; Humans; Methods; Middle Aged; Pituitary Hormones, Posterior; Sodium Chloride Symporter Inhibitors; Statistics as Topic; Vasopressins

In seven patients with cranial diabetes insipidus an analogue of vasopressin, DDAVP, produced an antidiuresis lasting up to 20 hours after a single intranasal dose. Lysine vasopressin (LVP) in the same dose produced a less potent antidiuresis which lasted for only three to four hours. The plasma half life of DDAVP was 7.8 and 75.5 min for the fast and slow phases, compared with 2.5 and 14.5 min for LVP. Radioiodine-labelled DDAVP was not destroyed by incubation with late pregnancy plasma, which contains an enzyme that inactivates vasopressin. The slow metabolic clearance of DDAVP, its absorption through the nasal mucosa, and its lack of side effects make this the ideal drug for the treatment of vasopressin-sensitive diabetes insipidus. Patients usually require 10 to 20 mug DDAVP given intranasally twice daily for good clinical control of their diabetes insipidus.

Topics: Adolescent; Adult; Antibodies; Blood; Child, Preschool; Clinical Trials as Topic; Diabetes Insipidus; Diuresis; Humans; Injections, Intravenous; Iodine Isotopes; Middle Aged; Nasal Mucosa; Nose; Osmolar Concentration; Protein Binding; Urine; Vasopressins

Topics: Adult; Child; Child, Preschool; Clinical Trials as Topic; Clofibrate; Diabetes Insipidus; Diuresis; Drug Synergism; Female; Gonadotropins, Pituitary; Growth Hormone; Humans; Male; Middle Aged; Osmolar Concentration; Pituitary Gland; Placebos; Polyuria; Thyroid Gland; Time Factors; Vasopressins

Topics: Adult; Blood Glucose; Chlorpropamide; Creatinine; Diabetes Insipidus; Diet; Diet, Sodium-Restricted; Diuresis; Diuretics; Drug Synergism; Ethanol; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Osmolar Concentration; Placebos; Tannins; Tolbutamide; Vasopressins

Topics: Carbutamide; Chlorpropamide; Clinical Trials as Topic; Clopamide; Craniocerebral Trauma; Diabetes Complications; Diabetes Insipidus; Diuresis; Furosemide; Glomerular Filtration Rate; Humans; Male; Middle Aged; Vasopressins

Topics: Adult; Beverages; Chlorpropamide; Clinical Trials as Topic; Diabetes Insipidus; Diuresis; Ethanol; Female; Humans; Hypoglycemic Agents; Hypothalamo-Hypophyseal System; Male; Neurosecretion; Osmolar Concentration; Urine; Vasopressins

Topics: 17-Hydroxycorticosteroids; Acromegaly; Adenoma, Chromophobe; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Brain Diseases; Central Nervous System Diseases; Clinical Trials as Topic; Craniocerebral Trauma; Diabetes Insipidus; Female; Humans; Hypothalamo-Hypophyseal System; Intracranial Pressure; Male; Metyrapone; Pituitary Diseases; Pituitary Function Tests; Pituitary Neoplasms; Pseudotumor Cerebri; Vasopressins

Topics: Adult; Angiotensin II; Diabetes Insipidus; Diuresis; Female; Glomerular Filtration Rate; Humans; Kidney Tubules; Male; Middle Aged; Natriuresis; Urea; Vasopressins

Primary central nervous system lymphoma (PCNSL) rarely originates in the hypothalamus. Hypothalamic PCNSL can present with various symptoms specific to dysfunction of the hypothalamus, including consciousness disturbance, cognitive impairment, hypopituitarism, and diabetes insipidus (DI). However, it remains unclear whether syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can present as an initial sign of hypothalamic PCNSL.. Ninety-nine patients with PCNSL were diagnosed between January 2006 and December 2020 at our institutes. The initial symptoms and signs, hypothalamic-pituitary functions, serum sodium (Na) value, Karnofsky Performance Status (KPS) score on admission, and duration from onset to diagnosis were retrospectively investigated from the medical charts.. Eight and 91 patients had hypothalamic PCNSL (hypothalamic group) and PCNSL located in other regions (control group), respectively. Patients' pathological diagnoses were diffuse large B-cell lymphoma (97 patients) and intravascular lymphoma (two patients). Six patients presented with hyponatremia derived from SIADH or suspected SIADH, and one presented with DI. Statistically significant differences between the hypothalamic and control groups were detected only in the preoperative serum Na values and KPS scores.. SIADH can be an initial presentation of hypothalamic PCNSL. Early detection of hypothalamic PCNSL from SIADH may lead to proper management and improved prognosis.

Topics: Diabetes Insipidus; Humans; Hyponatremia; Hypothalamus; Inappropriate ADH Syndrome; Retrospective Studies; Vasopressins

Familial pituitary diabetes insipidus has been described only in an autosomal dominant or recessive mode of inheritance.. This work aims to determine the cause of a novel form of familial diabetes insipidus (DI) that is controlled by desmopressin therapy but segregates in an X-linked recessive manner.. Thirteen members from 3 generations of the kindred with familial DI were studied. Water intake, urine volume, urine osmolality, plasma osmolality, and plasma vasopressin were measured under basal conditions, during fluid deprivation, 3% saline infusion, and water loading. Magnetic resonance images of the posterior pituitary also were obtained. In affected males, the effects of desmopressin therapy and linkage of the DI to markers for chromosome Xq28 were determined. In addition, the genes encoding vasopressin, aquaporin-2, the AVPR2 receptor, and its flanking regions were sequenced.. This study showed that 4 males from 3 generations of the kindred have DI that is due to a deficiency of vasopressin, is corrected by standard doses of desmopressin, and segregates with markers for the AVPR2 gene in Xq28. However, no mutations were found in AVPR2 or its highly conserved flanking regions. Exome sequencing confirmed these findings and also revealed no deleterious variants in the provasopressin and aquaporin-2 genes. The 4 obligate female carriers osmo-regulated vasopressin in the low normal range.. X-linked recessive transmission of DI can be due to a defect in either the secretion or the action of vasopressin. Other criteria are necessary to differentiate and manage the 2 disorders correctly.

Topics: Aquaporin 2; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Mellitus; Female; Humans; Male; Receptors, Vasopressin; Vasopressins

We studied the growth dynamics of Walker 256 carcinosarcoma in recombinant progeny of dihybrid crosses of Brattleboro and WAG rats. A mutation in the vasopressin gene determining hypothalamic diabetes insipidus was detected in Brattleboro rats. WAG rats are carriers of normal vasopressin gene. Another interlinear difference was linked to tyrosinase gene controlling melanin synthesis. WAG rats express mutant allele determining albino phenotype. Brattleboro rats had normal working tyrosinase gene. F2 segregation yielded phenotypic classes with two patterns of tumor growth: linear growth or regression. Tumors regression was not linked to tyrosinase activity and was observed only in rats with diabetes insipidus. Analysis of mutants in next generations F3 and F4 confirmed this regularity in the Walker 256 carcinosarcoma growth pattern.

Topics: Animals; Carcinoma 256, Walker; Carcinosarcoma; Diabetes Insipidus; Diabetes Mellitus; Melanins; Monophenol Monooxygenase; Rats; Rats, Brattleboro; Vasopressins

A 49-year-old man developed severe hyponatremia associated with transient headache and was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction and sodium supplementation corrected the hyponatremia. However, several days later, the patient exhibited hypernatremia with thirst and polyuria. A detailed examination indicated central diabetes insipidus (CDI) with an intrasellar cystic lesion indicative of Rathke's cleft cyst (RCC). A case of RCC exhibiting headache, hyponatremia, and subsequent hypernatremia has been reported. Our case shows that CDI may appear after SIADH in patients with RCC, especially in those with serum sodium levels that unexpectedly increase rapidly beyond the reference range.

Topics: Central Nervous System Cysts; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Vasopressins

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common problem during the postoperative course after pituitary surgery. Although treatment of this condition is well characterized, prevention strategies are less studied and reported. The authors sought to characterize outcomes and predictive factors of SIADH after implementation of routine postoperative fluid restriction for patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma.. In March 2018, routine postoperative fluid restriction to 1000 ml/day for 7 days was instituted for all patients who underwent surgery for pituitary adenoma. These patients were compared with patients who underwent surgery for pituitary adenoma between March 2016 and March 2018, prior to implementation of routine fluid restriction. Patients with preoperative history of diabetes insipidus (DI) or concern for postsurgical DI were excluded. Patients were followed by neuroendocrinologists and neurosurgeons, and sodium levels were checked between 7 and 10 days postoperatively. SIADH was defined by a serum sodium level less than 136 mmol/L, with or without symptoms within 10 days after surgery. Thirty-day readmission was recorded and reviewed to determine underlying reasons.. In total, 82 patients in the fluid-unrestricted cohort and 135 patients in the fluid-restricted cohort were analyzed. The patients in the fluid-restricted cohort had a significantly lower rate of postoperative SIADH than patients in the fluid-unrestricted cohort (5% vs 15%, adjusted OR [95% CI] 0.1 [0.0-0.6], p = 0.01). Higher BMI was associated with lower rate of postoperative SIADH (adjusted OR [95%] 0.9 [0.9-1.0], p = 0.03), whereas female sex was associated with higher rate of SIADH (adjusted OR [95% CI] 3.1 [1.1-9.8], p = 0.03). There was no difference in the 30-day readmission rates between patients in the fluid-unrestricted and fluid-restricted cohorts (4% vs 7%, adjusted OR [95% CI] 0.5 [0-5.1], p = 0.56). Thirty-day readmission was more likely for patients with history of hypertension (adjusted OR [95% CI] 5.7 [1.3-26.3], p = 0.02) and less likely for White patients (adjusted OR [95% CI] 0.3 [0.1-0.9], p = 0.04).. Routine fluid restriction reduced the rate of SIADH in patients who underwent surgery for pituitary adenoma but was not associated with reduction in 30-day readmission rate.

Topics: Adenoma; Diabetes Insipidus; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Sodium; Vasopressins

Familial neurohypophyseal diabetes insipidus (FNDI) is a rare disorder characterized by childhood-onset progressive polyuria and polydipsia due to mutations in the arginine vasopressin (AVP) gene. The aim of the study was to describe the clinical and molecular characteristics of families with neurohypophyseal diabetes insipidus.. Five Portuguese families with autosomal dominant FNDI underwent sequencing of the AVP gene and the identified mutations were functionally characterized by in vitro studies.. Three novel and two recurrent heterozygous mutations were identified in the AVP gene. These consisted of one initiation codon mutation in the signal peptide coding region (c.2T > C, p.Met1?), three missense mutations in the neurophysin II (NPII) coding region (c.154T > C, p.Cys52Arg; c.289C > G, p.Arg97Gly; and c.293G > C, p.Cys98Ser), and one nonsense mutation in the NPII coding region (c.343G > T, p.Glu115Ter). In vitro transfection of neuronal cells with expression vectors containing each mutation showed that the mutations resulted in intracellular retention of the vasopressin prohormone. Patients showed progressive symptoms of polyuria and polydipsia, but with wide variability in severity and age at onset. No clear genotype-phenotype correlation was observed.. The intracellular accumulation of mutant vasopressin precursors supports the role of cellular toxicity of the mutant proteins in the etiology of the disorder and explains the progressive onset of the disorder. These findings further expand the AVP mutational spectrum in FNDI and contribute to the understanding of the molecular pathogenic mechanisms involved in FNDI.

Topics: Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Humans; Mutation; Neurophysins; Pedigree; Polydipsia; Polyuria; Vasopressins

Topics: Diabetes Insipidus; Diabetes Mellitus; Humans; Vasopressins

Topics: Diabetes Insipidus; Diabetes Mellitus; Humans; Vasopressins

Aquaporin-2 (AQP2) is a key water channel protein which determines the water permeability of the collecting duct. Multiple phosphorylation sites are present at the C-terminal of AQP2 including S256 (serine at 256 residue), S261, S264 and S/T269, which are regulated by vasopressin (VP) to modulate AQP2 trafficking. As the dynamics of these phosphorylations have been studied mostly in rodents, little is known about the phosphorylation of human AQP2 which has unique T269 in the place of S269 of rodent AQP2. Because AQP2 is excreted in urinary exosomes, the phosphoprotein profile of human AQP2 can be easily examined through urinary exosomes without any intervention.. Human urinary exosomes digested with trypsin or glutamyl endopeptidase (Glu-C) were examined by the liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) phosphoproteomic analysis.. The most dominant phosphorylated AQP2 peptide identified was S256 phosphorylated form (pS256), followed by pS261 with less pS264 and far less pT269, which was confirmed by the western blot analyses using phosphorylated AQP2-specific antibodies. In a patient lacking circulating VP, administration of a VP analogue showed a transient increase (peak at 30-60 min) in excretion of exosomes with pS261 AQP2.. These data suggest that all phosphorylation sites of human AQP2 including T269 are phosphorylated and phosphorylations at S256 and S261 may play a dominant role in the urinary exosomal excretion of AQP2.

Topics: Aquaporin 2; Chromatography, Liquid; Diabetes Insipidus; Exosomes; Female; Humans; Immunoblotting; Middle Aged; Phosphorylation; Tandem Mass Spectrometry; Vasopressins

Vasopressin has achieved common usage for the treatment of catecholamine-requiring and catecholamine-resistant shock. Diabetes insipidus is a syndrome characterized by excretion of abnormally large volumes of dilute urine. To date, very few reports of diabetes insipidus after discontinuation of vasopressin infusion have been published; the majority of previous reports describe neurosurgical patients. The purpose of the present study was to investigate the occurrence rate of diabetes insipidus after discontinuation of vasopressin infusion among patients treated with vasopressin infusion for shock.. Retrospective analysis of electronic health records of patients receiving continuous vasopressin infusion for the treatment of shock within a 5-year period (2012-2016).. Medical, surgical, and cardiothoracic ICUs within one academic medical center.. One-thousand eight-hundred ninety-six patients received vasopressin infusion for the treatment of shock.. None.. The occurrence rate of diabetes insipidus after discontinuation of vasopressin infusion was 1.53% among all patients. Sixteen of 29 patients with diabetes insipidus after discontinuation of vasopressin infusion had undergone cardiothoracic intervention, such as coronary artery bypass graft and valve replacement surgery, extracorporeal membrane oxygenation, and placement of ventricular assist devices. No neurosurgical patients were identified in our cohort. In a control group of patients receiving norepinephrine but not vasopressin infusion for treatment of shock, criteria for diabetes insipidus were observed in two of 1,320 subjects (0.15%).. Despite a paucity of published reports, diabetes insipidus after discontinuation of vasopressin infusion appears not to be a rare phenomenon, and is likely to be encountered by intensivists who regularly employ vasopressin for the treatment of vasoplegic shock. Previous reports consisted predominantly of neurosurgical patients. Our findings demonstrate the occurrence of diabetes insipidus after discontinuation of vasopressin infusion among patients with septic shock as well as vasoplegic shock after cardiothoracic intervention. The mechanism of diabetes insipidus after discontinuation of vasopressin infusion remains to be elucidated but may involve transient downregulation of V2 receptors induced by exposure to supraphysiological doses of vasopressin.

Topics: Adult; Child, Preschool; Diabetes Insipidus; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Shock; Vasopressins; Withholding Treatment; Young Adult

Dysregulated arousal often accompanies neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism spectrum disorder. Recently, we have found that adolescent homozygous Brattleboro (Hom) rats, which contain a mutation in the arginine vasopressin (AVP) gene, exhibit lower behavioral arousal than their heterozygous (Het) littermates in the open field test. This hypoaroused phenotype could be due to loss of AVP in magnocellular cells that supply AVP to the peripheral circulation and project to limbic structures or parvocellular cells that regulate the stress axis and other central targets. Alternatively, hypoarousal could be a side effect of diabetes insipidus - polydipsia and polyuria seen in Hom rats due to loss of AVP facilitation of water reabsorption in the kidney. We developed a viral-rescue approach to "cure" magnocellular AVP cells of their Brattleboro mutation. Infusion of a recombinant adeno-associated virus (rAAV) containing a functional Avp gene and promoter (rAAV-AVP) rescued AVP within magnocellular cells and fiber projections of the paraventricular nucleus of the hypothalamus (PVN) of male and female adolescent Hom rats. Furthermore, water intake was markedly reduced, ameliorating the symptoms of diabetes insipidus. In contrast, open field activity was unaffected. These findings indicate that the hyporaoused phenotype of adolescent Hom rats is not due to the loss of AVP function in magnocellular cells or a side effect of diabetes insipidus, but favors the hypothesis that central, parvocellular AVP mechanisms underlie the regulation of arousal during adolescence.

Topics: Animals; Arousal; Behavior, Animal; Dependovirus; Diabetes Insipidus; Female; Male; Paraventricular Hypothalamic Nucleus; Phenotype; Promoter Regions, Genetic; Rats, Brattleboro; Vasopressins

Despite widespread use of vasopressin for the treatment of septic shock, few cases of diabetes insipidus (DI) following its discontinuation have been reported.. A 54-year-old man presented with pneumonia progressing to septic shock, requiring norepinephrine and vasopressin for refractory hypotension. After clinical improvement, the patient on 3 separate occasions developed polyuria and severe hypernatremia upon discontinuation of vasopressin, with prompt recovery upon its resumption.. Occurrence of DI upon discontinuation of vasopressin infusion appears to be rare, but incidence may be underestimated due to a paucity of published reports. Actual incidence and underlying mechanism of this phenomenon remain to be elucidated.

Topics: Diabetes Insipidus; Humans; Male; Middle Aged; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known.. A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived. During her hospitalization, she complained of gradually increasing symptoms of polyuria and polydipsia. The serum level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP tablets were not necessary to control her polyuria thereafter. Based on these observations, clinical diagnosis of GDI was confirmed. Pathophysiological analyses revealed that vasopressinase expression was more abundant in the GDI patient's syncytiotrophoblast in placenta compared with that in a control subject. Serum vasopressinase was also observed during gestation and disappeared soon after delivery. Vasopressinase is reportedly identical to oxytocinase or insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly, the expression and subcellular localization of GLUT4 appeared to occur in a vasopressinase (IRAP)-dependent manner.. Because placental volume may be associated with vasopressinase overproduction in GDI, vasopressinase (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this case.

Topics: Adolescent; Antidiuretic Agents; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Neurophysins; Pregnancy; Pregnancy Complications; Prognosis; Protein Precursors; Vasopressins

A 38-year-old Japanese man who had undergone clipping surgery for a ruptured aneurysm of the anterior communicating artery 2 days prior, suddenly developed refractory hypernatremia (serum sodium (Na) 156 - 162 mmol/L). Symptoms included low plasma vasopressin, fluctuating urine osmolality (120 - 710 mOsm/kg) and lack of thirst, all suggesting adipsic diabetes insipidus (ADI). Hypernatremia was corrected by scheduled water intake with desmopressin administration. During 1-year follow-up after the surgery, his serum Na level normalized despite the suspension of desmopressin, but neither thirst nor osmolality-dependent vasopressin release recovered. Meanwhile, his urine osmolality shifted to a constant high level. The present case suggests that renal compensatory adaptation, apparently independent of the circulating vasopressin level, plays a major role in water handling in longitudinal ADI.
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Topics: Adaptation, Physiological; Adult; Aneurysm, Ruptured; Body Water; Diabetes Insipidus; Humans; Intracranial Aneurysm; Kidney; Male; Vasopressins

Topics: Diabetes Insipidus; Endoplasmic Reticulum-Associated Degradation; Homeostasis; Humans; Vasopressins

Diabetes insipidus (DI) and primary polydipsia (PP) are characterised by polyuria and polydipsia. It is crucial to differentiate between these two disorders since the treatment is different. The aim of this study was to evaluate the diagnostic value of the short and an extended variant of the water deprivation test (WDT) and of measuring urinary vasopressin (AVP) in patients with polyuria and polydipsia.. A retrospective, single-centre study based on WDTs performed between 2004 and 2014 including 104 consecutive patients with the polyuria-polydipsia syndrome. During a strict water deprivation, weight, urinary osmolality, urinary vasopressin and specific gravity were collected until one of the following was reached: i) >3% weight reduction, ii) Urinary specific gravity >1.020 or, urinary osmolality >800 mOsm/L, iii) Intolerable adverse symptoms such as excessive thirst.. Out of 104 patients (67 women, 37 men), 21 (20%) were diagnosed with DI and 83 (80%) with PP. The median (interquartile range; range) test duration was 14 hours (10-16; 3-36) in patients with DI and 18 hours (14-24; 7-48) in patients with PP (P=0.011). Of those diagnosed with PP, 22 (26%) did not reach urinary specific gravity >1.020 nor urine osmolality >800 mOsm/L. Urine AVP did not overlap between patients with PP and patients with central DI.. The short WDT is of limited value in the diagnostic work-up of polydipsia and polyuria and a partial DI may have been missed in every fourth patient diagnosed with PP. Urinary AVP has excellent potential in discriminating PP from central DI.

Topics: Adult; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Neurophysins; Polydipsia; Polydipsia, Psychogenic; Polyuria; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Syndrome; Vasopressins; Water Deprivation

Aggregation of peptide hormone precursors in the trans-Golgi network is an essential process in the biogenesis of secretory granules in endocrine cells. It has recently been proposed that this aggregation corresponds to the formation of functional amyloids. Our previous finding that dominant mutations in provasopressin, which cause cell degeneration and diabetes insipidus, prevent native folding and produce fibrillar aggregates in the endoplasmic reticulum (ER) might thus reflect mislocalized amyloid formation by sequences that evolved to mediate granule sorting.. Here we identified two sequences responsible for fibrillar aggregation of mutant precursors in the ER: the N-terminal vasopressin nonapeptide and the C-terminal glycopeptide. To test their role in granule sorting, the glycopeptide was deleted and/or vasopressin mutated to inactivate ER aggregation while still permitting precursor folding and ER exit. These mutations strongly reduced sorting into granules and regulated secretion in endocrine AtT20 cells.. The same sequences - vasopressin and the glycopeptide - mediate physiological aggregation of the wild-type hormone precursor into secretory granules and the pathological fibrillar aggregation of disease mutants in the ER. These findings support the amyloid hypothesis for secretory granule biogenesis.

Topics: Amino Acid Sequence; Amyloid; Animals; Cell Line, Tumor; Diabetes Insipidus; Endoplasmic Reticulum; Genes, Reporter; Glycopeptides; Humans; Mice; Mutant Proteins; Protein Aggregates; Protein Folding; Protein Transport; Secretory Vesicles; Sequence Deletion; Vasopressins

Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published.. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain.. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies.

Topics: Age of Onset; Child, Preschool; Diabetes Insipidus; Heterozygote; Humans; Male; Neurophysins; Point Mutation; Protein Precursors; RNA Splice Sites; Vasopressins

Topics: Adult; Antidiuretic Agents; Biopsy; Diabetes Insipidus; Diagnosis, Differential; Female; Histiocytosis, Langerhans-Cell; Humans; Inpatients; Prognosis; Radiography; Risk Factors; Vasopressins

Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

Topics: Atrophy; Cognition Disorders; Confusion; Diabetes Insipidus; Female; Humans; Hyponatremia; Hypothalamus; Magnetic Resonance Imaging; Middle Aged; Multiple Sclerosis, Chronic Progressive; Polydipsia; Sodium; Vasopressins

Polydypsia and polyuria are frequent symptoms in patients with sellar masses caused by neurohypophyseal diabetes insipidus. Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the arginine vasopressin (AVP) -neurophysin II (NPII) gene, should be considered as a rare differential diagnosis. A delayed diagnosis bears the risk of life-threatening electrolyte imbalances and permanent urinary tract damage, leading to impaired quality of life.We present a Caucasian kindred of at least 4 generations with FNDI.Clinical histories, endocrine para-meters, and results of molecular analyses of the AVP gene are presented with a review of the literature on diabetes insipidus (DI) related urinary tract dilatation.Polyuria and polydipsia were only reported based on explicit and thorough interrogation after more than 4 years of clinical follow-up. A novel heterozygous mutation in the AVP gene was found in all examined symptomatic subjects (c.1-33_c.4del37nt). A literature review revealed that non-obstructive hydronephrosis (NOH) is a rare but known complication of DI.Since increased fluid intake is often a typical familial pattern in adFNDI, it is frequently missed as being pathologic in affected patients, therefore a detailed clinical history of drinking volumes is of critical importance. AVP gene testing is an important component in the confirmation of the diagnosis. Otherwise unexplainable NOH should lead to further investigations and evaluation of rare diseases like FNDI.

Topics: Arginine Vasopressin; Child; Delayed Diagnosis; Diabetes Insipidus; Dilatation, Pathologic; DNA Mutational Analysis; Follow-Up Studies; Humans; Hydronephrosis; Kidney Function Tests; Kidney Pelvis; Magnetic Resonance Imaging; Male; Neurophysins; Pedigree; Protein Precursors; Sequence Analysis, DNA; Ureter; Urinary Bladder; Urinary Retention; Vasopressins

Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.

Topics: Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diagnosis, Differential; Humans; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Pituitary Diseases; Pituitary Gland, Posterior; Receptors, Vasopressin; Sodium Chloride; Vasopressins; Water-Electrolyte Imbalance

An increasing number of neurologic diseases is associated with autoimmunity. The immune effectors contributing to the pathogenesis of such diseases are often unclear. To explore whether self-reactive CD8 T cells could attack CNS neurons in vivo, we generated a mouse model in which the influenza virus hemagglutinin (HA) is expressed specifically in CNS neurons. Transfer of cytotoxic anti-HA CD8 T cells induced an acute but reversible encephalomyelitis in HA-expressing recipient mice. Unexpectedly, diabetes insipidus developed in surviving animals. This robust phenotype was associated with preferential accumulation of cytotoxic CD8 T cells in the hypothalamus, upregulation of MHC class I molecules, and destruction of vasopressin-expressing neurons. IFN-γ production by the pathogenic CD8 T cells was necessary for MHC class I upregulation by hypothalamic neurons and their destruction. This novel mouse model, in combination with related human data, supports the concept that autoreactive CD8 T cells can trigger central diabetes insipidus.

Topics: Animals; CD8-Positive T-Lymphocytes; Cells, Cultured; Cytotoxicity, Immunologic; Diabetes Insipidus; Disease Models, Animal; Encephalomyelitis; Genes, MHC Class I; Humans; Interferon-gamma; Mice; Mice, Inbred BALB C; Mice, Transgenic; Neurons; Vasopressins

Topics: Adult; Blood Gas Analysis; Diabetes Insipidus; Female; Fluid Therapy; Humans; Osmolar Concentration; Perioperative Care; Pituitary Gland; Pituitary Neoplasms; Polyuria; Postoperative Complications; Sodium; Vasopressins; Water-Electrolyte Imbalance

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI.. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life.. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population.. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population.

Topics: Adolescent; Central Nervous System Neoplasms; Child; Child, Preschool; Cohort Studies; Diabetes Insipidus; Female; Histiocytosis, Langerhans-Cell; Humans; Infant; Male; Peptide Hormones; Prospective Studies; Quality of Life; Retrospective Studies; Vasopressins

Diabetes insipidus is caused by insufficient secretion of vasopressin (ADH) or by an inability of the kidneys to respond to ADH. Pregnancy-associated DI occurs rarely but is connected with severe complications such as preeclampsia and hepatic function abnormalities. The following paper presents the case of a 36-year-old patient who had been diagnosed with diabetes insipidus in the 34th week of pregnancy.

Topics: Adult; Diabetes Insipidus; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Vasopressins; Women's Health

Morphological characteristics of the inner medullary zone in the kidneys in Brattleboro and Wistar rats were studied during blockade of prostaglandin synthesis. The absence of a diuretic effect of prostaglandins on the kidneys was accompanied by structural changes in the transepithelial and interstitial barriers for an osmotic flow of water.

Topics: Animals; Cell Shape; Diabetes Insipidus; Diclofenac; Epithelium; Extracellular Matrix; Glucuronidase; Hyaluronic Acid; Kidney Concentrating Ability; Kidney Medulla; Osmolar Concentration; Prostaglandins; Rats; Rats, Brattleboro; Rats, Wistar; Vasopressins

Neurological involvement of the central nervous system in brucellosis is uncommon. We describe a rare case of meningoencephalitis due to Brucella melitensis infection, associated with the syndrome of inappropriate antidiuretic hormone secretion and leading to diabetes insipidus and hypothyroidism. Neurobrucellosis, although rare, should be considered in cases of neurological disease of unknown etiology.

Topics: Adolescent; Brucella melitensis; Brucellosis; Diabetes Insipidus; Humans; Hypothyroidism; Male; Meningoencephalitis; Vasopressins

Diabetes insipidus is an ancient disease considered under the rubric of diabetes, the Greek descriptive term for polyuria, which was unrecognized even after the sweetness of urine was reported as a characteristic of diabetes mellitus in the 17th century. It would be another century before diabetes insipidus was identified from the insipid rather than saccharine taste of urine in cases of polyuria. After its increased recognition, pathologic observations and experimental studies connected diabetes insipidus to the pituitary gland in the opening decades of the 20th century. Simultaneously, posterior pituitary lobe extracts were shown to be vasoconstrictive (vasopressin) and antidiuretic (antidiuretic hormone). As vasopressin was purified and synthesized and its assay became available, it was shown to be released in response to both osmotic and volume stimuli that are integrated in the hypothalamus, and vasopressin thereby was essential to maintaining internal water balance. The antidiuretic properties of vasopressin to treat the rare cases of diabetes insipidus were of limited clinical utility until its vasoconstrictive effects were resuscitated in the 1970s, with the consequent increasing wider use of vasopressin for the treatment of compromised hemodynamic states. In addition, the discovery of antidiuretic hormone receptor blockers has led to their increasing use in managing hypo-osmolar states.

Topics: Diabetes Insipidus; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Hypothalamus; Pituitary Gland; Polyuria; Vasopressins; Water-Electrolyte Balance

Peptides with agonist activity at the vasopressin V(2) receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. Of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V(1b) receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V(2) receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT((R))), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V(2) receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V(2) receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V(2) receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V(2) receptor agonist deficiency.

Topics: Animals; Antidiuretic Agents; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Humans; Male; Mice; NIH 3T3 Cells; Peptides; Pharmaceutical Preparations; Rats; Rats, Brattleboro; Receptors, Vasopressin; Vasopressins

To investigate the clinical feature, treatment and prognosis of both the mother and the fetus with gestational diabetes insipidus.. A total of 7 cases of gestational diabetes insipidus collected in the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Combination of Traditional Chinese Medicine with Western Medicine Hospital, and Zhejiang Taizhou Hospital from June 1993 to June 2006 were analyzed retrospectively.. Seven cases symptoms all characterized by excessive thirst polydipsia and polyuria. The average 24 h urinary output was between 11 L to 13 L and manifested of hypobaricuria. After effective treatment (three cases were treated with 1-deamino-8-D-arginine vasopressin, another three patients were managed with hydrochlorothiazide, and the last one was cured with antisterone), seven patients with gestational diabetes insipidus did not have any severe consequences. Their symptoms of excessive thirst, polyuria, and polydypsia disappeared from 7 days to 3 months after parturition. Urinary volume returned to normal standard of 1000-2000 ml during 24 hours. Specific gravity of urine recovered normally between a range 1.015-1.025 and serum sodium recovered between 135-147 mmol/L. The average duration of illness was 52 days. Eight newborn infants survived. Two of them were sent to neonatal intensive care unit for treatment. One was because of premature delivery caused by antepartum eclampsia, and the other case was one of the twins who had hydronephrosis. The baby of the first case left hospital after 3 weeks' treatment. The latter one's symptom disappeared 2 weeks after delivery. No obvious symptom was discovered among all the babies through follow-up telephone calls 42 days after childbirth.. Gestational diabetes insipidus is a rare endocrinopathy complicating pregnancy. This disorder is characterized by excessive thirst, polydypsia, polyuria, hypobaric urine and electrolyte disturbances usually manifesting in the third trimester of pregnancy or puerperium. This is a transient syndrome. The first treatment of choice in patients with gestational diabetes insipidus is 1-deamino-8-D-arginine vasopressin and the second-choice is hydrochlorothiazide. Early diagnosis and appropriate management of the disease may reduce the hazard for both the mother and the fetus during perinatal period.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hydrochlorothiazide; Infant, Newborn; Polyuria; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prognosis; Retrospective Studies; Sodium; Vasopressins; Young Adult

Diabetes insipidus (DI) is a rare clinical condition, which is usually caused by neurohypophyseal or pituitary stalk infiltration in cancer patients.. we present a 62-year old metastatic breast cancer woman with DI. She admitted to the hospital because of nausea, vomiting, polyuria and polydipsia, while she was on no cytotoxic medication. She had no electrolyte imbalance except mild hypernatremia. The CT scan of the brain yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI) of pituitary. Water deprivation test was compatible with DI. A clinical response to nasal vasopressin was achieved.. Cancer patients who have symptoms such as nausea, vomiting, polyuria and polydipsia while they are not on chemotherapy should be evaluated for not only metabolic complications like hypercalcemia but also posterior pituitary or stalk metastasis MRI could be the choice of imaging for pituitary metastasis.

Topics: Administration, Intranasal; Breast Neoplasms; Diabetes Insipidus; Female; Humans; Magnetic Resonance Imaging; Nausea; Pituitary Neoplasms; Polyuria; Thirst; Vasopressins; Vomiting

Holoprosencephaly is a developmental defect caused by incomplete cleavage of the embryonic forebrain structures during early embryogenesis. We describe a 3-month-old boy with median cleft palate, surgically reconstructed cleft lip, hypotelorism with a flat nose, cryptorchidism, clubfoot, and microcephaly. During the laboratory investigation, his blood sodium level was 154 mmol/L and urine specific gravity was 1.007. Serum osmolarity was 317 mOsm/kg and urine osmolarity was 268 mOsm/kg. Given these findings and the clinical response to vasopressin, diagnosis of central diabetes insipidus was made. Magnetic resonance imaging revealed semilobar holoprosencephaly. The patient responded very well to vasopressin treatment with restoration of serum electrolytes, which remained within normal limits on follow-up. In case of midline facial defects accompanied by hypotelorism with or without developmental delay, the brain should be imaged to confirm its morphology and investigations should be directed by a high index of suspicion of associated endocrinologic dysfunctions.

Topics: Brain; Cleft Palate; Clubfoot; Comorbidity; Diabetes Insipidus; Diagnosis, Differential; Eye Abnormalities; Holoprosencephaly; Humans; Hypothalamus; Infant; Magnetic Resonance Imaging; Male; Microcephaly; Osmolar Concentration; Vasopressins

Neuropeptide Y (NPY) is one of the most important brain peptides involved in feeding behavior. It influences both food choice and fluid homeostasis. The paraventricular and arcuate nuclei belong to the main pathway through which NPY stimulates carbohydrate intake. In this study, we measured NPY in various hypothalamic microdissected areas in Brattleboro di/di rats, a rat model of diabetes insipidus with specific dietary preferences. We confirmed that this rat is characterized by an increased fat intake (+10%; p<0.001) and a decreased carbohydrate intake (-10%; p<0.001) leading to a completely different dietary profile than that of di/+ controls. This profile was associated with a decrease in NPY in the paraventricular nucleus (-33%; p<0.005) and in the ventromedial nucleus (-24%; p<0.002). Intake of carbohydrate was negatively correlated with the gradient of NPY concentration between the arcuate and paraventricular nuclei. NPY could therefore contribute to the qualitative changes of feeding behavior in the Brattleboro rat through altered transport/release of the peptide and participate in the balance of neuropeptides that determines food choice in this strain of rat.

Topics: Animals; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Diabetes Insipidus; Dietary Carbohydrates; Dietary Fiber; Disease Models, Animal; Down-Regulation; Feeding Behavior; Male; Neural Pathways; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Species Specificity; Up-Regulation; Vasopressins; Ventromedial Hypothalamic Nucleus

Vasopressin, a peptide hormone functioning also as a neurotransmitter, neuromodulator and regulator of the stress response is considered to be one of the factors related to the development and course of depression. In the present study, we have tested the hypothesis that congenital deficit of vasopressin in Brattleboro rats leads to attenuated depression-like behavior in tests modeling different symptoms of depression. In addition, hypothalamic-pituitary-adrenocortical axis activity was investigated. Vasopressin deficient rats showed signs of attenuated depression-like behavior in forced swimming and sucrose preference tests, while their behavior on elevated plus maze was unchanged. Vasopressin deficiency had no influence on basal levels of ACTH and corticosterone and had only mild impact on hormonal activation in response to forced swimming and plus-maze exposure. However, vasopressin deficient animals showed higher level of dexamethasone induced suppression of corticosterone response to restraint stress and higher basal levels of corticotropin-releasing hormone mRNA in the hypothalamic paraventricular nucleus. In conclusion, present data obtained in vasopressin deficient rats show that vasopressin is involved in the development of depression-like behavior, in particular of the coping style and anhedonia. Moreover, behavioral and endocrine responses were found to be dissociated. We suggest that brain vasopressinergic circuits distinct from those regulating the HPA axis are involved in generating depression-like behavior.

Topics: Adaptation, Psychological; Adrenocorticotropic Hormone; Animals; Behavior, Animal; Corticosterone; Depression; Diabetes Insipidus; Food Preferences; Hypothalamo-Hypophyseal System; Male; Maze Learning; Pituitary-Adrenal System; Rats; Rats, Brattleboro; Swimming; Vasopressins

Septo-optic dysplasia (SOD) (De Morsier's syndrome) is a complex developmental disorder marked by variable and often incomplete formation of cranial midline structures, resulting in absence of the septum pellucidum, optic nerve hypoplasia, and hypothalamic-pituitary dysfunction. We describe a patient with SOD who manifested symptoms in the early neonatal period with severe deficiencies of multiple pituitary hormones including anti-diuretic hormone (ADH). Her congenital diabetic insipidus (DI), consequence of an anatomic defect, can be argued to be of the most severe type. Our patient resolved her severe DI 8 years after her initial presentation, suddenly requiring no further medical treatment for DI following longstanding pharmacological replacement of ADH. This is the first report of a patient with SOD with spontaneous resolution of congenital DI.

Topics: Child; Diabetes Insipidus; Female; Humans; Infant, Newborn; Magnetic Resonance Imaging; Pituitary Gland, Posterior; Remission, Spontaneous; Septo-Optic Dysplasia; Vasopressins

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 +/- 14 ml/24 h), whereas spironolactone decreased (74 +/- 11 ml/24 h) urine production compared with rats treated with lithium only (120 +/- 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.

Topics: Aldosterone; Animals; Aquaporin 2; Cell Membrane; Diabetes Insipidus; Kidney; Kidney Tubules; Lithium; Male; Protein Transport; Rats; Rats, Inbred BB; Rats, Wistar; Spironolactone; Time Factors; Urination; Vasopressins

Chronic diabetes mellitus (DM) induces hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA). Our present study addresses the role of vasopressin (AVP) in maintaining adrenocortical responsiveness during DM. AVP-deficient mutant Brattleboro rats were used with heterozygous controls and the V2 agonist, desmopressin was infused to replace peripheral AVP. To induce DM the rats were injected by streptozotocin (STZ, 60 mg/ml/kg i.v.) and studied 2 weeks later. The acute stress stimulus was 60 min restraint. The signs of DM (the increase in water consumption and in blood glucose levels) were discovered in all rats. The diuretic effect of the lack of AVP was additional to the DM-induced osmotic diuresis. DM induced significant, chronic stress-like somatic changes on which AVP-deficiency had no effect and although desmopressin infusion normalized the water consumption and the body weight gain in AVP-deficient rats, it had no effect on DM-induced changes. The acute stress-induced plasma ACTH elevation was smaller in AVP-deficient or DM rats but these effects were not additive. Desmopressin did not normalize the decreased ACTH-elevation of AVP-deficient animals. The resting morning plasma corticosterone level was elevated both in DM and AVP-deficient rats without interaction. The restraint-induced corticosterone rise was influenced neither by the lack of AVP nor by DM and the basal and stress-induced prolactin levels were smaller in DM rats without any effect of AVP-deficiency. In conclusion, our data suggest that AVP does not play a crucial role in HPA axis regulation during DM-induced chronic stress. In contrast, the role of AVP seems to be more important during acute stress, however, it is restricted to the ACTH regulation. According to the water consumption data diabetes insipidus seems to be an additional risk factor for DM.

Topics: Adrenocorticotropic Hormone; Animals; Corticosterone; Diabetes Insipidus; Diabetes Mellitus, Experimental; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Prolactin; Rats; Rats, Brattleboro; Stress, Psychological; Vasopressins

A 39-year-old man was hospitalized after divalproate self-poisoning. He presented coma requiring tracheal intubation and mechanical ventilation at 11 hours and central diabetes insipidus. Serum valproic acid concentration was 590 mg/l at 30 hours. Progressive improvement occurred after hydratation and administration of vasopressin.

Topics: Adult; Bipolar Disorder; Coma; Diabetes Insipidus; Fluid Therapy; Humans; Intubation, Intratracheal; Male; Poisoning; Polyuria; Respiration, Artificial; Suicide, Attempted; Valproic Acid; Vasopressins

Topics: Diabetes Insipidus; Humans; Receptors, Vasopressin; Vasopressins

Topics: Diabetes Insipidus; Female; Humans; Incidence; Polyuria; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Prognosis; Risk Assessment; Vasopressins

Transient diabetes insipidus may rarely present during late pregnancy and/or the immediate puerperium, and if unrecognized, may cause neurologic injury and threaten the lives of mother and fetus. However, when recognized early and treatment is initiated with desmopressin acetate, an analog of vasopressin that is resistant to vasopressinase, water loss in the urine is eliminated and complications may be abrogated. This report aims to increase the awareness of this disorder and describes appropriate treatment.. Two cases of diabetes insipidus, believed to be due to excess vasopressinase, are presented to demonstrate the clinical features, pathogenesis, and treatment of this syndrome.. Awareness of the syndrome of transient diabetes insipidus may lead to early diagnosis and appropriate treatment that will reduce the risks of maternal and fetal morbidity.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Follow-Up Studies; Humans; Maternal Age; Polyuria; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Risk Assessment; Treatment Outcome; Vasopressins

Managing children with diabetes insipidus (DI) in the perioperative period is complicated and frequently associated with electrolyte imbalance compounded by over- or underhydration. In this study the authors developed and prospectively evaluated a multidisciplinary approach to the perioperative management of DI with a comparison to 19 historical control children. Eighteen children either with preoperative DI or undergoing neurosurgical operations associated with a high risk for developing postoperative DI were identified and managed using a standardized protocol. In all patients in whom DI occurred during or after surgery, a continuous intravenous infusion of aqueous vasopressin was initiated and titrated until antidiuresis was established. Intravenous fluids were given as normal saline and restricted to two thirds of the estimated maintenance rate plus amounts necessary to replace blood losses and maintain hemodynamic stability. In all children managed in this fashion, perioperative serum sodium concentrations were generally maintained between 130 and 150 mEq/L, and no adverse consequences of this therapy developed. In the 24-hour period evaluated, the mean change in serum sodium concentrations between the historical controls was 17.6 +/- 9.2 mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol. Hyponatremia occurred less frequently in the children managed with this protocol compared with historical controls.

Topics: Adolescent; Child; Child, Preschool; Clinical Protocols; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hyponatremia; Hypotonic Solutions; Infusions, Intravenous; Male; Neurosurgical Procedures; Perioperative Care; Postoperative Complications; Prospective Studies; Renal Agents; Seizures; Sodium; Vasopressins; Water-Electrolyte Balance

Brattleboro diabetes insipidus mutant rats and normal WAG rats were subjected to water loading or thirst during 3 days. It was found that tropomyosin-encoding gene expression has a tissue-specific pattern in the kidney. Northern blot and western blot analysis had shown that the main expression of Tpm3(3) takes place in the renal medulla, and its intensity differs in normal and mutant rats. The differences between mutants with an ineffective vasopressin synthesizing system and the rats having an intact vasopressin gene were more distinct under long-lasting dehydration. The ratio between renal medullary tropomyosin of Brattleboro and WAG lines of rats was 39.76 +/- 0.90 versus 18.29 +/- 0.86 under water loading, and 46.12 +/- 2.14 versus 13.83 +/- 0.66 in thirst.

Topics: Animals; Diabetes Insipidus; Gene Expression Regulation; Kidney; Kidney Medulla; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reference Values; Thirst; Tropomyosin; Vasopressins

The use of vasopressin for the treatment of septic shock is increasing. Few reports of fluid and electrolyte complications of this therapy have been reported. A neurologically impaired, 53-year-old man with a history of syndrome of inappropriate antidiuretic hormone developed apparent transient diabetes insipidus and acute hypernatremia after being treated with vasopressin. He was treated for presumed septic shock with intravenous vasopressin 0.01-0.10 U/minute. His blood pressure did not improve with this therapy, and his course was complicated by hyponatremia during the vasopressin infusion. Discontinuation of the infusion was followed by a profound (8.4 L) diuresis and rapid onset of hypernatremia (serum sodium concentration increased from 132 to 157 mEq/L over 8 hrs). Although urine osmolality was not measured during the patient's diuresis, the rapid changes in serum sodium concentration can be explained only by an inappropriate water diuresis. The diuresis ceased when the vasopressin infusion was resumed. We concluded that these findings are most consistent with transient diabetes insipidus. The safety and efficacy of intravenous vasopressin have not been established in patients with septic shock and underlying disorders of water homeostasis. The drug may have diminished vasoconstrictive effects in this patient population. Careful monitoring of water and sodium balance is warranted in all patients treated with vasopressin for septic shock.

Topics: Acute Disease; Diabetes Insipidus; Humans; Hypernatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Vasoconstrictor Agents; Vasopressins

These studies were aimed at an initial characterization of the human vasopressin precursor and the evaluation of factors leading to misfolding by the pathological 87STOP mutation. This mutation deletes the precursor's glycosylated copeptin segment, which has been considered unnecessary for folding, and the last seven neurophysin residues. We investigated the role in folding of the last seven neurophysin residues by comparing the properties of the 87STOP precursor and its derivative neurophysin with those of the corresponding wild-type proteins from which copeptin had been deleted, leading to the following conclusions. First, despite modulating effects on several protein properties, the last seven neurophysin residues do not make a significant net thermodynamic contribution to precursor folding; stabilities of the mutant and wild-type precursors to both guanidine denaturation and redox buffer unfolding are similar, as are in vitro folding rates. Second, the monomeric forms of both precursors are unstable and predicted to fold inefficiently at physiological pH and temperature, as evidenced by precursor behavior in redox buffers and by thermodynamic calculations. Third, both precursors are significantly less stable than the bovine oxytocin precursor. These results, together with earlier studies elsewhere of vasopressin precursor behavior within rat neurons, are shown to represent a self-consistent argument for a role for glycosylated copeptin in vasopressin precursor folding in vivo, copeptin most probably assisting refolding by facilitating interaction of misfolded monomers with the calnexin/calreticulin system. This hypothesis provides an explanation for the absence of copeptin in the more stable oxytocin precursor and suggests that the loss of copeptin contributes to 87STOP pathogenicity. Reported cell culture studies of rat precursor folding are also discussed in this context. Most generally, the results emphasize the significance of monomer stability in the folding pathways of oligomeric proteins.

Topics: Amino Acid Sequence; Amino Acid Substitution; Animals; Cattle; Diabetes Insipidus; Dimerization; Gene Expression; Glutathione; Glycopeptides; Guanidine; Humans; Kinetics; Molecular Sequence Data; Mutagenesis, Site-Directed; Neurophysins; Nuclear Magnetic Resonance, Biomolecular; Oxytocin; Protein Conformation; Protein Denaturation; Protein Folding; Protein Precursors; Recombinant Proteins; Thermodynamics; Vasopressins

Managing children with diabetes insipidus (DI) in the perioperative period is complicated and frequently associated with electrolyte imbalance compounded by over- or underhydration. In this study the authors developed and prospectively evaluated a multidisciplinary approach to the perioperative management of DI with a comparison to 19 historical control children. Eighteen children either with preoperative DI or undergoing neurosurgical operations associated with a high risk for developing postoperative DI were identified and managed using a standardized protocol. In all patients in whom DI occurred during or after surgery, a continuous intravenous infusion of aqueous vasopressin was initiated and titrated until antidiuresis was established. Intravenous fluids were given as normal saline and restricted to two thirds of the estimated maintenance rate plus amounts necessary to replace blood losses and maintain hemodynamic stability. In all children managed in this fashion, perioperative serum sodium concentrations were generally maintained between 130 and 150 mEq/L, and no adverse consequences of this therapy developed. In the 24-hour period evaluated, the mean change in serum sodium concentrations between the historical controls was 17.6 +/- 9.2 mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol. Hyponatremia occurred less frequently in the children managed with this protocol compared with historical controls.

Topics: Adolescent; Child; Child, Preschool; Clinical Protocols; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hyponatremia; Hypotonic Solutions; Infusions, Intravenous; Male; Neurosurgical Procedures; Perioperative Care; Postoperative Complications; Prospective Studies; Renal Agents; Seizures; Sodium; Vasopressins; Water-Electrolyte Balance

In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.. Diabetes insipidus was determined by either standard criteria for diagnosis in the immediate postoperative period, or by water deprivation test, in all craniopharyngioma and pituitary tumour patients who underwent surgery in Beaumont Hospital between the years 1986 and 1998. Osmoregulated thirst and vasopressin release were studied during a 2-h infusion of hypertonic (5%) saline followed by a 30-min period of free access to water.. Data on the incidence of postoperative diabetes insipidus was collected in 26 patients with craniopharyngioma and 154 patients with pituitary adenomata. We recruited 16 healthy control patients, 16 patients with cranial diabetes insipidus following pituitary tumour surgery and 16 patients with cranial diabetes insipidus following craniopharyngioma resection for the hypertonic saline infusion study.. Twenty-five patients out of 26 (96%) patients developed diabetes insipidus after surgery for craniopharyngioma, a much higher incidence than after surgery for suprasellar (26/88, 30%, P < 0.001) or intrasellar pituitary tumours (9/66, 14%, P < 0.001). Hypertonic saline infusion identified abnormal thirst responses in five of the 16 craniopharygioma patients studied; all of the pituitary tumour patients had a normal thirst response. Three of the craniopharyngioma patients had adipsic diabetes insipidus whilst two had polydipsic diabetes insipidus.. This study demonstrates following surgery for craniopharyngioma there is a high incidence of cranial diabetes insipidus and a significant incidence of abnormal thirst responses to osmotic stimuli.

Topics: Adult; Blood Pressure; Cohort Studies; Craniopharyngioma; Diabetes Insipidus; Drinking; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Osmolar Concentration; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Saline Solution, Hypertonic; Thirst; Vasopressins

Traumatic hypopituitarism was diagnosed in an 11-month-old male neutered cat. The presenting complaints were polydipsia, polyuria and lethargy of three months' duration. Craniocerebral trauma, as a result of a road traffic accident, had preceded the onset of clinical signs by six weeks. Neurological examination revealed right-sided mydriasis, reduced visual and tactile left forelimb placing reflexes and decreased proprioception in both the left fore- and hindlimb. Initial laboratory findings included hypernatraemia, hyperchloraemia, mild azotaemia, eosinophilia and isosthenuria. Low basal cortisol, thyroxine, thyroid-stimulating hormone and insulin growth factor-1 were noted. Subsequent to treatment with prednisolone, a water deprivation test confirmed the presence of central diabetes insipidus and therapy with synthetic antidiuretic hormone successfully ameliorated the polydipsia.

Topics: Accidents, Traffic; Adrenal Insufficiency; Animals; Cat Diseases; Cats; Craniocerebral Trauma; Diabetes Insipidus; Diagnosis, Differential; Male; Vasopressins

An increase in urinary albumin excretion (UAE) represents an early predictor of glomerular damage in diabetes mellitus (DM) and a risk factor for cardiovascular complications in hypertension. Vasopressin is elevated in DM and in some forms of hypertension. Previous studies in rats suggested that this hormone could play a role in the albuminuria observed in chronic renal failure or diabetic nephropathy, but no information is available concerning the mechanism of these effects and the possible influence of vasopressin on UAE in the healthy kidney. The present study was thus designed to evaluate whether vasopressin influences UAE in normal rats and humans, whether this effect is V(2)-receptor-dependent, and whether it is mediated by the renin-angiotensin system.. UAE was measured in normal Wistar rats and healthy humans, or in subjects with various forms of diabetes insipidus (DI), before and after acute or chronic infusion of the vasopressin V(2) receptor agonist dDAVP. Chronic dDAVP administration was also performed in normal Wistar rats previously submitted to either chronic angiotensin-converting enzyme inhibition (ACEI) or chronic blockade of AT1 receptors (ARB).. In rats, acute or chronic dDAVP infusion increased UAE significantly and reversibly (4-fold and 6-fold, respectively). In healthy subjects, acute infusion of dDAVP tripled UAE (P<0.01) but did not change creatinine and beta(2)-microglobulin excretion, thus suggesting that the rise in UAE was due to an increased glomerular leakage of albumin. dDAVP also increased UAE in patients with central DI and in patients with hereditary nephrogenic DI bearing AQP2 mutations. However, UAE was not increased in patients with hereditary nephrogenic DI bearing mutations of the V(2) receptor. In rats, ACEI and ARB blunted the dDAVP-induced rise in UAE by 70% (P<0.05) and 50% (NS), respectively.. The present studies reveal for the first time that vasopressin induces a marked increase in UAE in healthy rats and humans. This albuminuric effect seems to result from increased glomerular leakage, requires functional vasopressin V(2) receptors, and is, at least in part, mediated by the renin-angiotensin system. These results bring additional support for an involvement of vasopressin in the albuminuria observed in pathological states such as diabetes mellitus or hypertension.

Topics: Adult; Albuminuria; Animals; Blood Pressure; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Rats; Receptors, Vasopressin; Reference Values; Renal Agents; Renin-Angiotensin System; Vasopressins

Literature data and original experience of the authors with 6890 cases of respiratory sarcoidosis (stage I-III) suggest that diabetes ipsipidus in respiratory sarcoidosis (RS) can present as hypothalamic-hypophysial form (observed at the stage I-II by physicians since 1935) and a new form--nephrogenic (vasopressin-resistant) at stage II of pulmonary sarcoidosis. The latter form is little known. It was found that in stage III sarcoidosis patients who have severe fibrosis of the lungs and a long history of corticosteroid hormone treatment the nephrogenic form of the pathogenesis is caused by defects in calcium metabolism leading to nephrocalcinosis with low sensitivity of renal tubular receptors to ADH. Adiurecrine treatment is unefficient. It is recommended to use chlorpropamide which raises sensitivity of the tubules to ADH.

Topics: Diabetes Insipidus; Drug Resistance; Humans; Hypothalamo-Hypophyseal System; Kidney; Renal Agents; Retrospective Studies; Sarcoidosis, Pulmonary; Severity of Illness Index; Vasopressins

Age-dependant dynamics of the kidney inner medullary 120-kDa protein content in vasopressin-deficient Brattleboro rats with di/di mutant genotype was studied in comparison with WAG rats with genotype and normal vasopressin expression. Age-dependant dynamics of vasopressin content in neurohypophysis of WAG rats was also examined. It was shown that 10-day-old WAG rats were unable to elevate the synthesis of the 120 kDa protein in respond to long-term dehydration, while this tendency was clearly observed in the 15-day-old rats and later in the development. In WAG rats the onset of this specific feature was time correlated with the development of the respond to hydration by the elevation of vasopressin synthesis and release from neurohypophysis into blood. In the di/di rats dehydration had no effect on the kidney 120-kDa protein synthesis in all ages examined. These results point to the interaction between the di alleles and the 120-kDa protein-encoding gene in the course of development.

Topics: Age Factors; Alleles; Animals; Animals, Newborn; Diabetes Insipidus; Drinking; Gene Expression Regulation, Developmental; Kidney; Molecular Weight; Mutation; Pituitary Gland, Posterior; Proteins; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins

A patient with a history of schizophrenia was brought to the emergency department with extensive self-inflicted soft tissue injuries. Primary polydipsia was evident on admission, because he had a maximally dilute urine, a urine flow rate of 10 ml/min, and hyponatraemia (100 mmol/l). During an imaginary consultation with Professor McCance in which he applied basic principles of integrative physiology and a deductive analysis in quantitative terms, other reasons for the polyuric state were considered. Moreover, based on the very low value for the concentration of urea in plasma (< 0.7 mmol/l, BUN 1 mg /dl), the goals of therapy to prevent osmotic demyelination became evident. Applying this simple approach, a more comprehensive and accurate differential diagnosis, and a plan for therapy to avoid serious complications was compiled.

Topics: Adult; Diabetes Insipidus; Diagnosis, Differential; Diuresis; Humans; Hyponatremia; Male; Polyuria; Renal Agents; Schizophrenia; Urea; Vasopressins

Topics: Adult; Blood Chemical Analysis; Diabetes Insipidus; Drinking Behavior; Female; Follow-Up Studies; Humans; Infant, Newborn; Liver Function Tests; Polyuria; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Risk Assessment; Thirst; Twins; Urinalysis; Vasopressins

It has long been known that under intracellular conditions vasopressin associates tightly to neurophysin, which is present in the same prohormone. As the association has been suggested to play a role during hormone biosynthesis, its role was studied in a cellular context by expressing mutant vasopressin precursors in Neuro2A cells. Mutant vasopressin precursors, in which the association between the vasopressin and neurophysin domains was prevented either by deleting the vasopressin domain from the precursor or by substitution of the essential Tyr2 residue in vasopressin for Gly, were neither processed nor targeted into secretory granules. Rather, both provasopressin mutants were retained in the endoplasmic reticulum. Our results demonstrate that the vasopressin domain is crucial for correct trafficking of the prohormone through the secretory pathway, and suggest that vasopressin-neurophysin association provides correct prohormone folding in the endoplasmic reticulum.

Topics: Animals; Cell Line, Tumor; Diabetes Insipidus; Endoplasmic Reticulum; Gene Expression; Mutagenesis; Neuroblastoma; Neurophysins; Protein Folding; Protein Structure, Tertiary; Protein Transport; Rats; Secretory Vesicles; Vasopressins

Morphofunctional immune disorders were revealed in vasopressin-deficient Brattleboro rats with diabetes insipidus during ontogeny. We observed a permanent decrease in the number of blood lymphocytes, increase in neutrophil count, reduced activity of macrophages, early involution of the thymus and spleen, and suppression of antibody production. These changes reflect impaired general resistance of these animals.

Topics: Animals; Antibody-Producing Cells; Blood Cell Count; Diabetes Insipidus; Drinking; Embryonic and Fetal Development; Immune System; Immune System Diseases; Macrophages; Neutrophils; Rats; Rats, Brattleboro; Rats, Inbred Strains; Spleen; Thymus Gland; Vasopressins; Water

We report a case of transient diabetes insipidus in late pregnancy. This rare condition is characterised by excessive thirst and polyuria and is associated with pre-eclampsia. The aetiology is most likely due to increased vasopressinase activity. Suspected cases should be referred to an obstetric centre, since termination of pregnancy is recommended. The condition normally resolves within a few days of delivery.

Topics: Adult; Cesarean Section; Diabetes Insipidus; Diabetes, Gestational; Female; Humans; Pregnancy; Vasopressins

The diabetes insipidus mutation is displayed in homozygotes in the form of diabetes insipidus with water consumption from 30 to 100% of body weight per day. We developed two inbred sublines of the di/di Brattleboro rats as well as the recombinant inbred subline by integrating genes of August rats into the di/di mutant genome. Changes in the genetic background proved to have no effect on the quantitative parameters of the diabetes insipidus. The intensity of the secondary immune response and the content of tropomyosin in the medulla of the rat kidney can serve as additional marker traits of the di/di genotype.

Topics: Animals; Diabetes Insipidus; Drinking; Gene Expression; Kidney Medulla; Mutation; Rats; Rats, Brattleboro; Tropomyosin; Vasopressins

There is growing evidence of local protein synthesis in neuronal dendrites, especially in relation to synaptic activity. The hypothalamic magnocellular system is a robust model for peptidergic neurons, especially for the study of dendrites. Quantitative electron microscopy, immunocytochemistry and non-radioactive in situ hybridization (with tyramide signal amplification) were used to compare dendrites of magnocellular neurons in the supraoptic nucleus of wild-type rats and of homozygous Brattleboro (BB) rats which are subject to long-term hyper-osmotic stimulation because they cannot secrete vasopressin. The dendrites contained free polyribosomes, cisterns of rough endoplasmic reticulum (ER) and small Golgi-like elements. These were clustered in the dendrites, mostly near the plasma membrane. All were increased in amount in the enlarged dendrites of the BB rats. The presence of polyribosomes and cisterns of rER implies that both cytosolic and membrane-inserting proteins are synthesized in the dendrites. The ER marker protein disulfide isomerase extended far into dendrites, but Golgi element markers (mid-Golgi and trans-Golgi network) were distributed mainly in their proximal parts. In BB rats, all the labeling was stronger. 28S rRNA, initiator tRNA(Met), and poly(A) mRNA were revealed extending into proximal and middle parts of dendrites where intensely reactive punctate structures were common. 28S rRNA could be detected in the distal parts of the dendrites. The length of positively stained dendrites was increased significantly for all these RNAs in BB rats. The results provide morphological evidence that magnocellular dendrites have the capacity for local protein syntheses and that this is increased in chronic hyperosmotic stress.

