deamino-arginine-vasopressin and Water-Electrolyte-Imbalance

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Deamino Arginine Vasopressin; Humans; Hyperkalemia; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Membrane Potentials; Morpholines; Osmolar Concentration; Potassium; Randomized Controlled Trials as Topic; Sodium; Spiro Compounds; Survival Rate; Tolvaptan; Water-Electrolyte Imbalance

Hyponatremia, defined as a serum sodium < 135 mmol/l, is one of the most commonly encountered and serious electrolyte disorders of clinical medicine. The predominant cause of hyponatremia is an inappropriate elevation of circulating vasopressin levels relative to serum osmolality or the 'syndrome of inappropriate antidiuretic hormone secretion' (SIADH). Fortunately, the degree of the hyponatremia is limited by a process that counters the water-retaining action of vasopressin, namely 'vasopressin escape'. Vasopressin escape is characterized by a sudden increase in urine volume with a decrease in urine osmolality independent of circulating vasopressin levels. Until recently, little was known about the molecular mechanisms underlying escape. In the 1980s, we developed an animal model for vasopressin escape in which male Sprague-Dawley rats were infused with dDAVP, a V2-receptor-selective agonist of vasopressin, while being fed a liquid diet. Rats drank a lot of water in order to get the calories they desired. Using this model, we demonstrated that the onset of