Topics: Animals; Dendrites; Diabetes Insipidus; Endoplasmic Reticulum; Golgi Apparatus; Immunohistochemistry; In Situ Hybridization; Male; Microscopy, Electron; Nerve Tissue Proteins; Neurons; Neurosecretory Systems; Oligonucleotides; Organelles; Oxytocin; Rats; Rats, Brattleboro; Rats, Long-Evans; Vasopressins

In a previous study we observed that acute administration of the selective antagonist of vasopressin (AVP) V2 receptors, SR 121463A (SR), aggravated the symptoms of diabetes insipidus (DI) in homozygous Brattleboro rats (an AVP-deficient strain). The present study investigates in more details the acute and chronic effects of SR in DI rats.. In experiment A, different groups of rats received acute i.p. injections of SR (0.001-10 mg/kg) or vehicle alone, and urine was collected for the next 24 h. SR dose-dependently increased urine flow rate and decreased urine osmolality with no significant change in solute excretion, thus confirming a pure 'aquaretic' effect. In experiments B and C, the chronic effects of orally administered SR were evaluated over 8 days in Brattleboro DI rats (experiment B, 1 mg/kg/day) and in adult Sprague-Dawley rats with normal AVP secretion (experiment C, 3 mg/kg/day). In DI rats, the aquaretic effects of SR persisted with the same intensity over the 8 days. In Sprague-Dawley rats, SR induced a sustained, stable aquaretic effect and also increased non-renal water losses, suggesting an effect of AVP on water conservation in extrarenal sites. Because oxytocin (OT) synthesis is elevated in DI rats and OT is known to bind to V2 receptors, we evaluated the antidiuretic effects of OT in DI rats in experiment D. Chronic infusion of OT (3 microg/kg/h, i.p.) induced a marked antidiuresis, and acute SR (1 mg/kg) in OT-treated DI rats completely abolished this antidiuretic effect, thus indicating that it was due to binding of OT to V2 receptors.. (i) SR is a potent orally active aquaretic and induces stable effects during 1 week in rats with or without endogenous AVP secretion. (ii) Significant V2 receptor-mediated water reabsorption occurs in collecting ducts of Brattleboro DI rats because their usual urine osmolality is about twofold higher than the minimum observed during SR-induced maximum diuresis. (iii) This V2 agonism could be mediated in part by OT binding to V2 receptors. Small amounts of endogenous AVP, known to be produced by adrenal and testis in DI rats, could also contribute to this V2 agonism, as well as a possible constitutive activation of the V2 receptors. (iv) In normal rats, AVP probably reduces water losses through extrarenal sites, probably the lungs.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Diabetes Insipidus; Male; Morpholines; Rats; Spiro Compounds; Vasopressins; Water

A water deprivation test or a hypertonic saline infusion test with the measurement of plasma osmolality and plasma vasopressin are the gold standard tests in the differential diagnosis of polyuric syndromes. Because commercially available vasopressin kits are too insensitive for this approach, and the concentration of vasopressin in urine is much higher than in plasma, urinary vasopressin measurements may be an alternative to the more difficult plasma vasopressin measurement.. The diagnostic value of the measurement of urinary vasopressin with a rather insensitive commercially available vasopressin kit was compared with plasma vasopressin measurement by a highly sensitive radioimmunoassay (RIA).. Thirteen normal subjects and 27 patients with polyuria/polydipsia were examined by an 8-h fluid deprivation test. In all blood samples (0800 h, 1200 h, 1400 h and 1600 h) and in all urine collections (2-hourly fractions), osmolality as well as vasopressin were measured.. Using plasma vasopressin measurement with a highly sensitive RIA as gold standard test, nine patients were classified as having primary polydipsia, whereas 18 had partial or complete cranial diabetes insipidus. Whereas the substitution of plasma vasopressin measurement by urinary vasopressin measurement alone did not provide 100% separation between both groups, the product of urinary vasopressin and urinary osmolality related to plasma osmolality completely separated the patients with primary polydipsia from those with diabetes insipidus. Urinary measurement of vasopressin and osmolality alone, which was recommended as a noninvasive diagnostic procedure in children, was too insensitive for exact differential diagnosis in our adult patients.. The simultaneous measurement of plasma vasopressin and plasma osmolality in a dehydration test is the most powerful diagnostic tool in the differential diagnosis of polyuria/polydipsia. However, if highly sensitive assays for plasma vasopressin measurements are not available, the measurement of urinary vasopressin with commercially available, less sensitive RIAs may be a diagnostic alternative, which showed nearly the same sensitivity as plasma vasopressin measurement in our study population.

Topics: Adult; Aged; Case-Control Studies; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Drinking; Female; Humans; Male; Middle Aged; Osmolar Concentration; Polyuria; Predictive Value of Tests; Radioimmunoassay; Vasopressins

To re-examine the controversial possibility that prolactin exerts renal effects, using recombinant mouse prolactin (rmP), in the presence and absence of circulating vasopressin.. In experiment 1, the renal effects of rmP were examined in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) lacking circulating vasopressin and normal animals of the parent Long Evans (LE) strain. In experiment 2, salt and water excretion were studied in fluid-loaded normal Sprague-Dawley (SD) rats, some of which received rmP.. In experiment 1, BDI and LE rats maintained in fluid balance were infused i.v. with each of three concentrations of rmP (10, 20 and 40 microg/ml per h) or maintained on 150 mmol/l NaCl vehicle (controls). In experiment 2, the SD rats were infused with 75 mmol/l NaCl in order to induce a state of diuresis comparable to that of BDI rats, some of them then receiving the rmP i.v.. A profound rmP-induced dose-dependent decrease in urine excretion (P<0.005) and a lesser decrease in sodium excretion in the BDI rats was in marked contrast with the small but significant increase in urine excretion in the LE rats compared with controls (P<0.025). The rmP-infused fluid-loaded SD rats also demonstrated a significant (P<0.05) dose-related antidiuresis compared with the control animals, in addition to a decrease in sodium excretion.. These results show that prolactin has a profound antidiuretic effect in the absence of circulating vasopressin. In contrast, when vasopressin is present in the circulation rmP has a small, but opposite, diuretic effect. Thus the use of a recombinant prolactin has provided evidence for renal effects of this hormone which are modified in the presence of the circulating neurohypophysial hormone vasopressin.

Topics: Anesthetics, Intravenous; Animals; Diabetes Insipidus; Kidney; Male; Potassium; Prolactin; Rats; Rats, Brattleboro; Rats, Long-Evans; Rats, Sprague-Dawley; Recombinant Proteins; Sodium; Thiopental; Urination; Vasopressins

Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant trait in which expression of a mutant vasopressin prohormone reduces vasopressin production. We investigated the NP85 Cys-->Gly mutant vasopressin prohormone in a large kindred in The Netherlands. We demonstrate that growth retardation is an important early sign in two children from this kindred, which recuperates by substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of FNDI, we analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. This defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle. We hypothesize that disturbance of the endoplasmic reticulum results in dysfunction and ultimately cell death of the cells expressing the mutant prohormone. Our data support the hypothesis that FNDI is a progressive neurodegenerative disease with delayed onset of symptoms. Its treatment requires early detection of symptoms for which growth parameters are useful.

Topics: Adult; Animals; Cell Death; Child; Child, Preschool; Diabetes Insipidus; Dimerization; Endoplasmic Reticulum; Female; Fluorescent Antibody Technique; Growth Disorders; Humans; Immunosorbent Techniques; Male; Mice; Mutation; Netherlands; PC12 Cells; Pedigree; Pituitary Neoplasms; Protein Precursors; Rats; Transfection; Tumor Cells, Cultured; Vasopressins

Endoscopic third ventriculostomy has been found to be successful for treating occlusive hydrocephalus. The complication rate ranges from 6 to 12%. Intraoperative bleeding is the most common incident. Endocrinological failures are rare, mainly due to the proximity of the hypothalamic structures. We report the case of a 33-year-old man who was referred in emergency for subacute hydrocephalus related to a tentorium meningioma. The hydrocephalus was treated by endoscopic third ventriculostomy. During the procedure, the floor of the third ventricle was found to be thick but fenestration was performed without incident. After surgery, the clinical signs of hydrocephalus disappeared but diabetes insipidus was diagnosed the same day. There were no other endocrinology disorders. Medical treatment with vasopressin allowed resolution of the diabetes insipidus in fifteen days. Surgical debulking of the meningioma was then achieved via a subtemporal approach. There was no recurrence of the endocrinology disorder. Diabetes insipidus is an unpredictable complication of third ventriculostomy. The mechanism is not well known. It is however a transient disorder that can easily be treated with vasopresin and therefore should not modify the indications of third ventriculostomy, especially in tumor-related hydrocephalus.

Topics: Adult; Diabetes Insipidus; Humans; Hydrocephalus; Male; Meningeal Neoplasms; Meningioma; Vasopressins; Ventriculostomy

To study clinical, morphological and molecular characteristics in a Swiss family with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI).. A 15-month-old girl presenting with symptoms of polydipsia and polyuria was investigated by water deprivation test. Evaluation of the family revealed three further family members with symptomatic vasopressin-deficient diabetes insipidus. T1-weighted magnetic resonance images of the posterior pituitary were taken in two affected adult family members and molecular genetic analysis was performed in all affected individuals.. The water deprivation test in the 15-month-old child confirmed the diagnosis of vasopressin-deficient diabetes insipidus and the pedigree was consistent with autosomal dominant inheritance. The characteristic bright spot of the normal vasopressin-containing neurophypophysis was absent in both adults with adFNDI. Direct sequence analysis revealed a new deletion (177-179DeltaCGC) in exon 2 of the AVP-NP II gene in all affected individuals. At the amino acid level, this deletion eliminates cysteine 59 (C59Delta) and substitutes alanine 60 by tryptophan (A60W) in the AVP-NP II precursor; interestingly, the remainder of the reading frame remains unchanged. According to the three-dimensional structure of neurophysin, C59 is involved in a disulphide bond with C65.. Deletion of C59 and substitution of A60W in the AVP-NP II precursor is predicted to disrupt one of the seven disulphide bridges required for correct folding of the neurophysin moiety and thus disturb the function of neurophysin as the vasopressin transport protein. These data are in line with the clinical and morphological findings in the reported family with adFNDI.

Topics: Amino Acid Sequence; Arginine Vasopressin; Base Sequence; Diabetes Insipidus; Female; Genes, Dominant; Humans; Infant; Magnetic Resonance Imaging; Molecular Biology; Molecular Sequence Data; Neurophysins; Pedigree; Protein Precursors; Switzerland; Vasopressins

The herbicide BASTA (AgrEvo, Germany), containing glufosinate ammonium (20%) and an anionic surfactant, polyoxyethylene alkylether sulfate (33%), is widely used. In acute oral BASTA poisoning, patients develop a variety of clinical signs, including disturbed consciousness, convulsions, and apnea. These effects are suspected to be due to the effects of glufosinate on the central nervous system.. A 60-year-old man ingested 500 mL of BASTA herbicide in a suicide attempt. He developed not only unconsciousness, respiratory distress, and convulsions but also an increase in urine output (7885 mL/d), elevated serum sodium (167 mEq/L), elevated plasma osmolality (332 mOsm/kg), and a decrease in both urine osmolality (200 mOsm/kg) and urine specific gravity (1.003), which suggested the development of diabetes insipidus. The plasma level of antidiuretic hormone remained within the normal range (1.3 pg/mL), despite high plasma osmolality. The administration of desmopressin was successful in normalizing urine volume, specific gravity, and osmolality. Serum sodium corrected gradually within 48 hours. The possible mechanisms causing the diabetes insipidus are discussed.

Topics: Aminobutyrates; Deamino Arginine Vasopressin; Diabetes Insipidus; Hemoperfusion; Herbicides; Humans; Male; Middle Aged; Poisoning; Renal Dialysis; Suicide, Attempted; Urine; Vasopressins

Renal and metabolic adverse effects of lithium therapy are illustrated by the case report of a manic depressive woman aged 78 years, so treated for about 25 years. Long term lithium therapy with plasma lithium level in the therapeutic range impairs renal concentrating ability in 25-50% of the patients (when the total ingested amount reaches 100-200 mol, 700-1400 g). About 10-15% of the patients have overt nephrogenic diabetes insipidus (NDI) with elevated antidiuretic hormone plasma level and unresponsiveness to desmopressin. In rats, lithium treatment down regulates expression of the main water channel, aquaporin 2, in the renal collecting duct. NDI may be complicated by hypernatremic dehydration if the access to water is restricted, whatever the cause. Treatment of NID is best started with nonsteroidal antiinflammatory drugs, being then substituted for amiloride. Prolonged lithium therapy may induce chronic interstitial nephritis. In some patients this may result in mild or moderate non progressive chronic renal insufficiency. Acute lithium intoxication (with supratherapeutic doses) may be complicated by acute renal failure (ARF); even in the absence of ARF hemodialysis is indicated when plasma lithium level reaches 4 mmol/l or more. Other metabolic adverse effects of lithium therapy include: hypercalcemia due to hyperparathyroidism (in 5-10% of the patients); hypothyroidism (often latent); hyperthyroidism. In conclusion, these renal and metabolic adverse effects are generally mild or moderate, allowing the continuation of lithium therapy in most affected patients.

Topics: Aged; Animals; Antidepressive Agents; Bipolar Disorder; Blood Proteins; Calcitriol; Calcium; Diabetes Insipidus; Electrolytes; Female; Humans; Lithium Carbonate; Parathyroid Hormone; Phosphates; Rats; Thyrotropin; Time Factors; Vasopressins

Biosynthesis of the vasopressin (VP) prohormone in magnocellular neurones of the hypothalamo-neurohypophysial system comprises endoplasmic reticulum (ER) transit, sorting into the regulated secretory pathway and subsequent processing in the individual proteins VP, neurophysin and a glycoprotein. These processes are severely disrupted in the homozygous diabetes insipidus (di/di) Brattleboro rat, which expresses a mutant VP precursor due to a single nucleotide deletion in the neurophysin region of the VP gene resulting in VP deficiency. Previous studies have shown the presence of additional frameshift mutations in VP transcripts, in solitary magnocellular neurones of the di/di rat due to a GA dinucleotide deletion resulting in two different mutant VP precursors with partly restored reading frame. Frameshifted VP precursors are also expressed in several magnocellular neurones in wild-type rats. In this study, we determined if the +1 frameshifted precursors from di/di and wild-type rats can lead to biosynthesis of the hormone VP. Therefore, eukaryotic expression plasmids containing the frameshifted VP cDNAs were transiently expressed in peptidergic tumour cell lines, and cells were analysed by reversed phase high-performance liquid chromatography and specific radioimmunoassays, and by immunofluoresence. Neuro2A neuroblastoma cells expressing the +1 frameshifted precursors of di/di rats retained products in the cell body. Only precursor or insignificant quantities of neurophysin-immunoreactive products were detected. In contrast, in AtT20 cells, frameshifted VP precursors were at least partly processed to yield the VP peptide, indicating that they have access to the regulated secretory pathway. Comparison between the two cell lines showed a very slow ER transit of the wild-type prohormone combined with inefficient processing in Neuro2A cells. The results show that mutant precursors can reach the regulated secretory pathway if ER transport is sufficiently rapid as in the case of AtT20 cells. This suggests that the di/di rat may regain the capacity to biosynthesize authentic VP through these +1 frameshifted precursors in magnocellular neurones.

Topics: Animals; Biological Transport; Diabetes Insipidus; Endoplasmic Reticulum; Frameshift Mutation; Gene Deletion; Mice; Protein Precursors; Protein Processing, Post-Translational; Rats; Rats, Brattleboro; Tissue Distribution; Tumor Cells, Cultured; Vasopressins

Renal proteins were studied in Brattleboro rats of the didi genotype and in Wistar and Sprague-Dawley rats with normal alleles +2 of this loci. In animals of the +2 genotype maintained under conditions of water deprivation, the content of 120 kDa protein increased significantly in inner medulla of the kidney over 3 days. No changes in the amount of this protein were observed in rats of the didi genotype under the same conditions. We suggest that the congenital inability of didi mutants to synthesize vasopressin accounts for the distinctions observed in the reactions of rats with different genotypes.

Topics: Animals; Diabetes Insipidus; Kidney; Mutation; Proteins; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Rats, Wistar; Vasopressins

Topics: Adult; Amenorrhea; Diabetes Insipidus; Dwarfism, Pituitary; Female; Gonadotropins; Humans; Infertility, Female; Insemination, Artificial; Pregnancy; Pregnancy Outcome; Vasopressins

Status epilepticus causes significant morbidity and mortality. A case of generalized status epilepticus followed by massive pulmonary aspiration, acute respiratory failure and transient central diabetes insipidus is presented. Seizures were promptly controlled, but the patient required mechanical ventilation and correction of polyuria with desmopressin acetate. During hospitalization mental status improved, diabetes insipidus spontaneously remitted and he was discharged without neurologic sequelae. The clinical and pathophysiological features of this case are discussed.

Topics: Acute Disease; Adult; Diabetes Insipidus; Humans; Male; Pneumonia, Aspiration; Respiratory Insufficiency; Status Epilepticus; Vasopressins

Familial neurohypophyseal diabetes insipidus is an autosomal dominant disorder characterized by post-natal development of arginine vasopressin (AVP) deficiency due to mutations in the AVP gene. All published mutations affect the signal peptide or the neurophysin-II carrier protein and are presumed to interfere with processing of the preprohormone, leading to neuronal damage. We studied an unusual Palestinian family consisting of asymptomatic first cousin parents and three children affected with neurohypophyseal diabetes insipidus, suggesting autosomal recessive inheritance. All three affected children were homozygous and the parents heterozygous for a single novel mutation (C301->T) in exon 1, replacing Pro7 of mature AVP with Leu (Leu-AVP). Leu-AVP was a weak agonist with approximately 30-fold reduced binding to the human V2 receptor. Measured by radioimmunoassay with a synthetic Leu-AVP standard, serum Leu-AVP levels were elevated in all three children and further increased during water deprivation to as high as 30 times normal. The youngest child (2 years old) was only mildly affected but had Leu-AVP levels similar to her severely affected 8-year-old brother, suggesting that unknown mechanisms may partially compensate for a deficiency of active AVP in very young children.

Topics: Arginine Vasopressin; Child; Child, Preschool; Diabetes Insipidus; Female; Genes, Recessive; Humans; Male; Mutation; Neurophysins; Sequence Analysis, DNA; Vasopressins

Autosomal dominant neurohypophyseal diabetes insipidus is caused by mutations in the gene encoding the vasopressin precursor protein, prepro-vasopressin-neurophysin II. We analyzed the molecular consequences of a mutation (DeltaG227) recently identified in a Swiss kindred that destroys the translation initiation codon. In COS-7 cells transfected with the mutant cDNA, translation was found to initiate at an alternative ATG, producing a truncated signal sequence that was functional for targeting and translocation but was not cleaved by signal peptidase. The mutant precursor was completely retained within the endoplasmic reticulum. The uncleaved signal did not affect folding of the neurophysin portion of the precursor, as determined by its protease resistance. However, formation of disulfide-linked aggregates indicated that it interfered with the formation of the disulfide bond in vasopressin, most likely by blocking its insertion into the hormone binding site of neurophysin. Preventing disulfide formation in the vasopressin nonapeptide by mutation of cysteine 6 to serine was shown to be sufficient to cause aggregation and retention. These results indicate that the DeltaG227 mutation induces translation of a truncated signal sequence that cannot be cleaved but prevents correct folding and oxidation of vasopressin, thereby causing precursor aggregation and retention in the endoplasmic reticulum.

Topics: Amino Acid Sequence; Amino Acid Substitution; Animals; COS Cells; Diabetes Insipidus; Disulfides; Endoplasmic Reticulum; Guanosine; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Folding; Protein Precursors; Protein Sorting Signals; Vasopressins

Familial neurohypophysial diabetes insipidus is characterized by vasopressin deficiency caused by heterozygous expression of a mutated vasopressin prohormone gene. To elucidate the mechanism of this disease, we stably expressed five vasopressin prohormones with a mutation in the neurophysin moiety (NP14G-->R, NP47E-->G, NP47DeltaE, NP57G-->S, and NP65G-->V) in the neuroendocrine cell lines Neuro-2A and PC12/PC2. Metabolic labeling demonstrated that processing and secretion of all five mutants was impaired, albeit to different extents (NP65G-->V >/= NP14G-->R > NP47DeltaE >/= NP47E-->G > NP57G-->S). Persisting endoglycosidase H sensitivity revealed these defects to be due to retention of mutant prohormone in the endoplasmic reticulum. Mutant prohormones that partially passed the endoplasmic reticulum were normally targeted to the regulated secretory pathway. Surprisingly, this also included mutants with mutations in residues involved in binding of vasopressin to neurophysin, a process implicated in targeting of the prohormone. To mimick the high expression in vasopressin-producing neurons, mutant vasopressin prohormones were transiently expressed in Neuro-2A cells. Immunofluorescence displayed formation of large accumulations of mutant prohormone in the endoplasmic reticulum, accompanied by redistribution of an endoplasmic reticulum marker. Our data suggest that prolonged perturbation of the endoplasmic reticulum eventually leads to degeneration of neurons expressing mutant vasopressin prohormones, explaining the dominant nature of the disease.

Topics: Biological Transport; Diabetes Insipidus; Endoplasmic Reticulum; Humans; Mutation; Neurosecretory Systems; Protein Precursors; Vasopressins

The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations of the gene that codes for the vasopressin-neurophysin II (AVP-NPII) precursor. The aims of the present study were to relate the clinical phenotype to the specific genotype and to the molecular genetic effects of the most frequently reported adFNDI mutation located at the cleavage site of the signal peptide of AVP-NPII [Ala(-1)Thr]. Genetic analysis and clinical studies of AVP secretion, urinary AVP, and urine output were performed in 16 affected and 16 unaffected family members and 11 spouses of a Danish adFNDI kindred carrying the Ala(-1)Thr mutation. Mutant complementary DNA carrying the same mutation was expressed in a neurogenic cell line (Neuro2A), and the cellular effects were studied by Western blotting, immunocytochemistry, and AVP measurements. The clinical studies showed a severe progressive deficiency of plasma and urinary AVP that manifested during childhood. The expression studies demonstrated that the Ala(- 1)Thr mutant cells produced 8-fold less AVP than wild-type cells and accumulated excessive amounts of 23-kDa NPII protein corresponding to uncleaved prepro-AVP-NPII. Furthermore, a substantial portion of the intracellular AVP-NPII precursor appeared to be colocalized with an endoplasmic reticulum antigen (Grp78). These results provide independent confirmation that this Ala(-1)Thr mutation produces adFNDI by directing the production of a mutant preprohormone that accumulates in the endoplasmic reticulum, because it cannot be cleaved from the signal peptide and transported to neurosecretory vesicles for further processing and secretion.

Topics: Adolescent; Adult; Aged; Arginine Vasopressin; Child; Child, Preschool; Diabetes Insipidus; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Female; Genotype; Humans; Male; Middle Aged; Mutation, Missense; Neurophysins; Protein Precursors; Vasopressins

Topics: Diabetes Insipidus; Humans; Vasopressins

Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

Topics: Albuminuria; Animals; Creatinine; Diabetes Insipidus; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Glomerular Filtration Rate; Glycosuria; Hypertrophy; Kidney; Kidney Failure, Chronic; Male; Nephrectomy; Organ Size; Rats; Rats, Brattleboro; Rats, Long-Evans; Vasopressins

Cytoplasmic autoantibodies to vasopressin-cells (AVPcAb) have been detected not only in patients with overt central diabetes insipidus (CDI), but also in patients with endocrine autoimmune diseases without CDI. This suggests that complete CDI can be preceded by a preclinical stage. Among 878 patients with endocrine autoimmune diseases without CDI, 9 patients found to be AVPcAb positive and 139 AVPcAb-negative controls were enrolled in this open prospective study. They were evaluated for AVPcAb and posterior pituitary function at least yearly for about 4 yr (range, 37-48 months); during this span, magnetic resonance imaging (MRI) of posterior pituitary and stalk was performed only in the AVPcAb-positive patients. Five of the 9 AVPcAb-positive patients had normal posterior pituitary function at study entry. They were AVPcAb positive throughout the follow-up period. At later stages of the study, 3 of them developed partial CDI, and 1 developed complete CDI. The remaining 4 patients showed impaired response to the water deprivation test at study entry and were diagnosed as having partial CDI. Two of them agreed to receive desmopressin replacement for 1 yr. After this treatment, the patients became negative for AVPcAb and displayed normal posterior pituitary function until the end of the follow-up. Conversely, the 2 untreated patients with partial CDI remained AVPcAb positive. One of them developed overt CDI. None of the controls became AVPcAb positive or developed CDI. The normal hyperintense MRI signal of the posterior pituitary, present at study entry, persisted subsequently in all 9 AVPcAb-positive patients, including those developing overt CDI, only disappearing in the late phase of complete CDI. In asymptomatic subjects, the monitoring of AVPcAb, but not MRI, seems to be useful to predict a progression toward partial/overt CDI. Early desmopressin therapy in patients with partial CDI could interrupt or delay the autoimmune damage and the progression toward clinically overt CDI.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Pituitary Gland, Posterior; Prospective Studies; Vasopressins; Water Deprivation

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Creatinine; Diabetes Insipidus; Disease Models, Animal; Disease Progression; Kidney; Kidney Failure, Chronic; Male; Proteinuria; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Uremia; Vasopressins

Although disorders of ADH secretion associated with meningitis are usually consistent with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), central diabetes insipidus (DI) is an exceptional complication of meningitis. Transient DI as a complication of Escherichia coli (E. coli) meningitis due to ventriculoperitoneal shunt in an 18-month-old boy is presented. Blood and spinal fluid cultures yielded E. coli, sensitive to cefotaxime. The DI arose on the day 3 after admission and continued to the day 20. Treatment comprised cefotaxime, dexamethasone, fluid adjustment and vasopressin. The course of our case supports that in cases of bacterial meningitis, initial fluid restriction may occasionally result in dangerous conditions. Therefore, all children with bacterial meningitis should be followed closely not only in terms of SIADH but also DI. To our knowledge this is the first transient DI associated with E. coli-caused meningitis case reported.

Topics: Dandy-Walker Syndrome; Deamino Arginine Vasopressin; Diabetes Insipidus; Escherichia coli Infections; Humans; Infant; Male; Meningitis, Bacterial; Polyuria; Radioimmunoassay; Renal Agents; Tomography, X-Ray Computed; Vasopressins; Ventriculoperitoneal Shunt

We present the eldest case ever reported of central diabetes insipidus (DI) associated with infundibulo-neurohypophysitis. A 77-year old woman, who complained of recent development of excessive thirst, polyuria and polydipsia, was referred to our hospital. The daily urine volume was markedly increased to 6 L. DDAVP administration effectively reduced urine volume and increased urine osmolality. The loading test using high-osmolar sodium chloride showed impaired excretion of vasopressin discordant with plasma osmolar changes. The anterior pituitary function was normal. Pituitary magnetic resonance imaging (MRI) showed thickening of the pituitary stalk and a lack of high-intensity signal of the neurohypophysis on T1-weighted images, suggestive of lymphocytic infundibulo-neurohypophysitis. The thickness of pituitary stalk on MRI improved 6 months later. DI was controlled with DDAVP for 40 days. This was followed by stabilization of the daily urine volume to less than 2.5 L without DDAVP. Our case is the eldest case of central DI associated with infundibulo-neurohypophysitis. The rapid remission of pituitary changes on MRI provides an insight that spontaneously partial remission of central DI may occur, resulting in transient polyuria and polydipsia.

Topics: Aged; Blood; Chlorides; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Headache; Humans; Lymphocytes; Magnetic Resonance Imaging; Osmolar Concentration; Pituitary Diseases; Pituitary Gland, Posterior; Potassium; Sodium; Thirst; Urine; Vasopressins

To study the role of vasopressin in osmoregulation in two successive pregnancies in a woman with Sheehan's syndrome.. Diabetes insipidus (DI) became manifest during two pregnancies in a woman with postpartum hypopituitarism.. Water deprivation-vasopressin administration tests demonstrated partial central DI, corrected with vasopressin in week 12, but only with desmopressin in the third trimester, when placental cystylamino peptidase (vasopressinase) contributes to the severity of the DI.. If DI occurs during pregnancy it may be the first manifestation of a latent central DI, which is often idiopathic, but rarely the first symptom of a pituitary or hypothalamic abnormality. It may also be part of Sheehan's syndrome.

Topics: Adult; Cystinyl Aminopeptidase; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Gestational Age; Humans; Hypopituitarism; Osmolar Concentration; Ovulation Induction; Placenta; Pregnancy; Pregnancy Complications; Urine; Vasopressins; Water Deprivation

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disease caused by deficiency in the antidiuretic hormone arginine vasopressin (AVP) encoded by the AVP-neurophysin II (AVP-NPII) gene on chromosome 20p13. In this study, we analyzed two families with FNDI using direct automated fluorescent, solid phase, single-stranded DNA sequencing of PCR-amplified AVP-NPII DNA. In one of the families, affected individuals presented a novel nonsense mutation in exon 3 of the gene, consisting in a G to T transition at nucleotide 2101, which produces a stop signal in codon 82 (Glu) of NPII. The premature termination eliminates part of the C-terminal domain of NPII, including a cysteine residue in position 85, which could be involved in the correct folding of the prohormone. In the second family, a G279A substitution at position -1 of the signal peptide was observed in all affected individuals. This missense mutation, which replaces Ala with Thr, is frequent among FNDI patients and is thought to reduce the efficiency of cleavage by signal peptidases.

Topics: Adolescent; Amino Acid Sequence; Base Sequence; Child, Preschool; Diabetes Insipidus; Humans; Male; Mutation; Neurophysins; Pedigree; Pituitary Diseases; Pituitary Gland, Posterior; Spain; Vasopressins

Three patients, 11, 17 and 41 days old with various degrees of central nervous system (CNS) lesions developed central diabetes insipidus as a complication of hypothalamic damage. Two of the children had congenital CNS malformations including meningomyelocele, hydrocephalus, and prosencephaly, while the third child presented Streptococcus agalactiae meningitis, complicated with CNS hemorrhage and hypertensive dilatation of the lateral ventricles. All of them fulfilled the criteria for central diabetes insipidus, reaching high levels of serum sodium and osmolality, along with hypotonic urine. The responses to intranasal arginine-vasopressin were prompt, normalizing the serum levels of sodium and increasing urinary osmolality, allowing a better metabolic balance, avoiding continuing damage to the already compromised CNS. The neonatologist must be aware of the possibility of this kind of complication even in a normal child with CNS infection. Imaging studies showing hemorrhage in the region of the posterior hypothalamus must be a sign that this type of complication is able to occur.

Topics: Adolescent; Brain; Diabetes Insipidus; Female; Humans; Infant; Infant, Newborn; Meningitis, Bacterial; Streptococcal Infections; Streptococcus agalactiae; Vasopressins

In the kidney, facilitated urea transport in precise vascular and tubular structures is mainly involved in water conservation. Three urea transporters have been cloned: UT2-long expressed in terminal inner medullary collecting duct (IMCD), UT2-short expressed in thin descending limb, and UT11 in descending vasa recta. The effect of arginine vasopressin (AVP) administration on mRNA expression of these three transporters was examined in Brattleboro rats with diabetes insipidus. V2 effects were discriminated from combined V1 + V2 effects by comparing treatments with 1-deamino-8-D-AVP (dDAVP) (selective V2 agonism) and AVP (V1 and V2 agonism). Acute and chronic treatments were studied. Abundance of specific mRNA was assessed by quantitative Northern blot analysis of RNA extracted from two regions of inner stripe of outer medulla and from two regions of inner medulla (IM). The results show that mRNA of these urea transporters are differently regulated by AVP. (1) Long-term treatment with either AVP or dDAVP does not alter UT2-long mRNA in tip IM (terminal IMCD) except for a transient initial decrease. (2) Unlike AVP, dDAVP induces the appearance of significant expression of UT2-long mRNA in base IM (initial IMCD), indicating a major V2 effect. (3) UT2-short mRNA in deep inner stripe of outer medulla and base IM (thin descending limb of short and long loops, respectively) is progressively upregulated with duration of AVP or dDAVP treatment. (4) The much higher changes in UT2-long and UT2-short induced by dDAVP compared with AVP suggest that they are dependent mainly on V2 agonism, and likely attenuated by V1 agonism. (5) UT11 mRNA expression in tip IM is equally depressed by AVP and dDAVP, indicating that this vascular transporter is also influenced by AVP and/or urine-concentrating activity, via an indirect mechanism that remains to be determined.

Topics: Animals; Arginine Vasopressin; Carrier Proteins; Deamino Arginine Vasopressin; Diabetes Insipidus; Gene Expression; Kidney; Kidney Tubules; Male; Membrane Glycoproteins; Membrane Transport Proteins; Rats; Rats, Brattleboro; RNA, Messenger; Tissue Distribution; Urea; Urea Transporters; Vasopressins

We report a case of central diabetes insipidus with spontaneous remission 8 months after clinical beginning of the disease. A 20 years-old man developed polydipsia and polyuria in October 1994. A water deprivation study showed a defect in the urine concentrating function, which was corrected by vasopressine. A Magnetic Resonance imaging of the skull revealed a thickening of the pituitary stalk. His condition was well controlled by nasal DDAVP administration and 6 months later patient reduced spontaneously medication dose without clinical worsening. 8 months after clinical beginning, patient has become completely free from the need for medication to control clinical symptoms and urine concentrating function, as demonstrated by a re-evaluation study with water deprivation. A control Magnetic Resonance showed the regression of stalk enlargement. The clinical and radiological features of this case are discussed.

Topics: Adult; Brain; Diabetes Insipidus; Humans; Magnetic Resonance Imaging; Male; Polyuria; Remission, Spontaneous; Renal Agents; Vasopressins

Topics: Adolescent; Animals; Arginine Vasopressin; Diabetes Insipidus; Disease Progression; Exons; Genes, Dominant; Humans; Male; Point Mutation; Protein Precursors; Rats; Rats, Brattleboro; Vasopressins

Familial diabetes insipidus (FDI) is a syndrome of central vasopressin deficiency that is inherited in an autosomal dominant manner and that typically becomes clinically apparent in the first decade of life. Two novel mutations of the vasopressin gene have been identified in two previously unstudied kindreds with FDI. In each kindred, the inheritance of the FDI phenotype was consistent with an autosomal dominant mode of inheritance. In each proband, the diagnosis of central diabetes insipidus had been confirmed previously with a water deprivation protocol. After extraction of genomic DNA from each individual, the three exons of the vasopressin gene were separately amplified by PCR and directly sequenced using an automated dye termination method. In the proband and two other carriers of one kindred, a heterozygous C to T mutation was identified at nucleotide 1857. This is predicted to produce a serine to phenylalanine substitution at residue 56 of the vasopressin-related neurophysin peptide encoded by the mutated allele. The mutation also abolished an MspI site in the vasopressin sequence, and analysis of genomic DNA from eight members of the kindred (five with FDI) confirmed segregation of the mutation with the FDI phenotype. Another member of the kindred, a 13-month-old infant, also has the heterozygous C to T mutation, but a formal water balance study showed no evidence of diabetes insipidus. In the proband of the other kindred, a heterozygous G to A mutation was identified at nucleotide 1873. This mutation would be predicted to cause a cysteine to tyrosine substitution at residue 61 of the neurophysin encoded by the mutated allele. This heterozygous mutation was confirmed by the presence of an RsaI restriction site in one vasopressin allele in two members of the kindred. Therefore, two novel heterozygous mutations of the vasopressin gene have been identified in FDI kindreds. In one kindred, an asymptomatic carrier infant was identified and will require continued observation to determine whether she will develop clinical diabetes insipidus. The presence of these two novel mutations in a region of the vasopressin gene where other FDI mutations have been reported suggests that the part of the neurophysin peptide encoded by these sequences may be critically important in the appropriate expression of vasopressin.

Topics: Diabetes Insipidus; Exons; Genetic Carrier Screening; Humans; Infant; Male; Mutation; Pedigree; Polymorphism, Restriction Fragment Length; Vasopressins

Wolfram syndrome (WS) is characterized by optic atrophy, insulin-dependent diabetes mellitus, vasopressin (VP)-sensitive diabetes insipidus, and neurosensory hearing loss. Here we report a disturbance in VP precursor processing in the supraoptic and paraventricular nuclei of WS patients. In these patients with diabetes insipidus we could hardly detect any cellular immunoreactivity for processed VP in the supraoptic and paraventricular nuclei. On the other hand, in the paraventricular nucleus a considerable number of cells immunoreactive for the VP precursor were present. In addition, the proprotein convertase PC2 and the molecular chaperone 7B2 were absent. As expression of PC2 and 7B2 was detected in the nearby nucleus basalis of Meynert of one WS patient and in the anterior lobe of the other WS patient, the absence of the two proteins in the paraventricular nucleus was not due to mutations in their genes. These results indicate that in WS patients with diabetes insipidus, not only does VP neuron loss occur in the supraoptic nucleus, but there is also a defect in VP precursor processing.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Molecular Chaperones; Nerve Tissue Proteins; Neuroendocrine Secretory Protein 7B2; Paraventricular Hypothalamic Nucleus; Pituitary Hormones; Proprotein Convertase 2; Protein Precursors; Protein Processing, Post-Translational; Subtilisins; Supraoptic Nucleus; Vasopressins; Wolfram Syndrome

Indices of carbohydrate and lipid metabolism were investigated in male New Zealand genetically hypertensive and normotensive rats. Cross-breeding of male rats of these strains with female Brattleboro diabetes insipidus rats also provided the opportunity to examine the metabolic impact of vasopressin and its deficiency in hypertensive and normotensive rats. Hypertensive and normotensive rats, with or without diabetes insipidus, were fasted for 24 h, exsanguinated and their blood/plasma analysed for various indices of carbohydrate and lipid metabolism. Whilst each group of rats maintained fasted normoglycemia, hypertensive rats, with or without vasopressin-deficiency, were hypoinsulinaemic relative to normotensive counterparts. Moreover, hypertensive or normotensive vasopressin-deficient rats were hypoinsulinaemic relative to vasopressin-replete counterparts. In vasopressin-replete rats, the apparently improved insulin sensitivity in hypertension was associated with significant falls in plasma glucagon, triglycerides and total cholesterol. Finally, normotensive vasopressin-deficient rats were hypoglucagonaemic relative to the vasopressin-replete group. These data demonstrate that independent of vasopressin status, hypertension in the New Zealand strain and the diabetes insipidus hybrid was associated with improved insulin sensitivity. However, endogenous vasopressin exercises an influential role in carbohydrate and lipid metabolism in normotensive rats.

Topics: Animals; Blood Glucose; Cholesterol; Crosses, Genetic; Diabetes Insipidus; Female; Glucagon; Hypertension; Insulin; Lipids; Male; Rats; Rats, Brattleboro; Triglycerides; Vasopressins

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a familial form of diabetes insipidus due to progressive vasopressin deficiency with onset typically at 1-6 yr of age. Affected individuals demonstrate specific degeneration of the vasopressinergic magnocellular neurons in the hypothalamic supraoptic and paraventricular nuclei and loss of the posterior pituitary bright spot on magnetic resonance imaging. The genetic locus of ADNDI is the arginine vasopressin-neurophysin II (AVP-NPII) gene. Mutations that cause ADNDI have been found to occur both within the signal peptide of the prepro-AVP-NPII precursor and within the coding sequence for neurophysin II, but not within the coding sequence for AVP itself. We evaluated the AVP-NPII genes in two independent families with ADNDI and identified a mutation (C280-->T) in the coding sequence for the signal peptide of the prepro-AVP-NPII precursor in both families. This mutation encodes an Ala-->Val substitution at the C-terminus of the signal peptide (-1 amino acid). This mutation predicts the complete inability of signal peptidase to cleave the signal peptide from the preproprecursor and supports the hypothesis that the progressive neural degeneration that underlies ADNDI is caused by accumulation of malprocessed precursor. However, considerable heterogeneity in the age of onset (1-28 yr of age) and the severity of diabetes insipidus among affected members of these two families suggests that additional factors modulate the rate and extent of progression of the neurodegeneration that results from this one specific ADNDI mutation.

Topics: Alanine; Arginine Vasopressin; Diabetes Insipidus; DNA Restriction Enzymes; Female; Humans; Infant; Male; Middle Aged; Mutation; Neurophysins; Pedigree; Pituitary Gland, Posterior; Polymerase Chain Reaction; Protein Precursors; Protein Sorting Signals; Valine; Vasopressins

Neurohypophyseal function was studied by hypertonic saline infusion with plasma vasopressin measurement in 3 patients with adrenal insufficiency before and after cortisol replacement. Although each patient had different causes of adrenal insufficiency, all showed impaired water excretion before replacement. The first patient with isolated adrenocorticotropin deficiency had marked hyponatremia and inappropriate vasopressin secretion which was normalized after replacement, indicating vasopressin hypersecretion during hypoadrenocorticism. The second patient had combined anterior and posterior pituitary deficiency due to postpartum hypopituitarism and showed completely absent vasopressin secretion, with her polyuria being masked before cortisol replacement, suggesting a vasopressin-independent intrarenal mechanism of antidiuresis. The third patient with panhypopituitarism due to a pituitary tumor also had preexisting diabetes insipidus with defective vasopressin secretion. In this case, however, plasma vasopressin was found to be elevated when adrenal insufficiency and hyponatremia subsequently developed. Together, these results indicate that vasopressin hypersecretion does occur during adrenal insufficiency, but that the accompanying urinary diluting defect may be attributable either to vasopressin-dependent or to vasopressin-independent mechanisms.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Diabetes Insipidus; Female; Humans; Hydrocortisone; Hyponatremia; Hypopituitarism; Male; Pituitary Neoplasms; Polyuria; Vasopressins; Water-Electrolyte Balance

It has been shown that vasopressin receptors are upregulated in the brain and that the central vasopressin pathway is involved in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. However, it is unclear whether central vasopressin, in itself, is essential for this type of hypertension. To clarify this issue, the effect of centrally administered vasopressin on the development of DOCA-salt hypertension was studied in homozygous Brattleboro rats which genetically lack vasopressin. In homozygous Brattleboro rats, treatment with intracerebroventricular infusion of vasopressin (1 ng/h) alone or DOCA-salt (weekly subcutaneous injection of 30 mg/kg deoxycorticosterone acetate and 0.3% NaCl to drink) alone had no effect on systolic blood pressure (SBP). On the other hand, hypertension was partially restored in homozygous Brattleboro rats treated with intracerebroventricular infusion of vasopressin and DOCA-salt (SBP: 175 +/- 4 mmHg), although the magnitude of elevation of SBP was one-third of that in Long Evans rats treated with DOCA-salt (278 +/- 15 mmHg). These hypertensive homozygous Brattleboro rats showed an increase in fluid intake and urinary sodium excretion, as observed in DOCA-salt hypertensive Long Evans rats. These results suggest that central vasopressin is required for the complete development of DOCA-salt hypertension and the mechanism is, in part, due to enhanced sodium intake through the additive effect of central vasopressin and DOCA-salt.

Topics: Animals; Blood Pressure; Body Weight; Desoxycorticosterone; Diabetes Insipidus; Disease Models, Animal; Hypertension; Male; Rats; Vasopressins

Central diabetes insipidus is a chronic disorder which in most patients occurs secondary to tumor, infection, trauma or other lesions. In about 20-30% of patients etiology is unclear, however a destructive autoimmune process in the hypophysis may play a role. We report the case of an 18-year-old girl with central diabetes insipidus. Vasopressin levels were typically decreased. Examinations performed 1.5 years after manifestation showed no pathologic changes on MRI and no additional endocrine disorder. MRI was repeated 1.5 years later whereon a thickening of the pituitary stalk as a typical sign of hypophysitis was apparent. No other reasons could be found for the vasopressin deficiency. The finding of hypophysitis in our patient 3 years after disease manifestation suggests that the characteristic MRI changes may take as long as 3 years to become apparent.

Topics: Adolescent; Diabetes Insipidus; Disease Progression; Female; Humans; Inflammation; Magnetic Resonance Imaging; Pituitary Diseases; Pituitary Gland; Vasopressins

There is increasing evidence that ovarian steroids inhibit vascular responsiveness to the neurohypophysial hormone vasopressin. The present study examined the recovery of the arterial blood pressure following a single (2 ml/100 g body weight) haemorrhage in ovariectomized (OVX) Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) and rats of the parent Long Evans (LE) strain. Some groups of OVX rats received subcutaneous implants of either 17 beta-oestradiol (E2) or progesterone 7 days prior to haemorrhage. The arterial blood pressure recovery immediately following haemorrhage was significantly impaired in both groups of steroid-treated OVX LE rats compared with the OVX controls (both comparisons P < 0.05). The impairment in blood pressure recovery seen in the steroid-replaced OVX LE rats was similar to that seen in pro-oestrous rats (when ovarian steroid levels are raised) compared with male rats of this strain (P < 0.05). In contrast, ovariectomy with or without steroid replacement in BDI rats had no further effect on the already attenuated recovery of arterial blood pressure after haemorrhage in this strain. Heart rate responses to haemorrhage also showed strain differences, which were dependent on steroid treatment. Pro-oestrous female LE rats showed a small decrease in heart rate after haemorrhage, followed by a recovery process, and this initial bradycardia was markedly enhanced in the OVX steroid-treated animals. In contrast, untreated OVX LE rats showed an initial and sustained increase in heart rate which was significantly higher than in the steroid-treated OVX animals (P < 0.05). All BDI rats, irrespective of treatment, consistently showed an increased heart rate after haemorrhage. In conclusion, ovarian steroid replacement in OVX LE, but not vasopressin-deficient BDI, rats was associated with an attenuated pressor recovery after haemorrhage. This provides further evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin. The initial decrease in heart rate observed in pro-oestrous and steroid-treated OVX LE rats after haemorrhage also appears to be related to an ovarian steroid-vasopressin interaction.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Estradiol; Female; Heart Rate; Hemorrhage; Male; Ovariectomy; Progesterone; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Vasopressins

We report nine consecutive children and adolescents [five females and four males; aged 2 yr 8 months (m) to 18 yr 1 m] studied over the last 5 yr with idiopathic central diabetes insipidus. In addition to vasopressin deficiency, anterior pituitary hormone deficiencies were detected, either on evaluation at presentation or during follow-up studies over the following 3 yr. Four patients had an increased concentration of plasma PRL. One patient had multiple pituitary hormone deficiencies at diagnosis, and two others developed the same by 21 m of follow-up. Brain magnestic resonance imaging scans, performed at presentation, were originally interpreted as normal in four of nine patients, except for absence of the bright posterior pituitary signal; after retrospective review, two of nine were considered normal. All of the brain magnetic resonance imaging (MRI) scans showed positive findings by 14 m of follow-up. The first abnormal finding in all patients was isolated pituitary stalk thickening. Evaluation of cerebrospinal fluid (CSF) for hCG was positive in three of eight evaluated patients; the three positive CSF values were found at presentation and 3 and 9 m after presentation. All eight patients assessed were negative for CSF alpha-fetoprotein and cytology, and no patient had serum tumor markers. Transsphenoidal biopsy of the lesion in seven of nine patients showed a germinoma in six patients and inflammatory cells in one. The six patients with documented germinoma comprise 31% of the intracranial germinomas diagnosed in this age group at the University of California-San Francisco during the last 5 yr. The patient with mononuclear inflammatory cells on biopsy along with one other patient have had spontaneous resolution of their stalk thickening. So-called "idiopathic" central diabetes insipidus warrants close follow-up to determine the etiology, especially if anterior pituitary hormone deficiencies are detected. Normal brain MRI scans or scans that show isolated pituitary stalk thickening merit follow-up with serial contrast enhanced brain MRI for the early detection of an evolving occult hypothalamic-stalk lesion. CSF evaluation is recommended at presentation because elevated CSF hCG may precede MRI abnormalities.

Topics: Adolescent; alpha-Fetoproteins; Biopsy; Brain Neoplasms; Child; Child, Preschool; Chorionic Gonadotropin; Diabetes Insipidus; Female; Germinoma; Humans; Hypothalamus; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Hormones, Anterior; Vasopressins

Topics: Animals; Body Temperature; Circadian Rhythm; Diabetes Insipidus; Feeding Behavior; Heart Rate; Male; Motor Activity; Rats; Rats, Brattleboro; Vasopressins

Topics: Animals; Diabetes Insipidus; Diuresis; Female; History, 20th Century; Hypothalamic Diseases; Male; Rats; Rats, Brattleboro; Vasopressins

Hyponatremia after pituitary surgery is presumed to be due to antidiuresis; however, detailed prospective investigations of water balance that would define its pathophysiology and true incidence have not been established. In this prospective study, the authors documented water balance in patients for 10 days after surgery, monitored any sodium dysregulation, further characterized the pathophysiology of hyponatremia, and correlated the degree of intraoperative stalk and posterior pituitary damage with water balance dysfunction. Ninety-two patients who underwent transsphenoidal pituitary surgery were studied. To evaluate posterior pituitary damage, a questionnaire was completed immediately after surgery in 61 patients. To examine the osmotic regulation of vasopressin secretion in normonatremic patients, water loads were administered 7 days after surgery. Patients were categorized on the basis of postoperative plasma sodium patterns. After pituitary surgery, 25% of the patients developed spontaneous isolated hyponatremia (Day 7 +/- 0.4). Twenty percent of the patients developed diabetes insipidus and 46% remained normonatremic. Plasma arginine vasopressin (AVP) was not suppressed in hyponatremic patients during hypoosmolality or in two-thirds of the normonatremic patients after water-load testing. Only one-third of the normonatremic patients excreted the water load and suppressed AVP normally. Hyponatremic patients were more natriuretic, had lower dietary sodium intake, and had similar fluid intake and cortisol and atrial natriuretic peptide (ANP) levels compared with normonatremic patients. Normnonatremia, hyponatremia, and diabetes insipidus were associated with increasing degrees of surgical manipulation of the posterior lobe and pituitary stalk during surgery. The pathophysiology of hyponatremia after transsphenoidal surgery is complex. It is initiated by pituitary damage that produces AVP secretion and dysfunctional osmoregulation in most surgically treated patients. Additional events that act together to promote the clinical expression of hyponatremia include nonatrial natriuretic peptide-related excess natriuresis, inappropriately normal fluid intake and thirst, as well as low dietary sodium intake. Patients should be monitored closely for plasma sodium, plentiful dietary sodium replacement, mild fluid restriction, and attention to symptoms of hyponatremia during the first 2 weeks after transsphenoidal surgery.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Child; Diabetes Insipidus; Diuresis; Female; Fluid Therapy; Humans; Hydrocortisone; Hyponatremia; Incidence; Intraoperative Complications; Male; Natriuresis; Pituitary Diseases; Pituitary Gland; Pituitary Gland, Posterior; Postoperative Complications; Prospective Studies; Renal Agents; Sodium; Sodium, Dietary; Sphenoid Bone; Thirst; Vasopressins; Water; Water-Electrolyte Balance; Water-Electrolyte Imbalance

Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.

Topics: Acute Disease; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Autonomic Nerve Block; Benzazepines; Cardiovascular System; Deamino Arginine Vasopressin; Diabetes Insipidus; Heart; Hemorrhage; Male; Nervous System; Rats; Rats, Brattleboro; Rats, Inbred Strains; Receptors, Vasopressin; Recurrence; Vasopressins

The neurochemical and behavioural effects of a novel stereotaxic surgical method developed for interrupting the nerve fibres running through the rat pituitary stalk to the posterior pituitary gland was studied. The cerebrospinal fluid (CSF) vasopressin (AVP) and oxytocin (OT) content as well as changes in aggressiveness were measured in rats one week and one month after the surgical intervention. The main results are as follows: (1) the compression of the pituitary stalk elicits a chronic increase in water consumption, as well as in CSF vasopressin and oxytocin content; (2) the surgical intervention increased the frequency of clinch fighting after one week. The increase in aggressiveness accentuated after one month and, in addition, operated animals showed reduced scores of resting while exploratory and social behaviours increased; (3) there was a strong positive correlation between water consumption, vasopressin, and aggressiveness; (4) oxytocin changes showed a positive correlation with variation in social behaviour. The surgical intervention may serve as a model for lesions of the pituitary stalk and formation of ectopic neurohypophyses in humans.

Topics: Aggression; Animals; Behavior, Animal; Chronic Disease; Diabetes Insipidus; Drinking; Male; Nerve Compression Syndromes; Oxytocin; Pituitary Gland; Rats; Rats, Wistar; Social Behavior; Vasopressins

Lanreotide is a somatostatin analog which possesses antidiuretic activity in the rat. To determine whether vasopressin participates in the antidiuretic response to lanreotide, experiments were performed with diabetes insipidus (DI) rates homozygous for vasopressin deficiency. Lanreotide significantly increased urine osmolality and decreased urine volume and free water clearance during the 2-h period after injecting 400 microgram/kg s.c. in 12 awake Wistar-Kyoto rats that were undergoing water diuresis. Although lanreotide decreased serum growth hormone levels (24.2 +/- 6.1 vs. 0.9 +/- 0.1 ng/ml, P < .01), administration of recombinant human growth hormone (1 mg/kg s.c.) did not affect the renal response. Lanreotide (200 microgram/kg s.c.) also significantly increased urine osmolality and free water reabsorption and tended to decrease urine volume in 15 water-loaded Long-Evans rats. In contrast, lanreotide (200 or 400 microgram/kg s.c.) did not affect urine osmolality, urine volume or free water clearance when administered acutely or chronically to DI rats. These results suggest that vasopressin plays a role in the renal response to lanreotide in the rat

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Insipidus; Disease Models, Animal; Male; Osmolar Concentration; Peptides, Cyclic; Rats; Rats, Inbred WKY; Somatostatin; Time Factors; Urination; Vasopressins

A corticotropin-releasing hormone (CRH) test was performed on 7 patients with central diabetes insipidus (DI) and on 7 healthy subjects. The test was repeated on the patients with DI after 3 days of oral treatment with captopril at a dose of 100 mg daily. No significant difference in the responses of plasma ACTH and cortisol to CRH between the patients and the controls was found. The short-term captopril treatment resulted in a significant decrease of both basal and CRH-stimulated ACTH and cortisol levels in the patients with DI. CRH did not induce any changes in the stable metabolite of prostaglandin E2 13, 14-dihydro-15-keto-prostaglandin E2 (PGE2-M) in the patients with DI before or after the captopril treatment. The results obtained suggest that vasopressin is not an obligatory factor for a normal ACTH response to CRH. Angiotensin II (A II) is involved in the regulation of ACTH. This study confirmed our previous data showing the lack of any specific effect of CRH on PGE2 production.

Topics: Adrenocorticotropic Hormone; Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Corticotropin-Releasing Hormone; Diabetes Insipidus; Dinoprostone; Female; Humans; Hydrocortisone; Male; Middle Aged; Vasopressins

Familial hypothalamic diabetes insipidus is an autosomal dominant disorder characterized by deficient vasopressin synthesis. Different point mutations in the vasopressin-neurophysin (VP-NP) precursor gene have been found in affected families. In a Dutch kindred, a single G to T transversion in the NP-encoding exon B of one allele converts the highly conserved glycine 17 to a valine residue. In order to examine whether this point mutation affects the processing and transport of the VP-NP precursor, the normal (HV2) and mutant (MT6) vasopressin cDNAs were stably expressed in the mouse pituitary cell line AtT20. The normal precursor was correctly glycosylated and processed, and NP was detected in the culture medium. Secretion of NP was stimulated by 8-bromo-cAMP, indicating that the normal precursor was targeted to the regulated secretory pathway. In contrast, the mutant precursor was synthesized, but processing and secretion were dramatically reduced. The mutant precursor was core-glycosylated but remained endoglycosidase H-sensitive, suggesting that the protein did not reach the trans-Golgi network. These results were supported by immunocytochemical studies. In HV2 cells, NP derived from the precursor was concentrated in the tips of the cell processes where secretory granules accumulate. In MT6 cells, NP staining was restricted to the endoplasmic reticulum (ER) as determined by colocalization with an ER-resident protein, BiP. These results suggest that the mutation within the conserved part of NP alters the conformation of the precursor and thus triggers its retention in the ER.

Topics: Amino Acid Sequence; Animals; Arginine Vasopressin; Cell Line; Conserved Sequence; Cyclic GMP; Diabetes Insipidus; Fluorescent Antibody Technique; Glycine; Glycosylation; Humans; Mice; Netherlands; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Point Mutation; Protein Precursors; Recombinant Proteins; Transfection; Valine; Vasopressins

We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.

Topics: Adenoma; Adult; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypoglycemic Agents; Magnetic Resonance Imaging; Osmolar Concentration; Pituitary Function Tests; Pituitary Gland, Anterior; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Pregnancy Trimester, Third; Time Factors; Urine; Vasopressins

Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na) and chloride (Cl) contributed to the development of polyuria and dysnatremia in two patients during the acute postoperative period after neurosurgery. To minimize difficulties in diagnosis and projections for therapy, two available (but not often used) clinical tools were helpful. First, the osmole excretion rate early on revealed the co-existence of central DI and an osmotic diuresis. The osmoles excreted were largely Na salts; after antidiuretic hormone acted, this electrolyte diuresis caused the urine flow rate to be much higher than otherwise anticipated. Interestingly, part of this saline diuresis occurred when the extracellular fluid volume was contracted. The tool to explain the basis for the dysnatremias was a tonicity balance. Hypernatremia, which developed before treatment of central DI, was primarily a result of a positive balance for Na rather than a large negative balance for water. Moreover, hyponatremia that developed once antidiuretic hormone acted was primarily a result of a negative balance for Na; the urine volume was large and its Na concentration was hypertonic. To prevent a further decline in the plasma Na concentration, either the Na concentration in the urine should be decreased by provision of urea or a loop diuretic while replacing all unwanted water and electrolyte losses; alternatively, the fluid infused should have a similar Na concentration and volume as the urine (infuse hypertonic saline).

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Hypernatremia; Hyponatremia; Male; Natriuresis; Osmosis; Postoperative Complications; Sodium; Vasopressins

The main phenotypic expression of mutation di is diabetes insipidus, which is pronounced in didi homozygotes. Additional physiological traits have been revealed that are associated with diabetes insipidus and are accounted for by the pleiotropic effect of gene di on the function of the reproductive system, metabolism of neurotransmitters in brain, and central regulation of the stress response. In didi mutants, the age-related decrease in fertility is retarded, the increase in B monoamine oxidase activity associated with aging is shifted to an older age, and the level of corticosteroid-binding globulin is decreased in young animals.

Topics: Aging; Alleles; Animals; Diabetes Insipidus; Fertility; Gene Expression Regulation; Genetic Variation; Homeostasis; Homozygote; Monoamine Oxidase; Phenotype; Point Mutation; Rats; Rats, Wistar; Vasopressins; Water-Electrolyte Balance

Topics: Aquaporin 2; Aquaporin 6; Aquaporins; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Ion Channels; Kidney; Vasopressins

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI+DDAVP). Long-Evans rats (LE) served as controls. DI+DDAVP rats were given for 3 days sc. injections of 0.5 micrograms 1-desamino-8-D-arginine vasopressin in 1 mL saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI+DDAVP rats had significantly (P < 0.05) higher concentration of ANP than LE rats (15.8 +/- 4.4 vs. 3.4 +/- 0.6 ng mg-1 tissue). The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts of ANP mRNA than LE rats (0.5 +/- 0.2 vs. 1.3 +/- 0.2 and 0.5 +/- 0.1 vs. 1.3 +/- 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P < 0.05) lower both in DI and in DI+DDAVP rats than in LE rats (9.3 +/- 1.3 vs. 14.5 +/- 1.6 and 6.1 +/- 0.6 vs. 14.5 +/- 1.6 pg mg-1 tissue). To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Brain; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Heart Atria; Heart Ventricles; Hypoglycemic Agents; Male; Myocardium; Organ Size; Rats; Rats, Brattleboro; RNA, Messenger; Urination; Vasopressins; Water-Electrolyte Balance

Endocrinologic and metabolic changes after brain death (BD) have not yet been investigated in a validated animal model. Therefore, the effects of BD on hormonal and metabolic function were studied in 10 dogs (23 to 31 kg).. BD was induced by intracranial pressure increase and validated neuropathologically. Plasma concentrations of pituitary, thyroid, adrenal, and pancreatic hormones were measured pre/post BD. The results are expressed as mean (+/- SEM).. A Cushing reflex and diabetes insipidus occurred after BD. Elevated catecholamine levels were documented after 15 minutes whereas the pituitary gland hormones vasopressin and adrenocorticotrophic hormone (ACTH) decreased significantly after 15 and 45 minutes of BD respectively. Thyroxine, triiodothyronine, and glucagon decreased significantly (P < .01) from 0.58 ng/mL (+/- 0.05), 2.20 micrograms/dL (+/- 0.15), and 49.7 pg/mL (+/- 9.1) respectively to 0.34 ng/mL (+/- 0.03), 1.14 micrograms/dL (+/- 1.14), and 6.9 pg/mL (+/- 1.4) respectively 420 minutes after BD. The hematocrit increased significantly after BD and declined toward the end of all experiments. Metabolic acidosis occurred immediately after BD and at the end of the experiments.. In a simple, reproducible, and reliable animal model of BD, a catecholamine storm, vasopressin and ACTH cessation, and diabetes insipidus were consistent findings. The decrease in cortisol and vasopressin levels warrant consideration of hormonal therapy.

Topics: Acidosis, Lactic; Adrenocorticotropic Hormone; Animals; Brain Death; Catecholamines; Diabetes Insipidus; Disease Models, Animal; Dogs; Glucagon; Hematocrit; Male; Reproducibility of Results; Thyroid Hormones; Time Factors; Vasopressins

To investigate the role of the hormone vasopressin (VP) in mediating the response of the body to stress, corticosterone levels of VP-containing (LE) rats and VP-deficient (DI) rats were compared following administration of the dexamethasone suppression test (DST) under stressed and nonstressed conditions. The stressor utilized was immobilization, an acute physical stressor. Dexamethasone (DEX), a synthetic glucocorticoid, was injected subcutaneously at a dose of 0.025 mg/kg. This dose of DEX was found to significantly suppress plasma corticosterone in the nonstressed animals (both DI and LE) via feedback inhibition of the hypothalamic-pituitary-adrenocortical (HPA) axis. In the stressed situation, however, LE animals exhibited "escape" from DEX suppression, whereas DI animals did not. Escape indicates a resistance of the HPA axis to the suppressive action of DEX. Thus, in the absence of corticotropin-releasing factor, which is inhibited by DEX, VP alone appears to be sufficient to elicit significant corticosterone release. These results support the hypothesis that VP plays an important role in the regulation of glucocorticoid release in acute stress via the HPA axis.

Topics: Animals; Corticosterone; Dexamethasone; Diabetes Insipidus; Hydrocortisone; Male; Rats; Rats, Brattleboro; Rats, Mutant Strains; Rats, Sprague-Dawley; Restraint, Physical; Vasopressins

Almost all cases of congenital nephrogenic diabetes insipidus (NDI) are transmitted in an X-linked recessive manner by an asymptomatic carrier female to her affected son. Severe symptomatic NDI has not previously been reported in a female with X-linked recessive NDI. Each of the three members of this family has an abnormal V2 receptor gene, which results in truncation of the V2 receptor beginning at arginine-337. This prematurely terminates the receptor at the carboxy-terminal tail and very likely disrupts receptor function. The son has an abnormal V2 receptor gene on his X-chromosome, whereas the mother and daughter have one normal and one abnormal gene for the V2 receptor. The infusion of desmopressin into the mother and son reveals a total lack of antidiuretic response, whereas the daughter increases urinary osmolality normally. The plasma factor VIII concentration after the infusion of desmopressin in the son does not rise, whereas the mother and daughter have half of the normal factor VIII response, similar to asymptomatic female carriers of NDI. These responses to desmopressin in daughter and son are those of a typical carrier female and male affected with NDI. In contrast, the mother acts as an NDI patient when the urine concentration is measured, but acts as a carrier in terms of the factor VIII response to desmopressin. We postulate that the renal tubular cells of the mother demonstrate extreme lyonization of X-chromosome inactivation, whereas in the tissue that subserves the hematological response to desmopressin, X-chromosome inactivation followed a more typically random distribution.

Topics: Adult; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drug Resistance; Factor VIII; Female; Genes, Recessive; Genetic Linkage; Humans; Kidney Concentrating Ability; Male; Osmolar Concentration; Receptors, Vasopressin; Vasopressins; X Chromosome

We previously identified six V2 vasopressin receptor mutations in five unrelated nephrogenic diabetes insipidus (NDI) families. In order to elucidate the effect of these mutations on the function of the V2 vasopressin receptor, we introduced these six and two additional, naturally occurring mutations into the V2 vasopressin receptor gene by in vitro mutagenesis. Five of the mutants (two frameshift, one nonsense, and two missense) failed to stimulate adenylyl cyclase due to their inability to bind vasopressin under the experimental conditions. In contrast, ligand binding and cAMP accumulation were normal for two other mutations, a A61V missense mutation and an in-frame deletion of four amino acids (Arg-247 to Gly-250), suggesting that they are not the cause of NDI in these families. The deletion mutation was found in a family in conjunction with a second mutation, R181C, which yielded a much reduced ligand-binding capacity. The KD of R181C was at least 26 times higher than that of the wild type. Further characterization by an immunofluorescent assay showed that the R181C mutant receptor is expressed and distributed on the cell surface in a manner similar to that of the wild type. This finding indicates that the inability of this mutant to stimulate adenylyl cyclase is caused by the reduced capacity for vasopressin binding and that the R181C mutation is responsible for NDI in this family.

Topics: Adenylyl Cyclases; Amino Acid Sequence; Diabetes Insipidus; Enzyme Activation; Epitopes; Humans; Immunologic Techniques; In Vitro Techniques; Molecular Sequence Data; Mutation; Receptors, Vasopressin; Signal Transduction; Transfection; Vasopressins

Topics: Benzothiadiazines; Carbamazepine; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuretics; Female; Humans; Indomethacin; Life Style; Pregnancy; Pregnancy Complications; Sodium Chloride Symporter Inhibitors; Thirst; Vasopressins; Water

Patients who have suprasellar germinomas in childhood often present with central diabetes insipidus (CDI). The authors investigated the use of aqueous vasopressin (AVP) by continuous infusion to control the fluid and electrolyte balance in germinoma patients with CDI during aggressive fluid hydration as a part of a preirradiation chemotherapy protocol.. Three patients with suprasellar germinomas and CDI were treated with four courses of preirradiation chemotherapy. Two patients were treated with a continuous AVP infusion at an initial rate of 0.08-0.10 mU/kg per hour during hydration. Fluid intake, urine output, body weight, urine specific gravity, and serum electrolyte concentrations were monitored closely, and the infusion rate was adjusted accordingly.. Very low dose AVP infusion controlled fluid balance while allowing appropriate diuresis during chemotherapy. Fluid intake and output were markedly less in the AVP-treated patients (3.8 L/m2 per day) than in the untreated patient (20 L/m2 per day).. The use of very low dose AVP infusion at an initial rate of 0.08-0.10 mU/kg per hour during hydration therapy allowed easily titratable control of fluid and electrolyte balance in the patients studied and avoided the complications associated with desmopressin acetate antidiuresis or withholding antidiuretic treatment altogether.

Topics: Adolescent; Brain Neoplasms; Child; Combined Modality Therapy; Diabetes Insipidus; Female; Germinoma; Humans; Infusions, Intravenous; Male; Vasopressins

The immunolocalization of cathepsin L in the hypothalamus of normal rats was compared with the distribution of the enzyme in streptozotocin-treated animals and in vasopressin-deficient rats (Brattleboro strain). In rats with a normal metabolic status the neurons of magnocellular nucl. supraopticus and paraventricularis stood out by intense immunostaining for cathepsin L. In rats suffering from an experimentally induced diabetes mellitus and in homozygous Brattleboro rats we observed a strong reduction in enzyme immunoreactivity in these nuclei. Since cathepsin L is capable of splitting certain hypothalamic neuropeptides that are changed in diabetic animals, a role of the enzyme in the metabolism of these peptides is imaginable. Decrease in immunoreactive cathepsin L in vasopressin-deficient rats points to a possible involvement of the enzyme in the control of fluid homeostasis.

Topics: Animals; Cathepsin L; Cathepsins; Cysteine Endopeptidases; Diabetes Insipidus; Diabetes Mellitus, Experimental; Endopeptidases; Hypothalamus; Immunohistochemistry; Rats; Rats, Brattleboro; Streptomycin; Vasopressins

We report on two healthy white men who sustained high-voltage electrical burns and were transferred to our regional burn center for specialized care. Within 24 hours of admission, both patients developed clinical signs and laboratory evidence of diabetes insipidus. With appropriate treatment, no sequelae occurred and their endocrinopathy spontaneously resolved. Diabetes insipidus following traumatic events is not uncommon; however, it has never been reported following an electrical injury.

Topics: Adult; Burns, Electric; Diabetes Insipidus; Diagnosis, Differential; Hand Injuries; Humans; Male; Polyuria; Vasopressins

Topics: Adult; Carbamazepine; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Twins; Vasopressins

The Brattleboro rat with hypothalamic diabetes insipidus (BDI) has an abnormal aversion to drinking quinine-adulterated water compared with normal rats of the parent Long Evans (LE) strain. This BDI animal tolerates marked hypovolemia and decreased body weight in preference to drinking the quinine-adulterated fluid, indicative of a reduced motivation to drink. Acute or chronic treatment of BDI rats with desamino-8D arginine vasopressin (DDAVP) restored to normal their drinking response to quinine solution. Partial restoration of fluid turnover in BDI rats with hydrochlorothiazide, which has an antidiuretic effect in diabetes insipidus (when vasopressin is absent), failed to abolish the abnormal drinking response to quinine-adulterated solution in 8 out of 12 animals. In contrast, induction of diabetes mellitus in LE rats, which resulted in a marked polydipsia and polyuria even though vasopressin was still present, did not impair the drinking response to quinine solutions. These results suggest that the abnormal drinking response to quinine-adulterated fluid in BDI rats is reversed by treatment with the vasopressin V2-receptor agonist DDAVP but is unlikely to be a consequence of the restoration of fluid turnover to normal levels by a renal action. A possible central action involving vasopressin and the motivation to drink is discussed.

Topics: Animals; Avoidance Learning; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Habituation, Psychophysiologic; Hydrochlorothiazide; Male; Motivation; Premedication; Quinine; Rats; Rats, Brattleboro; Streptozocin; Taste; Vasopressins

A 55-year-old male smoker developed polyuria and polydipsia in November 1983. A water deprivation study revealed a defect in the urine concentrating function, which was corrected by vasopressin. Plasma antidiuretic hormone (ADH) was not increased by smoking. His condition was well controlled by deamino-D-arginine vasopressin. However, since February 1992 he has become completely free from the need for medication to control his urine volume. Re-evaluation studies with water deprivation and smoking revealed dramatic improvements in the urine concentrating function and ADH response. A patient with idiopathic diabetes insipidus with spontaneous remission after 8 years is reported.

Topics: Diabetes Insipidus; Humans; Male; Middle Aged; Remission, Spontaneous; Vasopressins; Water Deprivation

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Brain; Cerebellar Neoplasms; Combined Modality Therapy; Cyclophosphamide; Deamino Arginine Vasopressin; Dexamethasone; Diabetes Insipidus; Doxorubicin; Humans; Hydrocortisone; Lymphoma; Magnetic Resonance Imaging; Male; Thyroxine; Vasopressins; Ventriculoperitoneal Shunt; Vincristine

Topics: Adult; Diabetes Insipidus; Diuresis; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Vasopressins

A case of transient diabetes insipidus in pregnancy occurring in a 26 year-old woman is reported, and possible mechanisms leading to this disorder are considered. Delivery of a healthy boy was uneventful after induction of labor with prostin, and the condition remitted spontaneously shortly after delivery, following a short period of exogenous desmopressin administration. A water deprivation test confirmed undetectable serum ADH values, presumably due to temporary inappropriate ADH secretion or excessive vasopressinase activity.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Pregnancy; Pregnancy Complications; Vasopressins

The renal and endocrine actions of atrial natriuretic peptide (ANP) administered at a rate to induce plasma concentrations within the physiological range have been re-examined in conscious rats in which body fluid volume was maintained by infusion of replacement fluid at a rate to match spontaneous urine losses (servo-controlled replacement) throughout experimentation. The involvement of vasopressin in the actions of ANP was assessed by comparing the responses induced in Brattleboro (DI) and Long-Evans (LE) rats. A rate of ANP administration inducing a less than twofold increment in circulating ANP concentration evoked a small but significant diuresis and natriuresis. In contrast to previous studies during which body fluid balance had not been maintained and the response to ANP was transient, renal responses were rapid in onset and sustained over the period of hormone administration. The change in renal excretion occurred without concomitant changes in mean arterial blood pressure, haematocrit or glomerular filtration rate, and without consistent alterations in the circulating concentrations of angiotensin II, vasopressin, aldosterone or corticosterone. Furthermore, although small differences between the two strains in the character of the response could be demonstrated, the evoked response was of similar magnitude in vasopressin-replete and -deficient animals. In summary, in conscious rats in which body fluid volume was maintained, the profile of the diuretic and natriuretic responses evoked by low-rate ANP administration was different from that previously observed in anaesthetized and/or constantly infused preparations; being rapid in onset and sustained.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Diabetes Insipidus; Diuresis; Glomerular Filtration Rate; Hormones; Kidney; Male; Natriuresis; Rats; Rats, Inbred Strains; Vasopressins; Water-Electrolyte Balance

Topics: Diabetes Insipidus; Heart Failure; Humans; Hyponatremia; Kidney; Kidney Concentrating Ability; Male; Middle Aged; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Atrial Natriuretic Factor; Body Fluids; Brain; Diabetes Insipidus; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins

Topics: Animals; Diabetes Insipidus; Duodenum; Gastric Mucosa; In Vitro Techniques; Neurophysins; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reference Values; Stomach; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Brain; Diabetes Insipidus; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reference Values; Time Factors; Vasopressins

Topics: Aging; Animals; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Diabetes Insipidus; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reference Values; Vasopressins

Topics: Animals; Diabetes Insipidus; Food Deprivation; Heart Rate; Male; Rats; Rats, Inbred Strains; Stress, Physiological; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Brain; Diabetes Insipidus; Immersion; Injections, Intraventricular; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological; Vasopressins

The hypothesis that inhibition of vasopressin (VP) secretion initiates cold-induced diuresis was tested in six Brattleboro homozygous (diabetes insipidus, DI) rats exposed to 60 min at 5 degrees C. For 9-14 days before cold exposure (CE) the rats were treated with VP (750 pg.kg-1.min-1) subcutaneously via osmotic minipumps. Eight vehicle-treated Long-Evans (LE) rats characterized the response to acute exposure at 5 degrees C. Additional groups of six to eight LE and six DI rats were infused with VP (30-90 pg.kg-1.min-1 iv) on the day of CE. The DI rats receiving chronic VP replacement and untreated LE rats exhibited cold-induced diuresis, with peak increases in urine flow (V) of 63 +/- 12 (DIs) and 29 +/- 4 (LEs) microliters.min-1 x 100 g body wt-1. LE rats acutely infused with VP exhibited a diuresis at the two lower doses (peak V was 18 +/- 3 at the 30 and 18 +/- 4 microliters.min-1 x 100 g body wt-1 at the 60 pg.kg-1.min-1 dose), but the diuretic response was completely blunted at the uppermost dose of VP. Cold-induced diuresis was absent at the lowest VP dose in the acutely infused DI rats. A pressor response (30-36 mmHg) to CE was noted with all treatment groups, including those that did not exhibit a diuresis. No changes in glomerular filtration rate (GFR) with CE were observed. These data suggest that when plasma VP levels are controlled by prolonged infusion of VP in the DI rats, other mechanisms can operate to initiate cold-induced diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Blood Pressure; Body Temperature; Cold Temperature; Diabetes Insipidus; Diuresis; Glomerular Filtration Rate; Hematocrit; Kidney; Kinetics; Male; Osmolar Concentration; Rats; Rats, Brattleboro; Vasopressins

A 51-year-old Japanese man was referred for the evaluation of persistent hyponatremia. The serum sodium level remained around 120 mmol/l despite mild water restriction. His past history included chronic alcoholism, myocardial infarction and lumbar disc herniation. Carbamazepine (200 mg, b.i.d.) has been used for more than 8 years for low back pain. Serum sodium returned to normal after carbamazepine was stopped, and rechallenge produced acute symptomatic hyponatremia (117 mmol/l) on day 2 after a total dose of 600 mg. Hepatic, renal and endocrine function were within normal limits, and the response to a water load (20 ml/kg) was also normal. Partial central diabetes insipidus was diagnosed by his response to water restriction and nasal desmopressin administration. Polyuria and hypernatremia were not evident in this case, probably due to a combination of low solute intake and low, but not deficient, levels of plasma ADH. This case demonstrates that carbamazepine may cause acute hyponatremia even in central diabetes insipidus, probably by sensitizing the distal renal tubules.

Topics: Carbamazepine; Diabetes Insipidus; Humans; Hyponatremia; Male; Middle Aged; Vasopressins; Water-Electrolyte Balance

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.

Topics: Amino Acid Sequence; Amino Acids; Asian People; Base Sequence; Cloning, Molecular; Diabetes Insipidus; Endopeptidases; Exons; Female; Genome; Humans; Japan; Male; Membrane Proteins; Metabolism, Inborn Errors; Molecular Sequence Data; Mutation; Pedigree; Protein Biosynthesis; Protein Precursors; Protein Sorting Signals; RNA, Messenger; Sequence Analysis, DNA; Serine Endopeptidases; Transcription, Genetic; Vasopressins

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Infant, Newborn; Male; Vasopressins

The homozygote Brattleboro rat exhibits a hereditary diabetes insipidus due to a deficiency of vasopressin, the antidiuretic hormone. It has previously been shown that in this animal a single nucleotide deletion in the provasopressin gene leads to a mutant precursor with a C-terminal amino acid sequence different from that of the wild-type. However the N-terminal region including the hormone moiety, the processing signal as well as the first two-thirds of the neurophysin is entirely preserved and absence of maturation has to be explained by an additional cause. We show here that the neurohypophysis of the homozygote Brattleboro rat, in contrast to the adenohypophysis, displays a significant decrease in the Lys-Arg processing endopeptidase activity when compared to the heterozygote or the wild-type Wistar. It is suggested that hypothalamic vasopressinergic neurons of the homozygote Brattleboro rat display a deficiency in the processing enzyme in contrast to the oxytocinergic neurons in which processing of prooxytocin is normal.

Topics: Amino Acid Sequence; Animals; Arginine Vasopressin; Cytoplasmic Granules; Diabetes Insipidus; Endopeptidases; Female; Heterozygote; Homozygote; Male; Molecular Sequence Data; Neurophysins; Oxytocin; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Protein Precursors; Rats; Rats, Brattleboro; Rats, Wistar; Substrate Specificity; Vasopressins

The gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) have both been localized in the Xqter region by genetic mapping and functional expression studies, respectively. In this paper genetic evidence that the DIR locus is localized distal to the DXS305 locus and that the functional gene for the V2 receptor is localized between the markers DXS269 and F8 is presented. These further refinements in the localization of both genes strengthen the assumption that both genes are identical and provide a rationale for cloning the gene by reversed genetics strategies.

Topics: Animals; Arginine Vasopressin; Cell Line; Chromosome Mapping; Chromosomes; Cricetinae; Cyclic AMP; Diabetes Insipidus; Female; Genetic Linkage; Genetic Markers; Humans; Hybrid Cells; Lod Score; Male; Pedigree; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins

Antidiuretic hormone (arginine vasopressin) binds to and activates V2 receptors in renal collecting tubule cells. Subsequent stimulation of the Gs/adenylyl cyclase system promotes insertion of water pores into the luminal membrane and thereby reabsorption of fluid. In congenital nephrogenic diabetes insipidus (CNDI), an X-linked recessive disorder, the kidney fails to respond to arginine vasopressin. Here we report that an affected male of a family with CNDI has a deletion in the open reading frame of the V2 receptor gene, causing a frame shift and premature termination of translation in the third intracellular loop of the receptor protein. A normal receptor gene was found in the patient's brother. Both the normal and the mutant allele were detected in his mother. A different mutation, causing a codon change in the third transmembrane domain of the V2 receptor, was found in the open reading frame of an affected male but not in the unaffected brother belonging to another family suffering from CNDI.

Topics: Adult; Amino Acid Sequence; Base Sequence; Diabetes Insipidus; Female; Frameshift Mutation; Humans; Male; Molecular Sequence Data; Open Reading Frames; Pedigree; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins; X Chromosome

The binding of tritium-labelled arginine vasopressin to human platelet vasopressin receptors was investigated in patients with congenital nephrogenic diabetes insipidus. Binding characteristics, that is receptor affinity and the maximum number of binding sites, were not significantly different from those found in normal control individuals. The findings confirm the concept of intact V1 receptors in congenital nephrogenic diabetes insipidus. The defect in nephrogenic diabetes insipidus apparently only affects the cyclic adenosine monophosphate dependent V2 receptors.

Topics: Adolescent; Adult; Arginine Vasopressin; Binding Sites; Blood Platelets; Child; Diabetes Insipidus; Humans; Kidney Diseases; Receptors, Vasopressin; Vasopressins

Two cases, twins, affected by congenital nephrogenic diabetes insipidus (CNDI) with a high daily volume of dilute urine excretion and periods of compensatory high levels of antidiuretic hormone (ADH) simultaneously developed a fluctuating Menière-type hearing loss. It is well known that the kidney and the cochlea are linked by structural and anatomic characteristics, as well as by the physiologic mechanism of electrolytes and fluid regulation. The patients herein described seem to be paradoxical, because they suffered from hydropic hearing loss despite the pathophysiologic mechanism of CNDI and the possible role played by ADH in water regulation in the inner ear. The consequences on Menière's disease of the different therapeutic regimens followed by the two CNDI patients are discussed. To our knowledge these are the first cases of CNDI with Menière's disease described in the literature.

Topics: Audiometry, Pure-Tone; Diabetes Insipidus; Diseases in Twins; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Sensorineural; Hearing Tests; Humans; Male; Meniere Disease; Middle Aged; Vasopressins

Plasma concentrations of atrial natriuretic peptide (ANP) and other renally active hormones were measured in Long-Evans (LE) rats and vasopressin-deficient Brattleboro rats with diabetes insipidus (DI) in conditions of water repletion and deprivation, and in DI rats following chronic vasopressin replacement. In water-replete rats, vasopressin deficiency was associated with elevated circulating ANP and angiotensin II (AII) concentrations, while plasma adrenal steroid concentrations were depressed by comparison with LE rats. These differences were fully reversed after 7 days of vasopressin replacement in DI rats to restore normal water turnover. Water deprivation for 4 h had little effect on plasma tonicity or hormone profile in LE rats. In contrast, however, the unreplaced fluid loss during 4-h water deprivation in the DI rat was associated with a marked increase in plasma tonicity evident within 30 min. Plasma ANP concentrations fell substantially to levels below those in LE rats, coincident with a rise in adrenal steroid levels and independent of any clear change in AII. These changes in circulating ANP concentration were directly correlated with changes in plasma Na+ concentration, osmolality and tissue water content in the DI rats, underlining the importance of body fluid status in modulating the secretion of ANP. These data clearly show that plasma ANP concentration is increased in vasopressin deficiency, but emphasize the sensitivity of circulating hormone levels in vasopressin-deficient animals to acute changes in the state of hydration, underscoring the complex and labile interaction between body fluid and hormonal factors involved in the control of ANP secretion.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Corticosterone; Diabetes Insipidus; Male; Osmolar Concentration; Rats; Rats, Brattleboro; Rats, Inbred Strains; Sodium; Vasopressins; Water Deprivation

The posterior pituitary lobe and stalk were studied by magnetic resonance imaging in 20 children with diabetes insipidus of different origins: primary familial autosomal dominant (n = 2) or idiopathic (n = 2), and secondary to craniopharyngioma (n = 6, resected in 5), to Langerhans cell histiocytosis (n = 5), to excessive water intake (dipsogenic; n = 3), to renal vasopressin insensitivity (n = 1), and to osmoreceptor dysfunction (n = 1). Of the four children with primary diabetes insipidus, the posterior bright signal was recognizable in two with the familial autosomal dominant form and one with the idiopathic form; in the latter, the pituitary stalk was thin, while it was normal in the first two patients; no posterior hyperintense signal with enlarged and gadolinium-enhanced pituitary stalk was observed in the fourth. The posterior hyperintense signal was absent without evidence of ectopic posterior pituitary tissue regeneration in five children with surgically removed craniopharyngioma and was doubtful in the child with unresected craniopharyngioma; the stalk was unrecognizable in all patients. In the five children with Langherans cell histiocytosis, the posterior bright signal was absent, while the stalk was normal in two and unexpectedly enlarged in three (uniformly in two and mainly at the level of median eminence and hypothalamus in one). All five patients with dipsogenic or nephrogenic diabetes insipidus or osmoreceptor dysfunction had normal images of posterior pituitary lobe and stalk. Normal posterior pituitary bright signal and stalk were found in all 25 healthy control children. Plasma vasopressin was undetectable in all patients except in nephrogenic one, in the child with osmoreceptor dysfunction, and in two of three dipsogenic children, the third mimicking partial neurogenic diabetes insipidus.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Pituitary Gland, Posterior; Vasopressins; Water Deprivation

The role of antidiuretic hormone (ADH) in the renal concentration defect and hemodynamic changes in protein malnutrition was evaluated in rats with diabetes insipidus (DI) after 2 weeks of low protein feeding. Free water reabsorptive capacity (TcH2O), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in the protein deprived rats and in DI rats fed a normal protein diet. The effect of urea supplementation of the low protein diet on renal concentrating capacity was also evaluated. In addition, the renal hemodynamic response to acute administration of ADH was measured and correlated with changes in plasma renin concentration and renal renin content (RRC). Protein deprivation in DI rats resulted in reduced urine osmolality and urea excretion, differences which were reversed by urea supplementation. Protein deprivation did not affect free water reabsorptive capacity but did reduce GFR and RPF. Acute ADH administration significantly increased GFR and RPF in protein-deprived rats; these changes were associated with a reduction in RRC and release. These results suggest that dietary protein restriction does not directly affect the tubular capacity to generate and reabsorb free water. The hemodynamic changes seen in protein deprivation are not mediated by ADH and may be secondary to increased intrarenal angiotensin II.

Topics: Animals; Diabetes Insipidus; Hemodynamics; Kidney; Kidney Concentrating Ability; Protein Deficiency; Rats; Rats, Brattleboro; Renin; Urea; Vasopressins

We describe two children who after cardiopulmonary arrest developed hypernatremia at the terminal stage. Urinary antidiuretic hormone concentration was very low, indicating central diabetes insipidus. These cases illustrate the necessity of alertness to the development of central diabetes insipidus in patients with severe hypoxic brain damage.

Topics: Adolescent; Airway Obstruction; Brain Damage, Chronic; Cerebral Palsy; Diabetes Insipidus; Humans; Hypoxia, Brain; Infant; Male; Pituitary Gland, Posterior; Resuscitation; Vasopressins; Water-Electrolyte Balance

A boy presented with ectrodactyly (lobster claw deformity), bilateral cleft lip and palate, semilobar holoprosencephaly and microcephaly, associated with congenital hypogonadotropic hypogonadism and central diabetes insipidus. Other aspects of pituitary function were normal. We suggest that the ectrodactyly-ectodermal dysplasia-clefting syndrome can be associated with a variety of hypothalamo-pituitary dysfunctions, in addition to the already described isolated growth hormone deficiency.

Topics: Abnormalities, Multiple; Cleft Lip; Cleft Palate; Deficiency Diseases; Diabetes Insipidus; Ectodermal Dysplasia; Growth Hormone; Hand Deformities, Congenital; Holoprosencephaly; Humans; Hypogonadism; Infant, Newborn; Male; Microcephaly; Radiography; Vasopressins

We report on 2 intellectually normal sisters with vasopressin-resistant (nephrogenic) diabetes insipidus (NDI). The sex of the patients, the history of parental consanguinity, and the fact that both parents formed normally concentrated urine suggested that the NDI in the 2 sisters was the result of inheritance of an autosomal recessive mutation affecting renal tubular water reabsorption. The results of DNA analysis of the DXS52 locus with the use of St14 as probe, shown by Knoers et al. [1988] to be tightly linked to the NDI locus on the X-chromosome, showed that each girl inherited different Xq28 regions of the maternal X chromosomes, ruling out a diagnosis of classical X-linked NDI.

Topics: Consanguinity; Diabetes Insipidus; DNA; Drug Resistance; Female; Genes, Recessive; Humans; Infant; Male; Pedigree; Polymorphism, Restriction Fragment Length; Vasopressins

We report the histological findings in a case of hereditary diabetes insipidus (HDI) using vasopressin (VP) immunohistochemistry. The hypothalamus displayed a marked loss of magnocellular VP neurons, with preservation of the smaller cells. The neurohypophysis was severely atrophic with scanty immunoreactivity. Our results support the hypothesis that HDI results from a selective degeneration of VP neurons affecting chiefly the magnocellular elements projecting to the neurohypophysis. The sparing of the parvocellular component may reflect the projection of these neurons to non-pituitary targets.

Topics: Aged; Diabetes Insipidus; Humans; Hypothalamus; Immunohistochemistry; Male; Pituitary Gland; Staining and Labeling; Supraoptic Nucleus; Vasopressins

One purpose of this report is to illustrate that calculating the rate of excretion of osmoles in the urine can be of value in the differential diagnosis of hypernatremia and polyuria. A second purpose is to illustrate a clinical example where the osmolality of the urine did not reflect the lack of action of ADH. A patient with ethanol intoxication seemed to have central diabetes insipidus on clinical grounds. However, the osmolality of the urine was 287 mosm/kg H2O, a value which made this diagnosis unlikely. Since the concentration of ethanol in plasma was 119 mmol/L, we suspected that the urine contained an appreciable quantity of alcohol; this might obscure the lack of action of ADH. A study was performed to document the quantitative relationship between the concentrations of ethanol in plasma and urine. The concentration of ethanol in the urine was approximately 1.4-fold greater than in plasma. Using this correction factor, the osmolality of the urine adjusted for ethanol in the patient was only 120 mosm/kg H2O, a value more consistent with the diagnosis of central diabetes insipidus.

Topics: Adult; Alcoholic Intoxication; Artifacts; Diabetes Insipidus; Diagnosis, Differential; Diuresis; Ethanol; False Negative Reactions; Female; Humans; Hypernatremia; Osmolar Concentration; Pituitary Gland, Posterior; Polyuria; Urinalysis; Vasopressins

In congenital nephrogenic diabetes insipidus (NDI) blunted responses of plasma factor VIII, von Willebrand factor, and plasminogen activator to the synthetic V2 analogue 1-desamino-8-D-arginine vasopressin (DDAVP) have been reported. In addition, vasodilatory responses to DDAVP appear to be absent in NDI. We describe a boy, who presented shortly after birth with the typical features of NDI, but who showed normal coagulation, fibrinolytic and vasodilatory responses to DDAVP. We conclude that in this patient the defect is confined to the kidney, while in other NDI patients there may be a general V2 receptor abnormality. These findings point to heterogeneity in NDI.

Topics: Diabetes Insipidus; Humans; Infant, Newborn; Kidney Diseases; Male; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins

Topics: Body Water; Dehydration; Diabetes Insipidus; Diuretics; Drinking; Feedback; Glomerular Filtration Rate; Homeostasis; Humans; Inappropriate ADH Syndrome; Polyuria; Vasopressins; Water Intoxication

Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated.

Topics: Almitrine; Animals; Carotid Body; Chemoreceptor Cells; Denervation; Diabetes Insipidus; Diuresis; Kidney; Kidney Transplantation; Kidney Tubules; Male; Natriuresis; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins

Vasopressin (VP) was administered in the lateral cerebral ventricles of homozygous rats with congenital diabetes insipidus of Brattleboro (BB) strain as well as of normal animals of Long Evans strain (LE). The following parameters were studied: the latent period for achievement of maximal pressor response in seconds (LP), absolute value of the increase in arterial pressure in comparison with the initial V mmHg (delta AP) and cardiac frequency (CF). The initial values of AP in BB were lower than those values found in LE (BB-9, 10 +/- 0.57 kPa; LE-11, 31 +/- 0.53 kPa; p less than 0.01, while CF showed higher values in BB (350 +/- 8.5 min-1); LE (321 +/- 10 min-1); p less than 0.05. VP, administered intraventricularly, induced quick transitory elevation of AP in both groups, which did not differ substantially both in respect to LP (BB-55 +/- 11 s; LE-43 +/- 6.9) and also in respect to delta AP (BB-3.64 +/- 0.34; LE-3.14 +/- 0.62). CF was not changed in BB (347 +/- 8.9), while it was slightly increased in LE (334 +/- 11). The data show that exogenously administered VP affect the central VP-dependent mechanisms for regulation of AP in the same way in both groups of rats.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Heart Rate; Injections, Intraventricular; Rats; Rats, Brattleboro; Rats, Inbred Strains; Stimulation, Chemical; Vasopressins

Topics: Child, Preschool; Diabetes Insipidus; Factor VIII; Humans; Vasopressins; von Willebrand Factor

The role of vasopressin in the development of gastric hemorrhagic erosions induced by the oral administration of 1 mL of 75% ethanol in rats was studied. The area of the lesions in homozygous Brattleboro rats, having a defective vasopressin synthesis, was only 20% of that found in Wistar and heterozygous Brattleboro rats, which have normal vasopressin production. It is well known that vasopressin acts via the V1 (pressor) and V2 (antidiuretic) receptors. Administration of V1 and V2 vasopressin-receptor agonists and antagonists in this model showed that pressor-receptor activity is needed for the generation of all lesions in Wistar and heterozygous Brattleboro rats. Ethanol damage to the gastric mucosa was diminished by the V1 antagonist with similar efficacy as in the case of a vasopressin deficiency. Administration of the V1 antagonist and the absence of endogenous vasopressin were shown to protect the deeper layer of the gastric mucosa (assessed by histology) and to reduce significantly the ethanol-induced vascular injury and increase in vascular permeability (assessed by the monastral blue technique). Thus, endogenous vasopressin is clearly of great importance in the pathogenesis of gastric hemorrhagic lesions induced by ethanol. These results strongly suggest that vasopressin is an endogenous aggressor toward the gastric mucosa.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Ethanol; Female; Gastric Acid; Gastric Emptying; Gastric Mucosa; Hydrogen-Ion Concentration; Peptic Ulcer Hemorrhage; Rats; Rats, Brattleboro; Rats, Inbred Strains; Stomach; Vasopressins

To evaluate posterior pituitary function without any provocative examination, vasopressin (AVP) concentrations of random urine were measured by high-sensitive radioimmunoassay (AVP-RIA Kit, Mitsubishi Petrochemical Co., Ltd.). No apparent interference for the AVP measurement in unextracted urine was seen after appropriate dilution of urine sample. Urinary AVP did not degenerate at least for 24 hr at room temperature. AVP concentration of random urine was significantly correlated with AVP excretion in 24hr-urine in normal subjects. In 25 patients with neurogenic diabetes insipidus diagnosed by hypertonic saline infusion test, the AVP concentration in random urine was less than 13 pg/mg Cr. In approximately 1% of the normal subjects the urinary AVP level was below this range. Therefore, more intensive examinations should be planned to rule out the failure of AVP secretion in the case of such low AVP level in random urine. We also investigated the physiological changes in AVP secretion in 815 children and 352 pregnant women by measurement of urinary AVP. Even a large number of samples could be measured using this simple procedure.

Topics: Adolescent; Adult; Child; Child, Preschool; Diabetes Insipidus; Female; Humans; Infant; Male; Pituitary Function Tests; Pituitary Gland, Posterior; Pregnancy; Radioimmunoassay; Random Allocation; Reference Values; Vasopressins

Transient polyuria and polydipsia during pregnancy are rare, and their cause is not entirely clear. Possible explanations include the exacerbation of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity.. We studied two women in whom overt polyuria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal.. One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in response to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopressin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per liter) before and during hypertonic-saline infusion 30 months post partum. The other patient had partial neurogenic diabetes insipidus. She had subnormal basal plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin level and a subnormal decrease in urine flow in response to the administration of vasopressin, and a normal response to desmopressin. After pregnancy, when her urine volume was normal, she had no increase in plasma vasopressin in response to hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin level and a normal renal response to vasopressin administration.. Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypertonic Solutions; Osmolar Concentration; Polyuria; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Thirst; Vasopressins

Topics: Cystinyl Aminopeptidase; Diabetes Insipidus; Female; Humans; Pregnancy; Pregnancy Complications; Thirst; Vasopressins

Sarcoidosis is a generalized disorder which involves the central nervous system in 5 per cent of patients presenting with the disease. We describe the case of a 22-year-old man who developed central diabetes insipidus with a daily urine production of 14,81 seven weeks after diagnosis of pulmonary sarcoidosis and parotid gland enlargement. Computed tomography showed a contrast enhancement of pituitary gland and stalk, no other intracranial manifestations were demonstrated. Intranasal administration of synthetic antidiuretic hormone (ADH) reduced urine volume to normal levels immediately. After discontinuation of 15 months therapy with corticosteroids and administration of ADH for 29 months spontaneous urine volume didn't exceed 31. The patient has been free of symptoms since discontinuation of therapy.

Topics: Administration, Intranasal; Adult; Diabetes Insipidus; Humans; Lung Diseases; Male; Parotid Diseases; Pituitary Diseases; Sarcoidosis; Vasopressins

Topics: Adult; Diabetes Insipidus; Drug Resistance; Female; Humans; Pregnancy; Pregnancy Complications; Puerperal Disorders; Vasopressins

A comprehensive study of monoamine transmitter and metabolite concentrations measured by HPLC was undertaken in female (vasopressin-deficient) Brattleboro rats as compared to Long Evans rats. Noradrenaline was significantly increased in 8 out of 13 dissected brain regions, whereas concentrations of the metabolite 3-methoxy-4-hydroxyphenylglycol were not altered. The increases were not restricted to areas which are normally innervated by vasopressin-containing neurons. Serotonin was increased in 6 and dopamine in 4 regions and this was accompanied in some areas by increases in the metabolites 5-hydroxyindolacetic acid and dihydroxyphenylacetic acid. Only in the striatum, cerebellum, and the medulla-pons no changes could be detected in any of the compounds of interest. These results show that the long term absence of vasopressin in Brattleboro rats appears to be associated with increases in monoamine transmitter contents and decreased metabolite/transmitter ratios. The regional distribution of these changes does not bear any relationship to the regional distribution of vasopressin cell bodies or nerve endings.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Brain; Diabetes Insipidus; Dopamine; Female; Hydroxyindoleacetic Acid; Methoxyhydroxyphenylglycol; Norepinephrine; Rats; Rats, Brattleboro; Serotonin; Tissue Distribution; Vasopressins

The effects of quinpirole, a specific dopamine D2 receptor agonist, were investigated on cardiovascular responses and plasma levels of catecholamines and vasopressin in two groups of conscious dogs: (1) control dogs and (2) dogs with diabetes insipidus (i.e. animals surgically deprived of vasopressin). In normal dogs, i.v. quinpirole (30 micrograms/kg) elicited a decrease in blood pressure associated with a rise in both plasma catecholamine and vasopressin levels. In dogs with diabetes insipidus, i.v. quinpirole induced a more marked decrease in blood pressure than in normal dogs. Quinpirole did not change plasma noradrenaline and vasopressin levels in dogs with diabetes insipidus. The present study demonstrates that the decrease in blood pressure elicited by quinpirole is associated with an increase in vasopressin release, which counteracts the hypotensive effect of the the dopamine D2 receptor agonist.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Catecholamines; Diabetes Insipidus; Dogs; Dopamine Agents; Ergolines; Heart Rate; Hemodynamics; Quinpirole; Vasopressins

The analgesic effect of electrical stimulation of the hypothalamic paraventricular nucleus (PVN) was studied. Additionally, the involvement of vasopressin and opioid peptides in this process was examined by comparing vasopressin-deficient (Brattleboro) and Long-Evans rats and by administering the opiate antagonist naloxone. Rats were chronically implanted with a stimulating electrode in the parvocellular (PVN-Pc) and magnocellular (PVN-Mg) divisions of the PVN. At least 10 days after surgery, the analgesic effects of PVN stimulation were examined in lightly anesthetized rats, using the tail-flick method, and in unanesthetized rats, using the hot-plate test. PVN stimulation produced marked analgesia in both tests. Current threshold for analgesia was lower from PVN-Pc than from PVN-Mg. Threshold did not differ significantly between Brattleboro and Long-Evans rats and was not affected by naloxone administration. The results indicate that the PVN is part of the brain's pain inhibitory system, and show that the analgesia induced by PVN stimulation is not mediated by either vasopressin or opioid peptides.

Topics: Analgesia; Animals; Brain Stem; Diabetes Insipidus; Dynorphins; Electric Stimulation; Electrodes, Implanted; Endorphins; Male; Naloxone; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reaction Time; Spinal Cord; Vasopressins

To examine a possible role for atrial natriuretic peptide (ANP) in water and sodium metabolism disturbances associated with abnormal vasopressin (AVP) secretion, we measured plasma ANP concentrations in 15 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in 17 patients with central diabetes insipidus (DI). The mean plasma ANP concentration (30.2 +/- 10.4 pmol/L) in SIADH patients who had hyponatremia, plasma hypoosmolality, hyperosmolar urinary compared to plasma sodium levels, and increased plasma AVP levels relative to plasma osmolality was significantly higher than that in normal subjects (12.6 +/- 4.9 pmol/L), although there was a considerable individual variation in plasma ANP ranging from normal to clearly elevated levels (15.1-47.0 pmol/L). When hyponatremia was corrected by water restriction or demeclocycline administration, plasma ANP levels decreased significantly and fell into the normal range (12.5 +/- 4.3 pmol/L). DI patients who complained of polyuria and polydipsia and had hypoosmolar urine, normal or elevated plasma sodium concentrations, and decreased plasma AVP levels relative to plasma osmolality, on the other hand, had a significantly lower mean plasma ANP level (7.6 +/- 2.9 pmol/L) than normal subjects. There was, again, a considerable overlap between plasma ANP levels in individual DI patients (4.2-13.9 pmol/L) and those in normal subjects. Treatment with 1-desamino-8-D-arginine vasopressin resulted in a significant increase in the mean plasma ANP level (18.6 +/- 8.0 pmol/L). There were no significant correlations between plasma ANP and AVP levels in either group of patients. The results indicate that ANP secretion is modulated by changes in plasma volume consequent to abnormal AVP secretion, which may have a pathophysiological significance in maintaining volume homeostasis.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Blood Volume; Deamino Arginine Vasopressin; Demeclocycline; Diabetes Insipidus; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Polyuria; Sodium; Vasopressins; Water-Electrolyte Balance

1. The effect of an intracisternal injection of 20 micrograms kg-1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose-anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system). 2. Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus. 3. Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals. 4. Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels. 5. Acetylcholine significantly increased atrial natriuretic factor plasma levels only in control dogs. 6. Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group. 7. These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.

Topics: Acetylcholine; Anesthesia; Animals; Atrial Natriuretic Factor; Blood Pressure; Diabetes Insipidus; Dogs; Epinephrine; Female; Heart Rate; Hemodynamics; Injections, Intraventricular; Male; Norepinephrine; Pituitary Gland, Posterior; Renin; Supraoptic Nucleus; Vasopressins

Topics: Adult; Dexamethasone; Diabetes Insipidus; Humans; Lymphoma; Male; Osmotic Pressure; Vasopressins

Topics: Diabetes Insipidus; Diabetes Mellitus; Diagnosis, Differential; Diuresis; Humans; Hypothalamo-Hypophyseal System; Polyuria; Syndrome; Thirst; Vasopressins

Renal function was evaluated in normal and after 30 days of 5/6 renal mass reduction (CRF) in Munich-Wistar (MW) rats, spontaneously hypertensive rats with superficial glomeruli (EPM), and in Brattleboro rats with congenital diabetes insipidus (DI). Mean arterial pressure was higher in EPM-Control and EPM-CRF rats as compared with MW and DI rats. MW and EPM rats with CRF showed increases of 120% and 196%, respectively, in single nephron glomerular filtration rate as compared with their controls. However, DI rats with CRF did not show any increase in single nephron glomerular filtration rate as compared with the control group. Therefore, the data suggest that the presence of hypertension enhances the adaptive mechanisms on remnant kidney's function. Conversely, in the absence of antidiuretic hormone, adaptive mechanisms of remnant nephrons did not occur. In addition, it was observed that rats with CRF submitted to prostaglandin blockade with indomethacin showed for MW rats a 55% and 20% reduction in ultrafiltration coefficient and in single nephron glomerular filtration rate, respectively. Decreases of 60% and 30% in ultrafiltration coefficient and single nephron glomerular filtration rate, respectively, were observed for EPM rats. In contrast, DI rats did not show any alteration on renal function after indomethacin. It seems, therefore, that prostaglandins play a role in remnant nephron function of MW and EPM rats, but in the absence of antidiuretic hormone, prostaglandins do not affect remnant glomerular hemodynamics.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Glomerular Filtration Rate; Hypertension; Kidney Failure, Chronic; Kidney Glomerulus; Male; Nephrectomy; Nephrons; Prostaglandins; Rats; Rats, Inbred Strains; Vasopressins

The role of endogenous vasopressin in cardiovascular homeostasis was examined using vasopressin-deficient rats (Brattleboro) (n = 194) and their parent strain, Long-Evans rats (n = 181). Mean arterial pressure (blood pressure) and heart rate were measured every 4 seconds with or without infusion of drug solution for 21 hours, and mean values and their standard deviations (lability) were calculated. Blood pressure in Brattleboro rats (116 +/- 1.1 mm Hg, mean +/- SEM) was significantly higher than that in Long-Evans rats (96 +/- 0.7 mm Hg, p less than 0.001), whereas heart rates (381 +/- 3.3 and 375 +/- 2.9 beats/min, respectively) were similar. The lability of blood pressure and heart rate in Brattleboro rats (9.2 +/- 0.1 mm Hg and 42.3 +/- 0.7 beats/min) was also greater than that in Long-Evans rats (6.7 +/- 0.1 mm Hg, p less than 0.001 and 38.4 +/- 0.8 beats/min, p less than 0.01, respectively). In Brattleboro rats, intravenous vasopressin (0.1 ng/kg/min or 0.6 ng/kg/min) did not affect blood pressure, although it did reduce heart rate and decreased lability of blood pressure and heart rate. Intracerebroventricular (central) infusion of vasopressin (2 pg/kg/min) in Brattleboro rats induced initial hypertension and tachycardia followed by long-lasting hypotension and bradycardia, whereas in Long-Evans rats it induced only hypertension and tachycardia. In both strains, central vasopressin dramatically decreased the lability of blood pressure and heart rate. Neither intravenous (0.2 ng/kg/min) nor central desmopressin (2 pg/kg/min or 0.2 ng/kg/min), a V2 renal receptor agonist, changed any of these parameters in Brattleboro rats, although both diminished urinary volume. Neither intravenous (50 ng/kg/min) nor central (3.3 pg/kg/min) d(CH2)5-Tyr(Me)-arginine vasopressin, a vasopressin V1 receptor antagonist, modulated any of these parameters in Long-Evans rats. These results suggest that endogenous as well as exogenous vasopressin acts centrally as a cardiovascular inhibitor and stabilizer through a receptor mechanism other than V1 or V2 receptor mechanisms.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Deamino Arginine Vasopressin; Diabetes Insipidus; Heart Rate; Injections, Intravenous; Rats; Vasopressins

A case of pulmonary embolism associated with diabetes insipidus is reported in an 18-year-old male. The patient, who had been treated with DDAVP for diabetes insipidus and hydrocortisone for hypocorticism for two years after first operation for the removal of craniopharyngioma, was admitted with recurrence of that tumor. Diabetes insipidus immediately after second operation was controlled with intermittent drip infusion of a small amount of aqueous pitressin under monitorings of body weight hourly using a patient weighing system to keep the weight changes within +/- one kilogram. Serum and urine electrolytes levels, osmolarity, and free water clearance were also monitored every three hours to maintain water-electrolytes balances appropriately. Postoperative course had been uneventful except that CSF rhinorrhea occurred 7 days after operation. The patient was, then, kept in bed with horizontal plane to avoid further leakage of CSF. Two days later, he developed chest pain suddenly with tachypnea, tachycardia, and general cyanosis. The arterial-BGA showed PaO2 of 53.5mmHg and PaCO2 of 35.3mmHg in room air. The definite diagnosis of pulmonary embolism was made by technetium microaggregate lung perfusion scans and by pulmonary angiograms. The patient was treated with heparin, 15000IU/day, and urokinase, 720000IU/day. The symptoms due to pulmonary embolism had improved gradually within a couple of weeks. Recent articles have shown an unexpected high incidence of deep vein thrombosis and pulmonary embolism in neurosurgical patients associated with the elevation of blood coagulability. Brain tumors, especially suprasellar mass with hypothalamic dysfunction have been suggested to cause thromboembolic disorders frequently. The clinical course was described and factors causing pulmonary embolism on this patient was discussed.

Topics: Adolescent; Craniopharyngioma; Diabetes Insipidus; Heparin; Humans; Lung; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Postoperative Complications; Pulmonary Embolism; Radionuclide Imaging; Tomography, X-Ray Computed; Urokinase-Type Plasminogen Activator; Vasopressins

Two patients with post-traumatic diabetes insipidus (DI) are reported. One had suffered a fatal injury and the other a mild contusion without amnesia before DI developed. These two instances exemplify the wide spectrum of post-traumatic DI and, hence, the importance of ruling out DI even afer a mild closed-head injury.

Topics: Adult; Central Nervous System; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Male; Middle Aged; Vasopressins; Wounds and Injuries

Topics: Diabetes Insipidus; Humans; Pituitary Gland, Anterior; Vasopressins

Five children who developed diabetes insipidus as a manifestation of severe brain injury received continuous intravenous treatment with a solution containing both aqueous vasopressin and appropriate crystalloid replacement. Polyuria, hypernatraemia, and decreased urine osmolalities were safely corrected in all patients within eight to 28 hours.

Topics: Adolescent; Brain Injuries; Child; Diabetes Insipidus; Humans; Infant; Infusions, Intravenous; Osmolar Concentration; Sodium; Vasopressins

1. The cardiovascular effects of bolus intravenous injections of vasopressin, angiotensin II and noradrenaline were studied in 6-hydroxydopamine pretreated, anaesthetized Brattleboro rats with hereditary diabetes insipidus and normal rats of the parent Long Evans strain. 2. Pretreatment with 6-hydroxydopamine did not significantly affect control values for mean arterial blood pressure, cardiac output or total peripheral resistance in either Brattleboro or Long Evans rats but the pressor response to haemorrhage was reduced in both strains compared to the control animals. 3. The pressor responses of the untreated Brattleboro rats to 250 mu kg-1 vasopressin were significantly greater and more prolonged than in control rats of the Long Evans strain. 4. Pretreatment with 6-hydroxydopamine significantly enhanced the peak pressor response to vasopressin, but not to angiotensin II (1 microgram kg-1), in Brattleboro and Long Evans rats. 5. Pretreatment with 6-hydroxydopamine resulted in an enhanced pressor response to 1 microgram kg-1 noradrenaline in both Brattleboro and Long Evans rats, but the effect was significantly greater in the vasopressin-deficient animals. 6. These results indicate differences in the pressor responsiveness of Brattleboro rats to vasopressin and noradrenaline, but not to angiotensin II, compared with control Long Evans rats and provide evidence for important interactions between the sympathetic nervous system and these pressor hormones.

Topics: Angiotensin II; Animals; Diabetes Insipidus; Hemodynamics; Hydroxydopamines; Male; Norepinephrine; Oxidopamine; Rats; Rats, Brattleboro; Sympathetic Nervous System; Vasopressins

Topics: Adult; Creatinine; Diabetes Insipidus; Drinking; Female; Humans; Indomethacin; Kidney Concentrating Ability; Lithium; Lithium Carbonate; Male; Middle Aged; Osmolar Concentration; Polyuria; Urodynamics; Vasopressins; Water Deprivation

Aldose reductase (AR), an enzyme that catalyzes the conversion of glucose to sorbitol, has been implicated in the pathogenesis of many of the complications of diabetes mellitus, but its normal physiological function in various tissues remains uncertain. It has been suggested that in the kidney, sorbitol production may be an important cellular protection against medullary intersitital hypertonicity. Using in situ and Northern hybridization analyses, we found that at the time of birth, AR mRNA expression in the kidney was very low and seen only in the papilla. By 12 days of age, at about the time a corticopapillary osmotic gradient and the capacity for urinary concentration have developed, a striking increase in renal AR mRNA levels was seen. It was confined to the inner medulla and was characterized by a dramatic gradient of expression paralleling the corticopapillary osmotic gradient. Levels of expression were somewhat lower in adults, but showed the same inner medullary boundary and gradient. Under these hybridization and exposure conditions, no AR transcripts were detected in the outer medulla or cortex. Homozygous Brattleboro rats with congenital diabetes insipidus have relatively dilute corticopapillary osmotic gradients, and their level of medullary AR mRNA was significantly lower than that of controls. Conversely, normal rats made hyperosmotic and, hence, antidiuretic by salt loading showed a large increase in medullary AR mRNA. These changes in renal medullary AR gene expression in correlation with changes in medullary tonicity support the hypothesis that renal AR plays a role in cellular adaption to osmotic stress and suggest that local medullary osmolarity may regulate the level of AR gene expression.

Topics: Aging; Aldehyde Reductase; Animals; Blotting, Northern; Diabetes Insipidus; Gene Expression Regulation, Enzymologic; Hybridization, Genetic; Kidney Medulla; Male; Rats; Rats, Inbred Strains; RNA, Messenger; Sugar Alcohol Dehydrogenases; Transcription, Genetic; Vasopressins; Water-Electrolyte Balance

Topics: Adenylyl Cyclases; Diabetes Insipidus; Humans; Kidney Tubules; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins

Topics: Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Pituitary Function Tests; Radioimmunoassay; Reagent Kits, Diagnostic; Reference Values; Saline Solution, Hypertonic; Specimen Handling; Vasopressins

Topics: Diabetes Insipidus; Humans; Patient Care Planning; Vasopressins

To determine how the vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus produces increased renin secretion, homozygous and heterozygous Brattleboro rats were infused through subcutaneously implanted Alzet minipumps for 1 wk with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. In the homozygous animals, plasma renin activity (PRA) and the PRA response to immobilization remained elevated compared with Long-Evans controls. Propranolol reduced PRA to normal and markedly reduced the PRA response to immobilization. PRA was normal in heterozygous Brattleboro rats. The data indicate that the increased renin secretion in homozygous rats is a result of increased sympathetic activity, and because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

Topics: Animals; Diabetes Insipidus; Diuresis; Drinking; Heterozygote; Homozygote; Male; Natriuresis; Osmolar Concentration; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Vasopressins

The effects of water deprivation on the urinary excretion rate of prostaglandin E2 (PGE2) were examined in conscious Brattleboro rats. In order to study the time course of the changes in the PGE2 excretory rate, urine was collected in 6 periods,. 0-1 hour (h.). 1: 3-4.5 h., 8-10 h., III: 12-15 h., IV: 24-28 h. and V: 32-36 h. after removal of water and food. It was found that the PGE2 excretion rate changed in a biphasic pattern. During the first 2 experimental periods it increased. Thereafter it decreased towards the control value. There was an increase in PGE2 excretion with urinary flows down to 3 microliter/(min*100 g b. wt). At further reductions in urinary flow rate, PG excretion decreased towards basal levels.

Topics: Animals; Diabetes Insipidus; Dinoprostone; Male; Rats; Rats, Brattleboro; Time Factors; Urodynamics; Vasopressins; Water Deprivation

The authors discuss about five cases of diabetes insipidus observed in patients affected by traumatic cervical spine fractures and/or dislocations, without either evident lesions of the cerebral structures at CT scan examination, or important craniocerebral trauma. In all patients polyuria and hyperthermia arose some days after the traumatic accident and regressed spontaneously or after exogeneous vasopressin administration. Vasopressin urinary levels confirmed the presence of a true diabetes insipidus, the origin of which is in largely obscure. A central medullary vasopressin mediated pathway, demonstrated only in experimental animals, may be responsible for such a finding.

Topics: Adolescent; Adult; Cervical Vertebrae; Diabetes Insipidus; Female; Fever; Fractures, Bone; Humans; Hypothalamo-Hypophyseal System; Joint Dislocations; Male; Polyuria; Radiography; Spinal Cord Injuries; Syndrome; Vasopressins

The effects of the absence of various hormones (antidiuretic hormone, thyroid hormone, parathyroid hormone, and calcitonin) on proximal and distal structures were studied in diabetes insipidus (DI) Brattleboro rats. The cross-sectional area of the first segment of proximal convoluted tubules (S1) was significantly reduced in thyroparathyroidectomized (TPTX) DI rats compared with Long-Evans rats (the strain of origin of DI rats) and untreated DI rats. Administration of triiodothyronine (T3, 10 micrograms/day for 7 days) to TPTX-DI rats restored the proximal tubule structure. In the distal convoluted tubule (DCT) the cross-sectional area of the epithelium and the number of nuclei per cross-sectional area were significantly greater in untreated ADH-deficient DI rats than in the control Long-Evans rats. Daily administration of 1-desamino-8-D-arginine vasopressin (dDAVP, 500 ng/day for 3 wk) significantly reduced the size and the number of DCT cells in DI rats. Cortical micropuncture data indicated that the Na+ concentration in the fluid delivered to the DCT and the absolute amount of Na+ reabsorbed along the DCT were higher in DI than in dDAVP-treated DI rats. It is concluded that functional changes in the PCT, subsequent to chronic TPTX, are accompanied by marked alteration of the cell anatomy of this nephron segment, and that the processes that modify the Na load delivered to the DCT and the Na transport in the DCT are accompanied by structural modifications of this segment.

Topics: Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Kidney Tubules; Kidney Tubules, Distal; Kidney Tubules, Proximal; Nephrons; Parathyroid Glands; Peptides; Rats; Rats, Brattleboro; Rats, Inbred Strains; Thyroid Hormones; Thyroidectomy; Vasopressins

Acetylcholinesterase activity was demonstrated histochemically at light- and electron-microscopic levels, in Vibratome sections of the supraoptic nucleus of fixed hypothalami derived from osmotically stimulated and unstimulated Long Evans rats, from homozygous Brattleboro rats with hypothalamic diabetes insipidus, from lactating rats, from normal adult male house mice (Mus musculus) and from mice with hereditary nephrogenic diabetes insipidus (di/di). Reaction product was located in supraoptic magnocellular neurons; in dorsal and rostral aspects of the supraoptic nuclei lightly stained cells predominate, whereas in ventral and caudal regions densely staining perikarya predominate. Pre- and post-embedding immunocytochemical detection of oxytocin-neurophysin or vasopressin-neurophysin, combined with acetylcholinesterase histochemistry, showed that the lightly staining cells are oxytocinergic, and the densely staining cells vasopressinergic. Osmotic stimulation of the animals, either by substitution of drinking water for 3 days with 2.5% saline or reason of genetic defects which result in diabetes insipidus, enhanced the acetylcholinesterase activity of the vasopressin neurons but had little effect on the weekly acetylcholinesterase-reactive oxytocin cells. Acetylcholinesterase activity was particularly marked in the hypertrophied abnormal magnocellular neurons of homozygous Brattleboro rats which do not release significant amounts of vasopressin. The increased acetylcholinesterase activity in osmotically stimulated animals cannot, therefore, be a function of vasopressin. Acetylcholinesterase activity was also detected in large multipolar neurons lying dorsolateral to the supraoptic nucleus, and in their fine axonal processes which project towards the supraoptic nucleus. A very few synaptic boutons surrounded by acetylcholinesterase reaction product were found in contact with magnocellular neuron basal dendrites. However, much of the punctate acetylcholinesterase reactivity observed at the light microscopic level and previously interpreted as representing the loci of cholinergic synaptic boutons was shown to be intracellular, and probably caused by acetylcholinesterase activity in some large, secondary lysosomes.

Topics: Acetylcholinesterase; Animals; Diabetes Insipidus; Female; Lactation; Male; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Microscopy, Electron; Neurons; Oxytocin; Pregnancy; Rats; Rats, Brattleboro; Rats, Inbred Strains; Supraoptic Nucleus; Tissue Distribution; Vasopressins

The concentration of unextracted urinary arginine vasopressin (UAVP) was directly measured by high-sensitive radioimmunoassay (AVP-RIA Kit, Mitsubishi Petrochemical Co., Ltd.). Urine was diluted to eliminate interference of nonspecific substance without prior extraction. When urine aliquots were diluted in 4 to 32 fold in assay buffer, the relationship between UAVP concentration and dilution ratio corresponded exactly in a linear regression line. The elution pattern on Sephadex G-25 of UAVP immunoreactivity was identical with that of synthesized AVP. The AVP concentration in unextracted urine was not significantly different from that of extracted urine by Sep-Pak C18 column (Water Associates, Milford MA). The mean recovery of added AVP to urine specimens was 101.1 +/- 9.8% (mean +/- SD). The immunoreactivity of UAVP was not modified by either albuminuria (50 and 100 mg/dl) or glycosuria (1000 g/dl). Mean coefficients of variance between-assay and within-assay were 8.3% and 6.6% respectively. In normal subjects (n = 28), significant correlation was observed between UAVP concentration and simultaneously measured plasma AVP (r = 0.701, p less than 0.001). Moreover, AVP concentration in random urine was significantly correlated with AVP excretion in 24 hr-urine (r = 0.703, p less than 0.05, n = 9), and this suggested that random UAVP concentration may indicate daily UAVP secretion. In normal subjects, AVP concentration in random urine was widely scattered from 9.2 to 470.6 pg/mg Cr (89.5 +/- 76.4 pg/mg Cr, n = 211). In patients with diabetes insipidus (DI), UAVP concentration (1.6 to 13.0 pg/mg Cr, 6.94 +/- 2.77 pg/mg Cr, n = 25) was significantly lower (p less than 0.001) than that of normal subjects. UAVP concentration in a patient with primary polydipsia (43.2 pg/mg Cr) was not similar to that of ID but to that of normal subjects. UAVP concentration in 2 patients with SIADH was not more than that of normal subjects, indicating that random UAVP concentration is not suitable for detecting inappropriate AVP secretion. In this study, it is suggested that patients of random UAVP concentration below 13.0 pg/mg Cr should be recommended other intensive examination to diagnose DI, even though 2 normal subjects (0.9%) were incorrectly estimated as DI. In conclusion, radioimmunoassay of AVP in unextracted random urine is easy to sample and assay, and useful in screening polyuric patients.

Topics: Diabetes Insipidus; Female; Humans; Male; Mass Screening; Radioimmunoassay; Vasopressins

PGE2 synthesis was measured along the nephron of Brattleboro (DI) rats, lacking ADH, and control LE rats, using an enzyme immunoassay. Experiments were performed in vitro, in the absence of exogenous arachidonic acid, using microdissected tubular segments. The effect of a chronic treatment of dDAVP was tested on three ADH sensitive tubular segments, medullary thick ascending limb (MTAL), medullary collecting tubule (OMCD) and papillary collecting duct (IMCD). No difference in PGE2 synthesis was present between LE and DI in glomerulus and tubular segments up to OMCD. In both strains, values were low in the proximal tubule and the loop of Henle, and gradually increased along the collecting tubule. In IMCD, PGE2 synthesis was much higher in DI (12.8 +/- 2.0 pg per 30 min per mm tubular length) than in LE (3.8 +/- 0.5, LE vs. DI p less than 0.001). In MTAL and OMCD, dDAVP treatment did not affect PGE2 synthesis. In IMCD, dDAVP reduced PGE2 synthesis to values (5.3 +/- 0.8 pg per 30 min per mm tubular length), which were not significantly different from those of LE. Neither oxytocin, which has been shown to be elevated in DI rats, nor furosemide, that reduced papillary osmolarity to values comparable to those of DI rats, were able to increase PGE2 synthesis in IMCD of LE rats. The mechanism of the increase in PGE2 synthesis in IMCD of DI rats, and of the inhibitory effect of dDAVP is yet unknown; it may participate to compensate for the lack of ADH in the Brattleboro rat.

Topics: Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Dinoprostone; Diuresis; Female; Furosemide; Kidney Medulla; Kidney Tubules; Kidney Tubules, Collecting; Loop of Henle; Nephrons; Osmolar Concentration; Oxytocin; Rats; Rats, Brattleboro; Urine; Vasopressins

A continuous intravenous infusion of aqueous vasopressin (dosage range, 1.0 to 3.0 mU/kg/h) was administered to two patients (respective ages, 2 weeks and 3 years 1 month) who had postoperative central diabetes insipidus to determine if this mode of therapy is helpful in the very young patient. In both patients the polyuria and serum hyperosmolality were corrected. These findings suggest that an intravenous infusion of aqueous vasopressin can provide satisfactory control of the polyuria and electrolyte disturbances found in young children with acute postoperative central diabetes insipidus.

Topics: Brain; Child, Preschool; Diabetes Insipidus; Female; Humans; Infant, Newborn; Infusions, Intravenous; Male; Postoperative Complications; Vasopressins

Antidiuretic hormone is known to stimulate the renal synthesis of prostaglandins. These autacoids, in turn, modulate the pressure natriuresis phenomenon. Accordingly, the present study was done to test the hypothesis that, in the absence of antidiuretic hormone and antidiuretic hormone-dependent prostaglandin synthesis, the pressure natriuresis response is blunted. Experiments were performed on Brattleboro diabetes insipidus rats (n = 7) and Long Evans control rats (n = 14). A change in perfusion pressure in the Long Evans rats from 89.3 +/- 1.0 to 108.7 +/- 1.1 mm Hg (p less than 0.05) was associated with significant increases in the fractional excretion of sodium (1.1 +/- 0.2 to 2.3 +/- 0.3%) and the urinary prostaglandin excretion (32.6 +/- 6.8 to 56.6 +/- 10.0 pg/min). In contrast, a similar change in perfusion pressure in the diabetes insipidus rat from 88.6 +/- 1.4 to 106.2 +/- 1.5 mm Hg (p less than 0.05) resulted in no significant increases in either sodium or prostaglandin excretions. Treatment of a third group of diabetes insipidus rats (n = 9) with 1-desamino-8-D-arginine vasopressin (1 microgram/day) restored the natriuretic response to increases in renal perfusion pressure. Treated diabetes insipidus and Long Evans control rats had comparable natriuretic responses to increases in renal perfusion pressure. Untreated diabetes insipidus rats, on the other hand, had blunted responses. In summary, the pressure natriuresis response in diabetes insipidus rats is blunted compared with Long Evans control rats. We conclude that antidiuretic hormone is necessary for the complete expression of the pressure natriuresis response.

Topics: Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Kidney; Male; Natriuresis; Perfusion; Prostaglandins; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Urodynamics; Vasopressins

Acute cerebral compression by a supra- and infratentorial balloon produced a triphasic pattern of diuresis. The 1st phase was characterized by polyuria associated with five fold increase of plasma (p) antidiuretic hormone (ADH) concentration, decreased urine osmolality in spite of natriuresis and blood pressure elevation. The 2nd phase was characterized by oliguria, a decrease of pADH and reduced urine Na+ concentration, whereas urine osmolality transiently increased. At this stage there was respiratory arrest and fall of blood pressure. The final stage was diabetes insipidus (DI), when EEG activity had disappeared. An increase of serum osmolality mainly occurred during the last DI phase. Serum Na+ concentration fluctuated slightly during the whole period of diuresis. These results present evidence, that the diuresis pattern reflects the hypothalamo-hypophyseal antidiuretic system (HHAS) reaction to acute intracranial pressure (ICP) increase with the vegetative symptoms of cerebral shock.

Topics: Animals; Anuria; Cats; Diabetes Insipidus; Hypothalamo-Hypophyseal System; Oliguria; Osmolar Concentration; Polyuria; Pseudotumor Cerebri; Vasopressins; Water-Electrolyte Balance

Topics: Adenoma; Adult; Aged; Diabetes Insipidus; Hemodynamics; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Period; Vascular Resistance; Vasopressins

In two experiments, binding sites for atrial natriuretic factor (ANF) were studied in discrete areas of rat brain by quantitative autoradiography. In the first experiment, the maximum binding capacity of 125I-ANF was reduced significantly in the subfornical organ and choroid plexus of 4 and 14 week old spontaneously hypertensive (SHR) rats compared to aged-matched Wistar-Kyoto (WKY) normotensive controls. In contrast, the maximum binding capacity of 125I-ANF in the area postrema was similar for young and adult SHR and WKY rats. The second experiment involved a comparison of brain ANF binding sites in Long-Evans control rats and Brattleboro rats with inherited diabetes insipidus. The maximum binding capacity of 125I-ANF was significantly greater in the subfornical organ of Brattleboro rats compared to Long-Evans controls. However, no strain differences occurred for 125I-ANF binding in the choroid plexus or area postrema. These findings indicate that the number of ANF binding sites in discrete areas of rat brain may be influenced in a highly selective fashion by alterations in body fluid homeostasis (i.e., hypertension or diabetes insipidus). Changes in brain ANF binding sites within circumventricular areas may involve central as well as peripheral sources of ANF-related peptides.

Topics: Aging; Animals; Atrial Natriuretic Factor; Autoradiography; Brain; Diabetes Insipidus; Disease Models, Animal; Hypertension; Male; Neuropeptides; Rats; Rats, Brattleboro; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Atrial Natriuretic Factor; Vasopressins

Topics: Diabetes Insipidus; Humans; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Aged; Atrial Natriuretic Factor; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Middle Aged; Pituitary Gland, Posterior; Renin-Angiotensin System; Vasopressins

Topics: Aged; Diabetes Insipidus; Humans; Kidney Tubules; Kidney Tubules, Collecting; Lithium; Male; Prostaglandins; Vasopressins

Brattleboro rats are homozygous for diabetes insipidus (HO-DI), lacking the ability to synthesize vasopressin. Besides increasing water consumption, HO-DI rats may compensate for their excessive renal water loss by reducing their intake of and preference for substances that elevate plasma osmolarity. In two experiments we assessed this possibility. In Experiment 1, salt preference of HO-DI and control Long-Evans (LE) rats was measured by presenting the rats with two tubes: one filled with water and the other with NaCl. In the first part of the experiment, 18 NaCl concentrations were presented in increasing order (from 6 to 300 mM). In the second part, other groups of HO-DI and LE rats were presented with 6 concentrations of NaCl, ranging from 6 to 450 mM in either increasing or decreasing order of concentrations. In Experiment 2, preference for 6 concentrations of citric acid ranging from 0.1 to 6 mM was assessed. With NaCl concentrations greater than 100 mM, intake and preference declined rapidly for the HO-DI group but very gradually for the LE group. In contrast, the HO-DI rats preferred all citric acid solutions more than LE rats. The results suggest that HO-DI rats compensate for their inability to concentrate urine not only by increasing water consumption, but also by decreasing consumption of and preference for salty solutions.

Topics: Animals; Diabetes Insipidus; Food Preferences; Hypothalamus; Kidney Concentrating Ability; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Saline Solution, Hypertonic; Sodium, Dietary; Taste; Vasopressins; Water-Electrolyte Balance

Dehydrated patients usually present with an elevated serum urea level, owing in part to increased renal reabsorption of urea mediated by antidiuretic hormone (ADH). We carried out a study to examine whether, during dehydration, the variations in the serum urea level could discriminate patients with central diabetes insipidus (CDI) from those with dehydration not due to CDI. We studied retrospectively 27 episodes of dehydration in 23 patients with CDI and 14 episodes in 14 patients without CDI. The mean serum urea level was 2.9 mmol/L in the CDI group and 15.4 mmol/L in the patients without CDI (p less than 0.001); the mean serum sodium level was 155 mmol/L in both groups. All the patients with CDI had a sodium/urea ratio greater than 24.2, whereas the ratio was less than 21.7 in all the patients without CDI. In the patients with CDI a positive correlation was found between the magnitude of diuresis and the percentage decrease in the serum urea level compared with the level before dehydration (p less than 0.001). In the patients with CDI the serum urea level returned to the level before dehydration after the administration of vasopressin; a striking increase in the clearance of urea, which exceeded the creatinine clearance, was observed during dehydration in the three patients in whom clearance studies were done. The results suggest that serum urea values can be used to distinguish patients dehydrated because of CDI from those with hypertonic dehydration but without ADH deficiency and that during dehydration the net reabsorption of urea is dependent on the renal action of ADH.

Topics: Adult; Creatinine; Dehydration; Diabetes Insipidus; Female; Fluid Therapy; Humans; Hypernatremia; Male; Middle Aged; Osmolar Concentration; Prospective Studies; Retrospective Studies; Urea; Vasopressins

Nineteen children aged four months to 15 years with diabetes insipidus (DI) secondary to severe brain insults were studied. The main primary brain insult was severe head injury in 12, anoxic ischemic brain damage in four, encephalitis in two, Reye's syndrome in one. Sixteen children died, and three survived. The time from insult to onset of polyuria varied from several hours to one month, and was significantly shorter in head trauma patients, 1.8 +/- 0.9 vs. 9.3 +/- 1.9 days for patients with anoxic ischemic brain damage (p less than 0.03). Twelve of the 19 patients met the criteria for brain death at onset of DI. Treatment by appropriate fluids and vasopressin resulted in resolution of polyuria and increase in urine osmolality. Ten patients developed DI while being treated with dopamine for hemodynamic support. In two of these patients, the cessation of dopamine was time-related to the resolution of DI. Our results indicate that as many as 15% of children with DI (with 95% confidence) following severe brain injury may survive. Hence, despite the overall poor prognosis, its occurrence does not necessarily indicate brain death.

Topics: Adolescent; Brain Damage, Chronic; Brain Death; Brain Injuries; Child; Child, Preschool; Combined Modality Therapy; Diabetes Insipidus; Dopamine; Female; Fluid Therapy; Humans; Infant; Male; Prognosis; Vasopressins

The effects of lithium (Li) on the kidney were studied in normal Long Evans (LE) rats and in rats of the Brattleboro strain (DI rats) which have a congenital (hypothalamic) diabetes insipidus. The rats received a moderate daily oral dose of Li for 4 weeks. The renal cortex of untreated DI rats showed no changes compared with LE rats, but in their medullary collecting ducts (CD) the cells appeared more voluminous, and by light microscope morphometry (outer medulla) their volume fraction was increased. Furthermore, there was an increase in the enzyme histochemical activities of succinate and alpha-glycerophosphate dehydrogenases, most pronounced in the inner medullary zone. Li-treated LE rats and DI rats both showed the same degree of cortical and medullary changes. In the cortex, the light microscope and enzyme histochemical changes were confined to the connecting tubules (CNT) and CD. In the outer and inner medullary zones the increase in CD volume fraction and enzyme activity was much more pronounced than in untreated DI rats. Morphometry of the inner stripe of the outer medullary zone showed the same decrease in the volume fraction of the distal straight tubules (DST) in DI rats with and without Li treatment, as well as in Li-treated LE rats compared with normal LE rats. This decrease may be due to the lack of vasopressin-mediated cyclic AMP generation in the DST of these three groups of animals. It is concluded that the changes induced by Li in the DST are likely to be due to impairment of the vasopressin response known to be present in this segment. However, in the CNT and in the cortical and medullary CD there are changes which are effects of Li not related to the cellular actions of vasopressin.

Topics: Animals; Diabetes Insipidus; Kidney; Lithium; Male; Rats; Rats, Brattleboro; Vasopressins

This investigation examined the presence and abundance of vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, stroke-prone spontaneously hypertensive rats, and cross-bred diabetes insipidus x stroke-prone spontaneously hypertensive rats. A single-stranded RNA probe complementary to exon C of the vasopressin gene was utilized for in situ hybridization and identified hypothalamic 'vasopressinergic' neurons in tissue from all five strains of rats. The results obtained by solution and in situ hybridization suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous physiological data which suggests cross-bred diabetic-hypertensive rats inherit the mutated vasopressin gene of the Brattleboro rat.

Topics: Animals; Diabetes Insipidus; Hypertension; Male; Rats; Rats, Brattleboro; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transcription, Genetic; Vasopressins

Topics: Animals; Arginine Vasopressin; Blood; Diabetes Insipidus; DNA, Recombinant; Gene Expression; Male; Metallothionein; Mice; Mice, Transgenic; Neurophysins; Osmolar Concentration; Oxytocin; Protein Precursors; Protein Processing, Post-Translational; Vasopressins

To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells.

Topics: Animals; Bone Marrow; Diabetes Insipidus; HLA-D Antigens; Kidney Concentrating Ability; Kidney Medulla; Male; Microscopy, Electron; Rats; Rats, Brattleboro; Rats, Inbred WF; Vasopressins; Whole-Body Irradiation

To determine whether antibodies to vasopressin play a role in the development of diabetes insipidus or interfere with diagnosis and treatment.. Random plasma or serum samples for determining of antibodies to vasopressin were collected from patients and controls.. Referral university hospital with most patients studied in the clinical research center.. Twenty-nine healthy controls and 113 patients with polyuria (15 with primary polydipsia; 86 with neurogenic diabetes insipidus [60 studied before, 28 during, and 10 after antidiuretic hormone treatment]; and 12 with nephrogenic diabetes insipidus).. Antibodies were detected by incubating samples with radiolabeled 125I-arginine vasopressin. The effect of antibodies on diagnosis was studied by examining the relation of plasma vasopressin to osmolality measured during dehydration or infusion of hypertonic saline and the relation of urine osmolality to plasma vasopressin measured during dehydration.. Antibodies to vasopressin were not detected in patients with primary polydipsia, nephrogenic diabetes insipidus, or neurogenic diabetes insipidus studied before therapy with antidiuretic hormone. Antibodies were detected in 6 of 28 patients studied during such treatments. All 6 patients reported decreased antidiuretic response to previously effective therapy with arginine or lysine vasopressin but had normal response to desmopressin or chlorpropamide.. Diabetes insipidus does not result from spontaneously occurring antibodies to vasopressin. The antibodies occasionally develop during treatment with antidiuretic hormone and, when they do, almost always result in secondary resistance to its antidiuretic effect. Antibodies usually do not impair the response to other forms of therapy; they only rarely interfere with the diagnosis of diabetes insipidus, by falsely suggesting the presence of the partial nephrogenic form.

Topics: Adolescent; Adult; Aged; Antibodies; Arginine Vasopressin; Child; Child, Preschool; Diabetes Insipidus; Female; Humans; Infant; Male; Middle Aged; Osmolar Concentration; Vasopressins

Topics: Brain Diseases; Calcinosis; Child, Preschool; Diabetes Insipidus; Humans; Kidney Diseases; Male; Vasopressins

Previous studies have shown a disappearance of interstitial cells from the renal medulla of rats with hereditary diabetes insipidus (Brattleboro) when the animals were treated with vasopressin in high doses. The present study was undertaken to elucidate the mechanisms behind this cell loss. The disappearance of interstitial cells from the renal medulla of Brattleboro rats was quantitatively determined by electron microscopic stereology after various types of treatment. A considerable decrease in the volume density of interstitial cells was induced by the administration of either 8-arginine vasopressin or 1-desamino-8-D-arginine vasopressin. This lesion of the interstitial cells was not prevented by the simultaneous administration of oxytocin. Even a 48-hour period of water deprivation also resulted in a slight decrease in the volume density of interstitial cells. The results indicate that the observed loss of renal medullary interstitial cells is not a direct effect of the hormone on the cells but probably secondary to the marked increase in the renal medullary solute (urea) concentration. The fact that animals with hardly any renomedullary interstitial cells concentrated their urine to a virtually normal level shows that these cells cannot play an important role in the concentrating mechanism. The interstitial cells recovered rapidly when the vasopressin treatment was discontinued, but it could not be determined whether this was due to local proliferation or to the immigration of cells from extrarenal tissue.

Topics: Analysis of Variance; Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Kidney Medulla; Male; Microscopy, Electron; Osmolar Concentration; Oxytocin; Rats; Rats, Brattleboro; Rats, Inbred Strains; Urine; Vasopressins

Topics: Diabetes Insipidus; Humans; Polyuria; Vasopressins; Water-Electrolyte Imbalance

Cysteamine (beta-mercaptoethylamine, CSH) has been reported to have various effects on the neuroendocrine system. Reports indicate CSH decreases pituitary oxytocin (OT) without affecting pituitary vasopressin (VP). However, preliminary studies from our laboratory strongly indicate that CSH has an effect on VP release. Experiments were conducted with dibenzyline-treated, urethane-anesthetized, male Sprague-Dawley (SD) rats. Rats were injected with 4 mU of standard VP and 4 mg/100 g of CSH. Administration of VP resulted in an increase in mean arterial pressure (MAP) of 23.5 +/- 3.2 mm Hg. Administration of CSH resulted in a consistent, immediate decrease in MAP of 13.0 +/- 2.0 mm Hg prior to an increase of 21.0 +/- 2.6 mm Hg. The effects due to VP and CSH were strikingly different; the CSH-induced MAP rise took longer to peak and to return to baseline. Both the VP- and CSH-induced MAP rise were markedly inhibited by a prior administration of a specific VP antagonist d(CH2)5[Tyr(Me)]AVP. In addition, the typical increase in MAP observed in SD rats following CSH administration was substantially reduced when the same dose was administered in homozygous diabetes insipidus (HODI) rats. The data presented here strongly suggest that CSH-induced MAP elevation is due to the release of VP from the pituitary gland.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Cysteamine; Diabetes Insipidus; Male; Rats; Rats, Inbred Strains; Vasopressins

Topics: Bone Marrow Transplantation; Bronchial Neoplasms; Carcinoma, Small Cell; Cyclophosphamide; Dehydration; Diabetes Insipidus; Humans; Kidney Diseases; Liver Neoplasms; Male; Middle Aged; Vasopressins

Topics: Adult; Diabetes Insipidus; Humans; Hyperaldosteronism; Male; Polyuria; Thirst; Vasopressins

In four boys with congenital nephrogenic diabetes insipidus, plasma arginine-vasopressin (AVP) and urinary excretion of prostaglandins were studied in response to treatment with hydrochlorothiazide and indomethacin. An abnormal relationship between AVP and urine osmolality was demonstrated in all patients. In the first patient, treatment with indomethacin (3 mg/kg per day) resulted in a drop of the insulin and paraminohippurate clearances. In the other three patients urinary excretion of PGE2 was raised, and fell during treatment with hydrochlorothiazide (2 mg/kg per day) and indomethacin (2 mg/kg per day). Urine flow, free water clearance and osmolar clearance decreased during treatment. A combination of both drugs is more effective than hydrochlorothiazide alone and the effect appears to be additive.

Topics: Child; Child, Preschool; Diabetes Insipidus; Humans; Hydrochlorothiazide; Indomethacin; Infant; Kidney Diseases; Male; Prostaglandins; Vasopressins

Topics: Adult; Aldosterone; Child; Diabetes Insipidus; Female; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Renin-Angiotensin System; Vasopressins

Regeneration and functional recovery of the hypothalamoneurohypophysial system (HNS) in neurohypophysectomized rats treated with either saline or vasopressin (VP) were analyzed utilizing specific immunohistochemical and physiological measures. Neural lobe ablation combined with VP administration precipitated a profound diabetes insipidus (following cessation of VP delivery) that persisted for the duration of the experiment. Diabetes insipidus was correlated with a drastic reduction in the number of VP-positive neurons in magnocellular hypothalamic nuclei. In contrast, large numbers of oxytocin (OT)-positive neurons survived neurohypophysectomy in VP-treated neurohypophysectomized rats; OT neurons accounted for the vast majority of magnocellular profiles observed in Nissl-counterstained sections. VP-immunoreactive fibers could be observed in limited quantities in the external lamina of the median eminence of VP-treated neurohypophysectomized rats, with little staining evident in the internal lamina. Saline-treated neurohypophysectomized rats exhibited the recovery of antidiuretic function characteristically seen following this lesion, with evidence of survival of considerable numbers of VP and OT neurons and median eminence hypertrophy. Both the internal and external laminae of the median eminence were densely innervated by large-caliber VP and OT fibers. Sham-operated animals receiving VP treatment did not show any long-term deficit in water metabolism, changes in the complement of VP or OT perikarya in hypothalamus, or changes in the innervation of the median eminence. Results indicate that VP treatment following neurohypophysectomy results in extensive retrograde degeneration of magnocellular VP neurons without affecting the survival of OT cells.

Topics: Animals; Cell Survival; Diabetes Insipidus; Drinking Behavior; Histocytochemistry; Hypothalamus; Immunoenzyme Techniques; Male; Neurons; Osmolar Concentration; Pituitary Gland, Posterior; Rats; Time Factors; Urine; Vasopressins

The effect of furanthril after an acute (24 hours) and chronic administration (7 days), and the effect of 7-days sodium loading was followed on control Long Evans (LE) and Brattleboro rats with inherited hypothalamic diabetes insipidus (DI). In addition to the routine sodium-fluid balance study, plasma renin activity and prostaglandins excretion were examined. In control LE rats was found a typical diuretic- and natriuretic effect of furanthril only after an acute (14 hours) administration of the drug. This effect was attributed to the stimulation of renal PGE2 synthesis. In sodium-depleted state (7 days after administration of furanthril) the diuretic- and natriuretic effect was missing due to the extensive sodium deficit. In DI rats was found a paradoxical antidiuretic effect of furanthril after either an acute or chronic treatment, which was attributed to the per se stimulated renin-angiotensin system and suppressed PG-synthesis typical for these rats. The conclusion of this studies was that an availability of ADH is necessary for PG-response to sodium depletion. After sodium loading, an exaggerated natriuresis, decreased PRA, and depressed PG-synthesis was found in DI rats. The feedback mechanism between renin axis and prostaglandin system in the absence of ADH was discussed.

Topics: Animals; Benzothiadiazines; Diabetes Insipidus; Diuretics; Furosemide; Male; Prostaglandins; Rats; Rats, Brattleboro; Renin; Sodium; Sodium Chloride Symporter Inhibitors; Vasopressins; Water-Electrolyte Balance

A case of a pregnant woman with diabetes insipidus is reported. The course of the pregnancy was uneventful except for a slightly increased need for vasopressin during the last trimester. Neurophysin levels increased at a rate similar to that seen in the normal pregnant state. The combination of normal neurophysin physiology and undisturbed spontaneous labor demonstrating normal oxytocin secretion suggests that there is a singular deficiency of antidiuretic hormone in essential diabetes insipidus.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Neurophysins; Pregnancy; Pregnancy Complications; Vasopressins

A case of transient nephrogenic diabetes insipidus occurred in late pregnancy, the first associated with biopsy-proven hepatitis. Five previously reported cases occurred in pregnancy. All six patients demonstrated similar but transient signs, symptoms and laboratory abnormalities suggesting a syndrome peculiar to pregnancy. The characteristics of this syndrome are elevated liver function studies, decreased renal function, hyperuricemia and transient vasopressin-resistant diabetes insipidus.

Topics: Adult; Diabetes Insipidus; Female; Hepatitis; Humans; Kidney Diseases; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Uric Acid; Vasopressins; Water-Electrolyte Balance

We describe a patient with chronic hypernatraemia (plasma sodium 148-155 mmol/l) and partial nephrogenic diabetes insipidus who had received prolonged lithium treatment. Despite stopping the drug for one year the abnormalities remained. Infusion of hypertonic saline (NaCl 855 mmol/l) allowed the characterization of osmoregulation of thirst and vasopressin secretion. Linear regression analysis of plasma vasopressin and osmolality defined the function, pAVP = 0.27 (pOsm - 301), and analysis of thirst measured by a visual analogue scale and plasma osmolality, the function, thirst = 0.16 (pOsm - 302) where pAVP and pOsm represent plasma arginine vasopressin and osmolality respectively. The slopes of the regression lines which describe the sensitivity of the osmoreceptors were within the normal range, but both abscissal intercepts, which define the thresholds for vasopressin release and thirst, were markedly elevated in comparison to normal (upper limit less than 290 mOsm/kg). Other investigations of electrolytes, anterior pituitary function and high definition computed tomographic scanning of hypothalamo-pituitary region were all normal. We conclude that this patient's chronic hypernatraemia was due to resetting of the osmostats for both vasopressin release and thirst, a rarely described mechanism to account for hypernatraemia. Although it is probable that the partial nephrogenic diabetes insipidus was related to prolonged lithium therapy, the cause of the reset osmostats remains unclear.

Topics: Aged; Diabetes Insipidus; Female; Humans; Hypernatremia; Thirst; Vasopressins; Water-Electrolyte Balance

We describe three patients who have polydipsia and polyuria due to an abnormality in the osmoregulation of thirst. The clinical manifestations of the syndrome are similar to those of neurogenic diabetes insipidus. Thus, under basal conditions the patients have thirst, normal to high normal levels of plasma osmolality, and low levels of plasma vasopressin. Moreover, antidiuretic therapy greatly reduces thirst and polydipsia as well as polyuria. The only clinically distinguishing feature of the response is that thirst and water intake decrease less rapidly than water excretion. As a consequence, the patients with this syndrome develop variable degrees of dilutional hyponatremia and hypoosmolemia during treatment. The plasma vasopressin response to osmotic stimulation is relatively normal. In most of the patients, the osmotic threshold for vasopressin release is at the upper limit of normal, but this finding only explains their modest elevation in basal plasma osmolality. Thirst and water intake also change as a function of plasma osmolality. However, the threshold or "set" of the thirst osmostat appears to be abnormally low. The degree of downward resetting varies from patient to patient, but is always sufficient to stimulate thirst and water intake at levels of plasma osmolality below the normal range. This abnormality can account not only for the thirst and polyuria under basal conditions but also for the overhydration that occurs during antidiuretic therapy. The pathogenesis of the osmoregulatory abnormality is unknown but may be due to disruption of one or more of the afferent pathways that regulate the "set" of the thirst and vasopressin osmostats.

Topics: Adult; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Female; Humans; Male; Syndrome; Thirst; Urine; Vasopressins; Water-Electrolyte Balance

We examined the release of vasopressin and the renal response to exogenous vasopressin before and during desoxycorticosterone acetate (DOCA) administration in the dog. As treatment with DOCA produced potassium loss, urine volume increased, urinary osmolality decreased, and urinary PGE2 tended to increase. The increase in urine volume was accompanied by increases in serum sodium, in plasma osmolality and in plasma arginine vasopressin. The threshold for vasopressin release measured during polyuria was higher than control but the rate of vasopressin release was unchanged. The DOCA-induced polyuria was not affected by treatment with vasopressin which further increased plasma vasopressin. Treatment with indomethacin which corrected the increase in urinary PGE2 excretion but not the hypokalemia, restored the renal responsiveness to vasopressin, decreased the secretion of vasopressin, and corrected the polyuria and the hypernatremia. These findings suggest that DOCA-induced polyuria is attributable to a decrease in renal responsiveness to vasopressin which may be mediated in part by an increase in the renal synthesis of prostaglandins.

Topics: Animals; Body Water; Desoxycorticosterone; Diabetes Insipidus; Dinoprostone; Dogs; Female; Polyuria; Potassium; Prostaglandins E; Vasopressins

Using implanted minipumps it was shown over a period of 7 days that the vasopressin antagonist, 1-deamino-pentamethylene-2-D-Phe-4-Ile-arginine vasopressin, caused increased diuresis in normal rats and reversed vasopressin- or oxytocin-induced antidiuresis in Brattleboro rats. When the antagonist was infused alone in Brattleboro rats it induced a marked antidiuretic response, indicating that the analogue also possessed agonistic properties. The agonist action could not be demonstrated in anaesthetized, hydrated normal rats. In these animals the analogue behaved as a pure antagonist. It is concluded that analogues which behave as antagonists in one test model may display agonistic properties under different experimental conditions.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drug Synergism; Female; Infusions, Parenteral; Male; Osmolar Concentration; Oxytocin; Rats; Rats, Inbred Strains; Urine; Vasopressins

Topics: Adult; Brain Injuries; Diabetes Insipidus; Female; Humans; Kidney Concentrating Ability; Suicide, Attempted; Vasopressins

Topics: Animals; Diabetes Insipidus; Gene Expression Regulation; Genetic Code; Hypothalamic Diseases; Mutation; Rats; Rats, Brattleboro; RNA, Messenger; Vasopressins

Antidiuretic hormone (ADH) function was assessed in a group of 16 patients with Sheehan's syndrome and 17 controls. All patients were on adequate cortisone and thyroxine replacement therapy before testing. During the dehydration test the patients revealed an impairment of ADH function. The maximum urine osmolalities and the urine-plasma osmolality ratios were significantly lower in the patients with Sheehan's syndrome compared to controls (maximum urine osmolalities 633 +/- 38 (SEM) and 873 +/- 29 (SEM) mOsm/kg, respectively, P less than 0.001; urine-plasma osmolality ratios 2.15 +/- 0.14 (SEM) and 3.01 +/- 0.10 (SEM), respectively, P less than 0.001). Plasma osmolalities were significantly higher in the patients (296.1 +/- 1.2 (SEM) and 290 +/- 0.9 (SEM), respectively, P less than 0.001). The patients took a longer period to achieve these maximum urine osmolalities. Three of the patients with Sheehan's syndrome were diagnosed as having diabetes insipidus since their maximum urine osmolalities were below 600 mOsm/kg and following desmopressin all three had an increment in urine osmolality which exceeded 9%. In addition these three patients had a maximum urine-plasma osmolality ratio below 1.9. Thus, it appears the patients with Sheehan's syndrome have an impairment of ADH function which manifests in some as diabetes insipidus.

Topics: Adult; Diabetes Insipidus; Female; Humans; Hypopituitarism; Kidney Concentrating Ability; Middle Aged; Pituitary Gland, Posterior; Vasopressins

Topics: Adult; Diabetes Insipidus; Diuresis; Fatty Liver; Female; Humans; Liver; Pregnancy; Pregnancy Complications; Vasopressins

Injection of a synthetic progesterone, medroxyprogesterone acetate (MPA or Depo-ProveraR), a widely used contraceptive, into Chinese hamsters (Cricetulus griseus) induced a profound polyuria with daily output of dilute urine equal to about 50% body weight of the hamster. However, relatively normal ability for renal urine concentration was demonstrated by administration of exogenous vasopressin. Body weight did not increase during onset of MPA-induced polyuria or during interval of vasopressin-induced oliguria, suggesting that primary polydipsia was not etiologic. Administration of this steroid to Chinese hamsters was nontoxic, although these polyuric animals were unusually sensitive to water deprivation. This polyuria was not observed when progesterone alone was injected into Chinese hamsters or when MPA was given to other related hamster species (Armenian, Syrian, Turkish or Djzungarian). The MPA-injected Chinese hamster represents a unique model of vasopressin sensitive diabetes insipidus induced by a steroid in a species-specific fashion.

Topics: Animals; Arginine Vasopressin; Cricetinae; Cricetulus; Diabetes Insipidus; Disease Models, Animal; Female; Kidney Concentrating Ability; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Polyuria; Sex Factors; Species Specificity; Vasopressins; Water Deprivation

Kappa opioids produce diuresis presumably through ADH. We investigated further the role of ADH in kappa-induced diuresis by utilizing the Brattleboro rat, a strain lacking endogenous ADH. Ethylketocyclazocine (EKC), a kappa opioid prototype, increased urine formation in Sprague-Dawley, but not in Brattleboro rats. Furthermore, EKC pretreatment abolished the antidiuretic response to ADH administered exogenously to Brattleboro rats. Our study suggests that, in addition to a fall in plasma ADH reported previously, kappa opioids have direct effects on the renal response to ADH.

Topics: Animals; Cyclazocine; Diabetes Insipidus; Diuresis; Ethylketocyclazocine; Rats; Rats, Brattleboro; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Vasopressins

Intravenous (iv) administration of gamma-melanocyte-stimulating hormone (gamma-MSH) produces central sympathetically mediated pressor and cardioaccelerator effects and increases the activity of hypothalamic vasopressinergic neurons. The autonomic actions are similar to infusion of vasopressin (Vp) into the hindbrain of 4th ventricle (Ven). To ascertain whether activation of the central Vp system is the proximate cause of the pressor effects of gamma-MSH, we investigated the effects of gamma-MSH in rats pre- and postblockade of central nervous system Vp receptors and in rats with a hereditary lack of vasopressin (Brattleboro strain). Central Vp receptor blockade significantly reduced (80%) the pressor effects of iv gamma-MSH. As a control, iv administration of the antagonist, while effective in blocking the pressor effect of iv Vp, had no effect on the gamma-MSH pressor response. When compared with their genetic controls (Long-Evans strain), Brattleboro rats also had greater than 80% reduction in their pressor response to iv gamma-MSH. The results indicate that circulating gamma-MSH activates the central Vp system to produce its sympathoexcitatory pressor effects.

Topics: Animals; Blood Pressure; Brain; Diabetes Insipidus; Heart Rate; Male; Melanocyte-Stimulating Hormones; Pressoreceptors; Rats; Rats, Brattleboro; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Cell Surface; Receptors, Vasopressin; Sympathetic Nervous System; Vasopressins

The development of an acute hemorrhagic shock in rats with hereditary diabetes insipidus (DI), lacking vasopressin, is very dramatic, compared to rats of the parent strain Long Evans (LE). After removal of 50% of the circulating blood for LE, and 30% for DI, the mortality for both LE and DI groups was 50%, the shock index being 0.049 and 0.028, respectively. Infusion of either vasopressin (107 mU/100 g) or naloxone (0.2 mg/100 g) in DI rats, prevented the progression of hemorrhagic shock into irreversible stage, and augmented survival up to 66% and 57%, respectively. The specific opioid antagonist naloxone exerted a therapeutic effect on rats with hemorrhagic shock by antagonism of opioid receptors, without influencing ACTH and aldosterone secretion in DI rats. This is another evidence for the role of beta-endorphin in the pathogenesis of hemorrhagic shock.

Topics: Acid-Base Equilibrium; Adrenocorticotropic Hormone; Aldosterone; Animals; Blood Pressure; Diabetes Insipidus; Heart Rate; Male; Naloxone; Rats; Rats, Brattleboro; Receptors, Opioid; Renin; Respiration; Shock, Hemorrhagic; Vasopressins

The effect of vasopressin (VP) on prostaglandin (PG) synthesis in the renal collecting tubule remains equivocal. To further address this issue, the present study determined the effects of chronic absence of VP on renal medullary collecting tubule PG synthesis. Prostaglandin E2 (PGE2) synthesis was measured in both inner and outer medullary slices and collecting tubules microdissected from the inner medulla (PCD) and outer medulla (MCT) of Brattleboro homozygous diabetes insipidus (DI) rats, which are genetically devoid of VP, and from Long Evans (LE) control rats. In vitro PGE2 synthesis was significantly lower in both inner medullary (delta - 56%; p less than 0.001) and outer medullary (delta - 56%; p less than 0.01) slices of DI rats compared to controls. Vasopressin tannate treatment (0.5 U/day for 5 days) increased urinary PG excretion, and increased in vitro PGE2 synthesis in both inner and outer medullary slices of DI rats to levels that did not differ from vehicle-treated LE controls. In contrast, PGE2 synthesis in both PCD and MCT of DI rats did not differ from LE controls when incubated either in an isotonic (300 mOsm) medium, or in an hypertonic (1000 mOsm) medium. These results suggest that PGE2 biosynthetic capacity of medullary collecting tubules in the DI rat is not dependent on VP, while depressed PGE2 synthesis in renal medullary slices of DI rats, suggests that the interstitial cell is the primary medullary site of PG synthesis which is modulated by VP.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Dinoprostone; Homozygote; In Vitro Techniques; Kidney Medulla; Kidney Tubules, Collecting; Male; Osmolar Concentration; Prostaglandins E; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Urine; Vasopressins

In order to investigate the possible role of oxytocin in osmoregulation and its response to stress, plasma immunoreactive oxytocin was measured during hypertonic saline infusion and insulin-induced hypoglycaemia in a group of normal subjects, four patients with idiopathic diabetes insipidus and one patient with DIDMOAD syndrome (the syndrome of diabetes insipidus, diabetes mellitus, optic atrophy and deafness). The results were compared with those of plasma immunoreactive vasopressin to the same stimuli. As expected, there was a rise in plasma vasopressin in the normal subjects to both tests: this was absent in the patients with diabetes insipidus. Plasma oxytocin did not rise during hypertonic saline infusion in either group of subjects. The response of oxytocin to insulin-induced hypoglycaemia (0.15 U/kg soluble insulin) in normal subjects was much more variable. One highly symptomatic volunteer showed a marked rise in oxytocin. Two subjects also showed a rise when retested with 0.19 U/kg soluble insulin. There was no response of oxytocin to a standard-dose insulin test in the patients with diabetes insipidus. The data suggest that, in man, oxytocin is not involved in osmoregulation but that it may be secreted in response to marked hypoglycaemia.

Topics: Adult; Blood Glucose; Diabetes Insipidus; Female; Humans; Insulin; Male; Middle Aged; Oxytocin; Pituitary Gland, Anterior; Saline Solution, Hypertonic; Sodium Chloride; Vasopressins; Wolfram Syndrome

A case of hypodipsic hypernatremia in a 16-month-old Japanese boy is reported. Partial antidiuretic hormone deficiency was present. Computed tomography of the brain revealed absence of septum lucidum. No ophthalmological abnormality could be found. He had hyposmia, which has not been reported previously in association with hypernatremia due to hypodipsia. Forced fluid administration and nasal 1-deamino-8-d-arginine vasopressin treatment could maintain serum electrolyte levels within normal ranges. However, episodes of hypernatremia could not be completely avoided while he was treated with 1-deamino-8-d-arginine vasopressin and ad libitum oral fluid.

Topics: Central Nervous System; Diabetes Insipidus; Humans; Hypernatremia; Infant; Male; Olfactory Pathways; Septum Pellucidum; Thirst; Vasopressins

Hypothalamic vasopressin synthesizing nuclei (paraventricular and supraoptic) send vasopressin-containing projections to a number of neural target areas thought to be involved in cardiovascular regulation. One area known to receive vasopressinergic projections from the paraventricular nucleus is the pontine nucleus locus coeruleus. To examine the possible functional participation of vasopressin in central cardiovascular regulation, we examined mean arterial pressure (millimeters of Hg) and heart rate (beats per min) responses to electrical stimulation of the locus coeruleus in conscious, unrestrained vasopressin-deficient Brattleboro rats homozygous for diabetes insipidus (DI rats) and long Evans (LE) rats. Rats received chronic arterial and venous catheters and bipolar stimulating electrodes 3-5 days before experiment. Stimulation of the locus coeruleus (100 microA, 10-40 Hz) produced frequency-dependent increases in mean arterial pressure and heart rate in LE and DI, but the responses were significantly less in the latter group. The deficiency in mean arterial pressure and heart rate responses to locus coeruleus stimulation in DI rats was found to be centrally mediated in that responses to peripherally administered phenylephrine were the same as those for LE rats. Ganglionic blockade significantly attenuated responses to locus coeruleus stimulation in LE rats but had little effect in DI rats. Pretreatment of DI rats with chronic intracerebroventricular infusion of vasopressin (osmotic minipump) at a dose that had no effect peripherally increased the mean arterial pressure and heart rate responses to locus coeruleus stimulation. Our results suggest that vasopressin acts in the region of the locus coeruleus to exert a central action on sympathetic outflow.

Topics: Animals; Blood Pressure; Cerebral Ventricles; Chlorisondamine; Diabetes Insipidus; Electric Stimulation; Heart Rate; Hemodynamics; Locus Coeruleus; Male; Phenylephrine; Rats; Rats, Brattleboro; Vasopressins

The etiology of diabetes insipidus (DI) was determined in 73 children evaluated from 1962 through 1983. Intracranial tumors produced DI in 34 children, but 27 of these 34 children developed DI only after excision of the tumor. Diabetes insipidus occurred in ten children with intracranial birth defects, eight with severe central nervous system infections, and six with histiocytosis. Six had other causes. No etiology was detected in nine. Division of the cases into two time periods (1962 through 1972 and 1973 through 1983) revealed a decrease in the frequency of idiopathic DI (26.7% to 8.6%), an increase in the frequency of intracranial birth defects (0% to 17.3%), and an increase in the frequency of severe central nervous system infections (0% to 13.8%). Significant changes in therapy for DI have occurred during these 22 years. Use of desmopressin acetate has facilitated treatment of this complex management problem.

Topics: Brain Neoplasms; Child; Child, Preschool; Diabetes Insipidus; Female; Humans; Infant; Male; Vasopressins

Fetal vasopressin neurons were grafted into adult Long-Evans rats with vasopressin deficiencies created by neural lobe ablation one week prior to implantation. Control animals and recipients with ectopic grafts still possessed significant deficits in fluid regulation 6 weeks following implantation. However, recipients with grafts fused to the host median eminence and containing magnocellular vasopressin neurons juxtaposed to the host portal vasculature showed restored peripheral vasopressin activity as measured by normal urine volumes and osmolalities. These findings suggest that structural integration of grafted neuroendocrine tissue with the appropriate target in the host brain is a necessary prerequisite for physiological activity.

Topics: Animals; Brain; Denervation; Diabetes Insipidus; Fetus; Homozygote; Immune Sera; Neurons; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Vasopressins

These experiments studied the behavior of an inbred strain of vasopressin-deficient rat, the Roman high avoidance rat homozygous for diabetes insipidus (RHA: di/di). The RHA: di/di rat has been bred to be congenic with the parent normal Roman high avoidance (RHA: +/+) strain, differing from it only by the gene(s) coding for diabetes insipidus. Therefore, the RHA: +/+ strain represents an improved model system with which to study the behavioral effects of vasopressin-deficiency, given recent findings suggesting that considerable behavioral variation exists within the Long-Evans derived Brattleboro strain of vasopressin-deficient rat. We examined the behavior of RHA: di/di and RHA: +/+ rats in the open field and on tests of approach-avoidance, spatial memory and passive avoidance. RHA: di/di rats showed retarded habituation of ambulation and elevated incidence of rearing, defecation, and ambulation in the central area of the open field, relative to RHA: +/+ rats. The RHA: di/di and RHA: +/+ rat did not differ on measures of adaptation to a novel straight runway and both groups increased latencies to enter the goal box of the runway following shock, indicating memory. RHA: di/di rats did exhibit substantial recovery of goal-approach following shock, whereas RHA: +/+ rats did not. Both groups were able to solve a delayed non-match to sample task to receive reward. RHA: di/di rats showed a slower acquisition of the contingency and significantly faster run times of choice trials of the paired run procedure. No differences were evident between groups in memory of passive avoidance. The results of these experiments suggest that hereditary deficiency of vasopressin may influence physiological processes which determine arousal or attentiveness. The effects of vasopressin deficiency on performance of memory-indicating tasks appears to be secondary to modulations in arousal.

Topics: Animals; Arousal; Avoidance Learning; Behavior, Animal; Brain; Diabetes Insipidus; Female; Habituation, Psychophysiologic; Homozygote; Male; Memory; Rats; Vasopressins

The possibility that metoclopramide (MCP), a potent stimulator of aldosterone secretion, might influence vasopressin secretion in man was studied. MCP (10 mg, iv) increased plasma vasopressin (mean +/- SD) from 1.3 +/- 0.1 to 2.4 +/- 0.1 pg/ml at 10 min and to 2.65 +/- 0.1 pg/ml at 20 min (P less than 0.01) in 10 recumbent normal subjects. No changes in plasma osmolality or peripheral hemodynamics, which might have accounted for the increase in vasopressin, were found. Sulpiride (100 mg iv), haloperidol (2 mg, iv), and domperidone (20 mg, iv), three chemically unrelated antidopaminergic agents, as well as TRH (200 micrograms, iv), failed to modify plasma vasopressin, thus suggesting that the MCP effect on vasopressin is not linked to its antidopaminergic and/or PRL-releasing properties. MCP also was effective in releasing vasopressin in 5 dehydrated subjects, in whom plasma vasopressin increased from 1.9 +/- 0.2 to 3.1 +/- 4 pg/ml (P less than 0.05), and in 5 subjects during steady state water diuresis, in whom free water excretion decreased from 9 to 1 ml/min (P less than 0.01) and plasma vasopressin increased from 0.3 +/- 0.1 to 1.2 +/- 0.2 pg/ml (P less than 0.05). No changes in either vasopressin secretion or free water excretion occurred in 4 patients with severe central diabetes insipidus. These results suggest that MCP stimulates the release of biologically active vasopressin in man.

Topics: Adult; Blood Pressure; Dehydration; Diabetes Insipidus; Diuresis; Female; Heart Rate; Humans; Male; Metoclopramide; Middle Aged; Osmolar Concentration; Vasopressins; Water

These experiments were designed to characterize the nature and extent of diabetes insipidus present in a new model of genetic vasopressin (VP) deficiency, the Roman high avoidance rat homozygous for diabetes insipidus (RHA: di/di strain). The new strain was developed from an initial cross between Long-Evans derived Brattleboro (LE:di/di) rats and normal Roman high avoidance (RHA: +/+) rats, and has been bred to be congenic with the parent RHA: +/+ strain. RHA: di/di rats exhibited polydipsia, excreted dilute urine, and exhibited elevated plasma osmolality. RHA: di/di rats shows a similar urinary response to dehydration as LE: di/di rats. VP was undetectable by radioimmunoassay in the serum, brain, and neurohypophysis of RHA: di/di rats. VP-neurophysin containing cells were not observed in the brains of RHA: di/di rats upon immunocytochemical analysis. Thus, the new RHA: di/di strain exhibits essentially the same profile of diabetes insipidus as the LE: di/di rat. The congenic relationship between RHA: di/di and RHA: +/+ rats makes the RHA: di/di rat a useful model under circumstances where genetic variables unrelated to VP deficiency may confound the interpretation of data.

Topics: Animals; Avoidance Learning; Brain; Brain Chemistry; Crosses, Genetic; Diabetes Insipidus; Disease Models, Animal; Female; Heterozygote; Homozygote; Male; Neurophysins; Rats; Rats, Mutant Strains; Tissue Distribution; Vasopressins

A case of transient vasopressin-resistant diabetes insipidus is reported, which developed during the seventh month of pregnancy and remitted postpartum. The patient was resistant to large doses of deamino-D-arginine vasopressin as well as to aqueous pitressin. She was treated with hydrochlorothiazide. Evidence that prostaglandins may play a role in this syndrome is discussed.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Resistance; Female; Humans; Hydrochlorothiazide; Osmolar Concentration; Pregnancy; Pregnancy Complications; Time Factors; Vasopressins

Topics: Diabetes Insipidus; Diuresis; Humans; Vasopressins

The adrenal gland of the Brattleboro rat contains AVP-like immunoassayable material in amounts equal to those of the normal Long Evans animal--6.180 ng/g fresh tissue in LE and 6.108 ng/g fresh tissue in the Brattleboro rats. After an activation of sympathetic NS and vasopressin secretion by hemorrhagic shock, the adrenal AVP-like material in LE increased by 54% and in Brattleboro rats--by 58%. After hemorrhagic shock plasma AVP in LE rats increased 3.5 fold, but in Brattleboro rats remained undetectable. The possible physiological role of adrenal AVP was discussed.

Topics: Adrenal Glands; Animals; Chromatography, Gel; Diabetes Insipidus; Male; Rats; Rats, Brattleboro; Shock, Hemorrhagic; Vasopressins

Sequence analysis of cDNA clones derived from hypothalamic mRNA of diabetes insipidus (Brattleboro) rats shows that the vasopressin gene transcript also includes the single base deletion demonstrated in the gene. This causes a frame-shift in the C terminus of the vasopressin precursor with a reading frame open through the 3' end of the mRNA including the poly(A) sequence. Antibodies raised against a synthetic tetradecapeptide (CP-14) corresponding to the frame-shifted C terminus identified a product of mol. wt approximately 26 000 in a reticulocyte lysate system programmed with Brattleboro hypothalamic mRNA. Immunohistochemical analysis indicated that a similar precursor is also present in vivo in neurones of the Brattleboro hypothalamus. Electrophoretic analysis of vasopressin mRNA from wild-type and mutant rat tissues revealed that (i) the hypothalamic mRNA from Brattleboro rats contains a longer stretch of poly(A) sequence than the wild-type strains; (ii) vasopressin mRNA is also present in the adrenal, ovary, testis and cerebellum, at very low levels; however, (iii) the extra-hypothalamic mRNA is considerably shorter than that in the hypothalamus because of a curtailed poly(A) sequence. Thus similar vasopressin gene transcripts are subject to a tissue-specific differential polyadenylation.

Topics: Amino Acid Sequence; Animals; Cell-Free System; Cloning, Molecular; Diabetes Insipidus; DNA; Genes; Hypothalamus; Mutation; Protein Biosynthesis; Rabbits; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reticulocytes; RNA, Messenger; Species Specificity; Vasopressins

The role of blood volume regulatory mechanisms located in the low pressure system in the control of urinary excretion was studied using hypobaric pressure breathing in normal and diabetes insipidus (Brattleboro strain with a congenital lack of vasopressin) rats. Rats were placed in an altitude simulator chamber for 4 h. A pump maintained pressure reduced to 701, 577 and 472 mbar simulating respectively altitude of 3,000, 4,500 and 6,000 m. In normal rats, hypobaric breathing induced an increase in urine flow, urinary urea and K+ excretion and urinary pH but did not significantly modify creatinine and Na+ excretion. In diabetes insipidus rats, hypobaric breathing produced oliguria and an decrease in urea, creatinine, Na+, K+, Cl- urinary excretions. Since acute hypobaric pressure breathing induced opposed effects in normal and Brattleboro rats, it is suggested that this kind of experimental procedure which increases intrathoracic blood volume elicits a diuretic response through an inhibition of vasopressin release. These experiments confirm the main role of vasopressin in the control of central blood volume.

Topics: Air Pressure; Animals; Atmospheric Pressure; Blood Volume; Chlorine; Diabetes Insipidus; Disease Models, Animal; Diuresis; Male; Natriuresis; Oliguria; Pituitary Gland, Posterior; Potassium; Rats; Rats, Inbred Strains; Urea; Vasopressins

We studied the effects of chronic replacement with arginine vasopressin (AVP) or 1-desamino-D-arginine vasopressin (DDAVP), as well as acute replacement with AVP or DDAVP, on the responsiveness of oxytocin (OT) neurons as indexed by plasma oxytocin-associated neurophysin concentration [( OT-RNP]) during acute salt loading in conscious, chronically catheterized homozygous Brattleboro (DI) rats. Salt loading was carried out on days 5 and 12 of AVP (3,000 ng/day) or DDAVP (50 ng/day) treatment or 60 min after intraperitoneal injection of 1 microgram AVP or 25 ng DDAVP. All vasopressin treatments did not significantly alter the basal [OT-RNP]. In response to infusion of 18% saline, there were corresponding significant increases in plasma osmolality (Posmol) and [OT-RNP] in all animals. The increases in [OT-RNP] in vasopressin-treated DI rats were markedly reduced compared with those observed earlier for untreated DI animals despite similar rises in Posmol. The slopes of the relationship between delta [OT-RNP] and delta Posmol were 9.0 and 9.8 fmol X ml-1 X mosmol-1 X kg for chronically AVP-treated DI rats, 8.9, and 8.8 fmol X ml-1 X mosmol-1 X kg for chronically DDAVP-treated DI animals, 10.7 fmol X ml-1 X mosmol-1 X kg for acutely AVP-treated DI rats, and 8.3 fmol X ml-1 X mosmol-1 X kg for acutely DDAVP-treated animals compared with that of 34.9 fmol X ml-1 X mosmol-1 X kg for untreated DI rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood; Deamino Arginine Vasopressin; Diabetes Insipidus; Male; Neurons; Neurophysins; Osmolar Concentration; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Saline Solution, Hypertonic; Sodium Chloride; Vasopressins

The feeding responses induced by systemic administration of 2-deoxy-D-glucose (2-DG) and paraventricular hypothalamic injection of norepinephrine were assessed in Brattleboro rats deficient in vasopressin (VP). Controlling for the non-specific complications of diabetes insipidus, it was found that Brattleboro rats have a deficient 2-DG-feeding response, but an essentially normal noradrenergic-feeding response. Specific carbohydrate appetite abnormalities were also demonstrated. It is argued that VP influences 2-DG feeding by mobilizing endogenous energy stores following its acute release from the hypothalamoneurohypophysial system. A new function is thus ascribed for VP and the neural lobe of the pituitary. It is suggested that VP plays a role in stress-induced feeding and in specific aspects of carbohydrate appetite. The potential relevancy of vasopressin perturbations to bulimia nervosa and to the Prader-Willi obesity syndrome is also discussed.

Topics: Animals; Circadian Rhythm; Deoxyglucose; Diabetes Insipidus; Feeding Behavior; Female; Glucose; Hypothalamo-Hypophyseal System; Hypothalamus, Anterior; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Vasopressins

The activity of prostaglandin (PG)E2-9-ketoreductase (9KR), an enzyme catalyzing the conversion of PGE2 to PGF2 alpha, was significantly increased in glomerular and cortical homogenates of diabetes insipidus (DI) rats, as compared to normal Long Evans (LE) rats, and did not change with ADH treatment. Medullary 9KR was similar in the three groups and papillary 9KR was increased, but not significantly, in both groups of DI rats. Km values for PGE2 and NADH were compared in the various compartments of the kidney. Levels of 9KR were not correlated with the PGE/PGF ratio in urine or supernatants. The synthesis of PGE2 and PGF2 alpha by isolated glomeruli was increased in DI rats. This was not reversed by ADH treatment, PGE2 synthesis increasing even further, especially in the presence of arachidonic acid. In contrast, medullary slices produced significantly less PGs in DI than in LE rats and returned to normal with ADH treatment. Papillary slices produced similar quantities of prostaglandins in all groups. The results do not support the concept that the alterations in PG synthesis observed in DI rat are related only to changes in 9KR activity, but do not exclude the possibility that the enzyme participates in the regulation of PG biosynthesis.

Topics: Animals; Diabetes Insipidus; Female; Hydroxyprostaglandin Dehydrogenases; Kidney; NAD; Prostaglandins; Rats; Rats, Brattleboro; Vasopressins

35S-labeled synthetic oligodeoxyribonucleotide probes were used to measure levels of vasopressin (VP) and oxytocin (OT) mRNAs in rat hypothalamus by quantitative in situ hybridization histochemistry (ISHH). VP and OT mRNA-containing cells were seen in the paraventricular (PVN) and supraoptic (SON) nuclei. VP mRNA was found to increase five-fold in the parvocellular region of the PVN after adrenalectomy while no changes occurred in magnocellular VP or OT mRNA levels. In the Brattleboro rat, VP mRNA levels were decreased and OT mRNA levels increased in the magnocellular regions. RNA species containing the VP introns were present at one fortieth of the level of processed VP mRNA in control rats. We also performed ISHH followed by immunohistochemistry on the same sections. We found that VP and its encoding mRNA were always located together as were OT-neurophysin and its encoding mRNA. In this study, we extend previous work by showing the characteristic distributions in the PVN and SON of VP and OT mRNA-containing cells and by measuring neuropeptide mRNA changes.

Topics: Animals; Diabetes Insipidus; Histocytochemistry; Hypothalamus; Male; Nucleic Acid Hybridization; Oxytocin; Rats; Rats, Brattleboro; Rats, Inbred Strains; RNA, Messenger; Vasopressins

Topics: Animals; Cephaloridine; Diabetes Insipidus; Male; Polyuria; Rats; Rats, Inbred Strains; Vasopressins

A 7-month-old Suffolk-cross ram was examined because of polydipsia and polyuria of 2 months" duration. Neurogenic diabetes insipidus was diagnosed on the basis of failure to concentrate urine of low specific gravity in response to water deprivation and a positive response to antidiuretic hormone administration. Post-mortem examination of the brain revealed degeneration in the cerebral peduncles, an absence of pituitary neural tissue and evidence suggesting external pressure as the cause.

Topics: Animals; Diabetes Insipidus; Male; Sheep; Sheep Diseases; Vasopressins

Topics: Administration, Intranasal; Adult; Anesthesia, Spinal; Diabetes Insipidus; Humans; Iatrogenic Disease; Meningitis; Urethra; Vasopressins

The possibility that sympathetic nervous system activity may be altered in Brattleboro rats with diabetes insipidus (DI) was studied using the norepinephrine (NE) turnover technique. Female DI and Long-Evans rats were used. NE turnover in peripheral organs was calculated by measuring the decline in tissue [NE] after inhibition of tyrosine hydroxylase with alpha-methyltyrosine. NE turnover was increased significantly in the kidney of DI rats but was not significantly altered in other peripheral organs examined (heart, duodenum, skeletal muscle). Both NE and epinephrine concentrations in the adrenal gland were significantly higher in the DI rats. Treatment of DI rats for 7 days with vasopressin tannate (Pitressin, 100 mU/100 g) or 1-deamino-[8-D-arginine] vasopressin (DDAVP, 250 ng X kg-1 X day-1) reversed the changes in renal NE turnover and also decreased the turnover in other tissues. The results of these studies suggest that, compared with Long-Evans rats, DI rats have a selective increase in NE turnover in the kidney and the potential to release more catecholamines from the adrenal glands. The apparently nonspecific effect of antidiuretic therapy on NE turnover in DI rats is probably mediated by the epithelial receptor for vasopressin, because both Pitressin and DDAVP produced similar results.

Topics: Adrenal Glands; Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Duodenum; Female; Heart Ventricles; Kidney; Muscles; Norepinephrine; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins; Water-Electrolyte Balance

The rat kidney and brain are major target organs for vasopressin (VP). A procedure was developed for immunocytochemical staining of VP and its binding sites in the kidney. This procedure involved preincubation of kidney sections with the ligand, followed by immunocytochemical detection of VP. The staining in renal tubules from Wistar rats was enhanced by preincubation of tissue sections with increasing concentrations of VP (6-6000 nmol/l). Staining was present in the epithelium of distal convolutions and collecting ducts (medullary and cortical portions) and more pronounced in the apical zone of the tubular epithelium. With high concentrations of VP in the preincubation, staining was also obtained in the thick ascending limb of the loop of Henle. There was no staining under any circumstances in proximal tubules. In the kidney of the Brattleboro rat homozygous for hypothalamic diabetes insipidus (DI) which congenitally lacks VP but responds to the peptide, exactly the same staining pattern was observed after preincubation with VP, but the maximal staining was less intense. The VP binding to the DI rat kidney, after 2 weeks treatment with VP (using Accurel implants), reached levels seen in the Wistar kidney after in-vitro preincubation with high doses of VP.

Topics: Animals; Arginine Vasopressin; Binding Sites; Diabetes Insipidus; Immunoenzyme Techniques; Kidney; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Staining and Labeling; Vasopressins

Topics: Animals; Biological Transport; Cyclic AMP; Diabetes Insipidus; Humans; In Vitro Techniques; Kidney; Kidney Tubules, Collecting; Lithium; Microvilli; Vasopressins

Urinary adenosine 3',5'-monophosphate (cAMP) excretion before and after administration of aqueous vasopressin (pitressin) and 1-deamino-8-D-arginine vasopressin (DDAVP) was measured in congenital nephrogenic and in vasopressin sensitive diabetes insipidus (VS-DI). Excretion of cAMP into the urine increased markedly in response to pitressin (676%) and to DDAVP (252%) in VS-DI. Nephrogenic diabetes insipidus (N-DI) could be divided into two categories (type 1 and type 2) in respect to urinary cAMP responsiveness. In type 1, cAMP excretion showed no definite change after stimulation with pitressin (102%) or DDAVP (127%). On the other hand, urinary excretion of cAMP was significantly elevated in response to DDAVP in familial cases of N-DI type 2 (1269%) without producing any concentrating effect on the urine. Two different defects are considered to be involved in the pathogenesis of N-DI.

Topics: Adolescent; Adult; Child; Child, Preschool; Cyclic AMP; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Osmolar Concentration; Urination; Vasopressins

The medullary thick ascending limb (MAL), but not the medullary collecting tubule (MCT), has been shown to have an impaired adenylate cyclase (AC) responsiveness to ADH and a selective hypoplasia in Brattleboro diabetes insipidus (DI) rats. Since chronic ADH administration has been found to increase epithelium volume and basolateral membrane surface area in MAL but not in MCT, we investigated whether chronic ADH infusion would affect the hormone-sensitive AC and the Na-K-ATPase activity--two markers of the basolateral membrane--in single micro-dissected portions of thick ascending limb and collecting tubule in DI rats. Results indicate that 1. in MAL of ADH-treated rats, AC responses to in vitro AVP and glucagon and Na-K-ATPase activity increased to the same extent as did epithelium volume (60-80%); 2. changes in the other segments were independent of any morphological alteration. In the cortical thick ascending limb, AVP and glucagon-sensitive AC decreased by 30-40% whereas Na-K-ATPase activity did not change. In the collecting tubule, AC response to in vitro AVP was not altered by ADH-treatment but glucagon-sensitive AC dropped by 50% and Na-K-ATPase activity doubled, independently of any variation in plasma aldosterone and glucagon levels. These results show that, in the MAL, the ADH-induced variations in enzyme activity are a reflection of the enlargement of the basolateral membrane surface area. Further studies are needed to clarify the origin of enzymatic alterations in the other segments.

Topics: Adenosine Triphosphatases; Adenylyl Cyclases; Animals; Diabetes Insipidus; Kidney Tubules, Collecting; Male; Nephrons; Rats; Rats, Brattleboro; Sodium-Potassium-Exchanging ATPase; Time Factors; Vasopressins

Topics: Aged; Diabetes Insipidus; Female; Humans; Hypernatremia; Osmolar Concentration; Thirst; Vasopressins; Water-Electrolyte Balance

A sixth case in the world literature is reported of a 59-year-old male with diabetes insipidus (DI) associated with chronic myelogenous leukemia (CML). The patient is unique in that his CML was diagnosed 10 years before he presented with vasopressin-responsive DI. Radiation to the central nervous system failed to reduce the daily requirement of his need for vasopressin.

Topics: Diabetes Insipidus; Humans; Leukemia, Myeloid; Male; Middle Aged; Vasopressins

In order to assess the relative roles played by potassium (K) and the antidiuretic hormone (ADH) on the renal production of prostaglandins (PG) E2 and F2 alpha, the 24 hour urinary excretion of these substances was measured in Brattleboro rats (devoid of ADH) and in control Long Evans heterozygote rats. Rats of each strain received either a normal K intake or a K load for 8 days. Urinary PGE2 and PGF2 alpha were measured by radioimmunoassay in three consecutive 24 h urine collections obtained after the above periods. K loading induced an increase in PGF2 alpha (p less than 0.01), PGE2 showing a non significant trend to decrease. The E/F ratio was decreased in K loaded animals. The changes were qualitatively similar in presence or absence of ADH, but animals with diabetes insipidus had lower levels of PGs than control animals. The results suggest the possibility that K loading induces an increase in the activity of the renal enzyme PGE2-9-ketoreductase. The resulting increase in PGF2 alpha could play a role in K excretion and this response is probably independent of ADH.

Topics: Animals; Diabetes Insipidus; Dinoprost; Dinoprostone; Female; Hydroxyprostaglandin Dehydrogenases; Kidney; Potassium; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins; Water-Electrolyte Balance

Previously it was found that grafts of supraoptic plus paraventricular areas from 19-day-old foetal normal rats survived in the third ventricle of the brain of 4- to 6-day-old, vasopressin-deficient Brattleboro pups, but could not alleviate their polyuria. In the present series, factors important in graft development were analysed. Again using day-19 fetuses as donors, anterohypothalamus grafts as well as grafts placed near a crushed median eminence survived relatively poorly, but showed the presence of vasopressin neurons immunocytochemically one month post-grafting. Homotopic grafting in the supraoptic nucleus, however, even failed to show surviving vasopressin neurons. Graft survival was improved by the use of donor tissue of fetuses younger than day 19. Parvocellular vasopressin cells were frequently seen, organized into clusters resembling the normal suprachiasmatic nucleus. However, magnocellular neurons, as normally seen in supraoptic and paraventricular nuclei, only survived grafting when taken between days 11 and 15 of fetal age. It was concluded that only immature vasopressin neurons survived grafting under the condition employed. Magnocellular neurons had a limited fiber outgrowth into the host brain and median eminence. Most large neurons only stained with non-specific neurophysin antiserum, not with specific vasopressin-associated neurophysin antiserum. Thin fibers of the parvocellular vasopressin neurons provided only occasional and sparse innervation of the host median eminence and lateral septum (one case), but several examples of massive fiber bundles running dorsally from graft into host brain were observed. These fibers terminated in the thalamic periventricular area, a nucleus that is normally innervated by the vasopressin neurons of the suprachiasmatic nucleus. The failure of the grafts to provide adequate vasopressinergic innervation of the host median eminence probably explains why none of the nearly 200 Brattleboro neonates operated upon showed any sign of relief of their diabetes insipidus. It suggests, however, that the present procedures might be useful in restoring central vasopressinergic functions in the developing Brattleboro rat.

Topics: Aging; Animals; Animals, Newborn; Diabetes Insipidus; Fetus; Graft Survival; Hypothalamus, Anterior; Immunoenzyme Techniques; Median Eminence; Nerve Crush; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Rats, Inbred Strains; Supraoptic Nucleus; Vasopressins

Polyuria subsequent to pituitary surgery was studied in 64 cases. Most cases of postoperative polyuria were due to diabetes insipidus. These cases showed a triphasic pattern in daily urinary volume. Observation of hourly urinary volume in polyuria revealed four diurnal patterns of urinary excretion: rhythmic, continuous, transient, and unspecific. Clinical observation of diurnal patterns has an advantage, in terms of simplicity of procedure, in immediately determining the nature of the polyuria, prognosticating diabetes insipidus, and eliminating inappropriate procedures in treatment. Indomethacin suppository is considered to be a favorable agent in reducing polyuria without disturbing the diurnal pattern in diabetes insipidus.

Topics: Adenoma; Adolescent; Adult; Aged; Circadian Rhythm; Diabetes Insipidus; Female; Humans; Indomethacin; Male; Middle Aged; Pituitary Diseases; Pituitary Neoplasms; Polyuria; Postoperative Complications; Sodium; Vasopressins

Topics: Child; Diabetes Insipidus; Humans; Osmolar Concentration; Vasopressins; Water-Electrolyte Imbalance

The interaction between chlorpromazine (CPZ) and lithium on renal concentrating ability was studied in rats fed a Li-containing diet for 8 weeks (plasma-Li 0.6-0.7 mmol/l). CPZ (15 mg/kg daily orally) reduced the polydipsia and increased the ability to concentrate the urine upon water deprivation in rats treated with lithium. CPZ also reduced systolic blood pressure, but had no effect on the glomerular filtration rate or plasma levels of arginine vasopressin (AVP) in hydrated rats treated with lithium. However, CPZ prevented the rise in plasma AVP levels observed in lithium-polyuric rats in response to dehydration. During anaesthesia CPZ partially restored the impaired anti-diuretic response to exogenous AVP in rats treated with lithium. CPZ had no influence on plasma-Li levels in rats treated with lithium. It is suggested that CPZ by unknown mechanisms interferes with the effects of lithium on the water permeability response to AVP.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Chlorpromazine; Dehydration; Diabetes Insipidus; Female; Inulin; Lithium; Male; Osmolar Concentration; Rats; Rats, Inbred Strains; Vasopressins

Brattleboro rats homozygous for hypothalamic diabetes insipidus (DI rats) were anaesthetized with urethane. Extracellular recordings were made from antidromically identified neurones of the supraoptic nucleus. About half (77 out of 153) of the neurones recorded in DI rats showed phasic patterns of discharge activity similar to those which are characteristic of vasopressin-secreting neurones in normal rats during hyperosmotic stimulation. Significantly fewer neurones showed phasic activity in DI rats which had been pretreated with vasopressin tannate at a dose which significantly reduced urine volume, water intake and plasma osmolality. Acute systemic hyperosmotic stimulation, induced by an i.p. injection of 1 ml 1.5 M-NaCl, increased the discharge rate of each of 14 neurones from DI rats by 1-5 spikes/s. Hypo-osmotic stimulation, induced by an intragastric injection of 10 ml tap water, reduced the discharge rate of each of four neurones from DI rats by 50% or more. We conclude that supraoptic neurones in DI rats respond normally to acute systemic osmotic stimuli despite the total absence of vasopressin in these rats and despite their chronically disturbed water balance. This implies that the osmoreceptor mechanism which drives the supraoptic nucleus does not adapt substantially during prolonged disturbance of water balance and functions outside the normal physiological range of plasma osmolality, and that the reported alteration of noradrenergic innervation of the neurones in DI rats does not affect their osmotic responsiveness.

Topics: Action Potentials; Animals; Diabetes Insipidus; Neurons; Osmotic Pressure; Rats; Rats, Brattleboro; Supraoptic Nucleus; Vasopressins

Diabetes insipidus was encountered in a 58-year-old woman after injury in an closed space fire. Carboxyhemoglobin measured 26% after 30 minutes of assisted ventilation with an FIO2 of 1.0. The failure of antidiuretic hormone was a sign of a diffuse cerebral insult caused by carbon monoxide poisoning. The hormonal deficit was easily corrected by exogenous vasopressin. Mortality was related to the cerebral lesion.

Topics: Burns; Burns, Inhalation; Carbon Monoxide Poisoning; Diabetes Insipidus; Female; Humans; Middle Aged; Prognosis; Vasopressins

The effect of naloxone (0.6 mg; 1.2 mg; 2.4 mg X kg-1) were compared in normal Long Evans (N) and Brattleboro (D.I.) conscious rats. Naloxone did not change the values of drinking, diuresis, food intake, blood pressure, Na+ and K+ urinary excretion measured during 24 hours. During the two hours following drug injection, naloxone (1.2 and 2.4 mg X kg-1) reduced diuresis in normal as well as in D.I. rats. Water drinking was only modified in D.I. rats: this effect was shown to be a consequence of antidiuresis. These results suggest that the antidiuretic properties of naloxone are independent of vasopressin secretion. They do not support in a role of opiate receptors on vasopressin secretion in normal hydrated animals.

Topics: Animals; Body Water; Diabetes Insipidus; Diuresis; Drinking; Eating; Naloxone; Rats; Rats, Inbred Strains; Vasopressins

A case of delayed onset of diabetes insipidus (DI), which developed 27 days after a closed head injury, is reported. The patient sustained only a minor neurological deficit and, except for antidiuretic hormone (ADH) insufficiency, hypothalamic function was intact. This selective damage of posterior pituitary function was total and permanent. Ischemia due to vascular injury may be the most likely etiology. Once the diagnosis of delayed posttraumatic DI is confirmed, the treatment of choice is DDAVP (desmopressin acetate). In contradistinction to DI immediately following minor head injury, most patients with a delayed onset of DI after trauma have permanent ADH deficiency.

Topics: Adolescent; Brain Injuries; Diabetes Insipidus; Humans; Male; Vasopressins

Experiments were carried out to investigate whether vasopressin is involved in stress-induced analgesia. Intraperitoneal injection of hypertonic saline caused a significant and dose-related increase in the latency to the tail-flick response of the rat to noxious heat and was used as a stimulus for stress-induced analgesia. Neither the pituitary nor opioid peptides appeared to be involved, since the response occurred in hypophysectomized rats and was not reduced by the opiate antagonist naloxone. Furthermore hypertonic-saline analgesia was clearly potentiated in hypophysectomized rats in comparison to sham-operated controls. Hypertonic-saline analgesia was also observed in vasopressin-deficient (homozygous Brattleboro) rats similar in both magnitude and duration to that in normal rats of the same strain (Long Evans). It was concluded that vasopressin was not involved in stress-induced analgesia evoked by hypertonic saline.

Topics: Animals; Diabetes Insipidus; Homozygote; Male; Pain; Rats; Rats, Brattleboro; Saline Solution, Hypertonic; Sodium Chloride; Stress, Physiological; Vasopressins

Topics: Administration, Intranasal; Adult; Diabetes Insipidus; Female; Histiocytosis, Langerhans-Cell; Humans; Pregnancy; Pregnancy in Diabetics; Radiotherapy; Vasopressins

Anomalies in hormonal and neurotransmitter status during early stages of brain development, can lead to lifespan alterations in the functioning of central systems. The neuropeptide vasopressin is nowadays recognized as a putative neurotransmitter, after years of study on its neurosecretory hormonal aspect in water metabolism. Since vasopressin is moreover present early in the brain, and has various mitogenic, metabolic and physiological actions, one might expect vasopressin to be of importance for normal brain development as well. Indeed, the absence of brain vasopressin in the Brattleboro mutant rat coincides with impaired brain development, and some physiological and behavioral defects of these rats are not adjusted by treatment with vasopressin. Regionally the cerebellum seems to be the most affected brain area, both morphologically and biochemically. Only when vasopressin supplementation was done prenatally, this disturbed growth could be restored, which suggests an early role for vasopressin in neurogenesis. Enhanced levels of vasopressin during the perinatal period on the other hand, have been shown to affect permanently the 'setting' of peripheral vasopressin functions in cardiovascular and renal regulatory systems. It is not excluded as yet that after such treatments central organization of vasopressin systems is not impaired as well.

Topics: Aging; Animals; Brain; Brain Chemistry; Crosses, Genetic; Diabetes Insipidus; DNA; Female; Genotype; Heterozygote; Homozygote; Male; Organ Specificity; Rats; Rats, Brattleboro; Vasopressins

Susceptibility to ulceration induced by restraint, restraint plus intermittent shock, and activity stress was studied in 6 week and 18 week old Brattleboro and Long-Evans rats. Older animals developed more glandular ulcers than younger animals with Brattleboro rats having significantly greater ulceration than Long-Evans rats in both conditions. With activity stress, younger subjects developed significantly more glandular ulcers than older subjects; whereas, older subjects developed significantly more nonglandular ulcers than younger subjects. In both instances, the ulceration was significantly greater in Brattleboro rats than in Long-Evans rats. There were significantly high correlations among running behavior, survival time, and the development of glandular ulcers in younger animals exposed to activity stress. The presence of vasopressin, as well as the age of the subject and the nature of the stress, influences the type and degree of stomach pathology induced.

Topics: Aging; Animals; Diabetes Insipidus; Electroshock; Male; Motor Activity; Rats; Rats, Brattleboro; Rats, Inbred Strains; Restraint, Physical; Species Specificity; Stomach Ulcer; Stress, Psychological; Vasopressins

Observation of open field behavior of vasopressin-deficient (DI) and normal Long-Evans rats indicated elevated levels of open field activity for the DI rats. Exposure to an acoustic stressor resulted in decreased activity in both groups of animals but with a lesser effect on the DI rat. Handling prior to experimentation diminished the differences between DI and normal rats. Although both groups displayed an equivalent rise in plasma corticosterone in response to the open field, the addition of the acoustic stressor resulted in greater elevation of corticosterone in the normal animals. The behavioral and hormonal data suggest that the DI rat exhibits decreased emotional reactivity. Measurement of brain neurotransmitter levels revealed higher concentrations of serotonin, norepinephrine and dopamine in the limbic regions of the DI rat. These alterations may underlie the behavior reflecting decreased emotionality of the DI rat. In turn, the altered emotional state may be the basis for alteration in performance on learning/memory tasks of these animals. Thus, vasopressin effects on the retrieval and/or consolidation of information may not be direct but rather through its ability to influence the emotional state of the animal.

Topics: Acoustic Stimulation; Animals; Crosses, Genetic; Diabetes Insipidus; Emotions; Exploratory Behavior; Female; Male; Motor Activity; Rats; Rats, Brattleboro; Species Specificity; Stress, Psychological; Vasopressins

Topics: Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Polyuria; Syndrome; Thirst; Vasopressins

Topics: Brain Diseases; Calcinosis; Cerebral Cortex; Child, Preschool; Diabetes Insipidus; Humans; Kidney; Male; Tomography, X-Ray Computed; Vasopressins

A morphometric study was undertaken to quantitate the morphologic changes induced by ADH availability in the rat kidney. Homozygous Brattleboro rats with hereditary diabetes insipidus (DI) (no ADH) were compared to heterozygous Brattleboro control rats (HZ) and to DI rats after 5 to 6 weeks of continuous ADH infusion by implantable Alzet osmotic minipumps (TDI). ADH resulted in a 37% increase in mass of kidney per unit body wt. All kidney zones and all nephron segments were not increased uniformly. The inner stripe was enlarged more than other renal zones. It represented 15.5 +/- 0.7% of the total kidney height along the cortico-papillary axis in DI and 22.2 +/- 1.5% in TDI (P less than 0.025). The volume of the inner stripe in DI and TDI amounted to 10.9 +/- 0.9 and 18.0 +/- 1.0% of the total kidney volume, respectively (P less than 0.001). Selective increases in tubular diameter and cell height, due mostly to an hypertrophy of pre-existing cells, were observed in the earliest part of the thick ascending limbs (TAL) in the inner stripe, resulting in a twofold increase in epithelial volume per unit tubular length (P less than 0.001). Volume density of mitochondria and surface density of basolateral membranes were unchanged but, due to the increase in cell volume and inner stripe thickness, the amount of mitochondria and the surface area of basolateral membrane in the TAL were more than tripled in the inner stripe of treated rats. These changes provide a much greater salt transport capacity in the TAL of treated rats. They probably represent an adaptation of the early TAL to an enhanced sodium chloride transport in response to a direct ADH stimulation and/or to an increased salt delivery to this segment in the concentrating kidney.

Topics: Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Heterozygote; Kidney Concentrating Ability; Kidney Medulla; Loop of Henle; Male; Rats; Rats, Brattleboro; Vasopressins

Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) received daily subcutaneous injections of vasopressin in the form of Pitressin tannate (0.5 IU/24 hr). They were initially deprived of food and then trained to work for food reward in a Skinner box to a fixed ratio of ten presses for each pellet received. Once this schedule had been learned the rats were given a discrimination task daily for seven days. The performances of these BDI rats were compared with those of rats of the parent Long Evans (LE) strain receiving daily subcutaneous injections of vehicle (arachis oil). Comparisons were also made between these two groups of treated animals and untreated BDI and LE rats studied under similar conditions. In the initial learning trial, both control and Pitressin-treated BDI rats performed significantly better, and manifested less fear initially, than the control or vehicle-injected LE rats when first placed in the Skinner box. Once the initial task had been learned there was no marked difference in the discrimination learning between control or treated BDI and LE animals. These results support the view that vasopressin is not directly involved in all types of learning behaviour, particularly those involving positively reinforced operant conditioning.

Topics: Animals; Conditioning, Operant; Diabetes Insipidus; Drinking; Learning; Male; Rats; Rats, Brattleboro; Reinforcement, Psychology; Vasopressins

Topics: Antibody Specificity; Autoantibodies; Autoimmune Diseases; Diabetes Insipidus; Humans; Hypothalamus; Vasopressins

Topics: Adolescent; Adult; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Male; Polyuria; Pregnancy; Vasopressins

The coexistence of diabetes insipidus and pregnancy is uncommon and can be associated with worsening of the diabetes insipidus. We report a patient who developed a transient nephrogenic diabetes insipidus associated with a pregnancy complicated by preeclampsia. The diabetes insipidus resolved spontaneously within several days after delivery.

Topics: Adult; Diabetes Insipidus; Female; Humans; Kidney Concentrating Ability; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Vasopressins

Topics: Adolescent; Adult; Blood Pressure; Brain Injuries; Diabetes Insipidus; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Vascular Resistance; Vasopressins

We have previously described an increase of cytochrome oxidase (COX) activity in discrete hypothalamic nuclei of the Brattleboro rat (BR). The present experiments were done to investigate whether this increase in COX activity could be eliminated by administration of exogenous arginine vasopressin (AVP). Continuous infusion of AVP to BR for 7 days corrected the polyuria and the urine hypoosmolality, as expected, and it also eliminated the COX hyperactivity in the paraventricular nucleus and nucleus circularis of the BR hypothalamus. These results suggest that the hyperactivity of these nuclei in the BR is directly related to their inability to produce AVP.

Topics: Animals; Diabetes Insipidus; Electron Transport Complex IV; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Child; Cyclic AMP; Diabetes Insipidus; Humans; Vasopressins

Topics: Administration, Intranasal; Adult; Carbamazepine; Chlorpropamide; Chronic Disease; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drug Evaluation; Humans; Pituitary Hormones, Posterior; Vasopressins

Topics: Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Eruptions; Female; Humans; Urticaria; Vasopressins

Topics: Adenylyl Cyclases; Adult; Aged; Cyclic AMP; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Infant; Male; Vasopressins; Water Deprivation

Topics: Adolescent; Adult; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Hypertonic Solutions; Male; Osmolar Concentration; Polyuria; Sodium Chloride; Vasopressins; Water Deprivation

Topics: Diabetes Insipidus; Diagnosis, Differential; Humans; Vasopressins

Topics: Aged; Arginine Vasopressin; Calcinosis; Diabetes Insipidus; Female; Humans; Injections, Subcutaneous; Skin Diseases; Vasopressins

A large Canadian kindred of Irish extraction extending from Quebec to British Columbia with autosomal dominant diabetes insipidus responsive to exogenous antidiuretic hormone (ADH) is described. Out of 121 individuals 34 have been identified as affected in seven generations. The disorder is characterized by variability in age at onset and in severity, and by apparently spontaneous abatement in old age. The affected subjects do not appear to manifest hypertension or its sequelae. In three individuals tested the plasma ADH level was very low in spite of adequate osmotic stimulation. However, the level rose in two of them when they were given furosemide, which suggests an osmoreceptor defect and a normal ADH response to volume change.

Topics: Adult; Arginine Vasopressin; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Osmolar Concentration; Pedigree; Vasopressins

The effect of antidiuretic hormone on urinary electrolyte excretion was investigated by clearance techniques in conscious rats in metabolic cages. Brattleboro rats with hereditary diabetes insipidus (DI) (no ADH) were studied in the absence of exogenous ADH (control group = C, n = 4), and after several weeks of continuous dDAVP infusion (period A) followed by discontinuation of dDAVP (period B) (experimental group = E, n = 6). dDAVP, a non-pressor antidiuretic analogue to ADH, induced 1) a high urine concentration (2,645 +/- 44 (SEM) in group E vs 131 +/- 6 mosmol/kg H2O in group C), P less than 0.001; 2) no significant change in plasma osmolality (288 +/- 2 vs 297 +/- mosmol/kg H2O respectively) and in plasma concentration of major electrolytes, Na, K, Cl, Mg, and Ca; 3) a large decrease in urinary excretion of calcium and magnesium and no change in other electrolyte or total osmolar excretion. Fractional excretions in rats of groups C and E during period A were, respectively, for Na: 0.59 +/- 0.03 (SEM) and 0.51 +/- 0.33% (NS), for Ca: 2.92 +/- 0.62 and 0.34 +/- 0.05% (P less than 0.001) and for Mg: 7.75 +/- 0.83 and 1.38 +/- 0.28% (P less than 0.001). After treatment discontinuation, plasma osmolality in group E rose to 304 +/- 2 mosmol/kg H2O (P less than 0.01 compared to period A) with slight increases in plasma Na and Cl concentrations. Urine osmolality fell below, and urine flow rate rose above values observed in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Absorption; Animals; Behavior, Animal; Calcium; Consciousness; Diabetes Insipidus; Female; Hypothalamic Diseases; Kidney Tubules; Magnesium; Male; Rats; Rats, Brattleboro; Rats, Mutant Strains; Stimulation, Chemical; Vasopressins

The vasopressin gene from normal and diabetes insipidus (Brattleboro) rats has been isolated and sequenced. Except for a single deletion of a G residue in region coding for the neurophysin carrier protein the approximately 2300 nucleotides of both genes are identical. Blot analysis of hypothalamic RNA as well as transfection and microinjection experiments indicate that the mutant gene is correctly transcribed and spliced, however the resulting mRNA is not efficiently translated.

Topics: Animals; Base Sequence; Diabetes Insipidus; DNA; Genes; Mutation; Protein Biosynthesis; Rats; Rats, Brattleboro; RNA, Messenger; Transcription, Genetic; Vasopressins

Diabetes insipidus (DI) developed in 14 of 16 children who satisfied criteria for brain death. The occurrence of DI after an hypoxic/ischemic insult may represent midbrain death and seems to be a clinically useful sign in the diagnosis of brain death in children. In two patients, DI resolved spontaneously; these patients and children without DI may have had small areas of residual cerebral blood flow and brain function. The onset or cessation of DI was temporally associated with the use of dopamine in three patients.

Topics: Adolescent; Brain Death; Brain Injuries; Child; Child, Preschool; Diabetes Insipidus; Humans; Infant; Vasopressins

Topics: Diabetes Insipidus; Diabetes Mellitus; Diagnosis, Differential; Female; Humans; Male; Vasopressins

To study the relationship between vasopressin and the renal kallikrein-kinin system we measured the rate of excretion of kinins into the urine of anesthetized rats during conditions of increased and decreased vasopressin level. The excretion of immunoreactive kinins in Brattleboro rats with hereditary diabetes insipidus (DI) (24 +/- 3 pg min-1 kg-1) was lower than in the control Long Evans (LE) rats (182 +/- 22 pg min-1 kg-1; P less than 0.05). The DI rats also exhibited negligible urinary excretion of immunoreactive vasopressin, reduced urine osmolality, and increased urine flow and kininogenase excretion. In LE rats, volume expansion by infusion of 0.45% NaCl-2.5% dextrose to lower vasopressin secretion reduced (P less than 0.05) kinin excretion, vasopressin excretion, and urine osmolality to 41, 26, and 15% of their respective control values, while increasing (P less than 0.05) urine flow and kininogenase excretion. On the other hand, the infusion of 5% NaCl, which promotes vasopressin secretion, increased (P less than 0.05) the urinary excretion of kinins and vasopressin to 165 and 396% of control, while increasing (P less than 0.05) urine flow and kininogenase excretion. Infusion of vasopressin (1.2 mU/h, intravenous) enhanced (P less than 0.05) kinin excretion by two to threefold in DI rats and in LE rats during volume expansion with 0.45% NaCl-2.5% dextrose, while decreasing urine flow and increasing urine osmolality. This study demonstrates that the urinary excretion of immunoreactive kinins varies in relation to the urinary level of vasopressin, irrespective of urine volume and osmolality and of the urinary excretions of sodium and kininogenase. The study suggests a role for vasopressin in promoting the activity of the renal kallikrein-kinin system in the rat.

Topics: Animals; Diabetes Insipidus; Diuresis; Glucose; Kallikreins; Kinins; Male; Osmolar Concentration; Rats; Rats, Brattleboro; Saline Solution, Hypertonic; Sodium Chloride; Urine; Vasopressins

To define the importance of renal prostaglandins in nephrogenic diabetes insipidus (NDI), diuresis and the urinary excretion of PGE2 and PGF2 alpha were studied in a patient with NDI before and during inhibition of endogenous prostaglandin synthesis with either indomethacin (IND) or acetyl-salicylic acid (ASA). The excretion rates of PGE2 and PGF2 alpha were in the low normal range for the patient's age group, remained unchanged during 6 h of fluid deprivation and were suppressed by IND (150 mg/day), ASA (3 g/day), and by the combination of IND and hydrochlorothiazide (HCT, 50 mg/day). However, whereas IND, HCT, and the combination of IND and HCT reduced diuresis ASA did not. Free water clearance as determined during fluid deprivation remained positive during each phase of therapy. These data fail to demonstrate a direct effect of endogenous ADH on renal prostaglandin synthesis in NDI. The ineffectiveness of ASA to reduce diuresis indicates that indomethacin affects diuresis in NDI by a mechanism other than inhibition of cyclooxygenase.

Topics: Adolescent; Aspirin; Diabetes Insipidus; Diabetic Nephropathies; Dinoprost; Dinoprostone; Diuresis; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Indomethacin; Male; Osmolar Concentration; Prostaglandins E; Prostaglandins F; Sodium; Thirst; Vasopressins

Topics: Adolescent; Adult; Arginine Vasopressin; Diabetes Insipidus; Drug Tolerance; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Vasopressins

To characterize the influence of extracellular volume status on vasopressin pharmacokinetics, eleven young (aged 19-31 yr) and four old (aged 62-80 yr) subjects received bolus injections of 1 mU/kg Pitressin or synthetic arginine vasopressin following 6 days of sodium depletion (10 meq Na/day) or sodium loading (250 meq Na/day). In six young subjects the rapid decline in plasma vasopressin (pAVP) following the initial peak was interrupted by a second peak 5-30 pg/ml in magnitude 7.5-20 min after injection. In four of these subjects the second peak was larger following sodium depletion as compared with sodium loading. In the elderly a small (4 pg/ml) second peak was present in one sodium-depleted subject. Of five sodium-depleted subjects with central diabetes insipidus, none showed a secondary rise in pAVP. These results indicate that exogenous vasopressin may stimulate the release of endogenous AVP, an effect that appears to be enhanced by sodium depletion and is virtually absent in the elderly. There was no effect of age, volume status, or diabetes insipidus on AVP pharmacokinetics.

Topics: Adult; Age Factors; Aged; Arginine Vasopressin; Diabetes Insipidus; Extracellular Space; Female; Humans; Kinetics; Male; Middle Aged; Sodium; Stimulation, Chemical; Vasopressins; Water-Electrolyte Balance

Despite the absence of vasopressin, Brattleboro homozygous (DI) rats concentrate their urine to hypertonic levels when deprived of drinking water. Ultimately this rise in urine osmolality must follow from increased osmolality of the corticopapillary gradient and/or increased osmotic equilibration across the collecting ducts. In this study we examined the concentrations and contents of total solute, urea, and nonurea solute in tissue from cortex to papillary tip of DI rats before and after dehydration for 12, 24, and 48 h. The greatest increase in osmolality occurred during the first 12 h; both urea and nonurea solute concentrations increased, but urea preferentially. From 12 to 48 h there were only small further increases in these concentrations, largely as a result of decreased tissue water content. Osmotic equilibration (reflected by urine/papillary tip osmolality) increased dramatically during dehydration, presumably because of decreased flow rate, attaining full equilibration by 48 h. The rise in urine osmolality during the first 12 h of dehydration was due to increased osmotic equilibration and to the enhanced corticopapillary gradient; urine became more concentrated from 12 to 48 h largely as a result of increased osmotic equilibration.

Topics: Animals; Dehydration; Diabetes Insipidus; Female; Kidney Concentrating Ability; Kidney Cortex; Kidney Medulla; Male; Osmolar Concentration; Rats; Rats, Brattleboro; Urea; Vasopressins

The effects of naloxone (2 and 10 mg kg-1 s.c.) were compared in several kinds of experimental polyuria: alcohol- or water-loaded rats and Brattleboro rats (i.e. animals with congenital lack of vasopressin). In normal rats, both water and alcohol increased urine flow and decreased urinary osmolality. Alcohol induced a more marked diuretic response than water. In normally hydrated rats, naloxone (2 and 10 mg kg-1 s.c.) failed to modify urine flow, urinary osmolality, Na+ and K+ urinary excretion, and urine creatinine concentration. The two doses of naloxone decreased urine flow and increased osmolality in both water- and alcohol-loaded rats. In Brattleboro rats, naloxone (10 mg kg-1 s.c.) reduced urine flow and urinary creatine whereas the low dose (2 mg kg-1 s.c.) was without effect. Since it is well known that the mechanism of water- or alcohol-induced diuresis is an inhibition of vasopressin release, the present results suggest that naloxone could prevent this inhibition. They indicate that endogenous opioid peptides may exert an inhibitory control on vasopressin release.

Topics: Animals; Creatinine; Diabetes Insipidus; Diuresis; Ethanol; Male; Naloxone; Natriuresis; Potassium; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins; Water

Prostaglandin (PG) production by the kidney is known to be reduced both in vivo and in vitro in rats with hereditary diabetes insipidus (DI), totally lacking ADH. Exogenous ADH restores normal PG excretion in these rats. On the other hand, osmolality in vitro, and urine flow rate in vivo have been shown to influence PG synthesis rate. In order to determine whether the decreased PG synthesis of DI rats is due to the lack of antidiuretic hormone itself or to low tissue osmolality, we studied in vivo and in vitro PG production in DI rats in which urine osmolality had been raised either with ADH (infused by Alzet minipumps), or without ADH (by dehydratation) and in control DI rats. PGE2 and PGF2 alpha were measured by radioimmunoassay in the urines and in supernatants of papillary homogenates incubated at 37 degrees C for 15-120 min. ADH administration and dehydration led to similar urine osmolalities (congruent to 900-1,000 mosmol/kg H2O versus 150 in controls). However, only ADH administration but not dehydration increased PG urinary excretion (X 5, P less than 0.001) and subsequent in vitro papillary synthesis (X 1.6, P less than 0.01). These results show that antidiuretic hormone increases PG-synthesis of the renal papilla directly and not through its effects on papillary osmolality.

Topics: Animals; Dehydration; Diabetes Insipidus; Kidney Medulla; Osmolar Concentration; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro; Vasopressins

A report is presented of a male infant with nephrogenic diabetes insipidus type I. A low-solute-load diet and large fluid intake were not able to prevent hypertonic dehydration and to control the disease. It responded within 3 days to indomethacin (3 mg/kg body weight), a prostaglandin synthetase inhibitor. The boy is doing well on this regimen and no side-effects have been observed after 2 years of treatment. Hitherto only a few case reports have been published on this therapeutic regimen, but all confirm the high efficacy of prostaglandin synthesis inhibition as the treatment of choice in nephrogenic diabetes insipidus.

Topics: Diabetes Insipidus; Diabetic Nephropathies; Fluid Therapy; Humans; Indomethacin; Infant; Male; Prostaglandin Antagonists; Prostaglandins; Vasopressins

Topics: Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Vasopressins

Topics: Autoimmune Diseases; Benzothiadiazines; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuretics; Drinking; Humans; Osmolar Concentration; Polyuria; Sodium Chloride Symporter Inhibitors; Vasopressins

Brain water accumulation (1.2%) with an accompanying increase in the sodium content was observed in Wistar rats as early as 1 hour after experimental subarachnoid hemorrhage (SAH). After 6 and 24 hours, the water content was 1.3 and 1.4%, respectively, higher than that of control animals. In contrast, in Brattleboro diabetes insipidus rats the content of brain water and electrolytes had not changed significantly 1 hour after the administration of blood into the subarachnoid space. Increased brain water and sodium and a normal potassium content, indicative of a vasogenic type of brain edema, were seen at 6 hours after SAH. In these animals, known to be devoid of vasopressin, the increase in brain water 24 hours after SAH was 2.6%, compared with 1.4% for Wistar rats with SAH. It is suggested that the lack of vasopressin could alter the course of brain edema formation after experimental SAH in Brattleboro diabetes insipidus rats. It is hypothesized that vasopressin, by regulating the water permeability of the brain capillaries, the choroid plexus, and the cerebrospinal fluid absorption structures, plays an important role in controlling the brain fluid and electrolyte balance during the course of SAH.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Diabetes Insipidus; Female; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Subarachnoid Hemorrhage; Vasopressins; Water-Electrolyte Balance

A young male presented within hours after closed head injury with hypotension, tachycardia, and polyuria. A diagnosis of post-traumatic diabetes insipidus was made. Although a rare entity, the rapid diagnosis of diabetes insipidus and early treatment with vasopressin may have been life-saving in this case. A detailed approach for treatment with continuous intravenous vasopressin may be the most accurate and efficient method of managing acute onset diabetes insipidus, especially in the hemodynamically compromised patient. This will allow for a controlled fluid management in order to achieve hemodynamic stability and prevent aggravation of cerebral edema.

Topics: Acute Disease; Adult; Brain Edema; Diabetes Insipidus; Facial Bones; Humans; Male; Skull Fractures; Subarachnoid Hemorrhage; Vasopressins

Eighteen patients aged between 14 and 60 years suffering from diabetes insipidus were studied. Diabetes insipidus was diagnosed by means of Robertson's test. All patients underwent C.T. scanning and evaluation of PRL basally and after TRH (200 mcg e.v.). Twelve patients (66%) showed neurological lesions (secondary central diabetes insipidus). Six of these patients had hyperprolactinaemia. Our data suggest that most of central diabetes insipidus are associated with central system nervous (S.N.C.) damage. In same cases the presence of hyperprolactinaemia suggests a brain damage. Therefore neuroradiological study is very important in all cases of neurohypophyseal diabetes insipidus.

Topics: Adolescent; Adult; Diabetes Insipidus; Female; Humans; Hypopituitarism; Male; Middle Aged; Pituitary Gland, Posterior; Pituitary Neoplasms; Prolactin; Vasopressins

It is very rare for disturbances of water balance to occur as isolated phenomena. More commonly, mixed electrolyte abnormalities present. However, to permit the logical application of therapy an understanding of basic water balance in health and disease is essential.

Topics: Dehydration; Diabetes Insipidus; Diabetes Mellitus; Humans; Osmolar Concentration; Thirst; Vasopressins; Water; Water Intoxication; Water Loss, Insensible; Water-Electrolyte Imbalance

Electrolytic lesion of the medio-ventral septal (MVS) area produces, 3 days after the surgery, a remarkable increase of daily diuresis and water intake in the rat. This polyuria and polydipsia is associated with decreased levels of circulating radioimmunoassayable vasopressin. In addition, if these lesioned animals were water-deprived (48 h), the usual vasopressin release observed in sham-lesioned and normal controls was markedly blunted. These results suggest that the MVS area exerts a modulatory control on vasopressin secretion both in basal and thirst-evoked conditions.

Topics: Animals; Denervation; Diabetes Insipidus; Drinking; Male; Polyuria; Rats; Rats, Sprague-Dawley; Septum of Brain; Thirst; Vasopressins; Water Deprivation

Autoantibodies to vasopressin-secreting cells of human hypothalamus were detected by means of indirect immunofluorescence (IFL) in 13 patients with diabetes insipidus (DI). 11 of 30 patients (36 . 7%) with "idiopathic" and 2 of 32 (6 . 3%) with symptomatic DI were positive, and 139 control patients were negative. The specificity of the reaction vasopressin cells was demonstrated with a 4-layer double-fluorochrome IFL test in which the second sandwich consisted of rabbit antivasopressin or anti-oxytocin counterstained with rhodaminated anti-rabbit immunoglobulin. 5 patients had also antibodies to oxytocin-producing cells. The antibodies reacted with cytoplasmic components distinct from the hormone; they were of IgG, IgA, or IgM class or a combination of these classes, and half of them fixed complement. Maximum titres were 1:32, and the antibodies could not be absorbed out by incubation with vasopressin, oxytocin, neurophysin I, or neurophysin II. Some sera stained as yet unidentified small cells in the hypothalamus. This report suggests that autoimmunity extends to the hypothalamus. Vasopressin-cell antibodies may prove to be useful markers for the diagnosis of an autoimmune variant of diabetes insipidus.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Child; Diabetes Insipidus; Female; Fluorescent Antibody Technique; Humans; Hypothalamus; Male; Middle Aged; Organ Specificity; Paraventricular Hypothalamic Nucleus; Supraoptic Nucleus; Vasopressins

Topics: Adolescent; Adult; Child; Child, Preschool; Craniopharyngioma; Diabetes Insipidus; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Pituitary Neoplasms; Postoperative Complications; Vasopressins

Topics: Carcinoma, Small Cell; Diabetes Insipidus; Humans; Lung Neoplasms; Radioimmunoassay; Vasopressins

The very rare occurrence of an ADH-producing small cell carcinoma of the lung in a 52 year old male patient with cranial diabetes insipidus since childhood is described. In this case diabetes insipidus disappeared concomitantly with development of lung cancer and re-appeared with shrinkage of the lung tumour by radiation therapy. Further progressive expansion of the primary and metastatic tumours induced the syndrome of inappropriate ADH secretion once again (SIADH). This deterioration in the clinical course was reflected in the plasma levels of ADH and neurophysins. The existence of vasopressin in the tumour tissue was also demonstrated by means of an immunohistochemical staining technique combined with anti-vasopressin serum.

Topics: Carcinoma, Small Cell; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Neurophysins; Remission, Spontaneous; Vasopressins

Autoantibodies against vasopressin (AVP)-producing cells of the human pituitary gland as well as conventional antibodies were determined in 67 patients with central diabetes insipidus and in 141 controls without diabetes insipidus using an immunofluorescence technique. Eleven out of 30 patients (37%) with nonfamilial idiopathic diabetes insipidus, two out of 28 patients (7%) with symptomatic diabetes insipidus and none of the control persons had AVP-cell antibodies. Antibody titres were between 1 : 2 and 1 : 32, in 8 of the 13 cases the antibodies were complement-binding. In 9 patients with idiopathic diabetes insipidus and in none of the symptomatic cases one or more autoimmune diseases were demonstrable. Demonstration of autoantibodies against AVP-cells of the pituitary in the serum of patients with so-called idiopathic diabetes insipidus indicates an autoimmune basis of the disease. This interpretation of the new antibody results is supported by a frequent association of idiopathic diabetes insipidus with recognized auto-immune diseases.

Topics: Adolescent; Adult; Aged; Autoantibodies; Autoimmune Diseases; Child; Child, Preschool; Cross Reactions; Diabetes Insipidus; Female; Fluorescent Antibody Technique; Humans; Hypothalamus; Infant; Male; Middle Aged; Oxytocin; Vasopressins

Sodium excretion was studied following experimental elevation of cerebrospinal fluid (CSF) sodium in heterozygous and homozygous (DI) Brattleboro rats given exogeneous antidiuretic hormone. Sodium excretion increased 4.5-fold in heterozygous and 3.5-fold in DI rats. The natriuresis in both groups was rapid in onset and occurred with a simultaneous kaliuresis. Blood pressure increased approximately 10 mmHg in the heterozygous but not in the DI rats. Accordingly, increased blood pressure may contribute to the natriuresis but is not the sole mechanism. Plasma renin concentration did not change in the DI rats during high Na CSF infusion, and chronic bilateral renal denervation did not abolish the natriuresis. Glomerular filtration rate increased during the high Na period in both the intact and renally denervated rats. These data provide evidence that a natriuretic mechanism exists that is not mediated by changes in antidiuretic hormone, renal nerve activity, mean arterial pressure, aldosterone, or angiotensin II, and thus may be due to another circulating substance or natriuretic hormone. This hormone may act totally or in part by increasing glomerular filtration rate.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Dose-Response Relationship, Drug; Female; Heterozygote; Homozygote; Kidney; Male; Potassium; Rats; Rats, Brattleboro; Rats, Inbred Strains; Renal Circulation; Renin; Sodium; Vasopressins

Rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) which are devoid of vasopressin, excrete significantly increased amounts of immunoreactive thromboxane B2 in urine. The increase was corrected by treatment with vasopressin. These results suggest that, in the intact organism, thromboxane synthesis may be under tonic inhibitory control by vasopressin although other renal mechanisms explaining the increase in thromboxane cannot be excluded. Our observations further support an involvement of prostaglandins and thromboxanes in the regulation of water metabolism.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Hypothalamus; Kidney; Male; Rats; Rats, Brattleboro; Thromboxane B2; Thromboxanes; Vasopressins

Brattleboro rats, a strain with hereditary hypothalamic diabetes insipidus, were found to excrete significantly higher amounts of both renal (PGE2) and vascular (6-keto-PGF1 alpha) prostaglandins than control Long-Evans rats. The increased prostaglandin synthesis was reversed by vasopressin treatment. These results suggest that in the intact organism prostaglandin synthesis in the kidneys and in the endothelial cells of blood vessels may be under tonic inhibitory control by vasopressin. The findings further support the view that prostaglandins play an important role in the regulation of water excretion and in the pathogenesis of polyuric conditions.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Diabetes Insipidus; Dinoprostone; Female; Prostaglandins E; Rats; Rats, Brattleboro; Vasopressins

Three cases of transient central diabetes insipidus after cardiopulmonary bypass are presented. All 3 patients responded promptly to administration of vasopressin, and were completely recovered from polyuria 10 days after cardiac surgery. It is postulated that transient diabetes insipidus after cardiac operation occurred in some patients who had preexisting selective osmoreceptor dysfunction when cardiac standstill during extracorporeal circulation alters the left atrial nonosmotic receptor function, resulting in suppression of antidiuretic hormone release.

Topics: Arginine Vasopressin; Coronary Artery Bypass; Diabetes Insipidus; Diuresis; Humans; Male; Postoperative Complications; Time Factors; Vasopressins

We analyzed the effects of vasopressin in learning and memory of healthy individuals and patients with diabetes insipidus. The results of our investigations allow the conclusion that vasopressin effects a memory stimulation by influence of neurocentral mechanisms.

Topics: Adult; Arginine Vasopressin; Attention; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Lypressin; Memory; Memory, Short-Term; Mental Recall; Paired-Associate Learning; Retention, Psychology; Vasopressins

Three generations of a family with nephrogenic diabetes insipidus were studied. Treatment of a male infant patient with hydrochlorothiazide normalized the serum sodium concentration and improved the clinical condition, but did not influence the polyuria. Although indomethacin alone was without long-term effect, combined therapy with hydrochlorothiazide and indomethacin regulated serum sodium better than hydrochlorothiazide alone. The renin-aldosterone system was not activated in healthy carriers or patients with nephrogenic diabetes insipidus neither in infancy during severe hypernatremic dehydration nor in adult patients.

Topics: Adolescent; Adult; Diabetes Insipidus; Diabetic Nephropathies; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Indomethacin; Infant; Male; Renin-Angiotensin System; Sodium; Vasopressins

A 5-year-old, domestic long-haired cat was presented for examination because of polydipsia, polyuria and inappropriate urination of 3 months' duration. Neurogenic diabetes insipidus was diagnosed, based on hyposthenuria with failure to concentrate urine in response to water deprivation and positive response to antidiuretic hormone administration. Treatment with hydrochlorothiazide or chlorpropamide orally gave inadequate antidiuresis, but response to injections of vasopressin tannate in oil was sufficient for satisfactory management.

Topics: Administration, Oral; Animals; Arginine Vasopressin; Cat Diseases; Cats; Chlorpropamide; Diabetes Insipidus; Hydrochlorothiazide; Injections, Subcutaneous; Male; Vasopressins

Topics: Adult; Carbamazepine; Diabetes Insipidus; Female; Humans; Kidney Tubules; Male; Vasopressins

Topics: Animals; Antigen-Antibody Complex; Avoidance Learning; Brain; Diabetes Insipidus; Immune Sera; Memory; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Rats; Structure-Activity Relationship; Vasopressins

Topics: Animals; Axons; Brain; Diabetes Insipidus; Fetus; Mutation; Neurons; Rats; Rats, Mutant Strains; Vasopressins

The effects of naturally occurring lysine and arginine vasopressins (LVP and AVP) were compared with those of 1-deamino-8-D-arginine-vasopressin (dDAVP) and 1-deamino-4-valine-D-arginine-vasopressin (dVDAVP). The changes of minute diuresis, urinary osmolarity and the duration of action were followed. dDAVP and dVDAVP in a single intravenous and intranasal dose decreased the diuresis more markedly (3.5-fold) and for a longer duration (3.3-fold) than did LVP in patients with central diabetes insipidus. The administration of dDAVP and dVDAVP in the form of sublingual tablets also proved to be effective, where dVDAVP acted more markedly and longer (16 hrs) than dDAVP (12 hrs) in a single dose of 30 micrograms. During one week of sublingual dDAVP administration, the accumulation of the drug was indicated by the gradual decrease of diuresis and the increase of urine osmolarity. The misuse of such highly active drugs may even result in iatrogenic inappropriate ADH syndrome (Schwartz-Bartter). The danger of this syndrome will be demonstrated in a case history. Some more recently synthesized vasopressin analogues with antagonistic action on the diuresis may have an important role in the therapy of Schwartz-Bartter syndrome. The authors present their results with one of these antagonists [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin (d/CH2/5Tyr/Et/VAVP) both in Brattleboro and in R-Amsterdam rats. This analogue blocks the antidiuretic effect of both exogenous and endogenous vasopressin.

Topics: Animals; Body Water; Diabetes Insipidus; Humans; Rats; Vasopressins

Topics: Animals; Blood Pressure; Diabetes Insipidus; Humans; Rats; Vasopressins

Topics: Adult; Brain Death; Diabetes Insipidus; Female; Humans; Osmolar Concentration; Polyuria; Sodium; Sodium Chloride; Time Factors; Urea; Vasopressins

Angiotensinogen, the precursor of angiotensin II, was quantitated in 46 brain regions of Brattleboro rats, which lack antidiuretic hormone, and Long-Evans control rats. The regional distribution of angiotensinogen in the two strains was similar except for a small number of areas which in the Brattleboro rats displayed significant decreases; namely, lateral preoptic area, medial basal hypothalamus, medial dorsal hypothalamus, lateral hypothalamus, lateral mammillary bodies, periaquaductal gray and substantia nigra. Additionally, angiotensinogen in the posterior pituitary was significantly elevated in the Brattleboro strain. These results indicate that angiotensinogen is present in the Brattleboro rat brain and that hereditary deficiency of the ability to synthesize antidiuretic hormone may be associated with a localized alteration in angiotensinogen concentration.

Topics: Angiotensinogen; Angiotensins; Animals; Brain Chemistry; Diabetes Insipidus; Male; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Breast Neoplasms; Diabetes Insipidus; Female; Humans; Hypophysectomy; Pituitary Gland; Postoperative Complications; Vasopressins

Plasma concentrations of oxytocin and vasopressin were determined by radioimmunoassay in a woman with clinical diabetes insipidus. Plasma oxytocin levels were normal and ranged from less than 0.25 microU/ml to 76 microU/ml during the last month of pregnancy and during spontaneous labor. Vasopressin requirements did not change during pregnancy. Unexplained vasopressin resistance and massive diuresis occurred early in the postpartum period. Plasma vasopressin concentrations were undetectable in the nonpregnant state. The documentation of normal oxytocin production and total vasopressin deficiency suggests that an anatomic defect is unlikely to cause this disorder unless it is limited to axons and cell bodies containing vasopressin and not oxytocin.

Topics: Adult; Cesarean Section; Diabetes Insipidus; Female; Humans; Oxytocin; Pregnancy; Pregnancy in Diabetics; Vasopressins

Male and female Long Evan rats and Brattleboro rats with ADH-deficient diabetes insipidus were treated with lithium administered in the diet for 12 weeks. The plasma lithium level was about 1 mmol/l in all groups. Lithium caused polydipsia and polyuria and lowering of renal concentrating ability in normal rats. In rats with ADH deficiency lithium tended to increase water intake, but did not influence spontaneous urine osmolality or maximal urine osmolality during water deprivation. The results indicate that the renal concentrating defect caused by lithium in rats can be explained by ADH-blockade as the only mechanism. However, there is circumstantial evidence that lithium in addition may stimulate thirst mechanisms by an ADH-independent action.

Topics: Animals; Body Weight; Diabetes Insipidus; Drinking; Female; Kidney Concentrating Ability; Lithium; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins

Central vasopressin (VP) may modulate the functional activity of specific neuronal systems involved in cardiovascular regulation. To test this hypothesis we compared cardiovascular (CV) responses to electrical stimulation of the anteroventral region of the third ventricle (AV3V) in Brattleboro rats homozygous for diabetes insipidus (DI), in heterozygous DI rats (DI-HZ) and in normal Long-Evans rats (LE). We also studied the effects of peripheral and intracerebroventricular (ivt) treatment of DI rats with VP and treatment of LE rats with an antipressor blocker of VP on cardiovascular responses to AV3V stimulation. Stimulation of the AV3V region in anesthetized LE rats produced a frequency-dependent increase in renal (RVR) and mesenteric vascular resistance (MVR), a decrease in hindquarter vascular resistance (HQVR), and a decrease in arterial pressure (AP) and heart rate (HR). DI and DI-HZ rats showed significantly greater decreases in AP and HR and lesser changes in RVR, MVR, and HQVR. The deficiency in vasoconstriction in DI rats appeared to be centrally mediated inasmuch as vascular responses to peripherally administered phenylephrine and nerve stimulation were comparable in LE and DI rats. Treatment of DI rats with VP peripherally improved CV responses to AV3V stimulation. An even greater improvement in CV responses to AV3V stimulation was obtained when DI were given ivt infusion of VP. Finally, following intravenous administration of an antipressor VP blocker LE rats showed a greater decrease in AP and HR and lesser resistance changes in response to AV3V stimulation. Our data suggest that cardiovascular responses elicited from stimulation of the AV3V region may depend, in part, on a central vasopressin mechanism.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Cerebral Ventricles; Diabetes Insipidus; Electric Stimulation; Heart Rate; Male; Rats; Rats, Brattleboro; Regional Blood Flow; Vasopressins

The activity of protein carboxymethylase and the endogenous protein methyl acceptor capacity were examined in the posterior, intermediate, and anterior lobes of the pituitaries of homozygous Brattleboro rats with diabetes insipidus and in heterozygous Brattleboro and Long-Evans control rats. Protein carboxyl methylation is selectively altered in the posterior pituitary lobes of homozygous Brattleboro rats. Protein carboxymethylase activity is higher (+40%) and endogenous methyl acceptor protein capacity is lower (-80%) with respect to heterozygous Brattleboro and Long-Evans control rats. This latter change is correlated with decreased methylation of proteins of a molecular weight of approximately 11K daltons, is selective for the posterior pituitary lobe, since it does not occur in the intermediate and anterior lobes, and probably reflects the absence of vasopressin-associated neurophysin in homozygous Brattleboro rats. Our results support a physiological role of protein carboxyl methylation in the neurosecretory process in the posterior pituitary gland.

Topics: Animals; Diabetes Insipidus; Heterozygote; Homozygote; Male; Neurophysins; Organ Specificity; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Protein Methyltransferases; Protein O-Methyltransferase; Rats; Rats, Brattleboro; Vasopressins

Topics: Animals; Diabetes Insipidus; Diabetic Nephropathies; Diagnosis, Differential; Drinking; Female; Horse Diseases; Horses; Polyuria; Vasopressins

Topics: Action Potentials; Animals; Diabetes Insipidus; Evoked Potentials; Neurons; Rats; Rats, Brattleboro; Rats, Mutant Strains; Staining and Labeling; Supraoptic Nucleus; Vasopressins

Topics: Animals; Dehydration; Diabetes Insipidus; Glucagon; Insulin; Male; Neurotensin; Peptides; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Somatostatin; Substance P; Vasopressins

Topics: Acute Disease; Adenoma; Adult; Body Weight; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Solubility; Vasopressins

In the rat, angiotensin II (AII), following specific interaction with sensitive central nervous system (CNS) receptors promotes release of vasopressin (ADH). We have examined the integrity of this chain of events by comparing the concentration, Bmax, and dissociation constant, Kd, in the CNS of Brattleboro rats (BB), a strain incapable of synthesizing ADH, with Long Evans (LE) control rats that can synthesize ADH. AII binding properties in the hypothalamic-thalamic-septal-midbrain (HTSM) area from young and old BB and LE, as well as systolic blood pressure, were determined. There was a reduction in the HTSM-AII receptor concentration of young BB when compared with young LE rats. Young BB had lower pressure than age and sex matched LE controls. Neither Bmax nor pressure was significantly different between older BB and LE. A decline in HTSM-AII receptor concentration with age observed with LE is consistent with observations in SHR and WKY rats. Parallel Scatchard plots obtained indicated the presence of a single class of CNS AII receptors. These data suggest that ADH synthesis and AII receptor concentration are partially interdependent and that the CNS AII-ADH system is redundant in the maintenance of blood pressure.

Topics: Aging; Animals; Body Weight; Brain; Diabetes Insipidus; Female; Kinetics; Male; Rats; Receptors, Angiotensin; Receptors, Cell Surface; Species Specificity; Vasopressins

The activity of angiotensin-converting enzyme is significantly higher in the intermediate and posterior pituitary lobes of Brattleboro rats than in Long-Evans control rats. The high activity level was reversed by vasopressin treatment. Conversely, angiotensin-converting enzyme activity was significantly lower in the anterior pituitary of Brattleboro rats than in Long-Evans rats, and this activity level was not affected by vasopressin. these findings suggest an inverse relation between vasopressin and angiotensin systems in the posterior and intermediate lobes of the pituitary gland.

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Peptidyl-Dipeptidase A; Pituitary Gland, Posterior; Rats; Rats, Mutant Strains; Vasopressins

Lithium is increasingly prescribed by psychiatrists for manic-depressive psychosis and other affective disorders. Therefore, psychiatrists should be familiar with lithium-induced nephrogenic diabetes insipidus. Management of this condition is discussed. Thiazide diuretics have a paradoxical antidiuretic effect in lithium-induced diabetes insipidus. For this reason, it is no longer warranted to contraindicate concomitant use of lithium and thiazide diuretics.

Topics: Adult; Benzothiadiazines; Diabetes Insipidus; Diuretics; Drug Interactions; Female; Humans; Kidney; Lithium; Male; Middle Aged; Sodium Chloride Symporter Inhibitors; Vasopressins

The present study investigated whether or not the beta-sympathomimetic amine isoprenaline, given systemically to conscious rats, influences corticotrophin (ACTH) release and if so, what could be the role of vasopressin in this response. Isoprenaline (i.m.) elevated plasma ACTH-like immunoreactivity (ACTHi) in a time- and dose-dependent manner. The highest dose of isoprenaline used (240 microgram/kg) raised plasma ACTHi about six fold. Most of the ACTHi co-migrated with porcine ACTH-(1-39) on Sephadex G-50 column chromatography. The beta-receptor antagonist propranolol abolished the increase in plasma ACTHi induced by isoprenaline, as did dexamethasone pretreatment. The increase in plasma ACTHi following isoprenaline (120 microgram/kg) injection was diminished by about 35% in rats congenitally lacking vasopressin (Brattleboro rats), when compared to normal rats. The vasopressin analogue, [1-deaminopenicillamine, 2-(O-methyl)tyrosine]-arginine-vasopressin, almost completely prevented the rise in plasma ACTHi provoked by i.v. injection of arginine vasopressin and diminished by about 40% the isoprenaline-(120 microgram/kg)-caused ACTHi release. However, this vasopressin analogue had no effect in Brattleboro rats. These results indicate that isoprenaline, given systemically, stimulates the release of pituitary ACTH and this response appears to be mediated in part by vasopressin acting as an ACTH-releasing factor.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Dexamethasone; Diabetes Insipidus; Electroshock; Isoproterenol; Male; Propranolol; Rats; Rats, Inbred Strains; Time Factors; Vasopressins

Specific binding sites for blood-borne calcitonin were localized by means of quantitative radioautography to the circumventricular organs of the rat brain. By this method, using normal Long-Evans rats as controls, specific binding of blood-borne calcitonin in the median eminence region of the hypothalamus was reduced by one-third in homozygous Brattleboro rats, which are genetically deficient in vasopressin. Competitive binding analysis in vitro of the hypothalami from these animals confirmed the binding deficit in homozygous rats, and Scatchard analysis suggested a reduction in the number of binding sites. In homozygous rats daily vasopressin replacement therapy restored normal water balance but did not normalize the hypothalamic calcitonin binding deficit. These studies delineate for the first time specific sites within the central nervous system which could serve to mediate direct actions of blood-borne calcitonin on brain function. The deficit in the Brattleboro rat may provide a model for further investigation of the role of calcitonin within selective regions of the central nervous system.

Topics: Animals; Brain; Calcitonin; Diabetes Insipidus; Homozygote; Male; Median Eminence; Rats; Rats, Inbred Strains; Receptors, Calcitonin; Receptors, Cell Surface; Vasopressins

Topics: Adrenalectomy; Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Captopril; Castration; Diabetes Insipidus; Female; Hypophysectomy; Male; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Sex Factors; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Arginine Vasopressin; Chlorides; Diabetes Insipidus; Kidney Concentrating Ability; Lithium; Lithium Chloride; Osmolar Concentration; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Vasopressins

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Animals; Circadian Rhythm; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Fluorescent Antibody Technique; Histocytochemistry; Male; Pituitary Gland; Radioimmunoassay; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Corticotropin-Releasing Hormone; Diabetes Insipidus; Drug Synergism; Hypothalamus; Immune Sera; In Vitro Techniques; Male; Pituitary Gland, Anterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Corticotropin-Releasing Hormone; Diabetes Insipidus; Electric Stimulation; Median Eminence; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: 11-Hydroxycorticosteroids; Adrenocorticotropic Hormone; Angiotensin II; Animals; Diabetes Insipidus; Injections, Intraventricular; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Vasopressins

Topics: Animals; Arginine Vasopressin; Calcitonin; Diabetes Insipidus; Hypothalamus; Median Eminence; Rats; Rats, Brattleboro; Rats, Mutant Strains; Receptors, Calcitonin; Receptors, Cell Surface; Tissue Distribution; Vasopressins

Topics: Animals; Diabetes Insipidus; Fluorescent Antibody Technique; Histocytochemistry; Hypothalamus; Male; Neurons; Neurophysins; Oxytocin; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Adrenalectomy; Angiotensin II; Animals; Colchicine; Diabetes Insipidus; Histocytochemistry; Homozygote; Hypothalamus; Immunoenzyme Techniques; Neurophysins; Oxytocin; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Vasopressins

Topics: Animals; Diabetes Insipidus; Diet; Female; Male; Potassium; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Vasopressins

Topics: Adrenal Cortex; Aldosterone; Animals; Arginine Vasopressin; Cytoplasmic Granules; Diabetes Insipidus; Diet, Sodium-Restricted; Hypertrophy; Juxtaglomerular Apparatus; Male; Microscopy, Electron; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renin; Vasopressins

Topics: Administration, Intranasal; Adult; Arginine Vasopressin; Asthma; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Hypersensitivity; Humans; Male; Pulmonary Fibrosis; Vasopressins

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Heterozygote; Homozygote; Rats; Rats, Brattleboro; Rats, Mutant Strains; Terminology as Topic; Vasopressins

Topics: 1-Sarcosine-8-Isoleucine Angiotensin II; Angiotensin II; Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Male; Oxytocin; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Vasopressins

Topics: Action Potentials; Animals; Arginine Vasopressin; Diabetes Insipidus; Electric Stimulation; Evoked Potentials; Neurons; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Supraoptic Nucleus; Vasopressins

Topics: Aging; Animals; Dehydration; Diabetes Insipidus; Heterozygote; Male; Models, Biological; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Inbred F344; Rats, Mutant Strains; Vasopressins; Water Deprivation

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Erythrocyte Indices; Erythrocytes; Extracellular Space; Male; Membrane Potentials; Muscles; Potassium; Rats; Rats, Brattleboro; Rats, Mutant Strains; Sodium; Vasopressins

Topics: Animals; Diabetes Insipidus; Diuresis; Female; Glomerular Filtration Rate; Hydronephrosis; Kidney; Male; Osmolar Concentration; Rats; Rats, Brattleboro; Rats, Mutant Strains; Sex Factors; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Chlorides; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Kidney; Male; Natriuresis; Osmolar Concentration; Oxytocin; Pituitary Gland; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Kidney; Male; Norepinephrine; Rats; Rats, Brattleboro; Rats, Mutant Strains; Sodium Chloride; Vascular Resistance; Vasopressins

Topics: Animals; Animals, Newborn; Birth Weight; Diabetes Insipidus; Female; Fertility; Gestational Age; Labor, Obstetric; Litter Size; Male; Pregnancy; Rats; Rats, Brattleboro; Rats, Mutant Strains; Reproduction; Vasopressins

Topics: Animals; Atropine; Blood Pressure; Diabetes Insipidus; Heart Rate; Male; Methoxamine; Pressoreceptors; Propranolol; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Animals; Arginine Vasopressin; Cerebral Ventricles; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Sodium Chloride; Vasopressins

Topics: Animals; Blood Pressure; Diabetes Insipidus; Ethanol; Heart Rate; Hemorrhage; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Animals; Blood Pressure; Blood Volume; Cardiac Output; Diabetes Insipidus; Female; Hemodynamics; Heterozygote; Homozygote; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Animals; Arginine Vasopressin; Cytoplasm; Diabetes Insipidus; Kidney Medulla; Lipid Metabolism; Male; Microscopy, Electron; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Animals; Arginine Vasopressin; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drinking; Hypothalamus; Osmolar Concentration; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Thirst; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Female; Homozygote; Osmolar Concentration; Oxytocin; Rats; Rats, Brattleboro; Rats, Mutant Strains; Uterine Contraction; Vasopressins

Topics: Adenylyl Cyclase Inhibitors; Animals; Arginine Vasopressin; Chemical Phenomena; Chemistry; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Oxytocin; Rats; Structure-Activity Relationship; Vasopressins

Topics: Animals; Diabetes Insipidus; Dinoprostone; Diuresis; Drinking; Female; Kidney Concentrating Ability; Osmolar Concentration; Pregnancy; Pregnancy Complications; Prostaglandins E; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Topics: Animals; Carboxy-Lyases; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Hepatectomy; Kidney; Ornithine Decarboxylase; Polyamines; Rats; Rats, Brattleboro; Rats, Mutant Strains; Testosterone; Vasopressins

Topics: Animals; Blood Pressure; Cardiovascular Physiological Phenomena; Cerebral Ventricles; Diabetes Insipidus; Electric Stimulation; Heart Rate; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vascular Resistance; Vasopressins

Topics: Alcohol Drinking; Animals; Diabetes Insipidus; Drinking; Ethanol; Lypressin; Male; Oligopeptides; Peptide Fragments; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Analgesia; Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Immune Sera; Lypressin; Nociceptors; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Topics: Animals; Cell Nucleus; Cytoplasm; Diabetes Insipidus; Estradiol; Female; Hypothalamus; Neurons; Neurophysins; Oxytocin; Pituitary Hormones, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Tissue Distribution; Vasopressins

Topics: Animals; Body Water; Diabetes Insipidus; Diagnosis, Differential; Dog Diseases; Dogs; Drinking; Kidney; Kidney Concentrating Ability; Kidney Diseases; Polyuria; Thirst; Vasopressins

Topics: Animals; Biological Assay; Corticosterone; Corticotropin-Releasing Hormone; Diabetes Insipidus; Male; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Rats; Rats, Brattleboro; Rats, Mutant Strains; Tissue Extracts; Vasopressins

1. The influence of ADH and the state of potassium balance on the renin-angiotensin system was studied in rats with hereditary diabetes insipidus (DI rats). 2. Plasma renin concentration in DI rats was higher than in control Long-Evans rats. 3. Spontaneous reversal of the hypokalaemia normally found in DI rats did not reduce plasma renin concentration (p.r.c.), suggesting that potassium deficiency does not contribute significantly to the elevation of p.r.c. in DI rats. Similarly, a low potassium diet failed to further increase p.r.c. in DI rats. 4. In contrast, the p.r.c. of DI rats was significantly diminished by a high potassium intake both in the presence and absence of ADH. A highly significant inverse correlation was found between p.r.c. and urinary potassium excretion in both ADH-treated and untreated DI rats on low, normal and high potassium diets. 5. Plasma renin concentration was significantly lower in ADH-treated than in untreated DI rats on a high potassium intake, suggesting that the inhibitory effects of ADH and potassium are additive. 6. ADH consistently reduced p.r.c. in DI rats independent of the state of potassium balance. 7. ADH and potassium may inhibit renin secretion via different mechanisms of action.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Diet; Female; Hypokalemia; Male; Potassium; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System; Vasopressins

We examined plasma arginine-vasopressin concentrations by radioimmunoassay in two brothers, aged 6 and 7.5 years, with familial central diabetes insipidus inherited as an autosomal dominant trait. Plasma AVP was measured in relation to increasing plasma osmolality induced by water deprivation and hypertonic saline infusion. The brother with the more severe urinary concentrating defect had no detectable AVP when his plasma osmolality was as high as 306 mOsm/kg; the other brother had detectable but clearly subnormal AVP concentrations. The one brother tested had an apparently normal end-organ response to exogenous vasopressin. Chlorpropamide had a significant antidiuretic effect in the brother with detectable AVP levels, and a lesser effect in the other brother . Our findings suggest that intrafamilial variation in the severity of congenital DI is related to the degree of vasopressin deficiency.

Topics: Arginine Vasopressin; Child; Chlorpropamide; Diabetes Insipidus; Diuresis; Genes, Dominant; Humans; Male; Osmolar Concentration; Pedigree; Radioimmunoassay; Vasopressins

The Brattleboro homozygous diabetes insipidus (HOM-DI) mutant rat, incapable of synthesizing the neuropeptide vasopressin, has an impaired body growth of which the severity depends upon the conditions of reproduction. The comparison of homogeneously genotyped litters of HOM-DI and heterozygous (HET-DI) control pups, delivered and nursed by HOM-DI females, was regarded to be the only experimental design that practically excludes other influences on growth differences than the mutation itself. In this breeding scheme the postnatal growth of the HOM-DI brain is impaired, and the weight deficit persists into adulthood. Regionally, the neonatal development of cerebellum and medulla oblongata is most affected, and only slightly that of the cerebral cortex. The other separately isolated parts of the the brain seem to be unaffected (olfactory bulbs, hypothalamus, hippocampus, colliculi and thalamus plus basal ganglia). Cerebellum appeared to be the most consistently affected brain area of the HOM-DI Brattleboro rat since, unlike in the case of cerebral cortex and medulla oblongata, the weight deficit persisted throughout life. Olfactory bulb growth, on the other hand, appeared to continue after the first month of life, resulting in an increased weight at day 180. Water content of cerebral cortex and cerebellum of HOM-DI adults appeared slightly higher and might be explained by the generation of different brain water regulation systems for HET- and HOM-DI Brattleboro rats. Protein and DNA estimations of cerebral cortex, cerebellum and olfactory bulbs of male brains during development and in adulthood reflect the differences as found for weight, indicating no obvious changes in cell densities. It is concluded after comparison with other types of brain growth malformations, that the HOM-DI Brattleboro brain has its own particular etiology. The possible involvement of the action of vasopressin is postulated and discussed.

Topics: Aging; Animals; Body Weight; Brain; Diabetes Insipidus; Female; Homozygote; Male; Organ Size; Organ Specificity; Rats; Rats, Mutant Strains; Sex Factors; Vasopressins

Topics: Adolescent; Adult; Aged; Dehydration; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Osmotic Pressure; Vasopressins

Vasopressin contents of posterior pituitaries and intra- and extrahypothalamic nuclei of brains from 3-month and 24-month-old Long-Evans rats and from Brattleboro rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus were measured by radioimmunoassay. The pituitary content of vasopressin was highest in young rats and was significantly lower in HEDI tissue. The peptide was not detected in HODI pituitaries. In the brain regions studied both aged and HEDI rats showed reduced vasopressin contents as compared to young animals. In light of evidence of memory deficiencies in both HEDI and HODI rats, the possibility arises that memory decrements associated with senescence may be related to altered vasopressin synthesis and/or secretion occurring with aging of these neuronal systems.

Topics: Aging; Animals; Brain Chemistry; Diabetes Insipidus; Hippocampus; Hypothalamus; Locus Coeruleus; Male; Pituitary Gland; Rats; Septum Pellucidum; Tegmentum Mesencephali; Vasopressins

Topics: Animals; Animals, Newborn; Cataract; Diabetes Insipidus; Heterozygote; Homozygote; Rats; Rats, Inbred Strains; Selenious Acid; Selenium; Vasopressins

An attempt was made to produce one-clip, one-kidney hypertension in the rat with diabetes insipidus (DI). Renal artery constriction in unilaterally nephrectomized DI rats (DI-clip) resulted in an increased blood pressure in all 9 rats, but this response was only transient in 3 rats. The magnitude of the hypertension was less in the DI-clip rats than in Long-Evans rats subjected to the same protocol (LE-clip). Infusion of saralasin i.v. at doses of 10 and 30 micrograms/kg . min. 4 to 6 weeks after surgery was without effect on mean arterial pressure in LE-clip and control DI rats, but substantially lowered blood pressure in the DI-clip rats (p less that 0.05 - 0.01). It is concluded that vasopressin is not essential for the production of one-clip, one kidney hypertension in the rat, and that, in the DI rat, the renin-angiotensin system is an important factor in this form of hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Diabetes Insipidus; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension, Renal; Hypertension, Renovascular; Hypothalamic Diseases; Male; Muridae; Saralasin; Vasopressins; Water-Electrolyte Balance

Topics: Arginine Vasopressin; Body Water; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Complications; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Polyuria; Time Factors; Vasopressins

Papillary plasma flow (PPF) was measured by the albumin accumulation technique in rats of the Brattleboro strain with or without diabetes insipidus (DI and HZ respectively) and in Wistar rats. Measurements were also performed in DI rats receiving antidiuretic hormone for 30 min or 5 days and in dehydrated Wistar rats. PPf in HZ control and Wistar control rats was similar to previously published measurements. In contrast PPF was significantly higher in DI rats (461 +/- 26 microliters/min . g versus 263 +/- 28 in HZ) and decreased significantly after acute ADH administration. It returned to control values after prolonged ADH administration (262 +/- 40). Plasma flow entering the papilla was inversely correlated with urine osmolality up to 1000 mosmol/kg H2O. Further increases in urine concentration (dehydration of Wistar rats) did not modify further PPF (255 +/- 28 versus 270 +/- 16 in non dehydrated Wistar). PPF might be influenced indirectly by ADH or prostaglandins and seems to depend on the osmotic environment of the papilla up to a certain limit. The factors which maintain PPF at a given minimum level with further increases in urine concentration are not known.

Topics: Animals; Diabetes Insipidus; Kidney Medulla; Osmolar Concentration; Rats; Rats, Brattleboro; Rats, Inbred Strains; Renal Circulation; Urine; Vasopressins

The levels of dynorphin-(1-13), leucine enkephalin, beta-endorphin and vasopressin immunoreactivity (ir-DYN, ir-1-ENK, ir-beta-END, ir-VP) have been determined in the anterior and in the neurointermediate lobes of the pituitary of rats subjected to a variety of manipulations. Dehydration of rats by 5 days enforced inhibition of a 2% solution of NaCl resulted in a significant decrease in the levels of ir-DYN, ir-1-ENK and ir-VP, but not in those of ir-beta-END in the neurointermediate lobe of the pituitary. In contrast, substitution of drinking water by a solution containing 20 microgram/ml dexamethasone for 5 days produced a significant increase in the neurointermediate pituitary content of ir-DYN, ir-1-ENK and ir-VP, whereas levels of ir-beta-END remained unaffected. This treatment, however, resulted in a significant fall in the ir-beta-END content of the adenopituitary without changing levels of ir-DYN in this structure. Adrenalectomy was associated with a significant decrease in the ir-DYN, ir-VP and ir-1-ENK content of the neurointermediate lobe of the pituitary and a pronounced elevation in the ir-beta-END but not ir-DYN content of the adenohypophysis. These observations are indicative that the regulation mechanisms of the functional state of particular endorphins differ between the anterior and neurointermediate lobes of the pituitary. The concomitant alterations in levels of ir-DYN, ir-1-ENK and ir-VP detected suggest that a common or similar mechanism of regulation may exist for these peptides. A common biosynthetic origin, however, appears to be unlikely, since Brattleboro rats which are unable to synthesize vasopressin possess unchanged ir-DYN- and ir-1-ENK- levels in the pituitary.

Topics: Adrenalectomy; Animals; beta-Endorphin; Dehydration; Dexamethasone; Diabetes Insipidus; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalins; Male; Peptide Fragments; Pituitary Gland; Rats; Rats, Inbred Strains; Sodium Chloride; Vasopressins

Diabetes insipidus is seen most frequently in neurosurgical patients. The transient form is more common and usually subsides prior to discharge. Permanent DI is seen in patients with extensive damage in the hypothalamic area. Treatment of either form of DI is usually with a preparation of vasopressin. Nursing assessements and interventions are crucial to a successful outcome in patients with this disorder. Health teaching for patients with permanent DI is an integral part of the nursing responsibility.

Topics: Adult; Diabetes Insipidus; Drinking; Humans; Patient Education as Topic; Vasopressins

The mechanisms by which endogenous renal prostaglandins regulate water excretion were investigated in these studies. Inhibition of prostaglandin synthesis slowed water diuresis in water-loaded unanesthetized Sprague-Dawley rats and in Brattleboro rats with hereditary diabetes insipidus owing to absence of endogenous vasopressin. In both strains, treatment with indomethacin or meclofenamate increased the osmolality of the renal papilla by raising sodium and urea content, and also increased the osmolality of the urine. Endogenous creatinine clearance and solute excretion were unchanged. The data are consistent with an effect of prostaglandins on solute transport by renal tubules and demonstrate that endogenous prostaglandins influence water excretion by a mechanism independent of the presence of antidiuretic hormone.

Topics: Animals; Diabetes Insipidus; Dinoprostone; Diuresis; Indomethacin; Kidney; Kinetics; Meclofenamic Acid; Potassium; Prostaglandins E; Rats; Rats, Inbred Strains; Sodium; Species Specificity; Urea; Vasopressins

The influence of cervical vagotomy on the isoprenaline-induced renin and vasopressin release was investigated in rats. Plasma vasopressin levels were measured using a specific radioimmunoassay. Bilateral vagotomy enhanced the isoprenaline-provoked vasopressin release; however, the simultaneous increase in plasma renin concentration was diminished. This effect of bilateral vagotomy on renin release could be mimicked by i.v. infusion of vasopressin into rats whose vagi remained intact. On the other hand, in Brattleboro rats with vasopressin deficiency, bilateral vagotomy did not modify renin release. We conclude that, after bilateral vagotomy, isoprenaline elevated plasma vasopressin levels, which then attenuated the concurrent renin release, substantiating that endogenous vasopressin might participate in the control of renin release.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Isoproterenol; Male; Rats; Rats, Inbred Strains; Renin; Vagotomy; Vasopressins

The activity of the renal kallikrein-kinin system was investigated in male Brattleboro rats homozygous for hypothalamic diabetes insipidus (DI); Long-Evans rats (LE) were taken as controls. In the rats with DI, urinary kallikrein excretion was lower (P less than 0.05) than in the LE rats. However, when related to total renal mass or to body weight, there was no difference between the two strains. Kallikrein activity in the renal cortex was similar in the Brattleboro and the LE rats. Antidiuretic hormone (vasopressin tannate) in a dose of 100 mU given once daily for 3 days had no effect on urinary kallikrein excretion in either of the strains. Water deprivation for 24 h resulted, also in both strains, in a similar reduction in urinary kallikrein excretion. The renal kallikrein-kinin system of LE rats and that of DI rats does not principally differ in basic activity, nor in response to the administration of vasopressin, nor to water deprivation.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Diabetes Insipidus; Electrolytes; Kallikreins; Kidney; Kinins; Male; Osmolar Concentration; Rats; Renin; Species Specificity; Urination; Vasopressins; Water Deprivation

In a 10-year-old girl admitted to hospital for polyuria and polydipsia, the central nervous system origin of the symptoms was demonstrated by low antidiuretic hormone levels (inferior to 1 pg/ml) and reduction of diuresis after administration of 1-deamino-8D-arginine-vasopressin (DDAVP). A study of the girl's family history showed that the disease was hereditary and autosomal dominant. Intranasal instillations of DDAVP twice daily constitute the best known treatment of the condition.

Topics: Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Infant; Pedigree; Vasopressins

Topics: Adolescent; Adult; Clofibrate; Diabetes Insipidus; Female; Humans; Hyperlipoproteinemias; Male; Middle Aged; Vasopressins

The effects of 1-deamino-8-D-arginine vasopressin (DDAVP), 1-deamino-4-valin-8-D-arginine vasopressin (DVDAVP) and 8-arginine vasopressin (AVP) on water metabolism have been examined in 18 patients suffering from central diabetes insipidus. The hormone derivatives were sublingually administered. It was established that DDAVP and DVDAVP significantly reduced diuresis and increased urine osmolarity. DVDAVP was found to be more effective than DDAVP. AVP administered in equal doses had no significant effect on water metabolism. The duration of the action of sublingually administered DDAVP was 12 hrs; after dosing DVDAVP the effect lasted even 6 hrs. During one week of DDAVP administration, the accumulation of the drug was indicated by the gradual decrease of diuresis and the increase of the urine osmolarity. The sublingual administration of both DDAVP and DVDAVP tablets (3 X 30 micrograms/day) had an adequate therapeutic effect.

Topics: Adult; Aged; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Male; Middle Aged; Mouth Floor; Tablets; Valine; Vasopressins

Single nephron glomerular filtration rates (SNGFR) were measured by the [14C]sodium ferrocyanide infusion technique in superficial (S) and juxtamedullary nephrons (JM) of anesthetized Brattleboro rats with or without diabetes insipidus (DI and HZ, respectively). Glomerular volumes (GV) and proximal tubular lengths (PTL) were measured in the same nephrons after microdissection. Glomerular volumes were also assessed in Wistar, HZ, and DI rats in Microfil-injected kidneys. The well-known nephron heterogeneity of the mammalian kidney was absent or greatly reduced in DI compared to HZ rats. S/JM ratios for SNGFR, GV, and PTL averaged 0.71, 0.50, and 0.73 in HZ and 1.04, 0.77, and 0.90 in DI rats. This reduced nephron heterogeneity was due only to reduced dimensions and filtration rates in JM nephrons. The chronic administration of antidiuretic hormone (dDAVP or vasopressin tannate), begun at 2 wk of age and maintained until adulthood (8-10 wk), significantly decreased the S/JM ratios, i.e., restored a nearly normal nephron heterogeneity in DI rats. These results suggest that nephron heterogeneity in the rat kidney is dependent on the presence of antidiuretic hormone, and, more specifically, that ADH and/or its functional consequences can selectively induce an increase in size and filtration rate in deep nephrons.

Topics: Animals; Diabetes Insipidus; Female; Ferrocyanides; Glomerular Filtration Rate; Hypothalamus; Male; Nephrons; Rats; Vasopressins

Topics: Animals; Arginine Vasopressin; Blood Volume; Body Water; Carbon Tetrachloride; Diabetes Insipidus; Kidney; Liver Cirrhosis, Experimental; Male; Phenobarbital; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Renal Circulation; Sodium; Vasopressins

Topics: Arginine Vasopressin; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypernatremia; Hypoglycemia; Hyponatremia; Inappropriate ADH Syndrome; Pharmacology; Radioimmunoassay; Vasopressins; Water-Electrolyte Imbalance

The diagnoses provided by a standard indirect test of vasopressin function were compared with those obtained by radioimmunoassay of plasma vasopressin in 24 patients with nonglucosuric polyuria. All seven cases of severe neurogenic diabetes insipidus diagnosed by the indirect tests were confirmed by the vasopressin assay. However, two of six patients with partial neurogenic diabetes insipidus by indirect criteria had normal vasopressin secretion by the direct assay; one was found to have primary polydipsia, and the other nephrogenic diabetes insipidus. Moreover, three of 10 patients diagnosed as having primary polydipsia by the indirect test had clear evidence of partial vasopressin deficiency by the direct assay. The inability of the indirect test to distinguish accurately between partial neurogenic diabetes insipidus and primary polydipsia may be explained by increased sensitivity to low concentrations of vasopressin in the former disorder and a reduction of maximal concentrating ability in both. We conclude that the incorporation of a vasopressin assay improves accuracy in the differential diagnosis of polyuria.

Topics: Adolescent; Adult; Arginine Vasopressin; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; False Negative Reactions; Female; Humans; Male; Middle Aged; Osmolar Concentration; Polyuria; Radioimmunoassay; Saline Solution, Hypertonic; Vasopressins; Water Deprivation

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Osmolar Concentration; Polyuria; Radioimmunoassay; Saline Solution, Hypertonic; Vasopressins; Water Deprivation

1. The Na+ and K+ concentrations in plasma and cerebrospinal (c.s.f.), resting potentials in skeletal muscle fibres, cardiac beat to beat intervals and 90% repolarization times were measured in Long Evans rats (parent strain controls) and in Brattleboro rats with hypothalamic diabetes insipidus (DI). 2. Cation concentration measurements confirmed previous observations that Brattleboro DI rats are mildly hypokalaemic compared with rats of the parent Long Evans strain, and indicated that the c.s.f. [Na+] is significantly raised in the former group of animals while the [K+] in the c.s.f. samples is similar in the two groups. 3. The mean resting potential of deep skeletal muscle fibres in Brattleboro DI rats was significantly more negative than the corresponding value in the Long Evans rats, and this finding was in close agreement with the difference observed for the calculated K+ equilibrium potentials in the two groups of animals. 4. The beat to beat intervals and the 90% repolarization times of cardiac action potentials were also determined in Brattleboro DI and Long Evans rats, and the mean values for both variables were significantly shorter in the former group of animals. 5. The administration of Pitressin by subcutaneous injection (500-100 mu./24 hr) to Brattleboro rats abolished the hypokalaemia and the hyperpolarization of skeletal muscle fibre membranes but had no significant effect on c.s.f. cation concentrations. 6. The present findings suggest that the absence of vasopressin in the Brattleboro DI rats results in a hyperpolarization of muscle cell membranes, and in changes in the cardiac action potential. These effects may be partly related to the mild hypokalaemia present in these animals.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Heart; Male; Membrane Potentials; Muscles; Potassium; Rats; Rats, Inbred Strains; Sodium; Vasopressins

Topics: Adolescent; Brain Diseases; Diabetes Insipidus; Female; Humans; Hypoxia; Male; Middle Aged; Vasopressins

Topics: Animals; Diabetes Insipidus; Drug Resistance; Kidney Medulla; Mice; Mice, Mutant Strains; Molecular Weight; Osmolar Concentration; Phosphorylation; Proteins; Urine; Vasopressins

The proposition that rat prolactin has an intrinsic antidiuretic activity was examined using a conscious rat model (Brattleboro homozygotes, DI rats) which does not appear to produce arginine vasopressin (AVP). A preparation of rat prolactin obtained from NIAMDD, rat prolactin B1, produced a prompt antidiuresis when administered intravenously to these animals. Prolactin B1 was found to contain 150 ng of AVP/mg protein by RIA. All of the measurable AVP was removed from prolactin B1 by polyacrylamide gel electrophoresis and the electrophoresed prolactin was completely devoid of any antidiuretic activity. Addition of synthetic AVP to electrophoresed prolactin in an amount equivalent to the AVP contamination of prolactin B1 completely restored the originally observed antidiuretic activity. Synthetic AVP given alone produced a similar antidiuresis, but in the presence of electrophoresed prolactin these effects were produced by much smaller amounts of AVP. We believe that our data demonstrate that rat prolactin has no intrinsic antidiuretic activity, and that the antidiuretic activity associated with different prolactin preparations could be entirely due to their contamination with AVP. The data also show that the presence of prolactin enhanced by about five times the antidiuretic activity of AVP.

Topics: Animals; Arginine Vasopressin; Diabetes Insipidus; Electrophoresis, Polyacrylamide Gel; Kinetics; Osmolar Concentration; Prolactin; Radioimmunoassay; Rats; Vasopressins

Topics: Adolescent; Adult; Child; Child, Preschool; Diabetes Insipidus; Female; Humans; Infant; Kidney Concentrating Ability; Male; Middle Aged; Vasopressins

An adolescent boy with essential hypernatremia, absent corpus callosum, mental retardation, hypodipsia, and partial diabetes insipidus with "inappropriate" ADH regulation and secretion was studied regarding factors controlling ADH and neurophysin release. Persistent hyperosmolality was noted while on 100 mEq sodium intake daily. Endogenous vasopressin activity was demonstrated after prolonged water deprivation. Hypertonic saline infusion produced increased volumes but dilute urine. Aqueous pitressin increased urinary osmolality, decreased serum osmolality, urine flow rate, and free water clearance. Stable water diuresis was induced by water loading and on normal saline infusion. Nicotine-stimulated neurophysin remained unexpectedly low and below the level of detectability when sampled during the physiologic studies, whereas oestrogen-stimulated neurophysin was elevated during oestrogen stimulation, water loading, and orthostasis procedures. Plasma vasopressin was suppressed with water loading but remained suppressed 90 min after tilt table testing. These data indicate impairment of the osmoreceptor mechanism: however, since the patient had a normal response of oestrogen-stimulated neurophysin, that part of the neurohypophysis appears intact. Chlorpropamide was effective in alleviating the hyperosmolar state acutely and maintained normal osmolar concentrations during two years of therapy.

Topics: Adolescent; Chlorpropamide; Diabetes Insipidus; Diuresis; Electrolytes; Fluid Therapy; Humans; Hypernatremia; Intellectual Disability; Male; Neurophysins; Osmolar Concentration; Posture; Saline Solution, Hypertonic; Vasopressins; Water

A group of vasopressin-deficient rats (Brattleboro strain--DI) and a group of normal Long-Evans rats were successively evaluated on visual discrimination, olfactory discrimination, delayed alternation at short and long intertrial intervals (ITIs), approach-avoidance conflict in a straight runway, and open-field behavior. It was found that DI rats adapted more slowly than normal rats in the T-maze, in the straight runway, and they were slower to emerge into the open field. The DI rats were impaired relative to normal animals on the discrimination tasks (visual and olfactory), but they were not impaired on delayed alternation (at least for short ITIs). DI rats also showed better retention of the punishment effect in the approach-avoidance conflict test than normal animals. It is suggested that DI rats have defective reference-memory mechanisms, fairly intact working-memory processes and altered adaptability (timidity or cautiousness).

Topics: Animals; Appetitive Behavior; Avoidance Learning; Behavior, Animal; Diabetes Insipidus; Discrimination Learning; Habituation, Psychophysiologic; Homozygote; Male; Mental Recall; Orientation; Rats; Rats, Inbred Strains; Smell; Vasopressins; Visual Perception

The paraventricular nucleus of the rat hypothalamus has been shown to project to the medulla and spinal cord. The proportion of oxytocin-neurophysin (OTNP) axons to vasopressin-neurophysin (VPNP) axons in these structures is unknown. A major difficulty in resolving this problem in previous immunocytochemical studies was the lack of a specific antiserum to each rat neurophysin. In this study two approaches have been used: (1) comparison of immunostaining for neurophysin in normal versus homozygous Brattleboro rats with diabetes insipidus (HODI) which lack VPNP, and (2) application of an antiserum to both rat neurophysins absorbed with HODI rat hypothalamic-pituitary extracts which contain only OTNP. The latter would result in an antiserum specific for VPNP. Our results indicate that the axons which constitute the caudal projections from the paraventricular nucleus are predominately oxytocinergic, the vasopressinergic innervation being limited to the nucleus tractus solitarius, the dorsal motor nucleus of vagus, and the substantia gelatinosa. A similar number of reactive fibers were seen in the medulla and spinal cord of normal and HODI rats. No positive perikarya were observed caudal to the hypothalamus. Fibers in the medulla appeared to terminate in the nucleus of the solitary tract and in the dorsal motor nucleus of the vagus nerve. Positive fibers throughout the cord were present in the substantia gelatinosa and in the intermediolateral grey. The possible role(s) of these projections in integrating autonomic functions and afferent information with neuroendocrine regulation is discussed.

Topics: Animals; Axons; Diabetes Insipidus; Diabetes Mellitus; Hypothalamus; Immunoenzyme Techniques; Medulla Oblongata; Neural Pathways; Neurophysins; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Receptors, Cell Surface; Spinal Cord; Staining and Labeling; Vasopressins

Our previous studies (1974. J. Clin. Invest.54: 753-762.) suggested that impaired metabolism of cyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) and in medullary thick ascending limbs of Henle's loop (MAL) microdissected from control mice with normal concentrating ability and from mice with hereditary NDI. Adenylate cyclase activity stimulated by VP or by NaF was only slightly lower (-24%) in MCT from NDI mice, compared with controls. In MAL of NDI mice, basal, VP-sensitive, and NaF-sensitive adenylate cyclase was markedly (> -60%) lower compared with MAL of controls. The specific activity of cAMP-PDIE was markedly higher in MCT of NDI mice compared with controls, but was not different between MAL of control and NDI mice. Under present in vitro conditions, incubation of intact MCT from control mice with VP caused a striking increase in cAMP levels (>10), but VP failed to elicit a change in cAMP levels in MCT from NDI mice. When the cAMP-PDIE inhibitor 1-methyl-3-isobutyl xanthine (MIX) was added to the above incubation, VP caused a significant increase in cAMP levels in MCT from both NDI mice and control mice. Under all tested conditions, cAMP levels in MCT of NDI mice were lower than corresponding values in control MCT. Under the present experimental setting, VP and other stimulating factors (MIX, cholera toxin) did not change cAMP levels in MAL from either control mice or from NDI mice. The results of the present in vitro experiments suggest that the functional unresponsiveness of NDI mice to VP is perhaps mainly the result of the inability of collecting tubules to increase intracellular cAMP levels in response to VP. In turn, this inability to increase cAMP in response to VP is at least partly the result of abnormally high activity of cAMP-PDIE, a somewhat lower activity of VP-sensitive adenylate cyclase in MCT of NDI mice, and perhaps to a deficiency of some other as yet unidentified factors. The possible contribution of low VP-sensitive adenylate cyclase activity in MAL of NDI mice to the renal resistance to VP remains to be defined.

Topics: Adenylyl Cyclases; Animals; Cyclic AMP; Diabetes Insipidus; Female; Kidney Tubules; Kidney Tubules, Collecting; Male; Mice; Phosphoric Diester Hydrolases; Sodium Fluoride; Vasopressins; Xanthines

1. Hypothalamo-pituitary-adrenocortical activity in male homozygous and heterozygous Brattleboro rats was compared with that in normal (Long Evans) controls in an attempt to elucidate the role of vasopressin the control of the secretion of corticotrophin. 2. The concentrations of corticosterone and corticotrophin in the plasma, corticotrophin in the adenohypophyses and corticotrophin releasing factor in the hypothalami were lower in the heterozygotes than in the controls and lower still in the homozygotes. 3. The capacities of adenohypophyses and hypothalami to secrete in vitro corticotrophin and corticotrophin releasing factor respectively in response to trophic stimuli were also reduced in the heterozygotes and, to an even greater extent, in the homozygotes. 4. The results suggest that vasopressin is not the corticotrophin releasing factor but they do not exclude the possibility that it may be involved in the sequence of events which leads to the secretion of corticotrophin in the rat.

Topics: Adrenocorticotropic Hormone; Animals; Corticosterone; Corticotropin-Releasing Hormone; Diabetes Insipidus; Heterozygote; Homozygote; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Rats; Vasopressins

We investigated in conscious rats, whether vasopressin, whose release was stimulated by isoprenaline (i.m.), caused the simultaneous increase in plasma beta-endorphin-like immunoreactivity (beta-EI). The increase in plasma beta-EI following isoprenaline administration was diminished by about 50% in rats pretreated with a vasopressin antagonist and also in rats with a hereditary absolute lack of vasopressin. We conclude that the isoprenaline-induced release of beta-EI is mediated in part by vasopressin.

Topics: Animals; Arginine Vasopressin; beta-Endorphin; Diabetes Insipidus; Endorphins; Isoproterenol; Male; Rats; Vasopressins

Topics: Animals; Diabetes Insipidus; Diuresis; Dogs; Male; Morphine; Naloxone; Receptors, Opioid; Vasopressins

Topics: Animals; Body Fluids; Dendrites; Diabetes Insipidus; Haplorhini; Hypothalamus; Inappropriate ADH Syndrome; Macaca mulatta; Osmolar Concentration; Sensory Receptor Cells; Vasopressins; Water-Electrolyte Balance

A rare case of acute lymphoblastic leukemia presenting with vasopressin-responsive diabetes insipidus (DI) is reported. The patient presented with polydypsia and polyuria of 9 L/day. Findings from special investigations of the CNS, including brain scan, computerized tomographic scan, EEG, and lumbar puncture were within normal limits. The patient's condition improved substantially after receiving vasopressin injections and later chlorpropamide. The incidence and underlying mechanism of this rare complication of acute leukemia are reviewed, and the response of DI to chlorpropamide is discussed briefly. In this patient it is presumed that the DI was caused by leukemic infiltration of the supraopticohypophyseal tract, posterior pituitary, or hypothalamus.

Topics: Adult; Chlorpropamide; Diabetes Insipidus; Female; Humans; Leukemia, Lymphoid; Vasopressins

Topics: Animals; Desoxycorticosterone; Diabetes Insipidus; Female; Heterozygote; Homozygote; Kidney; Male; Rats; Renin; Time Factors; Vasopressins

The binding of [3H] corticosterone to hippocampal cytosol receptors of Brattleboro rats homozygous for diabetes insipidus (Ho-Di) and of normal Brattleboro rats (Ho-No) was investigated at 24 h after removal of the adrenals. The apparent maximal binding capacity of the Ho-Di hippocampal corticosterone receptor system was about 30% less than that of the Ho-No rats. Substitution of the vasopressin deficient rats with 1E pitressin tannate in oil partially restores the hippocampal corticosterone receptor level towards that of the control animals.

Topics: Adrenalectomy; Animals; Arginine Vasopressin; Diabetes Insipidus; Hippocampus; Homozygote; Male; Rats; Rats, Brattleboro; Receptors, Glucocorticoid; Receptors, Steroid; Vasopressins

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Humans; Rats; Rats, Inbred Strains; Vasopressins

Topics: Chlorothiazide; Chlorpropamide; Craniocerebral Trauma; Diabetes Insipidus; Dopamine; Humans; Vasopressins

Topics: Adult; Anemia, Hemolytic, Autoimmune; Carbamazepine; Diabetes Insipidus; Female; Humans; Jaundice; Vasopressins

Reported in this paper are peculiarities relating to pregnancy and labour of eight patients with diabetes insipidus. The disease took different courses. Pregnancy in such cases was found to be endangered quite often by abortion and premature birth. Adiurekrin was used in the treatment of diabetes insipidus. Developmental disorders were not recorded from the infants born by the above women.

Topics: Abortion, Spontaneous; Diabetes Insipidus; Female; Gestational Age; Humans; Infant, Newborn; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Vasopressins

Topics: Anuria; Diabetes Insipidus; Edema; Humans; Inappropriate ADH Syndrome; Oliguria; Syndrome; Vasopressins; Water-Electrolyte Balance

Topics: Diabetes Insipidus; Humans; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Diabetes Insipidus; Drug Resistance; Gout; Humans; Hydronephrosis; Kidney Diseases; Male; Vasopressins

Blocks of the anterior hypothalamus containing vasopressin neurons were grafted from normal 17-day-old rat fetuses into the median eminence of adult female rats with a congenital deficiency of vasopressin neurons (Brattleboro strain rats). Immunocytochemical staining of the transplants 40 days after grafting demonstrated the presence of magnocellular neurons which stained positively for vasopressin and neurophysin. Axons from these neurons could be traced into the median eminence and the primary capillary plexus of the hypothalamo-hypophyseal portal system. Water consumption decreased by as much as 63% in animals carrying viable grafts. The observation that water consumption decreased and remained depressed in hosts carrying viable grafts along with the immunocytochemical data suggest that the transplanted neurons are synthesizing, storing, and releasing biologically active VP.

Topics: Animals; Axons; Diabetes Insipidus; Drinking Behavior; Female; Fetus; Hypothalamo-Hypophyseal System; Median Eminence; Neurons; Pregnancy; Rats; Rats, Inbred Strains; Transplantation, Homologous; Vasopressins

Topics: Adult; Carbamazepine; Chlorpropamide; Chlorthalidone; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hydrochlorothiazide; Pituitary Function Tests; Vasopressins

Topics: Animals; Arginine Vasopressin; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Homozygote; Male; Osmolar Concentration; Prostaglandins E; Prostaglandins F; Rats; Sex Factors; Urine; Vasopressins

Indomethacin (40 mg kg-1 in a single dose) was applied by stomach tube to inhibit the synthesis of prostaglandins during extracellular fluid volume expansion with isotonic saline in normal and acutely (2 h) hypophysectomized Wistar rats and hydropaenic diabetes insipidus Brattleboro rats. In the normal rats indomethacin reduced urine output due to decreased free water excretion. In the rats deprived of antidiuretic hormone (ADH) by acute hypophysectomy or due to hereditary eror in ADH synthesis indomethacin also decreased the urine output and clearance of osmotically free water. It is concluded that also other mechanisms besides the established competition between ADH and prostaglandins for ADH receptors may be responsible for the indomethacin effect on the osmotic movement of water in the distal nephron.

Topics: Animals; Diabetes Insipidus; Hypophysectomy; Indomethacin; Kidney; Rats; Species Specificity; Vasopressins

A radioimmunoassay of ADH has been applied to the study of plasma ADH levels in various conditions. The validity of the assay has been evaluated by the usual quality control parameters of RIA and by the measure of plasma levels in 12 upright water deprived normal volunteers (mean 9.5 pg/ml, SEM +/- 1.5) in 8 resting and hydrated normal volunteers (1.3 +/- 0.4 pg/ml), in a case of diabetes insipidus (1.6 pg/ml), in 8 cases of SIADH Syndrome (range 13-77 pg/ml) and in 4 anesthetized dogs before (33.7 +/- 9.2 pg/ml) and after acute haemorrhage (66 +/- 9.5 pg/ml, p less than 0.02). The osmotoic challenge to ADH secretion has been studied in 8 patients with no overt endocrine pathology by salt perfusion and showed a significant rise (p less than 0.05) of plasma ADH from 6.3 +/- 3.1 pg/ml before, to 20.6 +/- 7.9 pg/ml during salt infusion corresponding to the significant (p less than 0.0001) rise of plasma osmolality from 273 +/- 2.8 to 288.2 +/- 1.1 m Osm/kg.

Topics: Animals; Dehydration; Diabetes Insipidus; Dogs; Hemorrhage; Humans; Inappropriate ADH Syndrome; Osmolar Concentration; Radioimmunoassay; Saline Solution, Hypertonic; Vasopressins

Topics: Analgesia; Animals; Cold Temperature; Diabetes Insipidus; Female; Morphine; Rats; Stress, Physiological; Swimming; Vasopressins

Topics: Child; Chlorpropamide; Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Diuresis; Humans; Lypressin; Thyroid Function Tests; Vasopressins

Topics: Diabetes Insipidus; Humans; Vasopressins

Blood free fatty acids (FFA) concentration was studied during 3 hrs after administration of I ml sunflower oil in consious normal and Brattleboro rats. Fasting FFA levels were similar in both groups of animals. In normal rats FFA concentration did not change significantly during the first 2 hrs after fat ingestion, the increase being observed to the end of the 3d hr. In DI-rats there was an increase in the concentration already to the end of the 1st hr which persisted till the end of experiment. The difference in FFA dynamics was observed just at the period when an antidiuretic reaction to fat ingestion was developed in normal animal. To establish whether the difference in FFA dynamics is actually due to the antilipolytic effect of vasopressin released after fat ingestion it is necessary to exclude the action of the hormone on fat absorption.

Topics: Animals; Diabetes Insipidus; Dietary Fats; Digestion; Fatty Acids, Nonesterified; Helianthus; Intestinal Absorption; Lipolysis; Oils; Rats; Vasopressins

Permanent diabetes insipidus following head trauma is uncommon, but potentially fatal. The neurologic, roentgenographic, and endocrinologic findings in ten patients with this condition are reported. Eight of the patients were males under the age of 35 years. Unconsciousness (nine) and skull fracture (seven) were frequent findings. Cranial nerve damage (four) and anterior pituitary hormone deficiency requiring replacement (one) were less frequent. An automobile accident caused the trauma in six patients. Standard water deprivation tests revealed that five of the patients had total deficiency of antidiuretic hormone (ADH), and the other five had partial deficiency. The diagnosis of diabetes insipidus was markedly simplified by using a new screening test based on comparing urine and plasma osmolality in candidates with those of normal subjects.

Topics: Adult; Craniocerebral Trauma; Diabetes Insipidus; Female; Humans; Male; Osmolar Concentration; Polyuria; Vasopressins

Clonidine, an alpha adrenergic agonist which causes a diuresis in experimental animals, was studied in unanesthetized, conscious Brattleboro rats heterozygous or homozygous for hereditary hypothalamic diabetes insipidus to determine if the diuresis was due to alpha adrenergic inhibition of antidiuretic hormone (ADH) release or to another mechanism of action. Heterozygous rats given clonidine s.c. in doses of 50 to 300 mu/kg b.w. exhibited a prompt dose-related diuresis. The diuresis was transient and could not be maintained beyond 4 hr even when clonidine was administered continuously by s.c. osmotic minipump. In response to clonidine-induced diuresis, plasma osmolality increased acutely from 300 +/- 1 to 310 +/- 1 mOsM/kg by 60 min after injection. Base-line plasma ADH was 5.1 +/- 0.9 mu/ml, remained unchanged at 15 min after clonidine injection but increased to 21.6 +/- 7.2 muU/ml by 60 min and was accompanied by an increase in urinary ADH excretion from 19.6 +/- 3.7 to 48.6 +/- 5.3 muU/hr. In parallel with the drug-induced diuresis, there was an increase in urinary excretion of creatinine, sodium and total solute. The alpha blocking agent phenoxybenzamine did not prevent the diuresis after clonidine injection. Clonidine antagonized the antidiuresis after clonidine injection. Clonidine antagonized the antidiuretic action of ADH administered to rats homozygous for diabetes insipidus. Thus, clonidine-induced diuresis does not appear to be due to alpha adrenergic inhibition of ADH release but rather to direct renal effects.

Topics: Animals; Clonidine; Creatinine; Diabetes Insipidus; Diuresis; Electrolytes; Kidney; Male; Osmolar Concentration; Phenoxybenzamine; Rats; Vasopressins

Topics: Benzothiadiazines; Carbamazepine; Chlorpropamide; Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuretics; Humans; Lypressin; Sodium Chloride Symporter Inhibitors; Vasopressins

Medullary thyroid carcinoma (MTC) is a known apudoma producing calcitonin, prostaglandins and serotonin. It can present itself as a familial or sporadic form or as part of a multiple endocrine adenomatosis. We present here the case of a patient admitted with a four-year history of diarrhea, enlargement of the thyroid and palpable lymph nodes in the right side of the neck. There was no uptake of 131I in the right lobe of the thyroid and the serum calcitonin levels were very high. With the diagnosis of MTC a total thyroidectomy mas performed developping within hours of the surgical procedure a picture of diabetes insipidus with 31 liters of urine output in the first 48 hours. It responded to vasopressin and disappeared spontaneously in two weeks. We have considered the different mechanisms that could explain the development of diabetes insipidus, and after failing to find one, we especulate at prostaglandins could play an important role in the synthesis and/or release of ADH. The sudden depletion of prostaglandins after removal of the neoplasm that produced them could account for the diabetes insipidus in our patient. We have not found any similar case described in the literature. We call attention to the need for a close postoperative observation of patients operated for MTC for the possible onset of diabetes insipidus.

Topics: Adult; Apudoma; Diabetes Insipidus; Humans; Male; Postoperative Complications; Thyroid Neoplasms; Thyroidectomy; Vasopressins

Topics: Blood Glucose; Child; Child, Preschool; Craniopharyngioma; Diabetes Insipidus; Diabetic Coma; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Pituitary Neoplasms; Postoperative Complications; Vasopressins

PGE2 synthesis rate was studied in vitro in isolated glomeruli and in papillary homogenates prepared from kidneys of Brattleboro rats with hereditary diabetes insipidus (DI) (no ADH) and of Brattleboro heterozygous control rats. Incubations were carried out in isotonic buffer at 37 degrees C in the presence or absence of arachidonic acid for 15, 30, 60 and 90 min. PGE2 production was measured in the supernatant by specific radioimmunoassay. Results were compared by analysis of variance. PGE2 production was significantly decreased in the papilla (p < 0.01) and increased in the glomeruli (p < 0.01) of DI rats compared to controls. Stimulation by arachidonic acid was similar in both groups. Chronic ADH deficiency thus modifies the ability of the kidney to produce PGE2 in vitro. The opposite effects observed in glomeruli and papilla suggest a different hormonal control of PGE2 synthesis in both tissues.

Topics: Animals; Arachidonic Acids; Diabetes Insipidus; Female; Kidney Glomerulus; Kidney Medulla; Male; Prostaglandins E; Rats; Vasopressins

1. The effect of chronic bile-duct ligation on systemic and renal haemodynamics and on the capacity to dilute the urine was studied in conscious rats. Sham-operated rats served as controls. 2. In the rats with bile-duct ligation, the maximal urinary diluting capacity was impaired, despite an expanded plasma volume, a normal mean arterial pressure and cardiac output, and normal intrarenal determinants of water excretion including distal delivery of fluid and function of the diluting segment. 3. In contrast, maximal urinary dilution capacity was intact in rats with congenital central diabetes insipidus and chronic bile-duct ligation. 4. It is concluded that the defect in urinary dilution in rats with chronic bile-duct ligation is dependent on antidiuretic hormone.

Topics: Animals; Bile Ducts; Cholestasis; Diabetes Insipidus; Glomerular Filtration Rate; Hemodynamics; Kidney; Liver; Male; Osmolar Concentration; Rats; Vasopressins

Diabetes insipidus can be delineated in the context of the normal physiology of water metabolism. This approach highlights the common pathway taken by the variety of diseases that can progress to an insufficiency of antidiuretic hormone (ADH) and to diabetes insipidus. A simple diagnostic approach uses homeostatic pathways to separate diabetes insipidus from the other polyuric states. New developments in the biochemical alteration of ADH have improved the ability to individualize hormonal replacement and promise better therapy in the near future.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Osmolar Concentration; Urine; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Vasopressin neurons, transplanted from normal rat fetuses into the third ventricle of adult Brattleboro rats, alleviate the polydipsia and polyuria of the hosts. Determination of the antidiuretic activity of grafted neurons in hosts with congenital diabetes insipidus provides a convenient model for analyzing the development, plasticity, and function of transplanted central nervous system neurons in mammals.

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Drinking Behavior; Hypothalamus; Kidney Concentrating Ability; Rats; Transplantation, Homologous; Vasopressins

Ninety three cases of diabetes insipidus are reviewed after 1 to 20 years follow-up. A codified water deprivation test realized in 50 cases revealed 31 severe cases and 19 partial forms. Apart from surgical causes of diabetes insipidus (16%), tumors represent the most frequent etiology (33.5%), essentially craniopharyngiomas and pinealomas. Histiocytosis X (16%) is also an important cause. In one third no cause could be found. Decreased secretion of anterior pituitary hormones is very common in association with surgical and tumoral causes and can also be found in idiopathic forms. Thus, in our experience, detection of a pituitary deficit is not necessarily associated with a tumor. It can be pointed out that when an etiology is found it is always discovered during the four years following the onset of diabetes insipidus. This implies that very careful neurological and neuroradiological follow-up is necessary during this period.

Topics: Adolescent; Adult; Child; Child, Preschool; Diabetes Insipidus; Female; Humans; Infant; Male; Vasopressins

The hypothalamic-neurohypophyseal system functions to maintain plasma osmolality within narrow limits. It also is an important mechanism in maintaining normal body fluid volume. The system exerts its influence via release or inhibition of vasopressin (antidiuretic hormone, ADH) which acts on the kidney to decrease water excretion. Deficiency of ADH is usually due to hypothalamic-neurohypophyseal lesions (central diabetes insipidus) or insensitivity of the kidney to ADH (nephrogenic diabetes insipidus). These patients, if untreated, have the predictable result of dehydration, hyperosmolality, hypovolemia, and eventual death in severe cases. On the other hand, ADH excess of the syndrome of inappropriate ADH secretion due to a variety of causes promotes water retention, hypoosmolality and hyponatremia which, if untreated, may progress to convulsions, coma, and death. It is obviously important to diagnose accurately these pathologic states of hydration. Not only is initiation of treatment in general dependent upon recognition of the disease, but each type of pathologic hydration state has specific treatment which rewards both patient and physician with effective correction of the problem.

Topics: Demeclocycline; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Kidney; Pituitary Gland, Posterior; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Corticotropin-Releasing Hormone; Diabetes Insipidus; Hypothalamo-Hypophyseal System; In Vitro Techniques; Pituitary-Adrenal System; Rats; Vasopressins

Topics: Adaptation, Psychological; Child, Preschool; Diabetes Insipidus; Female; Humans; Nicotine; Vasopressins

Topics: Activities of Daily Living; Diabetes Insipidus; Humans; Hydrocortisone; Hypophysectomy; Patient Education as Topic; Pituitary Gland; Pituitary Neoplasms; Self Administration; Vasopressins

Topics: Diabetes Insipidus; Female; Humans; Male; Vasopressins

Topics: Clofibrate; Craniopharyngioma; Diabetes Insipidus; Drinking; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Postoperative Complications; Sodium; Vasopressins

Topics: Absorption; Animals; Body Water; Clonidine; Diabetes Insipidus; Diuresis; Drinking; Electrolytes; Female; Glomerular Filtration Rate; Kidney Tubules; Male; Punctures; Rats; Vasopressins

We describe a patient with hypothalamic diabetes insipidus who after 20 years became refractory to the effect of commercial vasopressin injection. Vasopressin antibodies were measured using a sensitive hemagglutination technique. Resistance was associated with a high titer of antibodies that disappeared once vasopressin therapy was withdrawn and the diabetes insipidus was controlled with chlorpropamide. Antibodies were also measured in four additional patients with diabetes insipidus while they were or were not receiving vasopressin. A patient who had received the drug for only two years already had a substantial titer of antibodies to vasopressin, but in this case the response to the hormone was not impaired.

Topics: Adolescent; Adult; Antibodies; Chlorpropamide; Diabetes Insipidus; Drug Resistance; Female; Hemagglutination Inhibition Tests; Humans; Male; Middle Aged; Vasopressins

Topics: Acute Disease; Carbamazepine; Chlorpropamide; Chronic Disease; Clofibrate; Diabetes Insipidus; Diagnosis, Differential; Humans; Saline Solution, Hypertonic; Vasopressins

Topics: Child; Diabetes Insipidus; Female; Humans; Infant; Kidney; Male; Vasopressins

Despite the apparent absence of vasopressin (ADH), Brattleboro homozygotes [diabetes insipidus (DI) rats] can concentrate their urine when deprived of drinking water. Since other investigators have shown that reducing glomerular filtration rate (GFR) improves the concentrating ability of water-loaded dogs, the present studies were undertaken to quantify the magnitude and time course of changes in GFR during dehydration. Clearance experiments were performed in 10 conscious DI rats before and following 3, 6, 9, 12, 15, and 24 h of dehydration. Urine osmolality increased from 155.0 +/- 12.6 (SE) to 696.7 +/- 8.4 mosmol/kg H2O after 24 h. GFR averaged 984.3 +/- 79.6 microliters . min-1 . 100 g body wt-1 in the control phase, fell to about 80% of this value over the first 12 h of dehydration, and then declined to 27% at 24 h. The rats lost 20% of their body weight over the 24 h. The osmolality of the papillary tip averaged 896 +/- 44 mosmol/kg H2O at 24 h compared to a control value of 493 +/- 28. The lack of osmotic equilibration between urine and papillary interstitium suggests that dehydration did not appreciably increase the water permeability of the distal nephron. These experiments clearly show a progressive decline in GFR as urine becomes concentrated during dehydration in the absence of ADH; these events may or may not be causally related.

Topics: Animals; Dehydration; Diabetes Insipidus; Female; Glomerular Filtration Rate; Kidney Concentrating Ability; Kidney Medulla; Male; Osmolar Concentration; Rats; Urine; Vasopressins

Topics: Adult; Body Water; Diabetes Insipidus; Diuresis; Extracellular Space; Humans; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Intracellular Fluid; Kidney Concentrating Ability; Kidney Failure, Chronic; Osmolar Concentration; Sodium; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

Topics: Diabetes Insipidus; Diagnosis, Differential; Humans; Hydrochlorothiazide; Infant; Infant, Newborn; Male; Pedigree; Sodium; Vasopressins

Diabetes insipidus, resulting from metastatic involvement of the neurohypophysial system, is a rare complication of breast cancer. This review examined the clinical features, metastatic pattern, and radiological and postmortem findings of 39 breast cancer patients with this complication. All patients had polyuria and polydipsia, and all had evidence of advanced metastatic breast cancer. A high incidence of meningeal carcinoma carcinomatosis and/or sellar metastases was observed. In view of the anatomical proximity of the posterior pituitary to the dura mater and the sella turcica, our findings suggest that metastases to the neurohypophysis can occur not only as a result of hematogenous dissemination of malignant cells, but also from direct tumor extension and/or invasion from adjacent structures. Although satisfactory symptomatic relief can be obtained with vasopressin tannate, complete resolution of the diabetic insipidus syndrome was evident only in those patients who had achieved control of the underlying breast disease.

Topics: Adult; Aged; Breast Neoplasms; Diabetes Insipidus; Female; Humans; Meningeal Neoplasms; Menopause; Middle Aged; Neoplasm Metastasis; Pituitary Neoplasms; Sella Turcica; Vasopressins

Topics: Adolescent; Arginine Vasopressin; Dehydration; Diabetes Insipidus; Diagnosis, Differential; Eosinophilic Granuloma; Female; Humans; Hypothalamo-Hypophyseal System; Osmolar Concentration; Recurrence; Vasopressins

Topics: Diabetes Insipidus; Humans; Hypertonic Solutions; Osmotic Pressure; Vasopressins

Topics: Animals; Diabetes Insipidus; Dog Diseases; Dogs; Female; Vasopressins; Water Deprivation

Topics: Adult; Child; Diabetes Insipidus; Female; Humans; Kidney Diseases; Male; Osmotic Pressure; Sodium Chloride; Urea; Vasopressins

Rabbits immunized against vasopressin developed clinical signs of diabetes insipidus persisting for up to two months after the last boost. Ultrastructural and immunocytochemical studies of the neurohypophysis demonstrated autoimmune alterations: infiltration by immune cells and extracellular deposits of immunoglobulins. No alterations were observed in the hypothalamic nuclei synthesizing vasopressin nor in hormone-target cells of the kidney. Immunization against vasopressin may provide the first example of an autoimmune disease in the hypothalamo-neurohypophysial system.

Topics: Animals; Antibodies; Antigen-Antibody Complex; Autoantibodies; Axons; Capillaries; Diabetes Insipidus; Immunity, Cellular; Neurons; Neurosecretion; Pituitary Gland, Posterior; Rabbits; Vasopressins

Topics: Aldosterone; Calcium; Diabetes Insipidus; Electrolytes; Endocrine System Diseases; Humans; Parathyroid Diseases; Parathyroid Hormone; Sodium; Thyroid Diseases; Vasopressins; Water-Electrolyte Imbalance

Topics: Carbamazepine; Child; Clofibrate; Diabetes Insipidus; Diuresis; Drug Evaluation; Drug Therapy, Combination; Humans; Kidney Concentrating Ability; Male; Mannitol; Osmolar Concentration; Vasopressins

A patient with diabetes insipidus and hypothyroidism developed anovular menstrual cycles. Ovulation, which was followed by pregnancy, was induced by the administration of clomiphene. In the later stages of pregnancy, an increase in the dosage of vasopressin was necessary to achieve a satisfactory control of the symptoms of diabetes insipidus. Labour was induced before the estimated date of confinement by the intravenous administration of oxytocin and an intra-partum haemorrhage necessitated delivery by the lower-segment caesarean section. The post-partum period was uneventful. Lactation was suppressed on request from the patient.

Topics: Adult; Anovulation; Clomiphene; Diabetes Insipidus; Female; Humans; Hypothyroidism; Infertility, Female; Labor, Induced; Ovulation; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Vasopressins

Diabetes insipidus was diagnosed in a 6-year-old Holstein-Friesian cow with a history of recurrent fever, ketosis, lymphadenopathy, and inappetence. The diagnosis was based on the clinical findings, response to exogenous vasopressin, and lack of urine concentration in a water deprivation test. The disease gradually regressed over a period of 1 year and did not recur.

Topics: Animals; Cattle; Cattle Diseases; Diabetes Insipidus; Female; Fever; Urinary Catheterization; Vasopressins; Water Deprivation

1. The possible pressor effect of vasopressin immediately after acute haemorrhage has been studied using anaesthetized Brattleboro rats with diabetes insipidus and rats of the Long Evans parent strain.2. A blood loss of 0.5% of the body weight caused a significant decrease in mean arterial blood pressure, measured 10 min later, in Brattleboro rats, whereas this degree of haemorrhage was non-hypotensive in the control Long Evans rats. Following subsequent blood losses (each of 0.5% of the body weight), mean arterial blood pressure in Brattleboro rats was always significantly lower than in Long Evans rats.3. While no antidiuretic activity was at any time found in the plasma of Brattleboro rats, haemorrhages greater than 1% of the body weight were associated with marked increases in plasma arginine vasopressin (AVP) of Long Evans rats.4. When Brattleboro and Long Evans rats were subjected to a single haemorrhage of 2% of the body weight, the immediate decrease in arterial blood pressure was similar in the two groups. However, 5 and 10 min after the haemorrhage the arterial blood pressure was significantly higher in the Long Evans rats. When vasopressin was infused into Brattleboro rats so that plasma levels of the hormone approached those found in Long Evans rats, the mean arterial blood pressure 0, 5 and 10 min after haemorrhage was similar to that in the Long Evans animals.5. It is concluded that in the anaesthetized rat, vasopressin plays an important role in the regulation of arterial blood pressure during the period immediately following acute haemorrhage.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Heart Rate; Hemorrhage; Male; Rats; Vasopressins

Topics: Angiotensin II; Animals; Diabetes Insipidus; Diuresis; Dogs; Dopamine; Drinking; Isoproterenol; Male; Natriuresis; Vasopressins

A cyclic excess of cortisol secretion was detected in a patient with diabetes insipidus and diabetes mellitus. The cycles of hypercortisolism were of 7 days' duration, but during the nadir of these cycles urinary excretion of corticosteroids and 17-ketosteroids was within the normal range. The radiological appearance of the sella turcica was normal; however, computerized axial tomography of the head revealed a small tumor immediately superior to the sella turcica. At operation a small chromophobe adenoma superior to the diaphragma sellae and involving the hypophysial stalk was partially resected. Postoperatively, the patient continued to have 7-day cycles of increased corticosteroid excretion, but the amounts excreted were less than they had been preoperatively. Other patients have been described in whom Cushing's disease has been due to cyclic hypercortisolism. These cycles have been remarkably regular in individual patients, but of variable duration in different patients. Furthermore, cyclic hormonogenesis probably occurs in a variety of endocrinopathies. (Neurosurgery, 5: 598--603, 1979).

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma, Chromophobe; Adrenal Cortex; Adult; Cushing Syndrome; Dexamethasone; Diabetes Insipidus; Humans; Hydrocortisone; Male; Periodicity; Pituitary Neoplasms; Vasopressins

Topics: Brain Diseases; Cerebral Ventricles; Diabetes Insipidus; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Vasopressins

Administration of ovine or rat PRL to animals, including man, has resulted in decreased urine volume and increased urine osmolality. Contamination of PRL preparations with vasopressin is the most likely explanation for the apparent antidiuretic effect. In this study, diabetes insipidus rats lacking vasopressin(homozygous Brattleboro rats) had extra anterior pituitary glands implanted under the kidney capsule, resulting in hyperprolactinemia. The urine of such rats was not more concentrated than that of unoperated littermates or sham-operated littermates with diabetes insipidus. In fact, hyperprolactinemic male rats produced even less concentrated urine than control rats. Furthermore, the hyperprolactinemic rats responded to exogenous vasopressin in a manner similar to normoprolactinemic rats. These studies provide strong evidence against an antidiuretic action of PRL in mammals.

Topics: Animals; Diabetes Insipidus; Diestrus; Estradiol; Female; Hypothalamus; Male; Osmolar Concentration; Pituitary Gland; Pregnancy; Prolactin; Rats; Sheep; Transplantation, Homologous; Urine; Vasopressins

Polyuria and polydipsia developed in two cases during amphotericin B therapy for deep mycoses. Neither patient could concentrate his urine in response to water deprivation or exogenous vasopressin. Other causes of vasopressin-resistant nephrogenic diabetes insipidus were not present. Three months after amphotericin B therapy had been discontinued, concentrating ability improved toward normal. A third patient was further observed and demonstrated normal diluting capacity but impaired free-water reabsorption, suggesting a distal tubular defect consistent with nephrogenic diabetes insipidus. Four months after discontinuing therapy, renal concentrating ability was normal. Amphotericin B can induce a reversible form of nephrogenic diabetes insipidus.

Topics: Amphotericin B; Diabetes Insipidus; Humans; Kidney Concentrating Ability; Kidney Diseases; Male; Middle Aged; Osmolar Concentration; Urine; Vasopressins; Water Deprivation

This report describes the appearance of high affinity antibodies to human LH in a girl who had been treated for diabetes insipidus with injections of pitressin tannate, plus occasional nasal insufflations of posterior pituitary powder. Immunological studies indicated that the antibody was a 7S IgG directed against the beta subunit of LH, which is not species-specific. The demonstration of immunoassayable LH in a commercially available pitressin preparation strongly suggests that this patient was immunized by bovine or porcine LH. Although studies of her urinary LH excretion and serum LH (by an interstitial cell bioassay system) suggest that at least some of her endogenous LH is not bound by the antibody, the possibility remains that this type of immunization may have important implications for the development and maintenance of normal adult pituitary-ovarian relationships.

Topics: Antibodies; Arginine Vasopressin; Child, Preschool; Diabetes Insipidus; Female; Follicle Stimulating Hormone; Follow-Up Studies; Humans; Immunoelectrophoresis; Luteinizing Hormone; Pituitary Gland, Posterior; Radioimmunoassay; Tissue Extracts; Vasopressins

Nephrogenic diabetes insipidus occurred in a 7-year-old child who had received a high dose of demethylchlortetracycline hydrochloride (DMC). The patient had a relatively elevated urinary sodium concentration in addition to isosthenuria. The nephrogenic diabetes insipidus was completely reversible within one month after cessation of DMC administration.

Topics: Child; Demeclocycline; Diabetes Insipidus; Diabetic Nephropathies; Humans; Male; Vasopressins

The authors made conspicuous in the rat the appearance of "diabetes insipidus" induced by two lithium salts: chloride and carbonate administered orally, with increasing doses in food. The polyuria, polydipsia and urinary hypotony are reversible and disappeared with stopping the treatment. The animals became insensible to the exogenous antidiuretic hormon during the treatment and progressively became sensible again during the following twenty days so suggesting a nephrogenic mechanism by lithium: either a loss of ADH activity, either the abolition of intrarenal osmotic pressure gradient.

Topics: Animals; Diabetes Insipidus; Diuresis; Lithium; Male; Rats; Vasopressins

The hypothesis that the effects of ACTH 4-10 on avoidance are mediated via the release of endogenous vasopressin was investigated. To test this hypothesis, we observed the effect of ACTH 4-10 on the passive avoidance of Brattleboro rats with diabetes insipidus resulting from a total genetic deficiency of vasopressin (DI) and Brattleboro rats without diabetes insipidus (HE). Normal Long-Evans rats (LE) were also included for comparison purposes. The results did not support the hypothesis. ACTH 4-10 did influence the passive avoidance of DI rats; this should not have occurred if the release of endogenous vasopressin is necessary for ACTH 4-10 to influence avoidance.

Topics: Adrenocorticotropic Hormone; Animals; Avoidance Learning; Diabetes Insipidus; Female; Rats; Vasopressins

A 6-week-old girl with fever, hypernatraemia, dehydration, and polyuria failed to concentrate urine in response to exogenous vasopressin administration. There was no family history of nephrogenic diabetes insipidus. When she was 15 months old, the infusion of vasopressin did not produce an increase in urinary cyclic-AMP.

Topics: Cyclic AMP; Diabetes Insipidus; Female; Humans; Infant; Kidney Diseases; Vasopressins

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Catecholamines; Child; Child, Preschool; Diabetes Insipidus; Emotions; Endocrine System Diseases; Growth Disorders; Hormones; Humans; Hyperthyroidism; Hypopituitarism; Hypothyroidism; Infant; Infant, Newborn; Protein-Energy Malnutrition; Vasopressins

Urinary excretion of cyclic adenosine monophosphate (cAMP) is assessed in response to pitressin stimulation in three patients with nephrogenic diabetes insipidus, four carriers and seven controls. There is no significant difference in cAMP excretion between these groups when corrected for surface area, nor is there any significant increase in excretion after pitressin stimulation. There is very close correlation between urinary cAMP and both urinary concentration and urinary creatinine excretion. Urinary cAMP after pitressin stimulation does not discriminate between carriers of nephrogenic diabetes insipidus and control subjects.

Topics: Adult; Child; Child, Preschool; Creatinine; Cyclic AMP; Diabetes Insipidus; Female; Genetic Carrier Screening; Humans; Kidney Diseases; Male; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Diabetes Insipidus; Drinking Behavior; Injections, Intraventricular; Male; Rats; Vasopressins

Topics: Adult; Aerosols; Diabetes Insipidus; Female; Humans; Pregnancy; Pregnancy in Diabetics; Skull Fractures; Vasopressins

Normal Long-Evans rats (LE) exhibited diurnal variations of plasma arginine vasopressin (AVP) concentrations with peak values at 10 A.M. and minimum values at 1 P.M. Brattleboro rats heterozygous for hypothalamic diabetes insipidus (DI) had significantly reduced plasma AVP concentrations and increased plasma osmolalities when compared with LE rats. By prolonged injection of 100 mU/day of vasopressin tannate (VPT) into Brattleboro rats homozygous for DI, plasma AVP concentrations close to those of LE rats were achieved. Potassium was retained for 7 days until escape of vasopressin-induced potassium retention occurred. When 500 mU VPT were injected into DI rats, high plasma AVP levels were induced. Potassium was retained for 2-3 days. After initial sodium retention, periods of natriuresis occurred. During treatment with 100 mU VPT/day most of the alterations present in DI rats were corrected, which included increased water turnover and external water loss, increased hematocrit and plasma sodium concentrations (but not increased plasma osmolalities), hypokalemia, increased activity of the renin-angiotensin system, and reduced adrenocortical function.

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Animals; Arginine Vasopressin; Corticosterone; Diabetes Insipidus; Hematocrit; Male; Organ Size; Osmolar Concentration; Potassium; Rats; Sodium; Time Factors; Urea; Vasopressins

Post-traumatic diabetes insipidus was observed in 14 among 702 patients with severe trauma. The cause of the abnormal vasopressin secretion may be cerebral oedema, cerebral contusion near the hypothalamus, pull on the hypophyseal stalk by displacement or gross destruction of the brainstem. The hormonal hypofunction disappears once the cerebral damage has regressed. Treatment consists of exact balancing of water and electrolyte loss, using salt-free solutions. Drug treatment with vasopressin and with ADH-secretion stimulators has given unsatisfactory results, but should be used. Seven of the 14 patients died of their injuries. The symptoms of the diabetes insipidus syndrome regressed in the survivors.

Topics: Adult; Brain Concussion; Brain Edema; Brain Injuries; Brain Stem; Child; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Remission, Spontaneous; Vasopressins

Topics: Administration, Intranasal; Adolescent; Attitude; Child; Child Behavior; Child Development; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Vasopressins

We used dDAVP, the 1-desamino-8-D arginine analogue of arginine vasopressin with high antidiuretic and low vasopressor potency, to treat 29 patients with neurogenic diabetes insipidus for up to 22 months. Intranasal dDAVP, 2.5 to 15 microgram twice daily, provided excellent control in most patients. Individual responses were independent of age, weight, and severity of diabetes insipidus. Resistance to dDAVP may be a rare complication of prolonged therapy. Two patients with acute postoperative diabetes insipidus were effectively treated with 5 microgram of dDAVP every 14 to 18 h. Compared to previous therapy, side effects of dDAVP were minimal (headaches in two patients), and control of symptoms and urine volume was as good as with vasopressin tannate in oil or better than chlorpropamide and lysine vasopressin nasal spray. We conclude that intranasal dDAVP, because of efficacy, long duration of action, and infrequent side effects, is the preferred treatment of neurogenic diabetes insipidus in children and adults.

Topics: Adolescent; Adult; Aged; Arginine Vasopressin; Child; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Nervous System Diseases; Osmolar Concentration; Postoperative Complications; Vasopressins

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Vasopressins

An account is given of experience acquired with the prolonged administration of a new vasopressin analogue, 1-deamino-8-D-arginine vasopressin (DDAVP), to patients with diabetes insipidus. The antidiuretic effect of this compound was compared with that of the long-acting Pitressin Tannate, containing a pituitary extract. It was found that DDAVP induces a far more significant antidiuretic effect than does Pitressin Tannate. Its application is not accompanied by any side effects, nor is its effectiveness decreassed after repeated administration. Similar conclusions were reached with the outpatient treatment of diabetes insipidus patients. The results indicate that nasally-administered Adiuretein-SD can be well utilized in the prolonged treatment of diabetes insipidus.

Topics: Adult; Aged; Deamino Arginine Vasopressin; Depression, Chemical; Diabetes Insipidus; Diuresis; Female; Humans; Male; Middle Aged; Osmolar Concentration; Tissue Extracts; Vasopressins

The coexistence of diabetes insipidus (D.I.) and pregnancy is rare. Sixty-seven cases are reviewed, including one of our own. The condition tends to become worse in pregnancy, labor appears unaffected and lactation appears to lead to an improvement in D.I. Theories are discussed to account for the effect of pregnancy on D.I.

Topics: Adult; Diabetes Insipidus; Female; Humans; Labor, Obstetric; Lactation; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Vasopressins

Topics: Carbamazepine; Chlorpromazine; Clofibrate; Diabetes Insipidus; Diuresis; Drug Evaluation; Drug Therapy, Combination; Humans; Osmolar Concentration; Vasopressins

The effectiveness of therapy with carbamazepine and clofibrate (oral therapy), intramuscular pitressin-in-oil, and intranasal 1-deamino-8-D-arginine vasopressin has been compared in 15 children with partial or complete central diabetes insipidus. Mean daily urine volume without therapy was 5.4 l and dropped to 1.1 and 1.6 l/day while receiving pitressin and DDAVP, respectively. Oral agents decreased the daily urine volume to 2.2 l in patients with partial DI, with good symptomatic control except for some nocturia. These agents had no effect in patients with complete DI and did not alter pitressin requirements. Duration of pitressin action was 24 to 36 hours with a significant incidence of hyponatremia. The duration of DDAVP effect was 8 to 20 hours, varying in individual patients. Children with partial DI required smaller doses of DDAVP and the duration of action was longer than in those with complete DI. Control of serum electrolytes was excellent using two doses per day and nocturia was eliminated. All patients who had received pitressin had growth hormone antibodies, but continued to grow normally unless there was pre-existing growth hormone deficiency. These antibodies gradually disappeared after approximately one year of therapy with oral agents or DDAVP. DDAVP did not alter growth hormone, cortisol, or prolactin levels during sleep. DDAVP is the antidiuretic therapy of choice in children with either complete or partial DI; to date, no side effects have been demonstrated.

Topics: Adolescent; Carbamazepine; Child; Child, Preschool; Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Growth Hormone; Humans; Hydrocortisone; Infant; Oils; Osmolar Concentration; Prolactin; Time Factors; Vasopressins

Topics: Child, Preschool; Diabetes Insipidus; Female; Humans; Meningitis, Haemophilus; Vasopressins

Plasma and urinary arginine vasopressin (AVP) in normal subjects and in patients with various water metabolism disorders was measured using a sensitive, specific radioimmunoassay. The AVP plasma levels in normal subjects were 3.1 +/- 1.2 pg/ml. The parallel changes in plasma osmolality, plasma AVP concentration, and urinary osmolality were observed after water load. In patients with various kinds of hyponatremia and impaired water excretion, plasma AVP concentrations were within or over normal levels, suggesting that persistent secretion of AVP may play an important role in the pathogenesis of hyponatremia. Variable levels of plasma AVP were observed in patients with essential hypernatremia, which in turn suggested that osmoreceptors may be selectively damaged in some patients, and that ADH-secreting neurons are also involved in others. Our radioimmunoassay facility made it possible for us to measure plasma and urinary DDAVP in the treatment of diabetes insipidus.

Topics: Adrenal Insufficiency; Adult; Animals; Arginine Vasopressin; Ascites; Diabetes Insipidus; Dogs; Edema; Humans; Hypernatremia; Hyponatremia; Hypotension, Orthostatic; Infant; Neoplasms; Osmolar Concentration; Radioimmunoassay; Vasopressins; Water

Topics: Adolescent; Adult; Child, Preschool; Diabetes Insipidus; Female; Humans; Male; Vasopressins

Topics: Adolescent; Adult; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Vasopressins

A modified technique of amnnitol-induced diuresis is described, in order to assess renal concentrating ability in infants and children. The infusion of 10% mannitol in 0.9% saline avoided the hypertonic saline overload and the fluid restriction period, both badly tolerated by infants and small children. In a control group of children aged from two months to seven years, the values of T(H2O) plotted against C(OSM) allowed to calculate the adjustment curve y=0.80x0.75, r=0.98 (p is less than 0.0001). In six patients with pituitary diabetes insipidus (PDI), the test was used in order to quantify the degree of ADH deficiency and evaluate the carbamazepine and clofibrate effect, in the renal concentrating mechanism. The test was tolerated perfectly in every case, obtaining qualitative and quantitative data and avoiding the hyponatremia and hypokalemia produced by the mannitol.

Topics: Carbamazepine; Child; Child, Preschool; Clofibrate; Diabetes Insipidus; Diuresis; Evaluation Studies as Topic; Humans; Infant; Kidney; Kidney Concentrating Ability; Kidney Function Tests; Mannitol; Osmolar Concentration; Vasopressins

The hypothalamo-posthypophysial complex of the homozygous Brattleboro rat is characterized by a hyperactivity of its neurons. The neurosecretory fibers, especially in the neurohypophysis, show numerous signs of autophagy and tubular proliferation of the axoplasmic reticulum. These structural alterations, as well as the nematosomes of nucleolus-like bodies encountered in the perikarya, may be related to the chronic hyperactivity of the neurons. They can be reduced by administration of exogenous vasopressin. The numerous liposomes in the pituicytes are paralleled in the neuronal perikarya by a great number of lysosomes. Small dense core vesicles observed in the neurosecretory endings and perikarya may indicate a secretory product distinct from oxytocin and vasopressin. In the homozygous Brattleboro rat, endings of the aminergic type are more numerous than in the normal rat. With respect to the role they may play in the secretory processes, their increase might be secondary to the vasopressin deficiency.

Topics: Animals; Cytoplasmic Granules; Diabetes Insipidus; Golgi Apparatus; Heterozygote; Homozygote; Hypothalamo-Hypophyseal System; Rats; Vasopressins

Modification of the natural vasopressin molecule to form desmopressin acetate (DDAVP) resulted in a compound with prolonged antidiuretic activity and virtual elimination of vasopressor activity. Twenty-one patients with central diabetes insipidus who ranged in age from 3 to 68 years were treated with DDAVP, which was administered intranasally in a dosage ranging from 10 microgram every 12 hours to 20 microgram every eight hours. Effective control of symptoms was obtained in all cases. There were no consequential toxic effects. As previously reported, DDAVP appears to be the preferred drug for the management of central diabetes insipidus. Biochemical alteration of hormones may enhance desired therapeutic activity and eliminate toxic effects. The development of DDAVP is an example of the potential for development of useful therapeutic peptides.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Vasopressins

Topics: Adolescent; Adult; Aged; Animals; Diabetes Insipidus; Diuresis; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Osmolar Concentration; Rats; Vasopressins; Water-Electrolyte Balance

Studies demonstrating the antagonism by prostaglandins (PGs) of antidiuretic hormone (ADH) action led to the proposal that renal medullary PGs may act to attenuate the physiologic effects of ADH via a negative-feedback loop. Therefore, we examined urinary PG excretion, an indicator of renal PG synthesis, in rats with hereditary diabetes insipidus (DI) utilizing gas chromatography-mass spectrometry. The DI rats, devoid of ADH, excrete much less prostaglandin E2 (PGE2) than normal Long-Evans rats (39 +/- 5 vs. 228 +/- 53 ng/24 h, means +/- SE, P less than 0.005). DI and normal rats were treated for 35 days with ADH while separate groups of DI and normal controls received vehicle only. The ADH treatment increased urinary PGE2 excretion in DI rats to 233 +/- 35 ng/24 h whereas PGE2 excretion was unaffected by vehicle treatment. ADH treatment in normal rats similarly increased PGE2 excretion from 215 +/- 49 to 410 +/- 63 ng/24 h (P less than 0.05). To determine whether the rise in PGE2 excretion is the result of the rise in papillary osmolality, we subjected DI rats to dehydration, which increased urine osmolality from 130 +/- 10 to 302 +/- 12 mosmol/kg H2O but left urinary PGE2 unaffected. We conclude that ADH stimulates renal medullary PGE2 synthesis in vivo.

Topics: Animals; Creatinine; Diabetes Insipidus; Kidney Medulla; Male; Potassium; Prostaglandins E; Rats; Sodium; Thirst; Vasopressins

Two patients with hypodipsia and hypernatremia are described. The first patient, whose hypodipsia was of unknown cause, developed hypernatremia unless large volumes of fluid were urged upon him; upon treatment with chlorpropamide normal serum sodium levels were achieved with spontaneous fluid intake. The second patient had hypodipsia and diabetes insipidus resulting from a craniopharyngioma. Treatment with vasopressin and a prescribed daily water intake resulted in frequent hyper- and hyponatremia, but treatment with chlorpropramide yielded serum sodium values which were more often normal and less variable. In neither patient could the improved water regulation be attributed to an effect of chlorpropamide on renal water excretion. Possible mechanisms for the effect of chlorpropamide on thirst are discussed.

Topics: Adult; Chlorpropamide; Dehydration; Diabetes Insipidus; Humans; Hypernatremia; Male; Sodium; Thirst; Vasopressins

Topics: Animals; Castration; Depression, Chemical; Diabetes Insipidus; Female; Hypophysectomy; Male; Phenoxybenzamine; Propranolol; Rats; Renin; Sex Factors; Vasopressins

A follow-up study was carried out on 12 children with vasopressin sensitive diabetes insipidus. 1) Nine cases (75%) of 12 were finally diagnosed as having brain tumor in later course. There were 3 cases (25%) who could not be decided as having brain tumor during the follow-up period of more than 6 years. 2) There was one case who developed the overt signs of brain tumor 9 years after the onset of diabetes insipidus. Therefore, it seems necessary to follow-up cases with diabetes insipidus for at least 10 years before determining it as idiopathic type. 3) In cases with diabetes insipidus due to brain tumor, associated growth retardation, autonomic symptoms, behavior disorder, endocrine dysfunction and metabolic dysfunction were frequently observed. In the case where these symptoms become aggravated with lapse of time, these findings should be taken seriously as indicating brain tumor. 4) In the case showing either anterior or posterior focal slow waves in the EEG, if such focal slow waves aggravate with age, the findings should be considered as indicative of brain tumor. 5) We would like to emphasize the significance of brain tumor as the underlying pathology of childhood diabetes insipidus.

Topics: Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Diabetes Insipidus; Diagnosis, Differential; Electroencephalography; Female; Follow-Up Studies; Humans; Infant; Male; Vasopressins

Topics: Diabetes Insipidus; Humans; Hypoglycemic Agents; Methods; Vasopressins

The cases of diabetes insipidus (DI) after surgery of intracranial aneurysms were reported and discussed. 1. Of 112 patients operated on for intracranial arterial aneurysm (microsurgical approach), four patients (3.6%) showed DI in the postoperative period. In 3 cases of these 4, the aneurysms located on the anterior communicating artery and the remaining one was the posterior inferior cerebellar artery. 2. The exact mechanism of occurrence of DI is obscure. We suppose that not only vascular spasm of branches of the anterior cerebral and anterior communicating arteries supplying to the paraventricular and preoptic nucleus, but also surgical trauma with direct tissue injury might explain the symptoms. 3. All patients showed a monophasic type of DI which started 1 to 4 days after surgery and lasted from 6 up to 9 days. 4. Two patients with DI showed decreased plasma ADH values below 0.6 microunits/ml in the few days prior to the appearance of abnormally large amount of urinary output. Therefore, once the diagnosis of postoperative DI is made, the patients should be managed promptly with the replacement therapy of Aqueous pitressin. 5. A slow continuous infusion of Aqueous pitressin in the range of 1 to 1.5 IU/hr effectively reduce the polyuria which were not controlled by intermittent intramuscular injections.

Topics: Adult; Aged; Aldosterone; Diabetes Insipidus; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Postoperative Complications; Radioimmunoassay; Vasopressins

Topics: Adrenal Glands; Angiotensin II; Animals; Diabetes Insipidus; Hypothalamus; Male; Pituitary Gland, Posterior; Rats; Renin; Vasopressins

Freeze-fracture electron microscopy had previously revealed antidiuretic hormone-induced aggregates of intramembranous particles in amphibian urinary bladder. To investigate the effects of antidiuretic hormone (ADH) in another ADH-sensitive epithelium, namely, mammalian renal collecting ducts, freeze-fracture studies were carried out in Brattleboro homozygous rats. Collecting duct luminal membranes of ADH-treated homozygotes showed intramembranous particle clusters (117 +/- 17/100 micron2) that were loosely packed and that occurred on both exoplasmic (E) and protoplasmic (P) faces. Untreated, control homozygous rats had significantly less (3 +/- 1/100 micron2) clusters. Changes similar to those seen in ADH-treated rats were observed in water-deprived Wistar rats. The clustered particles differed from those seen in ADH-treated amphibian urinary bladder in that the latter occurred only on the P face and were more densely packed. Nevertheless, our observations suggest a common membrane effect for ADH action that may apply in mammals and amphibia alike.

Topics: Animals; Diabetes Insipidus; Freeze Fracturing; Kidney Tubules; Kidney Tubules, Collecting; Male; Rats; Vasopressins

Three cases of septo-optic dysplasia are related in infants. A neurogenic diabetes insipidus and an central adrenocortical insufficiency is proved. An growth hormone deficiency is founded in one case. The other anterior pituitary functions are normal. The pneumo-encephalography with congenital absence of septum lucidum and the ophtalmologic anomalies are typical. The treatment is envisaged. In one case an autopsy sustains the radiologic aspect.

Topics: Adrenal Insufficiency; Child, Preschool; Diabetes Insipidus; Female; Humans; Hypopituitarism; Infant; Infant, Newborn; Male; Optic Nerve; Septum Pellucidum; Vasopressins

On the assumption that the antagonism between prostaglandin E2 and vasopressin might represent a negative feedback system, we evaluated the hypothesis that vasopressin stimulates, in vivo, the renal production of prostaglandins. For these studies we used Brattleboro homozygous rats with diabetes insipidus and Long-Evans rats for controls, Brattleboro homozygotes show a substantial reduction in the renal excretion of prostaglandin E2 and prostaglandin F2alpha. Homozygotes excreted 39 +/- 5 ng/24 h prostaglandin E2 and 40 +/- 4 ng/24 h prostaglandin F2alpha, compared to 217 +/- 40 and 221 +/- 18 ng/24 h, respectively, in control rats (P less than 0.001). Therapy of homozygotes with vasopressin tannate in oil resulted in a prompt increase in the urinary excretion of prostaglandin E2 and prostaglandin F2alpha. 1-Desamino-D-arginine vasopressin, a nonpressor analogue of vasopressin, also enhanced the renal production of prostaglandin E2. We conclude that vasopressin (antidiuretic hormone) stimulates renal production and excretion of prostaglandin E2 and prostaglandin F2alpha in vivo. It is possible that this increment of prostaglandin synthesis serves a negative feedback function by modulating the action of vasopressin on the renal tubule.

Topics: Animals; Diabetes Insipidus; Kidney; Prostaglandins E; Prostaglandins F; Rats; Vasopressins

The water metabolism was studied in homo- and heterozygous Brattleboro rats suffering from hereditary hypothalamic diabetes insipidus. In homozygous Brattleboro rats the spontaneous water intake and urinary output and the diuretic reactions signficantly increased after water and salt loading. No antidiuretic activity was found in the urine, posterior pituitary or hypothalamus of these animals, and this state was not affected by hyperosmosis. For the heterozygous rats the spontaneous water intake and urinary output and the diuretic reaction exceed the respective control values, the posterior pituitary, the hypothalamus and the urine are of reduced antidiuretic activity and this activity is less mobilizable by hyperosmosis. It is concluded that the ADH-reserve deficiency is total in the homozygous Brattleboro rats, and partial in the heterozygotes. As a result of hyperosmosis, the vasopressin release is of a reduced extent, yet detectable in the heterozygotes.

Topics: Animals; Diabetes Insipidus; Drinking; Heterozygote; Homozygote; Hypothalamus; Male; Pituitary Gland, Posterior; Rats; Saline Solution, Hypertonic; Vasopressins; Water

A 4-month old child presented with facial malformations and severe hypernatremia. Hypernatremia was secondary to diabetes insipidus due to a disorder of ADH secretion, associated with cerebral malformations. Clofibrate treatment was ineffective. However, after the patient was treated by a low osmotic residue diet, an increased water-intake and hydrochlorothiazide, natremia became normal and growth resumed.

Topics: Abnormalities, Multiple; Clofibrate; Diabetes Insipidus; Face; Humans; Hydrochlorothiazide; Hypernatremia; Infant; Limbic System; Male; Vasopressins

Topics: Animals; Brain; Catecholamines; Diabetes Insipidus; Dopamine; Epinephrine; Homozygote; Methyltyrosines; Norepinephrine; Rats; Vasopressins

Topics: Benzothiadiazines; Chlorpropamide; Clofibrate; Demeclocycline; Diabetes Insipidus; Diuretics; Humans; Morphinans; Osmolar Concentration; Sodium Chloride Symporter Inhibitors; Syndrome; Vasopressins

Insulin-induced hypoglycaemia caused a threefold rise in plasma-arginine-vasopressin concentration (to 4-36 +/- 0-77 pmol/1) in ten subjects who had normal posterior-pituitary function. Plasma-arginine vasopressin reached a peak 30 min after injection of insulin. Plasma concentrations of arginine vasopressin obtained with hypoglycaemia were similar to those achieved after overnight dehydration for 14-16 h. No rise in plasma-arginine-vasopressin was observed in three patients with cranial diabetes insipidus in whom severe hypoglycaemia developed after insulin infusion. It is suggested that the measurement of arginine vasopressin during insulin-induced hypoglycaemia may be a useful clinical test of posterior-pituitary function.

Topics: Adolescent; Adult; Arginine Vasopressin; Blood Glucose; Diabetes Insipidus; Female; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Male; Middle Aged; Pituitary Function Tests; Pituitary Gland, Posterior; Time Factors; Vasopressins

The authors have evaluated urinary adenosine 3',5'-monophosphate (cyclic AMP) excretion and renal function during Pitressin administration, hypertonic saline administration, and water deprivation in two siblings with vasopressin-resistant diabetes insipidus and in normal control subjects. After vasopressin administration normal subjects experienced a 2-fold rise in urinary cyclic AMP excretion from 3.2 +/- 0.7 to 5.6 +/- 1.3 nmol/min (P less than 0.001) whereas cyclic AMP excretion was unchanged in both patients (patient AC 4.4 +/- 0.9 to 4.3 +/- 2.1; patient TC 2.2 +/- 0.9 to 2.6 +/- 0.9 nmol/min) with nephrogenic diabetes insipidus (NDI). Urinary cyclic AMP excretion was measured during infusion of 2.5% saline, after vasopressim administration, and after water deprivation. Cyclic AMP excretion was not different from control values in the NDI patients during any of the experimental conditions. Furthermore, there was no difference in cyclic AMP excretion when periods of dilute urine excretion (patient AC 4.5 +/- 1.1; patient TC 2.1 +/- 0.8 nmol/min) were compared with periods when urine concentration was greater than that of plasma (AC 3.5 +/- 1.3; TC 1.8 +/- 0.9 nmol/min). Both subjects responded to parathyroid hormone infusion with a 2-fold increase in urinary cyclic AMP excretion. Excretion of concentrated urine was paralleled by a marked decrease in urine flow to less than 1 ml/min/m2. During periods of hypotonic urine excretion (Uosm/Posm less than 1.0) average glomerular filtration rate (GFR) in patient AC was 67.0 +/- 3.0 ml/minm2 whereas in patient TC it was 70.1 +/- 8.1 ml/min/m2. When each patient was excreting a hypertonic urine (Uosm/Posm greater than 1.0) after fluid deprivation their GFR had decreased significantly (P = 0.001) to 31.6 +/- 8.9 and 33.3 +/- 10.3 ml/min/m2, respectively. Ability of these two subjects with NDI to concentrate their urine to Uosm/Posm greater than 1.0 in the absence of an increase in urinary cyclic AMP but associated with a decrease in GFR to 50% normal indicates that urinary concentration was effected by a reduction in GFR rather than a partial response to antidiuretic hormone (ADH). Their ability to concentrate their urine during periods of modest volume depletion would protect them from progressing to more severe stages of dehydration and result in the relatively benign course of their disease. It is feasible that in patients previously reported to have had clinically "partial" NDI this mechanism may have been

Topics: Adolescent; Cyclic AMP; Diabetes Insipidus; Glomerular Filtration Rate; Humans; Kidney Concentrating Ability; Kidney Tubules; Male; Saline Solution, Hypertonic; Vasopressins; Water-Electrolyte Balance

The antidiuretic and urinary cyclic AMP response to supramaximal vasopressin infusion was studied in normal rats and in rats with lithium-polyuria. The animals were anaesthetized and then infused with a solution designed to produce excessive water diuresis and to lower basal cyclic AMP excretion. In 6 control animals not infused with vasopressin (1) urinary cyclic AMP excretion decreased during the infusion period. Vasopressin infusion (300 muU/min.) consistantly induced antidiuresis in all of 13 control rats (II); but the urinary cyclic AMP response varied individually from a significant increase in 6 animals to either no change or to a decrease in the remaining animals. The antidiuretic response to vasopressin was inhibited by 85% in 10 animals with marked polyuria induced by lithium administration (III). None of the animals in this group showed a significant increase of cyclic AMP excretion in response to vasopressin. The average rate of cyclic AMP excretion, which was equal in the two groups before vasopressin, was signifimantly lower in group III than in group II during vasopressin infusion. It is suggested that the increase in cyclic AMP excretion during vasopressin antidiuresis, although not consistant, most likely reflects hormone-induced changes of intracellular cyclic AMP levels in the renal medulla. Thus, the data suggest that the nephrogenic diabetes insipidus syndrome produced by lithium is associated with a defect in the renal formation of cyclic AMP in response to vasopressin.

Topics: Animals; Cyclic AMP; Diabetes Insipidus; Diuresis; Infusions, Parenteral; Lithium; Male; Polyuria; Rats; Rats, Inbred Strains; Vasopressins

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.

Topics: Animals; Creatinine; Cyclic AMP; Diabetes Insipidus; Diuresis; Fluorides; Kidney; Kidney Concentrating Ability; Osmolar Concentration; Rats; Sodium Chloride; Sodium Fluoride; Vasopressins

The authors report the case of 13 year old girl presenting with chronic hypernatremia. This case should be considered as either neurogenic or essential hypernatremia. Partial diabetes insipidus and hypodipsia hypernatremia. Partial diabetes insipidus and hypodipsia are the cause of chronic hypovolemia and a new homeostasis with an exceptionally high level of sodium (isoosmotic point 154 mEq/l). No cause was found and in particular, the search for a cerebral disease was until now proved negative.

Topics: Adolescent; Blood Volume; Chlorpropamide; Diabetes Insipidus; Female; Humans; Hydrochlorothiazide; Hypernatremia; Thirst; Vasopressins

Topics: Animals; Blood Pressure; Cyclic AMP; Diabetes Insipidus; Diuresis; Glomerular Filtration Rate; Isoproterenol; Kidney; Kidney Medulla; Norepinephrine; Rats; Stimulation, Chemical; Urination; Vasopressins

Antisera, with cross reactive antibodies removed by affinity chromatography, were used in the immunoperoxidase-bridge technique to study the distribution of oxytocin and vasopressin together with neurophysin in the hypothalamo-neurohypophysial system of the rat. The hormones were demonstrated in different areas of the supraoptic nucleus (SON) and paraventricular nucleus (PVN), in neurosecretory fibres of the hypothalamo-neurohypophysial tract, median eminence, and in nerve terminals of the neurohypophysis. Intact normal and rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain), and rats dehydrated by the administration of oral hypertonic saline were studied. In dehydrated rats the hormone concentration in the neurons, and the number of neurons containing hormone varied according to the time of dehydration stress. The observations support the hypotheses that: 1) oxytocin and oxytocin-neurophysin, and vasopressin and vasopressin-neurophysin are synthesised in different neurons and are transported along different axons; 2) the SON and PVN are functionally indistinguishable in that neurons containing oxytocin or vasopressin are present in both nuclei; and 3) the two types of neurons respond to osmotic stimulation in a way that is qualitatively the same but quantitatively different.

Topics: Animals; Dehydration; Diabetes Insipidus; Female; Fluorescent Antibody Technique; Hypothalamo-Hypophyseal System; Immunoenzyme Techniques; Median Eminence; Neurons; Neurophysins; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains; Supraoptic Nucleus; Vasopressins

Marked polydipsia and polyuria developed subsequent to trauma in a 1 1/2-year-old male Abyssinian cat. Diabetes insipidus was suspected, inasmuch as intramuscualr vasopressin administration resulted in amelioration of polydipsia and polyuria. However, hypertonic (3%) saline solution given intravneously resulted in anuria, an indication of antidiuretic hormone activity. Polyuria and polydipsia were abolished by oral chlorpropamide therapy, which was indirect evidence for partial deficiency of antidiuretic hormone.

Topics: Animals; Cat Diseases; Cats; Chlorpropamide; Diabetes Insipidus; Dogs; Male; Pituitary Gland; Polyuria; Thirst; Vasopressins

Topics: Animals; Antibodies; Antibody Formation; Diabetes Insipidus; Humans; Immunoglobulin A; Rabbits; Radioimmunoassay; Vasopressins

In order to study the renal handling of lithium, I examined the relation between the lithium clearance and the urine flow in rats which had hereditary lack of vasopressin production and which had been given a test dose of lithium. The two variables were altered by varying the sodium intake. Rats with a low, medium and high sodium intake had a mean lithium clearance of 0.04, 0.22, and 0.40 ml/min./100 g body weight, respectively. When the sodium intake was increased from a medium to a high level, the lithium clearance and the urine flow rose in proportion to each other (r=0.90). When the sodium intake was decreased from a medium to a low level, the lithium clearance fell relatively more than the urine flow so that the proportion between the two was changed. The experiments show that when vasopressin-induced alterations of the urine flow are excluded and when the sodium intake is not extremely low, proportionality may occur between the lithium clearance and the urine flow. This suggests that the lithium clearance varies in proportion to and is determined by the delivery of sodium from the proximal tubules.

Topics: Animals; Diabetes Insipidus; Diet, Sodium-Restricted; Diuresis; Kidney; Lithium; Male; Rats; Rats, Inbred Strains; Sodium; Vasopressins

Diabetes insipidus following cardiac arrest and hypoxemic encephalopathy occurred in two patients. In both, severe hypoxemic brain damage was followed within three days by clinical and laboratory features of diabetes insipidus, which were corrected by administration of exogenous vasopressin. Hypothalamic injury resulting in diabetes insipidus should be considered in the differential diagnosis of polyuria and dehydration occurring in critically ill patients who have suffered cardiorespiratory arrest.

Topics: Adult; Diabetes Insipidus; Female; Heart Arrest; Humans; Hypothalamus; Hypoxia; Hypoxia, Brain; Respiratory Insufficiency; Vasopressins

Topics: Child; Diabetes Insipidus; Female; Goiter; Humans; Thyroid Function Tests; Thyroid Gland; Vasopressins

Topics: Body Water; Diabetes Insipidus; Humans; Kidney; Kidney Concentrating Ability; Osmolar Concentration; Thirst; Vasopressins

Twenty children with diabetes inspidus, 19 children and adolescents and one baby of 2 months, were treated with DDAVP. The drug was very effective, the average urine volume being 1.7 L/24 hours. The control of the diuresis in the baby was very satisfactory. There were no secondary effects and the only episode of water intoxication occurred in a girl with corticosteroid deficiency which was not well controlled. The effects of this drug are discussed in the light of the biochemistry and pharmacology and the activity compared with that of Lysine vasopressin (LVP). Plasma levels of DDAVP and LVP showed that DDAVP persists for longer which may explain its greater potency and duration of action.

Topics: Adenosine Diphosphate; Adolescent; Adult; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Infant; Lypressin; Male; Vasopressins

Topics: Animals; Diabetes Insipidus; Humans; Kidney Tubules; Male; Mice; Vasopressins

1 The effect of a combination of chloropropamide and chlorothiazide in Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI) treated with low doses of vasopressin (Pitressin tannate in oil) was investigated with particular reference to the time course of response from the initiation of treatment. 2 Analysis of the relationship between water intake and body weight indicated no real correlation and body weight accounted for only 4.4% of the variation in water intake. It was therefore decided to use whole body responses as the index in preference to the response per unit body weight. 3 The daily administration of 5 mg chlorpropamide combined with chlorothiazide in the drinking water (4 mg/1) to Pitressin-treated DI rats potentiated the response to small doses of vasopressin (25 and 50 mu Pitressin/24 hours). Water intake was reduced by the drug combination by an average of 12.35 ml/24 h, but only on the second day of treatment was the decrease of any real magnitude (30 ml/24 h but otherwise 9 ml/24 h or less). Analysis of urine volume measurements gave similar results to those obtained for water intake and the potency ratio measured in terms of free water clearance was 1.26 (agreeing closely with the ratio for water intake which was 1.24). 4 A reduction in the solute excretion was observed only in those DI rats treated with the higher dose of Pitressin (50 mu/24 h) combined with the two drugs. 5 Possible reasons for the discrepancy between the effect of the combination of chlorpropamide and chlorathiazide on water metabolism in the DI rat and the DI patient are discussed.

Topics: Animals; Body Weight; Chlorothiazide; Chlorpropamide; Diabetes Insipidus; Drinking; Female; Hypothalamus; Kinetics; Osmolar Concentration; Rats; Urine; Vasopressins

Topics: Adolescent; Asphyxia Neonatorum; Diabetes Insipidus; Female; Humans; Infant, Newborn; Male; Pituitary Gland, Posterior; Pregnancy; Vasopressins

In 13 patients with hypothalamic diabetes insipidus after daily single intravenous (0.04-24 mug) and single intranasal (5-320 mug) doses of 1-deamino-8-D-arginine vasopressin (DDAVP) the relationships between the log doses and antidiuretic responses (log osmolalities of 24-hour urine samples) were compared. On the basis of such comparisons the ratio of nasal per venous daily single dose requirement was determined and found to be 26:1. Similarly, the relative potency of venous DDAVP was investigated in two subgroups of patients classified according to their response to peroral drugs. Seven times more DDAVP was required for patients treated previously with high doses of peroral antidiuretics. It was concluded that in groups of patients with divergent peroral dose requirements different DDAVP single-dose treatment schedules should be planned.

Topics: Administration, Intranasal; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Injections, Intravenous; Vasopressins

The radioactive microsphere method was used to study the distribution of cortical blood flow in anesthetized dogs during water diuresis and during antidiuresis. Infusion of antidiuretic hormone (ADH) at rates ranging from 0.33 to 0.5 mU/kg-min into dogs previously volume expanded with 3% dextrose resulted in an increase in urinary osmolality and a significant increase in fractional flow in the inner cortex. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were unaltered by the infusion of ADH at these doses, suggesting that absolute, as well as fractional, blood flow to the inner cortex increased in response to ADH. In three additional experiments, termination of an infusion of ADH in hydropenic dogs and subsequent induction of water diuresis was accompanied by a shift in fractional cortical blood flow away from the inner cortex. The redistribution of cortical blood flow in response to ADH at a time when the kidney is producing a more concentrated urine supports the hypothesis that this vascular effect of ADH may have functional significance in the urinary concentration ability of the kidney.

Topics: Animals; Blood Circulation; Blood Volume; Diabetes Insipidus; Diuresis; Dogs; Extracellular Space; Glomerular Filtration Rate; Kidney Concentrating Ability; Kidney Cortex; Kidney Glomerulus; Kidney Medulla; Microspheres; Osmolar Concentration; Regional Blood Flow; Urine; Vasopressins

During the onset of malignant hypertension (MH) in rats treated with deoxycorticosterone trimethylacetate (DOC), plasma arginine vasopressin (AVP) concentrations increase tenfold as a consequence of hypovolemia and hyperosmolality. In benign hypertensive (BH) rats, plasma AVP is increased threefold in comparison with control animals. Plasma renin is markedly suppressed in both BH and MH animals. In MH rats, biologically active AVP antiserum lowers blood pressure (BP) transiently to normal or subnormal levels; in BH rats, a small BP-lowering effect of the AVP antiserum is seen. (Biologically active angiotensin II antiserum does not lower BP in MH rats.) The relationship between the height of BP and plasma AVP concentration in DOC hypertensive rats indicates, when compared with that relationship in diabetes insipidus rats infused with AVP, a marked enhancement of the vasopressor effect of AVP. These findings and the earlier observation of vasopressin-induced vascular damage by Byrom (F. B. Byrom, The Hypertensive Vascular Crisis. London: Heinemann, 1969) strongly suggest that ADH is involved as a vasopressor hormone in the pathogenesis of malignant DOC hypertension.

Topics: Angiotensin II; Animals; Antibodies; Arginine Vasopressin; Blood Pressure; Body Weight; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Hypertension, Malignant; Immune Sera; Male; Nephrectomy; Osmolar Concentration; Rats; Renin; Sodium; Urea; Vasomotor System; Vasopressins

Topics: Atrophy; Brain; Brain Diseases; Chlorpropamide; Diabetes Insipidus; Female; Humans; Leukemia, Lymphoid; Middle Aged; Pituitary Gland; Vasopressins

1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

Topics: Adrenal Cortex; Animals; Diabetes Insipidus; Diet; Drinking; Electrolytes; Endocrine Glands; Female; Hypothalamus; Kidney; Lithium; Male; Osmolar Concentration; Oxytocin; Pituitary Gland; Rats; Renin; Time Factors; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Lypressin; Vasopressins

The authors have developed a radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormon (ADH) levels as low as 0,8 pg/ml. The average plasma level of AVP after overnight water restriction was found to be 14,3 pg/ml (sd = 4,4 pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2 mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion; in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated.

Topics: Arginine Vasopressin; Blood; Diabetes Insipidus; Hormones, Ectopic; Humans; Hyponatremia; Nicotine; Osmolar Concentration; Psychoses, Alcoholic; Radioimmunoassay; Vasopressins

Three cases of compulsive polydipsia previously diagnosed as diabetes insipidus are presented. Abnormally dilated bladder and pyelocalyceal systems were accompanying features, as previously described for diabetes insipidus, particularly of renal orign. Results of the hypertonic saline (Hickey-Hare) test were positive in only one case. Results of restriction of liquids followed by intravenous injection of vasopressin (Miller test) favoured a diagnosis of complete diabetes insipidus. These two tests cannot, therefore, exclude compulsive polydipsia. The features suggesting a diagnosis of compulsive water drinking are low plasma osmolality, a decrease in 24-hour urine output following water restriction, and abnormal behaviour. The diagnosis is confirmed by an 18-hour dehydration test done after gradual fluid restriction, which favours partial restoration of the papillary osmotic gradient.

Topics: Adolescent; Compulsive Behavior; Dehydration; Diabetes Insipidus; Diagnosis, Differential; Drinking; Female; Humans; Hydronephrosis; Hypertonic Solutions; Infusions, Parenteral; Middle Aged; Osmolar Concentration; Urinary Bladder Diseases; Vasopressins

Topics: Adenylyl Cyclases; Animals; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Enzyme Activation; Fluorides; Glucose; Guanine Nucleotides; Heterozygote; Kidney; Lypressin; Male; Rats; Species Specificity; Vasopressins; Water Intoxication

Topics: Adrenalectomy; Animals; Dehydration; Dexamethasone; Diabetes Insipidus; Homozygote; Hypothalamo-Hypophyseal System; Median Eminence; Neurophysins; Rats; Vasopressins

Topics: Age Factors; Child; Diabetes Insipidus; Humans; Infant; Vasopressins

Six patients with vasopressin-responsive diabetes insipidus (DI) received clofibrate and chlorpropamide, singly and in combination. Decrease in urinary output averaged (mean +/- SEM): (1) clofibrate 2 g/day, 47% +/- 6%; (2) chlorpropamide 250 mg/day 59% +/- 5%; (3) clofibrate 2 g/day plus chlorpropamide 125 mg/day, 54% +/- 7%; (4) clofibrate 2 g/day plus chlorpropamide 250 mg/day 61% +/- 4%. Water deprivation tests before and during treatment showed significantly higher basal, final, and peak urinary osmolalities (Uosm) and lower free water clearance (CH20) on chlorpropamide, singly and in combination: clofibrate raised Uosm less but significantly decreased CH2O. Water load tests before and during treatment showed that chlorpropamide, singly and in combination, markedly decreased maximal urinary flow, maximal CH2O, percentage water load excreted, and increased minimal Uosm; clofibrate significantly decreased maximal urinary flow and CH2O only. One patient responded only to combination therapy. Chlorporpamide caused serious hypoglycemia in three of six patients. Clofibrate had no significant side effects.

Topics: Adolescent; Adult; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuresis; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osmolar Concentration; Vasopressins; Water Deprivation

Topics: Adolescent; Adult; Brain Injuries; Brain Neoplasms; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Kidney Diseases; Male; Vasopressins

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hydrolyzable Tannins; Male; Middle Aged; Vasopressins

Dietary protein and NaCl are the precursors of about 60% of the urinary osmoles (urea and NaCl). This investigation tested the hypothesis that in patients with dieabetes insipidus, intake of dietary protein and salt will directly influence the degree of polyuria. Four subjects with pituitary and one with nephrogenic diabetes insipidus were studied. All medications were discontinued. To provide diets ranging between "low-solute" and "high-solute," protein was varied in increments from 40 to 130 g/day and NaCl was varied simultaneously from 0.5 to 10 g/day. In all patients, each increment in protein and salt caused a prompt increase in 24-hr urinary osmoles in the form of urea, Na+, and Cl-. The 24-hr urine volume likewise increased progressively. Average increase in urine osmoles and volume from low- to high-solute diet was +224% and +127%, respectively. In four of the five patients, Reduction of protein/salt intake from habitual dietary at home to the recommedded daily allowance caused a 50 to 100% reduction in the magnitude of polyuria.

Topics: Adolescent; Child; Diabetes Insipidus; Dietary Proteins; Drinking; Drug Resistance; Female; Humans; Male; Osmolar Concentration; Polyuria; Sodium Chloride; Urine; Vasopressins

A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 microU/ml serum without extraction procedure. Normal subjects were found to have 5.7 +/- 4.4 microU/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration increased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values, when ascites was under control.

Topics: Arginine Vasopressin; Diabetes Insipidus; Evaluation Studies as Topic; Furosemide; Humans; Liver Cirrhosis; Lypressin; Osmolar Concentration; Oxytocin; Radioimmunoassay; Thirst; Vasopressins

A radioimmunoassay for AVP capable of measuring human plasma AVP is described. Iodination was performed by the chloramine T method and purified by chromatography on Sephadex G-25. Specific activity of 125I-AVP was 1710 +/- 155 Ci/mmol. Antiserum of high affinity (Keq = 2.7 X 10(11) 1/mol) has been raised in rabbits, which shows slight cross-reactivity with LVP and negligible reactivity with oxytocin. The aqueous assay is capable of detecting 0.4 fmol of AVP/tube and it is highly reproducible. A F lorisil extraction technique is described in detail and gives recovery of 70% of synthetic AVP added to plasma over a wide physiological range. The lowest detectable concentration of plasma AVP is 0.3 pmol/l. The method has been validated by studying changes in plasma AVP concentration following overnight dehydration (plasma AVP =3.46 +/- 1.89 (SD) pmol/l), and water loading (plasma AVP = 1.54 +/- 0.59 pmol/l), P less than 0.005, in normal subjects. A highly significant positive correlation has been found between plasma AVP and plasma osmolality (r =+0.75). Plasma AVP concentration has also been determined in patients with DI and the syndrome of inappropriate ADH secretion. No effect was found on the level of plasma AVP in normally hydrated volunteers undergoing postural change but levels rose following strenuous exercise from basal concentrations of 1.57 +/- 0.59 pmol/l to 4.77 +/- 3.43 pmol/l, P less than 0.01.

Topics: Arginine Vasopressin; Dehydration; Diabetes Insipidus; Humans; Immune Sera; Osmolar Concentration; Physical Exertion; Posture; Radioimmunoassay; Vasopressins

In three cases of established cranial diabetes insipidus, the effectiveness of the new vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) in controlling diabetes insipidus is demonstrated. A single dose of 20 micrograms of DDAVP given intranasally had an antidiuretic action from 16 to 24 hours in the three cases, and 10 micrograms given twice daily intranasally was effective in controlling the diabetes insipidus with no side effects. All the patients preferred this form of therapy to their previous treatment.

Topics: Adult; Deamino Arginine Vasopressin; Depression, Chemical; Diabetes Insipidus; Diuresis; Female; Humans; Male; Middle Aged; Vasopressins

Rats homozygous for the mutant gene for diabetes insipidus (Brattleboro strain) are stunted in growth compared to rats heterozygous for the mutant gene and normal rats without the mutant gene. The hypothesis was tested that normal growth depends upon the presence of vasopressin. It was expected that replacement therapy of vasopressin rats homozygous for diabetes insipidus would make possible a normal growth rate similar to that of rats heterozygous for diabetes insipidus. Rats heterozygous and homozygous for diabetes insipidus were treated with 0.25 U (Days 0-9) and 0.5 U (Days 10-29) of vasopressin during the first month of life. During the treatment period, vasopressin significantly increased the urine osmolatities of the homozygous rats demonstrating the renal effectiveness of the vasopressin. The results showed that remedial vasopressin administration could not produce normal growth rates in homozygous rats and may be detrimental. Six weeks following vasopressin treatment, homozygous, diabetes insipidus rats which had received vasopressin had increased 24 hr water intakes and decreased urine osmolalities compared to control, homozygous rats, Heterozygous rats also had decreased urine osmolalities resulting from vasopressin six weeks after the cessation of vasopressin treatment.

Topics: Aging; Animals; Body Height; Body Weight; Diabetes Insipidus; Drinking; Female; Genotype; Growth; Hypothalamus; Male; Osmolar Concentration; Rats; Vasopressins; Water

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Drinking; Drinking Behavior; Female; Food Deprivation; Hypothalamus; Hypothalamus, Middle; Hypothalamus, Posterior; Kidney Concentrating Ability; Kidney Function Tests; Male; Natriuresis; Oliguria; Pituitary Gland, Posterior; Rats; Vasopressins

Topics: Adult; Angiotensin II; Animals; Arginine Vasopressin; Diabetes Insipidus; Dogs; False Negative Reactions; Female; Humans; Male; Radioimmunoassay; Rats; Smoking; Stimulation, Chemical; Vasopressins

Topics: Adipose Tissue; Adult; Diabetes Insipidus; Female; Humans; Intestinal Mucosa; Liver; Lung; Lymph Nodes; Male; Ovary; Povidone; Vasopressins

The treatment of a patient with diabetes insipidus (DI) is described, and the general treatment of the syndrome is reviewed. The patient was a 16-year-old male who had experienced pain, inflammation and tenderness in the left gluteal region owing to an abcess at the site of intramuscular injection of vasopressin tannate in oil (VTO). (He had been diagnosed as having DI at age 8. Since then, he had been maintained on VTO, lypressin and posterior pituitary snuff.) After the abscess healed during hospital treatment, VTO was stopped and the patient's urinary output increased sharply; urine specific gravity and osmolarity decreased correspondingly. Three days after stopping VTO, the investigational drug, 1-deamino-8-D-arginine vasopressin (DDAVP), was begun at 10 microgram every 12 hours. The dose was eventually increased to 20 microgram every 12 hours, and the patient was discharged on this regimen which controlled his urine output, specific gravity and osmolarity. Other treatments reviewed include antidiuretic-hormone-replacement agents (vasopressin, lypressin) and drugs used to potentiate low ADH levels (chlorpropamide, clofibrate and carbamazepine).

Topics: Adolescent; Carbamazepine; Chlorpropamide; Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Synergism; Drug Therapy, Combination; Humans; Lypressin; Male; Vasopressins

Topics: Adrenalectomy; Animals; Diabetes Insipidus; Heterozygote; Homozygote; Hypothalamo-Hypophyseal System; Median Eminence; Neurophysins; Neurosecretion; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Posterior; Rats; Supraoptic Nucleus; Vasopressins

Topics: Adolescent; Adult; Brain Diseases; Diabetes Insipidus; Female; Humans; Hypernatremia; Kidney; Male; Middle Aged; Reference Values; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Glands; Blood Pressure; Cardiac Output; Catecholamines; Diabetes Insipidus; Humans; Hypertension; Kidney; Renin; Sleep; Smoking; Stress, Psychological; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasopressins

Rabbits immunized with lysine-vasopressin bovine serum albumin conjugate showed the diabetes insipidus syndrome intermittently manifested by polyuria and polydipsia with various degrees of peaking from the eighth to fourteenth day post injection during boosters. The antibody-antidiuretic hormone immune complexes which may interfere with the action of the endogenous vasopressin on the kidney were found in the diabetes insipidus rabbits. However, the degree of the polyuria was not necessarily related to the quantities of the formed immune complexes, the titer, nor the affinity of the antiserum. It is suggested that the degree of the polyuria is related not only to the binding ability of the antiserum to the endogeneous vasopressin, but also to other factors.

Topics: Animals; Antigen-Antibody Complex; Cross Reactions; Diabetes Insipidus; Immune Sera; Kidney; Lypressin; Rabbits; Urination; Vasopressins

A 38-year-old physician developed polyuria and hypodipsia four days after the onset of an upper respiratory tract infection. Subsequent investigation showed a concentration defect with dehydration that partially corrected with vasopressin injection (Pitressin) administration compatible with partial central diabetes insipidus (DI). Skull roentgenograms, EEG, and lumbar puncture were normal. The polyuria and hypodipsia slowly resolved without treatment. Normal urinary concentration ability was achieved by the 48th day, but a residual elevation in serum osmolarity persisted for one year. Review of the literature failed to show previous documentation of transient DI with elevated serum osmolarity from an acute, febrile illness. The mechanism is speculative, but may be related to a subclinical encephalitis. The true frequency of this syndrome and its relationship to the frequent observation of transient polydipsia and polyuria in "benign" febrile illness remains to be determined.

Topics: Acute Disease; Adult; Blood; Diabetes Insipidus; Humans; Hypothalamus; Kidney Concentrating Ability; Male; Osmolar Concentration; Polyuria; Respiratory Tract Infections; Thirst; Vasopressins

Interaction between lithium+ and water balance was studied in nine patients suffering manic-depressive trouble. Nephrogenic diabetes insipidus with polyuria and polydipsia was induced by Li+ in one case only. No trouble was apparent in eight cases. However, the applied method of investigation by lacking, and next, excess of water, vasopressin and ADH tests, measurements of urinary osmolarity and clearances, showed up a trouble of concentration in four cases, improved by ADH. The Li+ frequently (50%) induces a trouble of urinary concentration, without polyuria; it is brought to light only by biological investigations. Its origin is double, nephrogenic, which is the most important, and central by a pituitary component. In the other hand, the change in water metabolism, studied by the same tests, showed us a decrease of the clearance Li+ after lacking of water (deshydratation), and an increase after water surcharge. That result is not concordant, chiefly in regards to the water surcharge, with former experiments. It appears that our method (division by horary periods for measurement of clearance, study of circadian cycle of urinary Li+) permits some observations more precise than global gathering and measurement of clearances. That method also allows to make evident a circadian cycle of renal clearance of Li+, according to, for some part, with the renal movement of water. That remark would also have some consequence on lithium-therapy practice.

Topics: Bipolar Disorder; Diabetes Insipidus; Humans; Lithium; Osmolar Concentration; Polyuria; Thirst; Vasopressins; Water-Electrolyte Balance

Topics: Adrenalectomy; Animals; Body Weight; Calcium; Chlorides; Diabetes Insipidus; Drinking Behavior; Magnesium; Male; Potassium; Rats; Sodium; Urea; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Diabetes Insipidus; Diuresis; Female; Inulin; Kidney Tubules; Loop of Henle; Male; Osmolar Concentration; Rats; Vasopressins; Water

Three children with diabetes insipidus, diabetes mellitus, optic atrophy, and high-tone deafness were shown to lack vasopressin, indicative of degeneration of the cells of the hypothalamic supraoptic nuclei. The syndrome being due to a single gene defect, inherited as an autosomal recessive, is therefore likely to be the result of an inborn error of metabolism with variable periods of latency in those affected.

Topics: Adolescent; Child; Deafness; Diabetes Insipidus; Diabetes Mellitus, Type 1; Humans; Male; Optic Atrophy; Syndrome; Vasopressins

Topics: Anemia, Sickle Cell; Chronic Disease; Diabetes Insipidus; Diet; Humans; Hydrogen-Ion Concentration; Hypernatremia; Hyponatremia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Osmolar Concentration; Vasopressins; Water-Electrolyte Imbalance

Topics: Adrenocorticotropic Hormone; Bromocriptine; Clomiphene; Diabetes Insipidus; Female; Growth Hormone; Humans; Hyperpituitarism; Hypogonadism; Hypopituitarism; Infertility, Female; Male; Pituitary Diseases; Pituitary Gland; Pituitary Neoplasms; Prolactin; Thyrotropin; Vasopressins

The effect of prolactin on free water clearance (C(H2O)) and reabsorption (T(cH2O)) was assessed in hereditary hypothalamic diabetes insipidus (HHDI) and hydropenic Sprague-Dawley rats. Infusion of ovine prolactin (200 nmol/kg per h) ablated C(H2O) in HHDI rats but had no effect on T(cH2O) in hydropenic rats. Additional experiments in HHDI rats employing submaximal infusions of both ovine and rat prolactin indicated that with increasing infusion rates of these hormones, urine osmolality progressively increased with a maximum effect being reached at 30-40 nmol/kg per h with ovine and 15-20 nmol/kg per h with rat prolactin. In similar experiments, using synthetic lysine-arginine vasopressin, maximum effect on urine osmolality was achieved with an infusion rate of 25-75 pmol/kg per h. During infusion of all three hormones, urinary cyclic AMP excretion increased significantly in a similar fashion. These data suggested that prolactin had a direct effect on collecting tubule permeability and acted through stimulation of cyclic AMP production.

Topics: Animals; Cyclic AMP; Diabetes Insipidus; Kidney Concentrating Ability; Kidney Tubules; Osmolar Concentration; Prolactin; Rats; Vasopressins; Water

Topics: Arginine Vasopressin; Colchicine; Cyclic AMP; Cyclophosphamide; Dextropropoxyphene; Diabetes Insipidus; Diuresis; Humans; Kidney Tubules; Lithium; Methoxyflurane; Osmotic Pressure; Sulfonylurea Compounds; Tetracyclines; Vasopressins; Vinca Alkaloids; Water-Electrolyte Balance

Topics: Animals; Cell Membrane; Cell Membrane Permeability; Chlorpropamide; Cyclic AMP; Diabetes Insipidus; Drug Interactions; Humans; Phloretin; Receptors, Cell Surface; Sodium; Urea; Vasopressins; Water

The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria.

Topics: Animals; Cell Membrane Permeability; Cyclic AMP; Diabetes Insipidus; Kidney Concentrating Ability; Kidney Medulla; Lithium; Rats; Vasopressins; Water

Topics: Diabetes Insipidus; Goiter; Graves Disease; Humans; Hyperpituitarism; Hyperthyroidism; Hypothyroidism; Lithium; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; Vasopressins

The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.

Topics: Adolescent; Child; Child, Preschool; Cyclic AMP; Diabetes Insipidus; Diabetic Nephropathies; Humans; Infant; Kidney Failure, Chronic; Male; Parathyroid Hormone; Vasopressins

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Animals; Diabetes Insipidus; Heterozygote; Homozygote; Male; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Rats; Vasopressins

Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and insulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis.

Topics: Animals; Creatinine; Cyclic AMP; Diabetes Insipidus; Glomerular Filtration Rate; Kidney; Kinetics; Osmolar Concentration; Potassium; Prolactin; Rats; Regional Blood Flow; Sodium; Urine; Vasopressins

We observed idiopathic light-chain proteinuria in a patient with multiple abnormalities of proximal-tubule transport mechanisms (Fanconi syndrome), nephrogenic diabetes insipidus, and distal renal tubular acidosis. Seventeen of the 19 urinary amino acid levels measured were elevated. Uric acid and phosphate clearances were greater than 60 per cent and 50 per cent, respectively, of the simultaneous inulin clearance. When water deprivation was coupled with vasopressin administration, the maximum urinary concentration observed was 384 mOsm per kilogram of water. During ammonium-chloride loading, the level of hydrogen-ion concentration in the urine remained less than 100 times that in the blood. Kappa light-chain excretion was 149 mg per 24 hours. It appears that the concurrence of proximal tubular dysfunction, distal tubular dysfunction and light-chain proteinuria represents a distinct syndrome, which we call "combined light-chain nephropathy." Available evidence indicates that excessive light-chain production with subsequent filtration, reabsorption and catabolism, causes the complex tubular dysfunctions observed.

Topics: Acidosis, Renal Tubular; Ammonium Chloride; Bence Jones Protein; Diabetes Insipidus; Fanconi Syndrome; Female; Follow-Up Studies; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Kidney Concentrating Ability; Kidney Diseases; Kidney Tubules; Kidney Tubules, Distal; Middle Aged; Proteinuria; Renal Aminoacidurias; Syndrome; Vasopressins

Topics: Cerebral Hemorrhage; Diabetes Insipidus; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Parenteral Nutrition; Vasopressins

The physiologic factors involved in vaseopressin (ADH) release and action are reviewed with emphasis on the interaction between osmotic and volume stimuli to the discharge of ADH. Abnormalities in reception of stimuli to ADH release, and in the impaired synthesis and release of ADH, are reviewed in relation to the causes of diabetes insipidus, and information on the biochemical changes which have been described in patients with nephrogenic diabetes insipidus is also discussed. We summarize the pathologic lesions and associated diseases found in 54 of our patients with diabetes insipidus. Criteria for establishing the diagnosis of diabetes insipdus are reviewed with emphasis on the dehydration test, including the importance of measuring plasma osmolality at the conclusion of water deprivation. Treatment of diabetes insipidus is briefly discussed with emphasis on the use of DDAVP and oral agents. The syndrome of inappropriate ADH secretion (SIADH) is reviewed including our experience with 39 patients. The differential diagnosis of SIADH, including the value of water loading and the measurement of ADH levels, is discussed. We comment on treatment of these patients including the use of investigational drugs. Lastly, we review the pharmacologic features and clinical relevance of some drugs which alter the release and action of ADH.

Topics: Analgesics; Animals; Antidepressive Agents, Tricyclic; Antineoplastic Agents; Brain; Brain Neoplasms; Carbamazepine; Craniocerebral Trauma; Demeclocycline; Diabetes Insipidus; Diuresis; Diuretics; Humans; Lithium; Osmolar Concentration; Pituitary Gland, Posterior; Sodium Chloride; Sulfonamides; Sulfonylurea Compounds; Vasopressins

The development of a sensitive and specific radioimmunoassay for vasopressin is described. Antibodies were successfully produced following the coupling of synthetic arginine vasopressin with bovine serum albumin carried out with carbodiimide. In order to standardize the assay, the labelled hormone has to be separated twice using a DEAE-Sephadex-A-25 column and thin layer chromatography with cellulose plates. A further condition to obtain a reproducible standard curve is the use of a pure arginine vasopressin checked by cellulose chromatography. Most of the vasopressin batches available do not fulfil this requirement of purity. With the method described, vasopressin can be determined in unextracted human urine. The lower limit of detection is 2 pg/ml. Normal values are in the range of 67.5 +/- 34.3 ng/24 h (kappa +/- SD, n =45). No significant difference of AVP excretion was found between men and women. The usefulness of the assay is demonstrated in patients with hypothalamic or pituitary disorders.

Topics: Acromegaly; Adolescent; Adult; Aged; Arginine Vasopressin; Breast Neoplasms; Child; Chromatography, Thin Layer; Cushing Syndrome; Diabetes Insipidus; Female; Humans; Immune Sera; Immunodiffusion; Lypressin; Male; Middle Aged; Prostatic Neoplasms; Radioimmunoassay; Vasopressins

Topics: Animals; Clofibrate; Diabetes Insipidus; Diuretics; Gonadotropin-Releasing Hormone; Humans; Hypoglycemic Agents; Hypothalamus; Rats; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Adolescent; Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Vasopressins

Diabetes insipidus is an extremely rare condition complicating pregnancy. The deficiency in antidiuretic hormone production has led to the assumption that oxytocin synthesis may also be affected. For this reason spontaneous onset of labor in a number of previously reported cases has been considered as evidence against implicating oxytocin as a relevant factor in the evolution and maintenance of labor. For the first time, plasma oxytocin levels were determined in a patient with known idiopathic diabetes insipidus during pregnancy, labor, and postpartum, using radioimmunoassay. Oxytocin was not detectable in plasma before labor. There was however a surge of plasma oxytocin detected during labor and puerperium, a pattern somewhat similar to that seen in normal pregnancy. Our findings suggest that at least some patients with diabetes insipidus do secrete oxytocin and that the role of oxytocin, threfore, cannot be discounted in the labor process.

Topics: Adult; Cesarean Section; Diabetes Insipidus; Female; Fetal Heart; Humans; Labor, Obstetric; Monitoring, Physiologic; Oxytocin; Pregnancy; Pregnancy in Diabetics; Uterine Contraction; Vasopressins

Topics: Adult; Carbamazepine; Diabetes Insipidus; Humans; Male; Vasopressins

A few rare syndromes have been delineated in which diabetes mellitus is inherited in association with other conditions. This paper describes five patients, including four siblings in one family, who have diabetes insipidus, diabetes mellitus, optic atrophy and deafness (the DIDMOAD syndrome). The parents of both families are normal but are first cousins. All the patients have insulin-dependent diabetes mellitus with a typical juvenile-onset. The onset of diabetes insipidus was insidious and the symptoms could easily have been ascribed to poor control of diabetes mellitus. The importance of diagnosing diabetes insipidus is that all these patients had dilatation of the urinary tract varying from mild hydroureter to severe hydronephrosis and this improved with treatment of the diabetes insipidus. It is suggested that patients with diabetes mellitus and optic atrophy should have regular screening tests for diabetes insipidus since it is likely that they represent cases of the full syndrome with incomplete clinical expression. The occurrence of this rare syndrome in four siblings of unaffected parents indicates that the syndrome is due to a recessive gene, but the pathogenesis is unknown.

Topics: Adolescent; Adult; Deafness; Diabetes Insipidus; Diabetes Mellitus; Female; Genes, Recessive; Humans; Hydronephrosis; Male; Optic Atrophy; Osmolar Concentration; Pedigree; Syndrome; Urinary Bladder; Urine; Vasopressins; Water Deprivation

The etiology, diagnosis and management of lithium-induced diabetes insipidus (LIDI) is discussed, including the presentation of a case report. It is suggested that lithium provokes LIDI by decreasing the responsive ness of the kidney to the antidiuretic hormone. Lithium-induced polyuria may be managed by concomitant treatment with a thiazide diuretic or discontinuation of the lithium. Caution must be employed, however, when using thiazides with lithium as these diuretics decrease renal clearance of lithium.

Topics: Adult; Animals; Anura; Benzothiadiazines; Diabetes Insipidus; Diuretics; Humans; In Vitro Techniques; Lithium; Male; Sodium Chloride Symporter Inhibitors; Urinary Bladder; Vasopressins

1. After administration of a new vasopressin analogue (DDAVP), a marked and prolonged antidiuresis occurred in 10 patients with pituitary diabetes insipidus. 2. The antidiuretic effects of single intravenous doses of 0.04--24 mug DDAVP and single intranasal doses of 5--320 mug DDAVP were investigated. Time curves of the antidiuretic responses expressed in changes of urine osmolality (Uosm) and free water clearance per 100 ml GFR (CH2O X 100/GFR) are described. 3. Maximal "peak" response was obtained after an intravenous dose of 1 mug within the first 12 hrs (Uosm was 7--800 mOsm/KgH2O). Further increase of dosage resulted only in prolongation of duration of action (up to 48 hrs) and peak ("plateau") effect (up to 24 hrs). 4. There was a linear relationship between the log dose and log osmolality of urine collected in the second 12 hours after administration of single intravenous and intranasal doses of DDAVP. 5. Comparison of the effects of 1 mug lysine-vasopressin and 1 mug DDAVP revealed only slight differences in peak effects, but extreme differences in duration of action. 6. It is concluded that in the evaluation of a synthetic vasopressin analogue the maximal antidiuretic ability and the prolongation of action have to be analysed separately.

Topics: Absorption; Administration, Intranasal; Deamino Arginine Vasopressin; Depression, Chemical; Diabetes Insipidus; Diuresis; Humans; Injections, Intravenous; Kidney Concentrating Ability; Lypressin; Nasal Mucosa; Osmolar Concentration; Time Factors; Vasopressins

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Evaluation; Humans; Time Factors; Vasopressins

Duration of action of single intravenous and intranasal doses of 1-Deamino-8D-Arginine Vasopressin (DDAVP) was lengthened by "ineffective" doses of clofibrate (not affecting water metabolism when administered alone) in patients with pituitary diabetes insipidus. This interaction was observed when as low doses as 0.02 mug DDAVP were administered intravenously to one patient and as high doses as 1 and 2 mug DDAVP were given intravenously to another patient. Administration of less or more DDAVP than "optimal" for the interaction resulted in decreased or absent potentiation by clofibrate. The exact cause of the interaction is unknown.

Topics: Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drug Synergism; Humans; Time Factors; Vasopressins

The symptomatic treatment of diabetes insipidus with pitressin is well known and very effective. The only problem concerns the type of pitressin to be used. In the past, pitressin snuff and various other intranasal instillations have been used, but these either have not been very effective, or have resulted in unpleasant side effects such as rhinitis. Until recently, the only effective form of the drug available in Australia has been pitressin tannate in oil. This often has to be given as a daily injection, which, like all intramuscular injections, is painful and, being in an oily base, is particularly likely to result in abscess formation. The recent introduction of 1-deamino-8-D-arginine-vasopressin (DDAVP), which can be simply instilled into the nostril, appears to present an advance in therapy.

Topics: Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Male; Vasopressins

Patients underlying the permanent endocrine substitution need a particular control and a competent conduction on account of their endangering by intercurrent events. Highly specialised knowledge of the physician and intensive collaboration of the patient from this reciprocity lead to essential aspects of the prophylaxis of the crisis-like exacerbations exhibited in detail. The optimum substitution is supplemented by issuing information and emergency cards. When the patient possesses such cards they will become of decisive importance in an urgent therapy necessary outside the controlling facility.

Topics: Arginine Vasopressin; Brain Edema; Diabetes Insipidus; Dihydrotachysterol; Humans; Hydrocortisone; Hypoparathyroidism; Hypothyroidism; Muscle Cramp; Pituitary Diseases; Thyroid Hormones; Vasopressins

Topics: Adult; Benzothiadiazines; Carbamazepine; Chlorpropamide; Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuretics; Humans; Male; Sodium Chloride Symporter Inhibitors; Vasopressins

Topics: Chlorothiazide; Dehydration; Diabetes Insipidus; Fever of Unknown Origin; Humans; Hypernatremia; Infant, Newborn; Infant, Newborn, Diseases; Male; Renal Tubular Transport, Inborn Errors; Specific Gravity; Vasopressins

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypoglycemic Agents; Vasopressins

Topics: Adult; Diabetes Insipidus; Female; Humans; Male; Vasopressins

A 29-year-old woman with severe idiopathic diabetes insipidus, while being treated by a combination of chlorpropamide and chlorothiazide, developed the syndrome of inappropriate secretion of ADH (SIADH) following an overdose of chlorpropamide. The syndrome resolved as the serum chlorpropamide level fell. This report demonstrates that a chlorpropamide-induced SIADH can occur in a patient with idiopathic diabetes insipidus, and it appears that the antidiuretic effect of the drug is dose-related.

Topics: Adult; Chlorpropamide; Diabetes Insipidus; Female; Humans; Hyponatremia; Vasopressins

Topics: Child; Diabetes Insipidus; Diagnosis, Differential; Humans; Pituitary Gland, Posterior; Polyuria; Thirst; Vasopressins

Marked interindividual differences were found in the height and duration of the antidiuretic action induced by increasing single intravenous doses (0.5 mug and 8 mug) of DDAVP in patients with pituitary diabetes insipidus. It was assumed that differences in the duration of action reflected individual variations in the rate of removal of vasopressin.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Genetic Variation; Humans; Time Factors; Vasopressins

A patient is presented with diabetes insipidus secondary to craniofacial trauma. Diabetes insipidus can occur in any patient within ten days of craniofacial trauma. Even the masked disease in the unconscious patient can be diagnosed by observation of intake and output, urinary specific gravities, and appropriate chemical studies. The disease can recur following operative reduction of facial fractures. Diabetes insipidus can be successfully treated by intramuscular Pitressin and appropriate fluid intake.

Topics: Accidents, Traffic; Adolescent; Craniocerebral Trauma; Diabetes Insipidus; Facial Injuries; Humans; Male; Vasopressins

Topics: Diabetes Insipidus; Diagnosis, Differential; Humans; Kidney Diseases; Pituitary Gland, Posterior; Psychophysiologic Disorders; Vasopressins; Water-Electrolyte Balance

Avoidance learning and extinction of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) were studied in 2 experiments that differed only in shock intensity. In both experiments rats homozygous for diabetes insipidus were more deficient in both escape and avoidance responding than were their heterozygous or normal controls. Although the hterozygous animals showed improved escape performance at the higher shock intensity, their avoidance behavior was not improved. The superiority of normal and heterozygous animals in extinction performance, relative to the homozygous animals, was eliminated or reversed when the differences in terminal acquisition performance were taken into account by analyses of covariance. Deficiency of ADH, therefore, may not result in faster extinction of avoidance behavior.

Topics: Animals; Avoidance Learning; Diabetes Insipidus; Extinction, Psychological; Female; Heterozygote; Homozygote; Hypothalamus; Male; Rats; Vasopressins

Topics: Animals; Avoidance Learning; Diabetes Insipidus; Memory; Rats; Vasopressins

Vasopressin was virtually absent from 5 microdissected hypothalamic areas and from the posterior pituitary glands of homozygous Brattleboro rats. The oxytocin concentration was normal in all these areas except for the arcuate nucleus, where it was absent. These results support the concept that Brattleboro rats have a specific defect in biosynthesis of vasopressin. The significance of the absence of oxytocin from the arcuate nucleus in these rats remains to be determined.

Topics: Animals; Diabetes Insipidus; Hypothalamus; Male; Oxytocin; Pituitary Gland, Posterior; Rats; Vasopressins

Topics: Adult; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Enuresis; Humans; Kidney; Kidney Concentrating Ability; Vasopressins

Topics: Arginine Vasopressin; Diabetes Insipidus; Humans; Time Factors; Vasopressins

Topics: Diabetes Insipidus; Humans; Kidney; Pituitary Function Tests; Pituitary Gland, Posterior; Radioimmunoassay; Vasopressins

We describe a patient with histiocytosis X and compulsive water drinking. The association of diabetes insipidus with histiocytosis X is well recognized, and this patient was initially considered to have diabetes insipidus. It was only after further testing that the proper diagnosis was made.

Topics: Adult; Compulsive Behavior; Diabetes Insipidus; Diagnostic Errors; Drinking; Female; Histiocytosis, Langerhans-Cell; Humans; Kidney Concentrating Ability; Kidney Function Tests; Radiography; Vasopressins; Water

A sensitive and specific radioimmunoassay for arginine vasopressin (AVP) was developed utilizing the antisera against lysine vasopressin (LVP) in combination with a labeled AVP. The assay employs an acetone extraction procedure and detects as little as 0.8 pg. per milliliter of AVP in human plasma. In normal subjects the mean (+/- S.D.) plasma concentration of AVP was 4.9 +/- 1.2 pg. per mililiter after fluid deprivation and 1.2 +/- 0.4 pg. per milliliter after water loading. Plasma AVP levels correlated significantly with plasma osmolalities. In four patients with diabetes insipidus, plasma AVP concentrations ranged from less than 0.8 to 1.2 pg. per milliliter, whereas six patients with the syndrome of inappropriate ADH secretion showed plasma levels of AVP which correspond to those of the dehydrated state in normal subjects or greater, although plasma osmolalities were low in all cases. It was concluded that the present radioimmunoassay method for AVP provides a useful way of assessing neurohypophyseal function in man.

Topics: Arginine Vasopressin; Dehydration; Diabetes Insipidus; Humans; Lypressin; Osmolar Concentration; Radioimmunoassay; Vasopressins

Immuno-enzyme cytochemical investigations have shown that, (1) the hypothalamic supraoptic and paraventricular nuclei of the Brattleboro rat, as in the normal rat, contain separate neurons which produce oxytocin + neurophysin; (2) the hereditary inability of the Brattleboro rat to synthesize vasopressin and its associated neurophysin is due to a biochemical defect of separate "neurophysin-vasopressin" neurons in the supraoptic and the paraventricular nuclei. These observations strongly support the hypotheses that (1) vasopressin and its associated neurophysin are formed via a common precursor, and (2) the initial point of intracellular appearance of the hereditary defect in the Brattleboro rat lies in the synthesis of this precursor, which occurs on ribosomes. Moreover, observations have demonstrated that, in the Brattleboro rat, in addition to the hereditary inability of the hypothalamic magnocellular neurosecretory system to synthesize vasopressin, there also exists a similar hereditary defect in the hypothetical parvicellular suprachiasmatic-median eminence neurosecretory system.

Topics: Animals; Diabetes Insipidus; Histocytochemistry; Horseradish Peroxidase; Hypothalamus; Median Eminence; Neurophysins; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Supraoptic Nucleus; Vasopressins

Topics: Adult; Body Water; Brain Diseases; Child, Preschool; Diabetes Insipidus; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Vasopressins

DDAVP, 1-desamino-8-d-arginine-vasopressin, is a synthetic analogue of vasopressin with increased antidiuretic activity and decreased pressor activity. Whereas the antidiuretic-to-pressor ratio of arginine vasopressin is 1, the antidiuretic-to-pressor ratio of DDAVP is 4000. When administered as an intranasal spray, 5 to 20 mug of DDAVP produced eight to 20 hours of antidiuresis in patients with complete central diabetes insipidus. The minimum recommended therapeutic dose resulted in a maximum antidiuresis in most patients. No side effects of the drug were noted in clinical trials. DDAVP thus gives promise of becoming the standard treatment of severe central diabetes insipidus.

Topics: Catheterization; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Nose; Time Factors; Vasopressins

The distribution of labeled microspheres within the renal cortex was used to evaluate the influence of physiological amounts of antidiuretic hormone on intrarenal blood flow distribution in hypophysectomized dogs and in rats with hereditary diabetes insipidus. In both species, intravenous infusions of ADH caused a significant decrease in the ratio of inner to outer cortical blood flow. The change in blood flow distribution observed in the hypophysectomized dog with ADH was primarily a consequence of a decrease in inner cortical blood flow. No consistent changes in outer cortical blood flow were found. Also in the dog, glomerular filtration rates and electrolyte excretion rates (Na and K) increased following ADH. In contrast, ADH infusion into Brattleboro rats caused no change in glomerular filtration or excretion of Na and K.

Topics: Animals; Diabetes Insipidus; Dogs; Female; Hypophysectomy; Kidney; Kidney Cortex; Male; Natriuresis; Potassium; Rats; Regional Blood Flow; Vasopressins

Recently it was reported that vasopressin facilitates the development of resistance to the analgestic action of morphine. Therefore, the development of tolerance to daily administration of morphine-HCl (10 mg/kg i.p.) was studied in a series of trials on a hot plate using rats with hereditary diabetes insipidus (DI), which lack the ability to synthesize vasopressin. In contrast to heterozygous DI rats, who developed full tolerance after the fifth injection, homozygous DI rats showed a delayed development of tolerance. Substitution of HO-DI rats with either arginine-8-vasopressin (3 mug/rat, s.c. daily) or the endocrinologically inert fragment of vasopressin desglycinamide lysine-8-vasopressin (5 mug/100 g, s.c. daily) restored the impaired development of tolerance towards normal. The data support the notion that vasopressin is important to the development of tolerance to narcotic analgesics and that its mechanism of action is dissociated from its endocrine effect but rather resembles that of its known influence on memory consolidation.

Topics: Analgesia; Animals; Arginine Vasopressin; Diabetes Insipidus; Drug Tolerance; Heterozygote; Homozygote; Lypressin; Male; Memory; Morphine; Rats; Rats, Inbred Strains; Rodent Diseases; Vasopressins

Topics: Body Water; Diabetes Insipidus; Glomerular Filtration Rate; Humans; Osmolar Concentration; Time Factors; Urine; Vasopressins

Topics: Bone Marrow; Delayed-Action Preparations; Diabetes Insipidus; Drug Combinations; Humans; Liver; Male; Middle Aged; Muscles; Povidone; Skin; Vasopressins

Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron.

Topics: Animals; Diabetes Insipidus; Female; Glomerular Filtration Rate; Hypothyroidism; Inulin; Kidney; Kidney Concentrating Ability; Kidney Tubules; Kidney Tubules, Distal; Male; Organ Size; Rats; Thyroxine; Vasopressins

Immuno-enzyme cytochemical investigations, using single and double staining techniques, showed that the external region of the rat median eminence contains separate neurophysin-vasopressin fibres and neurophysin-oxytocin fibres. These neurophysin-hormone containing nerve fibres are influenced by bilateral adrenalectomy and by colchicine treatment. The external region of the median eminence of the homozygous Brattleboro rat contains neurophysin-oxytocin fibres. It does not contain immuno-reactive neurophysin-vasopressin fibres. Bilateral adrenalectomy also influences the neurophysin-vasopressin containing neurons of the suprachiasmatic nuclei. In the neurons of the parvicellular part of the rat hypothalamic paraventricular nuclei, staining for vasopressin and for oxytocin is completely absent.

Topics: Adrenalectomy; Animals; Axons; Colchicine; Diabetes Insipidus; Hypothalamo-Hypophyseal System; Median Eminence; Neurophysins; Oxytocin; Rats; Rats, Inbred Strains; Vasopressins

A new method is described for placing lesions in the supraoptico-neurohypophysial tract to produce diabetes insipidus. The method is particularly useful with species such as Macropus eugenii in which different individuals show a large variation in relative skull measurements. The development of the diabetes insipidus syndrome in the tammar wallaby (Macropus eugenii) is shown to have essentially the same triphasic pattern of urine production as in eutherians. Increased values of adrenal corticosteroids (less than 16 mug/100 ml plasma) were observed in the oliguric interphase. This has not been previously reported and we suggest that these increased values are most probably due to potentiation of corticotrophic releasing factor by the uncontrolled release of vasopressin during this phase.

Topics: Adrenal Cortex Hormones; Animals; Chlorides; Diabetes Insipidus; Disease Models, Animal; Diuresis; Feces; Macropodidae; Male; Marsupialia; Pituitary Gland, Posterior; Potassium; Sodium; Supraoptic Nucleus; Urine; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Oral carbamazepine has been shown to have antidiuretic activity in seven out of nine patients with neurohypophyseal diabetes insipidus. At the doses used side-effects were not a major problem. In the eighth patient a carbamazepine and clofibrate combination was effective but in the ninth carbamazepine was without effect. It is suggested that carbamazepine should be used initially in neurohypophyseal diabetes insipidus if oral therapy is indicated, but the mode of its antidiuretic action is as yet unclear.

Topics: Adolescent; Adult; Arginine Vasopressin; Body Water; Body Weight; Carbamazepine; Diabetes Insipidus; Diuresis; Drinking; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osmolar Concentration; Vasopressins

The authors have studied in the dog--normal or diabetic insipidus after hypothalamic lesion--submitted to oral ingestion of ethanol the effects of a few antidiuretic drug: chlorpropamid, atromid-S, carbamazepin and carisoprodol. The carisoprodol only can reduce the diuresis and the drinking provoked by ethanol.

Topics: Animals; Carbamazepine; Carisoprodol; Chlorpropamide; Clofibrate; Diabetes Insipidus; Dogs; Drinking; Ethanol; Kidney; Male; Polyuria; Vasopressins

Topics: Adenylyl Cyclases; Animals; Carbonates; Cyclic AMP; Diabetes Insipidus; Humans; Hyperthyroidism; Hyponatremia; Lithium; Osmolar Concentration; Rats; Sodium; Syndrome; Thyrotropin; Vasopressins

Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH.

Topics: Age Determination by Skeleton; Body Height; Craniopharyngioma; Diabetes Insipidus; Dwarfism, Pituitary; Female; Growth; Growth Hormone; Humans; Hypopituitarism; Hypothyroidism; Male; Thyroid Gland; Thyroxine; Vasopressins

The administration of c-AMP and DB c-AMP to six children with NDI has failed to yield an antidiuretic effect. From the present study it may be concluded that, at the doses used, neither c-AMP nor its dibutyryl derivative can mimic the action of ADH in NDI as they do in normal subjects. On the contrary, DB c-AMP increased urine volume and Cosm in a very marked way, without changing the creatinine excretion.

Topics: Bucladesine; Child; Child, Preschool; Creatinine; Cyclic AMP; Diabetes Insipidus; Diuresis; Female; Humans; Infant; Injections, Intravenous; Male; Osmolar Concentration; Vasopressins

A radioimmunoassay has been developed for plasma arginine-vasopressin in man and dog. The mean recovery of added arginine-vasopressin (AVP) was 60 +/-6.9 (S.D.)% and the lower threshold of detection 2.0 pmol/1. A close correlation was found between concurrent radioimmunoassay and bioassay values. The mean concentration found in peripheral venous blood in healthy men after overnight fasting was 5.3 pmol/1 (range 4.6-6.2 pmol/1.) In man, significant increases in plasma AVP occurred after dehydration (5-9-9-5 pmol/1) and significant decreases after oral water-loading (5.9-9.5 pmol/1). During i.v. infusion of graded doses of synthetic AVP in normal men, plasma levels were closely correlated with infusion rate. On stopping the infusion, plasma vasopressin fell exponentially with a half-life of between 7 and 8 min. In man, plasma AVP was unaffected by tilting head-up for 2 h, or by a non-hypotensive bleeding of 500 ml in 10 min. In the dog, haemorrhage of 5 ml/kg and over caused proportionate increases in AVP in the circulation. In normal men, plasma vasopressin was significantly correlated with concurrent urinary osmolality. Five patients with oat-cell bronchial carcinoma and hyponatraemia showed a marked increase of plasma vasopressin. Five patients with diabetes insipidus had significantly reduced, but detectable, levels of plasma AVP. The plasma concentration in these patients did not increase after water restriction.

Topics: Adult; Animals; Arginine Vasopressin; Biological Assay; Blood Volume; Bronchial Neoplasms; Carcinoma, Small Cell; Dehydration; Diabetes Insipidus; Dogs; Half-Life; Hemorrhage; Humans; Male; Osmolar Concentration; Posture; Radioimmunoassay; Urine; Vasopressins; Water; Water Deprivation

The activities of enzymes related to the cellular action of vasopressin as well as the activities of other enzymes were studied in an animal model of hypothalamic diabetes insipidus. Rats with hereditary hypothalamic diabetes insipidus (homozygotes of Bratteboro strain) were found to have significantly lower renal medullary adenylate cyclase activity, either basal activity or activity stimulated by vasopressin, as compared with controls (heterozygotes of the same strain). There were no differences between the two strains in the activities of cyclic AMP phosphodiesterase, other hormone-sensitive adenylate cyclases, or the other renal medullary enzymes studied, which are apparently unrelated to the vasopressin action. The treatment of rats with hereditary hypothalamic diabetes insipidus with exogenous vasopressin increased the activity of renal medullary adenylate cyclase stimulated in vitro by maximal doses of vasopressin, but had no effect on the basal activity of adenylate cyclase or on the activity of cyclic AMP phosphodiesterase. This suggests that low adenylate cyclase activity in the renal medulla of rats with diabetes insipidus may be related to the subnormal concentrating ability observed in these animals.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenylyl Cyclases; Animals; Diabetes Insipidus; Female; Heterozygote; Homozygote; Kidney; Kidney Medulla; Male; Rats; Vasopressins

We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion.

Topics: Carcinoma, Small Cell; Demeclocycline; Diabetes Insipidus; Humans; Hyponatremia; Kidney Diseases; Lung Neoplasms; Male; Middle Aged; Osmolar Concentration; Syndrome; Urine; Vasopressins

Topics: Accidents, Traffic; Adult; Anti-Bacterial Agents; Brain Concussion; Catheterization; Central Venous Pressure; Chlorides; Diabetes Insipidus; Female; Hemorrhage; Humans; Hydrogen-Ion Concentration; Infusions, Parenteral; Intracranial Pressure; Maxillofacial Injuries; Skull; Sodium; Urinary Catheterization; Vasopressins; Water; Water Intoxication

Topics: Animals; Avoidance Learning; Diabetes Insipidus; Genotype; Male; Memory; Pituitary Gland, Posterior; Rats; Reaction Time; Vasopressins

Topics: Adult; Aerosols; Creatinine; Diabetes Insipidus; Drug Combinations; Female; Humans; Lysine; Male; Middle Aged; Osmolar Concentration; Vasopressins

Antidiuretic hormone (ADH) and isoproterenol (ISO) both cause renal retention of water when infused iv into animals. It has been suggested that the agents share a common mechanism of action but the current work reveals marked differences in the effect of ISO and ADH on urinary excretion of sodium (ISO produces fall from 50 plus or minus 14 to 3 plus or minus 0.6 mu Eq per 20 min, P greater than 0.0005; ADH causes a fall from 62 plus or minus 14 to 45 plus or minus 9, P greater than 0.05) and creatinine (ISO causes a fall from 157 plus or minus 14 to 71 lus or minus 13, P greater than 0.0005; ADH produces fall from 155 plus or minus 12 to 145 plus or minus 14, P greater than 0.05), which suggest that the actions of the agents may differ. To study that possibility, ISO was infused into normal rats and rats with hereditary diabetes insipidus (DI rats) due to a genetic defect in ADH production. Doses previously used (0.2 mug per kg per min, and doses 10 and 100 fold less were infused. At 0.002 mug per kg per min, urine osmolality in both groups of rats declined (DI rats from 177 plus or minus 22 to 141 plus or minus 13 MOsm per kg, P greater than 0.01, and normals from 162 plus or minus 17 to 142 plus or minus 15 MOsm per kg, P greater than 0.05). At 0.02 mug per kig per min, there was no significant change is osmolality. At 0.02 mug per kig per min, osmolality rose in both groups but the response was significantly blunted in the DI rats (normals: 351 plus or minus 32 to 626 plus or minus 79 mOsm per kg, P greater than 0.005; DI rat: 204 plus or minus 23 to 241 plus or minus 30 P greater than 0.05). It is concluded that intravenous ISO has a dual effect on water excretion; at low doses it is associated with reduced urinary osmolality possibly by direct renal action and at high doses it is associated with antidiuresis by stimulating release of pituitary ADH.

Topics: Animals; Diabetes Insipidus; Diuresis; Female; Isoproterenol; Kidney; Kidney Function Tests; Osmolar Concentration; Pituitary Gland, Posterior; Rats; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Balance

The 3-layer immunoperoxidase-bridge technique was used to study the distribution of neurophysin and vasopressin in the neurosecretory neurons of rats homozygous and heterozygous for diabetes insipidus (Brattleboro strain). In the homozygous rats there was a marked hypertrophy of the hypothalamic magnocellular structures when stained either for neurosecretory material or neurophysin-like antigens. Neurophysin was present in both the paraventricular (PVN) and supraoptic nuclei (SON) of homozygous and heterozygous animals. Less than half of the cells in the PVN and SON were stained for neurophysin. This observation was less apparent when histochemical stains were used to visualize the distribution of neurosecretory material. Although it is generally considered that the homozygous Brattleboro rat does not synthesize vasopressin, a positive reaction was observed in the PVN and SON when anti-[8-lysine]-vasopressin serum was employed in the immunohistochemical procedure.

Topics: Animals; Diabetes Insipidus; Heterozygote; Histocytochemistry; Homozygote; Hypothalamus; Neurophysins; Peroxidases; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains; Vasopressins

The permeability of the tight junctions (zonulae occludentes) was evaluated along the entire length of the collecting duct of the rat using a lanthanum tracer technique. Nine rats with hereditary hypothalamic diabetes insipidus were studied using standard micropuncture and clearance techniques. Glomerular filtration rate (GFR) estimated from inulin clearance, urine and plasma osmolality (U/Posm) and urine flow rate (V) were determined in eight of nine animals. During either sustained diuresis (five animals) or vasopressin-induced antidiuresis (four animals), individual surface convolutions of distal convoluted tubules or early cortical collecting ducts were preserved for ultrastructural examination by intraluminal microperfusion with a glutaraldehyde-formaldehyde fixative followed by a second microperfusion with a lanthanum tracer. Mean GFR during diuresis was 6.31 plus or minus se 0.63 ml/min/kg of body wt and v=797 plus or minus se 108 mul/min/kg or 13.6 plus or minus se 2.2% of the filtered load of water. After administration of exogenous vasopressin, V fell to 311 plus or minus 157 mul/min/kg or 5.2 plus or minus se 3.8% of the filtered load of water and U/Posm rose from 0.658 plus or minus se 0.043 to 2.124 plus or minus 0.454. Tight junctions of cortical and outer medullary segments of the collecting duct resisted lanthanum penetration. Tight junctions of the inner medullary and papillary segments of the collecting duct were freely permeable to lanthanum suggesting the presence of a paracellular shunt pathway for solute and water movement. The results were independent of the presence or absence of vasopressin. Physiological studies have previously demonstrated that cortical and outer medullary segments of the collecting duct have a low urea permeability while inner medullary and papillary segments of the collecting duct have a relatively high urea permeability. The possibility is suggested that urea movement across the inner medullary and papillary segments of the collecting duct may occur, at least in part, via a paracellular pathway formed by the nonoccluding tight junction and the lateral intercellular space.

Topics: Animals; Blood; Diabetes Insipidus; Diuresis; Epithelial Cells; Epithelium; Female; Glomerular Filtration Rate; Hypothalamus; Inulin; Kidney; Kidney Cortex; Kidney Medulla; Kidney Tubules, Distal; Lanthanum; Male; Nephrons; Osmolar Concentration; Permeability; Rats; Urea; Urine; Vasopressins

Eighty-six intracranial cannula placements in 51 rats were tested with unilateral, 2-mul injections of a 0.60-osmol/kg solution, sucrose dissolved in isotonic sodium chloride. To assess antidiuretic hormone (ADH) release, a water diuresis was induced and spontaneous urinations were collected and analyzed for sodium by flame photometry. On alternate test days the 0.60-osmol/kg solution was injected into sleeping rats, and latencies to drink and volume drunk were recorded. Injections at 42 placements elicited neither drinking nor adtidiuresis on two separate test days each; at 15, both antidiuresis and drinking on at least two of three tests each; at 19, drinking but not antidiuresis; at 10, antidiuresis but not drinking. Positive drinking and ADH placements were not distinctly separated. They clustered in the bed nucleus of the stria terminalis, the preoptic areas, and the anterior portions of the hypothalamus. Placements in the medial forebrain bundle and dorsal to the anterior hypothalamic area elicited thirst but not ADH release for the most part. Placements nearest the supraoptic nucleus were weak or negative for ADH release. Central nervous system osmo-receptors exist and seem not to be the neurosecretorycells. Thirst osmoreceptors and antidiuretic osmoreceptors seem to be contiguous, but distinct.

Topics: Angiotensin II; Animals; Brain Mapping; Carbachol; Chemoreceptor Cells; Diabetes Insipidus; Diuresis; Drinking Behavior; Hypothalamus, Anterior; Infusions, Parenteral; Injections; Male; Osmotic Pressure; Preoptic Area; Rats; Sodium; Sucrose; Supraoptic Nucleus; Thirst; Urea; Vasopressins

Topics: Adolescent; Adult; Arginine; Diabetes Insipidus; Drug Combinations; Female; Humans; Male; Middle Aged; Vasopressins

Topics: Animals; Avoidance Learning; Body Weight; Conditioning, Operant; Corticosterone; Diabetes Insipidus; Electroshock; Exploratory Behavior; Heterozygote; Homozygote; Male; Memory; Motor Activity; Organ Size; Pituitary-Adrenal System; Rats; Testis; Vasopressins

Nephrogenic diabetes insipidus associated with high basal levels of plasma arginine vasopressin developed in a patient during lithium therapy. Fluid deprivation was accompanied by an increase in the concentration in peripheral venous plasma of vasopressin and angiotensin II, a rise in plasma osmolality and a modest rise in urine osmolality. Infusion of arginine vasopressin produced comparable levels of plasma vasopressin to those found during fluid deprivation, with no overall change in plasma angiotensin II and little change in urine volume or osmolality. It is suggested that angiotensin II may be responsible for the difference in ability to concentrate urine under these two conditions. Following death by self-poisoning, renal histology revealed distinct structural changes in the distal tubules: such lesions have not previously been described in man and it is suggested that the occurrence of nephrogenic diabetes insipidus while on lithium therapy may be related to tubular damage.

Topics: Adult; Angiotensin II; Arginine Vasopressin; Diabetes Insipidus; Humans; Kidney Diseases; Kidney Tubules, Distal; Lithium; Male; Osmolar Concentration; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Diabetes Insipidus; Genotype; Hypothalamus; Methods; Rats; Rats, Inbred Strains; Vasopressins

Arginine vasopressin (AVP) and vasotocin (AVT) were measured by radioimmunoassay in extracts of cerebral cortex, cerebellum, brain stem, pineal, hypothalamus, and neurohypophysis from normal Long-Evans rats. AVP was present in expected concentrations in pituitary and hypothalamus and there was no evidence of its accumulation elsewhere. AVT was not detectable in these tissues (within the limits imposed on our assay by the presence of excessive amounts of AVP) but was easily detectable in pineal tissue with a concentration of 22.4 plus or minus 6.6 muU/gland. Extracts of neurohypophysis and pineal glands from homozygous Brattleboro rats (rats with hereditary hypothalamic diabetes insipidus) revealed the total absence of AVP and AVT. We conclude that the Brattleboro rat is incapabel of synthesizing biologically active neurohypophyseal peptides which contain arginine in position 8.

Topics: Animals; Arginine Vasopressin; Brain Chemistry; Chromatography, Paper; Diabetes Insipidus; Homozygote; Hypothalamus; Pineal Gland; Pituitary Gland, Posterior; Radioimmunoassay; Rats; Vasopressins; Vasotocin

Topics: Adult; Diabetes Insipidus; Humans; Lithium; Male; Vasopressins

Excretion of free water was studied in 7 patients with pituitary diabetes insipidus before treatment and after withdrawal of antidiuretic drugs (chlorpropamide, carbamazepine, clofibrate) used on a long-term basis. A statistically significant decrease in free water clearance was found after 2-4 weeks of withdrawal of antidiuretic agents. This was considered as a clinical evidence for the permanently enhanced release of residual ADH induced by chlorpropamide, carbamazepine and clofibrate in patients with partial defect in ADH secretion.

Topics: Adolescent; Adult; Carbamazepine; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuresis; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Vasopressins

A study was made of the effect of the antiepileptic carbamazepine on the water metabolism in 13 vasopressin-sensitive and 4 ADH-resistant diabetes insipidus patients. It was found that in 12 ADH-sensitive diabetes insipidus cases the drug decreased the urinary output and the free water clearance, and increased the urinary osmolarity. The diuresis did not change in ADH-resistant diabetes insipidus patients. The investigations suggest that carbamazepine exerts an ADH-like effect, and can be applied with good results in the treatment of ADH-sensitive diabetes insipidus.

Topics: Adolescent; Adult; Carbamazepine; Creatinine; Diabetes Insipidus; Diuresis; Female; Humans; Male; Middle Aged; Osmolar Concentration; Vasopressins

The activity of dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to norepinephrine, was measured in the serum of a strain of Wistar rats homozygous and heterozygous for a genetic form of hypothalamic diabetes insipidus and in Wistar control rats. Serum dopamine-beta-hydroxylase activity and water intake was highest in the homozygous affected rats and lowest in normal controls. Treatment with pitressin tannate reduced serum enzyme activity and water intake in rats with diabetes insipidus to levels which did not differ from controls. Thus serum dopamine-beta-hydroxylase activity appeared to vary directly with changes in sympathetic nerve activity in response to intravascular volume depletion and repletion.

Topics: Animals; Blood Volume; Diabetes Insipidus; Dopamine beta-Hydroxylase; Drinking; Heterozygote; Homozygote; Hypothalamus; Male; Rats; Sympathetic Nervous System; Vasopressins; Water

Topics: Adolescent; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Vasopressins

Topics: Diabetes Insipidus; Diagnosis, Differential; Humans; Kidney Concentrating Ability; Kidney Diseases; Osmolar Concentration; Vasopressins

Topics: Administration, Intranasal; Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Infant; Male; Vasopressins

Topics: Child, Preschool; Chlorpropamide; Diabetes Insipidus; Female; Humans; Vasopressins; Water Deprivation

A 20-yr-old male was found to have diabetes insipidus is association with panhypopituitarism but without any focal neurological lesion being identified. He was initially treated with steroid supplements, the features of diabetes insipidus being controlled with a thiazide diuretic. Eighteen months later the patient lost thirst sensation and stopped treatment, subsequently being re-admitted with severe dehydration, oliguria and focal neurological signs. Further investigation, including brain biopsy, confirmed the presence of an atypical pinealoma which was considered inoperable. Measurements of plasma antidiuretic hormone (ADH) and angiotensin II (AII) concentrations during the severe dehydration showed very high levels of AII, but inappropriately low plasma ADH levels for the severity of dehydration. We consider that the evidence obtained from this case supports the view that the oliguria with hypertonic urine present during severe dehydration was due to a direct renal action of the very high AII levels, possibly supplemented by the residual ADH secretion.

Topics: Adult; Angiotensin II; Circadian Rhythm; Dehydration; Diabetes Insipidus; Growth Hormone; Humans; Hypopituitarism; Male; Osmolar Concentration; Time Factors; Urine; Vasopressins

Topics: Animals; Diabetes Insipidus; Diabetes Mellitus; Drinking Behavior; Female; Heterozygote; Homozygote; Hypothalamus; Male; Oxytocin; Pituitary Gland; Rats; Renin; Sex Factors; Urine; Vasopressins

The age-dependent polydipsia and polyuria observed in SWR/J mice was found to be caused by relative inability of the kidneys to respond to antidiuretic hormone (ADH), resulting in a concentrating defect, which persisted even following Pitressin injection or water deprivation. Posterior pituitaries contained large amounts of ADH, which was also found in the urine and increased in output following water deprivation, indicating normal, or above normal synthesis and release of ADH. Kidneys of polydipsic SWR/J mice weighed more than those of normal strains and sometimes contained a lesion in the medullary area. No clear relationship was found between the size of the lesion and water intake.

Topics: Animals; Diabetes Insipidus; Disease Models, Animal; Drinking; Female; Kidney Concentrating Ability; Kidney Diseases; Male; Mice; Mice, Inbred Strains; Organ Size; Osmolar Concentration; Pituitary Gland; Species Specificity; Vasopressins; Water Deprivation

1. Chlorpropamide, carbamazepine and clofibrate have an antidiuretic action in patients with neurohypophyseal diabetes insipidus which is qualitatively similar to that of antidiuretic hormone (ADH). 2. An additive antidiuretic effect is produced by combination of chlorpropamide and carbamazepine with small dosages of ADH. 3. After an immediate and transient antidiuresis, a single intravenous bolus injection of lysine vasopressin given during treatment with chlorpropamide, chlorpropamide with a continuous intravenous infusion of lysine vasopressin, carbamazepine or clofibrate, resulted in increased water diuresis for 12-24 h or longer. 4. This paradoxical diuresis was not observed during treatment with chlorothiazide. 5. It is suggested that the antidiuretic action of chlorpropamide, carbamazepine and clofibrate is localized at the receptor site for ADH in the distal renal tubular cell.

Topics: Adolescent; Adult; Aged; Carbamazepine; Chlorothiazide; Chlorpropamide; Clofibrate; Creatinine; Diabetes Insipidus; Diuresis; Drug Interactions; Female; Hemoglobins; Humans; Male; Potassium; Sodium; Vasopressins

The antidiuretic action of a number of vasopressin analogues has been measured in the rat and man in water diuresis. These analogues had the following categories of structural alteration: a) substitution of -CH2CH2-(dicarba) and -SCH2-(6-monocarba) for the natural -SS- bridge between residues 1 and 6, b) changes in the nature of the C-terminal tripeptide produced by substitution of D-arginine and L-Nalpha-methylarginine for L-arginine in sequence position 8 and L-leucine for proline in position 7, and c) combinations of a and b. In addition, a highly active analogue which results when valine is substituted for glutamine in position 4 was tested. Trained, unanesthetized rats and normal human volunteers were complemented by a volunteer patient with posttraumatic diabetes insipidus (DI) in the total group of experimental subjects. The only change in the C-terminal tripeptide which was associated with a high antidiuretic action was D-Arg substitution. The meArg and Leu analogues showed low to very little activity and no signs of antidiuretic antagonist action. All of the carba analogues showed both high potency and prolongation of antidiuretic action in the following order (for both potency and duration): monocarba + 8-D-Arg greater than 4-Val + 8-D-Arg greater than 8-D-Arg alone, all in deamino form. None of the 8-D-Arg analogues had any side effects on the cardiovascular system, gut, uterus, bladder, etc. The prolongation was such that even with a DI patient refractory to the action of lysine-vasopressin and relatively resistant to deamino-[8-D-Arg]-vasopressin, water turnover could be reduced from untreated levels of 20 to 30 liters/day to less than 2 liters/day with only a single administration of deamino-6-carba-[8-D-Arg]-vasopressin as nose drops. The significance of these structural alterations in the vasopressin molecule for interaction with both antidiuretic and smooth muscle receptors was discussed.

Topics: Adult; Animals; Arginine Vasopressin; Chemical Phenomena; Chemistry; Deamino Arginine Vasopressin; Diabetes Insipidus; Disulfides; Diuresis; Dose-Response Relationship, Drug; Female; Humans; Male; Peptides; Pregnancy; Rats; Structure-Activity Relationship; Vasopressins

Topics: Animals; Avoidance Learning; Diabetes Insipidus; Growth Hormone; Humans; Memory; Rats; Retention, Psychology; Vasopressins

Three male siblings with diabetes mellitus are described, two of whom also had coexistent diabetes insipidus. The co-existence of diabetes mellitus and insipidus appears to represent a single genetic abnormality and may or may not be accompanied by primary optic atrophy. Chlorpropamide was effective in controlling the symptoms of diabetes mellitus and diabetes insipidus.

Topics: Adult; Chlorpropamide; Diabetes Insipidus; Diabetes Mellitus; Diabetic Retinopathy; Humans; Kidney Concentrating Ability; Male; Middle Aged; Sex Chromosomes; Vasopressins

Topics: Animals; Castration; Diabetes Insipidus; Female; Male; Rats; Renin; Vasopressins

Topics: Clofibrate; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Vasopressins

A radioimmunoassay specific for arginine-vasopressin (AVP) developed in recent years has been applied to measurement of urinary AVP during physiological and clinical studies. Daily excretion of AVP was 34 +/- 10 ng (mean +/- SD) in 17 female normals and 69 +/- 45 ng in 17 male normals, this being a significant difference (p less than 0.01). After osmolar load (Carter-Robbins test) hourly excretion of AVP increased significantly in 7 males from 1.3 to 3.1 ng/h and in 6 females from 1.7 to 6.5 ng/h. Again the difference between male and female normals was significant. In both sexes a significant correlation between AVP excretion and either plasma osmolality or free-water clearance was found. When the osmolar load test was performed under constant angiotensin II perfusion in male subjects, their AVP excretion was significantly more elevated; this confirmed in man the hypothesis that angiotensin II is a stimulus to AVP secretion. Preliminary results of AVP excretion and response to osmolar load in diabetes insipidus are reported. Exceedingly high rate of excretion of AVP up to 55 330 ng/24 h have been found in cases of bronchial carcinoma with dilutional hyponatremia.

Topics: Aldosterone; Angiotensin II; Bronchial Neoplasms; Diabetes Insipidus; Female; Humans; Male; Osmolar Concentration; Thirst; Vasopressins; Water-Electrolyte Balance

The diuretic action of two new narcotic antagonists, oxilorphan and butorphanol, was studied in rats heterozygous for hereditary hypothalmic diabetes insipidus. Both drugs caused a prompt increase in urine volume and a decrease in urine osmolality with an associated decrease in urinary ADH excretion. The effects appeared to be dose related and of short duration. Tolerance to butorphanol administration was evident on repeated daily injections. The diuretic effect was not associated with alternation in creatinine excretion, but butorphanol resulted in decreased osmolal, sodium and potassium excretion. Butorphanol prevented the expected rise in urine osmolality and ADH excretion due to 31 h of dehydration. Oxilorphan did not interfere with the ability of administered ADH to cause an antidiuresis. The data indicate that these narcotic antagonists cause a diuresis by inhibiting ADH release from the neurohypophysis.

Topics: Animals; Diabetes Insipidus; Diuresis; Diuretics; Dose-Response Relationship, Drug; Narcotic Antagonists; Pituitary Gland, Posterior; Rats; Vasopressins

Topics: Animals; Avoidance Learning; Behavior, Animal; Conditioning, Operant; Diabetes Insipidus; Electroshock; Escape Reaction; Extinction, Psychological; Genetics, Behavioral; Heterozygote; Homozygote; Rats; Retention, Psychology; Species Specificity; Vasopressins

The effect on water metabolism of 1-deamino-8-D-arginine vasopressin and lysine vasopressin have been studied and compared in 20 vasopressin-sensitive and 2 ADH-resistant diabetes insipidus patients. In every case of ADH-sensitive diabetes insipidus, diuresis decreased and the urinary osmolality increased more markedly and for a longer time with the former than with the latter drug. Both drugs were ineffective in patients with ADH-resistant diabetes insipidus. Administration of 1-deamino-8-D-arginine vasopressin did not cause any side effect. It is concluded that 1-deamino-8-D-arginine vasopressin can successfully be employed in the treatment of ADH-sensitive diabetes insipidus.

Topics: Administration, Intranasal; Adolescent; Adult; Chemical Phenomena; Chemistry; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Injections, Intravenous; Lypressin; Male; Middle Aged; Osmolar Concentration; Time Factors; Vasopressins

A definite relationship was found between the dose of DDAVP (1-24 mug intravenously and 5-320 mug intranasally) and the antidiuretic effects (expressed in changes in free water clearance per 100 ml GFR and in urine osmolality determined in 24 hour urine collection periods) in 7 patients with diabetes insipidus. The relationship was more conspicuous when the second 12 hour antidiuretic responses were considered, indicating a dose-dependent prolongation of the antidiuretic action. Time-curves of the antidiuretic responses proved the dose-dependent prolongation of the duration of antidiuretic action. Second 12 hour antidiuretic response increased more markedly when DDAVP was given divided in two doses a day as compared to the effects of the same quantity of the drug given as a single dose; only by the administration of excessive single doses the effects of the divided doses could be reproduced.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Osmolar Concentration; Urine; Vasopressins

Topics: Animals; Arginine Vasopressin; Circadian Rhythm; Dehydration; Diabetes Insipidus; Heterozygote; Homozygote; Rats; Vasopressins

A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72%. The blank value measured in extracted samples of urine was 0.29 pg/ml +/- 0.21 (SEM) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13% and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.

Topics: Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hyponatremia; Lung Neoplasms; Male; Osmolar Concentration; Radioimmunoassay; Sex Factors; Syndrome; Thirst; Vasopressins

Topics: Adolescent; Child; Diabetes Insipidus; Follow-Up Studies; Hallucinations; Humans; Injections, Intramuscular; Male; Sweating; Urography; Vasopressins

Topics: Animals; Axonal Transport; Axons; Diabetes Insipidus; Hypertonic Solutions; Hypothalamo-Hypophyseal System; Hypothalamus; Microscopy, Electron; Microtubules; Peptides; Pituitary Gland; Rats; Stress, Physiological; Vasopressins

Topics: Diabetes Insipidus; Disseminated Intravascular Coagulation; Humans; Infant, Newborn; Infant, Newborn, Diseases; Listeria monocytogenes; Listeriosis; Male; Osmolar Concentration; Sodium; Specific Gravity; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Topics: Administration, Oral; Diabetes Insipidus; Diuresis; Diuretics; Glomerular Filtration Rate; Glyburide; Humans; Injections, Intravenous; Kidney; Lysine; Osmolar Concentration; Pituitary Gland; Time Factors; Vasopressins

Topics: Arginine; Diabetes Insipidus; Diuresis; Glomerular Filtration Rate; Glyburide; Humans; Osmolar Concentration; Time Factors; Vasopressins

Topics: Animals; Antigen-Antibody Reactions; Diabetes Insipidus; Diuresis; Glyburide; Humans; Iodine Radioisotopes; Kidney; Lysine; Male; Osmolar Concentration; Rats; Time Factors; Vasopressins

Topics: Adrenal Cortex Hormones; Arginine; Child; Child, Preschool; Diabetes Insipidus; Follicle Stimulating Hormone; Growth Hormone; Humans; Hydrocortisone; Hypopituitarism; Insulin; Luteinizing Hormone; Male; Optic Chiasm; Radiography; Sella Turcica; Skull; Thyrotropin-Releasing Hormone; Thyroxine; Tuberculoma; Tuberculosis, Meningeal; Vasopressins; Vision Disorders

Topics: Acne Vulgaris; Adult; Demeclocycline; Diabetes Insipidus; Female; Gonorrhea; Humans; Male; Polyuria; Vasopressins

Topics: Acromegaly; Addison Disease; Adrenalectomy; Blood Glucose; Cushing Syndrome; Diabetes Insipidus; Dwarfism; Dwarfism, Pituitary; Female; Glucagon; Growth Hormone; Humans; Hyperthyroidism; Hypogonadism; Hypopituitarism; Insulin; Lysine; Male; Pyrogens; Radioimmunoassay; Vasopressins

Topics: Adenylyl Cyclases; Animals; Cell Membrane; Cyclic AMP; Demeclocycline; Depression, Chemical; Diabetes Insipidus; Enzyme Induction; Epithelium; Fluorides; Humans; Kidney Concentrating Ability; Kidney Medulla; Kidney Tubules; Lithium; Nephrons; Osmolar Concentration; Phosphoric Diester Hydrolases; Potassium; Receptors, Cell Surface; Sodium; Stimulation, Chemical; Thiazoles; Vasopressins

Topics: Adenylyl Cyclases; Adult; Child; Child, Preschool; Cyclic AMP; Diabetes Insipidus; Humans; Inulin; Kidney Concentrating Ability; Kidney Diseases; Kidney Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Osmolar Concentration; Vasopressins

Topics: Adenylyl Cyclase Inhibitors; Adult; Cyclic AMP; Diabetes Insipidus; Digestive System; Humans; Hypothyroidism; Lithium; Male; Muscle, Smooth; Vasopressins

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Chlorpromazine; Corticotropin-Releasing Hormone; Diabetes Insipidus; Disease Models, Animal; Ethyl Ethers; Hemorrhage; Hypothalamo-Hypophyseal System; Laparotomy; Male; Morphine; Pentobarbital; Pituitary Gland; Pituitary-Adrenal System; Rats; Stress, Physiological; Vasopressins

Previous work has suggested that resistance to vasopressin in two strains of mice with nephrogenic deficiency of urinary concentration may entail a defect in the action of vasopressin at the cellular level. Several components involved in this action were therefore examined in vitro in renal medullary tissues from control mice (genotype VII +/+) and two genotypes with mild diabetes insipidus (DI +/+ nonsevere) and marked (DI +/+ severe) vasopressin-resistant concentrating defects. No significant differences were found in the affinity of adenylate cyclase for [8-arginine]-vasopressin (AVP), tested over a range of hormone concentration from 10(-10) to 10(-5) M. However, maximal stimulation of adenylate cyclase by saturating concentrations of AVP (intrinsic activity) was markedly decreased from control values in DI +/+ severe mice, and decreased to a lesser extent in DI +/+ nonsevere animals. A significant correlation was found between the activity of adenylate cyclase maximally stimulated by AVP in a given genotype, and the urine osmolality in the same animals. There were no significant differences in maximal stimulation of renal medullary adenylate cyclase in control experiments: not when stimulated nonspecifically by sodium fluoride, nor when stimulated by AVP in tissues from rats with induced water diuresis as compared to antidiuretic rats. Nor were there significant differences between VII +/+ and DI +/+ severe mice in the activity of renal cortical adenylate cyclase, either basal or when stimulated by parathyroid hormone. Furthermore, the abnormal genotypes did not differ significantly from control mice in the renal medullary activities of cyclic AMP phosphodiesterase or cyclic AMP-dependent protein kinase, nor in the content of microtubular subunits (assessed as colchicinebinding protein). The results are compatible with the view that impaired stimulation of renal medullary adenylate cyclase by vasopressin might be the sole or contributing cause of the vasopressin-resistant concentrating defect in the diseased mice; however, a causal relationship has not yet been proved.

Topics: Adenylyl Cyclases; Animals; Cyclic AMP; Cytosol; Diabetes Insipidus; Disease Models, Animal; Diuresis; Female; Genotype; Histones; Kidney; Kidney Concentrating Ability; Kidney Medulla; Kidney Tubules; Male; Mice; Microtubules; Phosphoric Diester Hydrolases; Protein Binding; Protein Kinases; Vasopressins

Topics: Adenylyl Cyclase Inhibitors; Chlortetracycline; Cyclic AMP; Cytosol; Demeclocycline; Diabetes Insipidus; Humans; In Vitro Techniques; Kidney; Kidney Medulla; Phosphodiesterase Inhibitors; Protein Kinase Inhibitors; Tetracycline; Vasopressins

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Chlorpropamide; Chromatography; Creatinine; Cyclic AMP; Depression, Chemical; Diabetes Insipidus; Female; Humans; Infant; Injections, Intravenous; Male; Osmolar Concentration; Radioimmunoassay; Stimulation, Chemical; Time Factors; Tritium; Vasopressins

Topics: Angiotensin II; Animals; Castration; Diabetes Insipidus; Enzyme Precursors; Female; Gonads; Male; Rats; Renin; Sex Factors; Vasopressins

Topics: Aldosterone; Angiotensin II; Animals; Diabetes Insipidus; Diuresis; Extracellular Space; Glomerular Filtration Rate; Glucose; Humans; Kidney; Polyuria; Potassium; Sodium; Sodium Chloride; Thiosulfates; Vasopressins; Water; Water-Electrolyte Balance

1. Long-lasting haemorrhagic hypotension (4.5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP(9a)), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP(9a) was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days.2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock.3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock.4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period.5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock.6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period.7. BPP(9a) had no measurable effect on the course of endotoxic shock.8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on th

Topics: Angiotensin II; Animals; Blood Pressure; Blood Volume; Cardiac Output; Diabetes Insipidus; Dogs; Heart Rate; Intestines; Kidney; Liver; Male; Oligopeptides; Peptides; Shock, Hemorrhagic; Shock, Septic; Stomach; Vasopressins

Topics: Carbamazepine; Chlorpropamide; Clofibrate; Diabetes Insipidus; Diuretics; Drug Synergism; Drug Therapy, Combination; Humans; Vasopressins; Water Intoxication

Topics: Acute Disease; Anuria; Child; Craniopharyngioma; Depression, Chemical; Diabetes Insipidus; Female; Humans; Injections, Intravenous; Phenytoin; Pituitary Neoplasms; Postoperative Care; Postoperative Complications; Secretory Rate; Sodium; Stimulation, Chemical; Time Factors; Vasopressins

Topics: Adolescent; Adult; Aged; Chlorpropamide; Clofibrate; Diabetes Insipidus; Dibenzazepines; Diuretics; Female; Humans; Hypothalamus; Kidney; Kidney Function Tests; Male; Middle Aged; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Vasopressins; Water

Topics: Arginine; Diabetes Insipidus; Humans; Hypertension; Hyponatremia; Radioimmunoassay; Vasopressins

Topics: Acute Kidney Injury; Aldosterone; Animals; Anuria; Burns; Diabetes Insipidus; Disease Models, Animal; Diuresis; Diuretics; Furosemide; Kidney; Male; Mineralocorticoid Receptor Antagonists; Rats; Shock, Traumatic; Sodium; Sodium Chloride; Time Factors; Urea; Vasopressins; Water

Topics: Adrenal Glands; Animals; Body Weight; Dehydration; Diabetes Insipidus; Drinking; Drug Resistance; Eating; Female; Kidney Glomerulus; Kidney Medulla; Kinetics; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred Strains; Osmolar Concentration; Sodium Chloride; Vasopressins; Water; Water Deprivation

Topics: Administration, Oral; Adolescent; Adult; Arginine; Body Weight; Carbamazepine; Creatine; Diabetes Insipidus; Female; Hemoglobins; Humans; Kidney Tubules, Distal; Male; Middle Aged; Osmosis; Potassium; Radioimmunoassay; Sodium; Urination; Vasopressins; Water

Topics: Adult; Aminohippuric Acids; Diabetes Insipidus; Diuresis; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Injections, Intravenous; Isoproterenol; Male; Metabolic Clearance Rate; Norepinephrine; Osmolar Concentration; Vasopressins

Topics: Blood Urea Nitrogen; Diabetes Insipidus; Diet Therapy; Humans; Hydronephrosis; Infant; Kidney Diseases; Male; Osmolar Concentration; Urethra; Urethral Diseases; Urethral Stricture; Urinary Tract Infections; Urography; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Body Weight; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Drinking; Hematocrit; Heterozygote; Homozygote; Male; Osmolar Concentration; Plasma Volume; Potassium; Rats; Sodium; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Adenylyl Cyclases; Animals; Diabetes Insipidus; Drinking; Drug Interactions; Injections, Intramuscular; Injections, Intraperitoneal; Kidney; Lithium; Male; Osmolar Concentration; Pituitary Gland, Anterior; Potassium; Rats; Sodium; Sodium Chloride; Thirst; Time Factors; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Topics: Animals; Biological Assay; Blood Pressure; Body Weight; Chromatography, Gel; Diabetes Insipidus; Freund's Adjuvant; Heterozygote; Homozygote; Iodine Radioisotopes; Male; Pituitary Gland, Posterior; Radioimmunoassay; Rats; Rodent Diseases; Tissue Extracts; Vasopressins

Topics: Aldosterone; Diabetes Insipidus; Diuresis; Ethacrynic Acid; Humans; Infant; Kidney; Kidney Tubules; Male; Metabolic Clearance Rate; Microscopy, Electron; Renin; Vasopressins

Topics: Arginine; Diabetes Insipidus; Humans; Vasopressins

The case of a fourteen year-old boy suffering from diabetes insipidus and polycythaemia is reported. The possible mechanisms resulting in the association of the two rare disorders are discussed in detail.

Topics: Adolescent; Diabetes Insipidus; Humans; Kidney Concentrating Ability; Male; Osmolar Concentration; Polycythemia; Vasopressins

Topics: Amino Acid Sequence; Animals; Avoidance Learning; Behavior, Animal; Diabetes Insipidus; Hypothalamus; Memory; Pituitary Gland, Posterior; Rats; Stress, Physiological; Structure-Activity Relationship; Supraoptic Nucleus; Vasopressins

Topics: Animals; Antibodies, Viral; Apnea; Autopsy; Blood; Brain; Carbon Dioxide; Child; Chlorpromazine; Diabetes Insipidus; Fluorescent Antibody Technique; Heart Arrest; Humans; Hydrogen-Ion Concentration; Hyperkinesis; Hypotension; Male; Mice; Oxygen; Rabies; Rabies virus; Seizures; Vasopressins

Topics: Diabetes Insipidus; Endocrinology; History, 20th Century; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Research; Vasopressins

Topics: Adult; Diabetes Insipidus; Humans; Hydronephrosis; Kidney Concentrating Ability; Male; Urinary Bladder; Urinary Bladder Neck Obstruction; Vasopressins

Topics: Action Potentials; Animals; Diabetes Insipidus; Electric Stimulation; Heterozygote; Homozygote; Hypothalamo-Hypophyseal System; Male; Neurons; Osmolar Concentration; Rats; Rats, Inbred Strains; Sodium; Vasopressins

Topics: Animals; Cat Diseases; Cats; Chronic Disease; Dehydration; Diabetes Insipidus; Hydrochlorothiazide; Kidney Diseases; Male; Urine; Vasopressins

Topics: Administration, Oral; Animals; Biological Assay; Carbamazepine; Diabetes Insipidus; Diuresis; Drinking; Female; Humans; Osmolar Concentration; Polyuria; Rats; Urination; Vasopressins

Topics: Adolescent; Adult; Blood Glucose; Diabetes Insipidus; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glucagon; Glucose Tolerance Test; Growth Hormone; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Tolbutamide; Vasopressins

Topics: Adolescent; Chlorpropamide; Diabetes Insipidus; Drinking; Female; Humans; Hydrochlorothiazide; Hypernatremia; Nicotine; Potassium; Sodium; Sodium Chloride; Spironolactone; Syndrome; Thirst; Urination; Vasopressins; Water Deprivation

Topics: Arginine; Child; Diabetes Insipidus; Histiocytosis, Langerhans-Cell; Humans; Male; Vasopressins

Topics: Animals; Aorta, Thoracic; Blood Pressure; Cardiac Output; Denervation; Diabetes Insipidus; Dogs; Dose-Response Relationship, Drug; Heart Rate; Hypophysectomy; Norepinephrine; Pituitary Gland; Pressoreceptors; Vasopressins

Topics: Administration, Intranasal; Adult; Arginine; Diabetes Insipidus; Drug Evaluation; Humans; Hypopituitarism; Male; Osmolar Concentration; Urination; Vasopressins

Topics: Adolescent; Aminohippuric Acids; Child; Diabetes Insipidus; Diuresis; Glomerular Filtration Rate; Humans; Infant; Inulin; Kidney Concentrating Ability; Kidney Diseases; Kidney Function Tests; Mannitol; Methods; Osmolar Concentration; Potassium; Sodium; Stimulation, Chemical; Vasopressins

Topics: Animals; Arginine; Deamination; Diabetes Insipidus; Diuresis; Structure-Activity Relationship; Time Factors; Vasopressins

Topics: Adult; Arrhythmias, Cardiac; Central Nervous System Diseases; Dehydration; Diabetes Insipidus; Electrocardiography; Female; Humans; Hypokalemia; Vasopressins

Topics: Animals; Circadian Rhythm; Diabetes Insipidus; Drinking; Female; Light; Male; Nephrectomy; Rats; Rats, Inbred Strains; Vasopressins; Visual Pathways

Topics: Adult; Diabetes Insipidus; Diuresis; Diuretics; Ethanolamines; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Methylamines; Osmolar Concentration; Phenols; Vasopressins; Water; Water-Electrolyte Balance

Topics: Carbamazepine; Clofibrate; Diabetes Insipidus; Drug Therapy, Combination; Humans; Vasopressins

Topics: Administration, Intranasal; Adolescent; Adult; Arginine; Child; Child, Preschool; Diabetes Insipidus; Diuresis; Female; Humans; Male; Osmolar Concentration; Time Factors; Vasopressins

Topics: Adult; Carbamazepine; Clofibrate; Diabetes Insipidus; Diuresis; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Lysine; Nephritis; Osmolar Concentration; Pituitary Gland; Vasopressins; Water

Topics: Animals; Body Weight; Diabetes Insipidus; Diet; Drinking; Lithium; Male; Osmolar Concentration; Photometry; Polyuria; Rats; Sodium; Time Factors; Urination; Vasopressins

Topics: Child, Preschool; Diabetes Insipidus; Humans; Kidney Tubules; Male; Mikulicz' Disease; Polyuria; Syndrome; Vasopressins

Topics: Adult; Demeclocycline; Diabetes Insipidus; Drug Resistance; Humans; Male; Polyuria; Thirst; Vasopressins

Topics: Acromegaly; Adenoma, Acidophil; Adenoma, Chromophobe; Adult; Brain Neoplasms; Craniopharyngioma; Diabetes Insipidus; Female; Humans; Luteinizing Hormone; Male; Meningioma; Metyrapone; Pinealoma; Pituitary Hormone-Releasing Hormones; Pituitary Neoplasms; Radioimmunoassay; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Adenylyl Cyclases; Amines; Animals; Cyclic AMP; Diabetes Insipidus; Fluorides; Kidney; Kidney Cortex; Kidney Medulla; Male; Rats; Sodium; Thiazoles; Vasopressins

Topics: Amiloride; Animals; Biological Transport; Bufo marinus; Choline; Cyclic AMP; Diabetes Insipidus; Drug Interactions; Female; Hydrogen-Ion Concentration; In Vitro Techniques; Kidney Diseases; Lithium; Magnesium; Membrane Potentials; Potassium; Propionates; Sodium; Triamterene; Urinary Bladder; Vasopressins

Topics: Bronchial Neoplasms; Carcinoma, Small Cell; Diabetes Insipidus; Humans; Hyponatremia; Iodine Isotopes; Radioimmunoassay; Vasopressins; Water; Water Deprivation

Topics: Adenylyl Cyclases; Animals; Cyclic AMP; Diabetes Insipidus; Diuresis; Drug Resistance; Female; Kidney; Mice; Osmosis; Syndactyly; Urine; Vasopressins; Water

Topics: Angiotensin II; Animals; Body Weight; Diabetes Insipidus; Feedback; Hematocrit; Heterozygote; Male; Radioimmunoassay; Rats; Sodium; Time Factors; Vasopressins; Water-Electrolyte Balance

A patient with ectopic pinealoma first presented with apparent anorexia nervosa and hypernatraemic coma. A history of diabetes insipidus two months previously was not known on admission to hospital. The diabetes insipidus was unmasked by the administration of steroids. Neuroendocrinal and neuropathological aspects of the case are discussed with reference to the march of symptoms due to the growth of the tumour. Histochemical evidence is presented supporting the similarity between ectopic pinealoma and seminoma which suggests that they may more properly be referred to as atypical teratomas.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Anorexia Nervosa; Brain Neoplasms; Coma; Diabetes Insipidus; Dihydrolipoamide Dehydrogenase; Dysgerminoma; Electron Transport Complex IV; Esterases; Female; Humans; Hydrocortisone; Hypernatremia; Hypothalamus; Male; Osmolar Concentration; Oxidoreductases; Pinealoma; Sodium; Testicular Neoplasms; Thyroxine; Tuberculosis; Vasopressins

Topics: Animals; Biological Assay; Dehydration; Diabetes Insipidus; Humans; Hypophysectomy; Pituitary Gland; Radioimmunoassay; Rats; Time Factors; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Topics: Amino Acid Sequence; Child; Diabetes Insipidus; Female; Humans; Hyperthyroidism; Hypothalamus; Male; Oxytocin; Pituitary Hormone-Releasing Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Antibody Formation; Antibody Specificity; Diabetes Insipidus; Drug Hypersensitivity; Electrocardiography; Humans; Hypergammaglobulinemia; Hypopituitarism; Iatrogenic Disease; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Male; Middle Aged; Pituitary Hormones, Posterior; Powders; Vasopressins

Topics: Chlorpropamide; Diabetes Insipidus; Diuresis; Humans; Osmolar Concentration; Vasopressins

Topics: Chlorpropamide; Creatinine; Diabetes Insipidus; Drug Synergism; Humans; Injections, Intravenous; Osmolar Concentration; Urination; Vasopressins

Topics: Animals; Diabetes Insipidus; Diuresis; Female; Glomerular Filtration Rate; Inulin; Kidney Concentrating Ability; Kidney Tubules; Kidney Tubules, Proximal; Male; Osmolar Concentration; Potassium; Punctures; Rats; Rats, Inbred Strains; Sodium; Vasopressins

Topics: Animals; Biological Transport, Active; Diabetes Insipidus; Female; Injections, Subcutaneous; Kidney; Male; Osmolar Concentration; Potassium; Rats; Sodium; Urea; Vasopressins

Normal subjects and patients with antidiuretic hormone (ADH) deficiency were studied to determine the mechanism of the antidiuretic action of clofibrate. Before clofibrate treatment, the patients' ability to concentrate urine with a standardized dehydration procedure correlated with the amount of ADH which was excreted. During clofibrate administration all six patients with ADH deficiency developed an antidiuresis which was like that of ADH, since there was no change in sodium, potassium, total solute, or creatinine excretion. There was a correlation between the patients' ability to concentrate urine during dehydration and the subsequent response to clofibrate, and the excretion of ADH during dehydration correlated with the excretion of ADH on clofibrate therapy. Clofibrate-induced antidiuresis in these patients was partially overcome by ethanol and by water loading. Clofibrate interfered with the ability of patients and subjects to excrete a water load and prevented the water load from inhibiting ADH excretion in the normal subjects. These studies suggested that clofibrate was acting through endogenous ADH and this thesis was supported by the failure of clofibrate to produce an antidiuresis when injected into rats with total ADH deficiency (Brattleboro strain) although an antidiuresis was produced in water-loaded normal rats. When the drug was injected into Brattleboro rats with exogenous ADH, clofibrate either did not alter or it inhibited the action of the ADH. The data demonstrate that clofibrate has a significant ADH-like action. This action appears to be mediated through the release of endogenous ADH.

Topics: Adult; Animals; Clofibrate; Creatinine; Dehydration; Diabetes Insipidus; Diuresis; Drinking; Ethanol; Female; Humans; Male; Middle Aged; Osmolar Concentration; Potassium; Rats; Sodium; Urination; Vasopressins

Topics: Adult; Body Water; Brain Injuries; Diabetes Insipidus; Facial Injuries; Female; Fractures, Bone; Humans; Hyponatremia; Hypothalamus; Male; Natriuresis; Osmolar Concentration; Pituitary Gland, Posterior; Prospective Studies; Skull Fractures; Sodium; Vasopressins

Topics: Administration, Intranasal; Adolescent; Arginine; Child; Child, Preschool; Delayed-Action Preparations; Depression, Chemical; Diabetes Insipidus; Diuresis; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Male; Osmolar Concentration; Time Factors; Vasopressins

Topics: Adolescent; Adult; Child; Chlorpropamide; Diabetes Insipidus; Diuresis; Ethanol; Female; Humans; Male; Middle Aged; Norepinephrine; Osmolar Concentration; Phenytoin; Vasopressins; Water Deprivation

Topics: Adolescent; Adult; Child; Chlorides; Cystic Fibrosis; Diabetes Insipidus; Female; Humans; Iontophoresis; Male; Potassium; Sodium; Sweat; Sweat Glands; Sweating; Vasopressins

Topics: Adolescent; Aminosalicylic Acids; Blood Glucose; Body Height; Calcinosis; Child; Child, Preschool; Diabetes Insipidus; Female; Growth Hormone; Hemiplegia; Humans; Hypopituitarism; Isoniazid; Obesity; Prednisone; Pyrazinamide; Streptomycin; Tuberculosis, Meningeal; Vasopressins

Topics: Aged; Diabetes Insipidus; Humans; Male; Meningitis, Pneumococcal; Spinal Puncture; Vasopressins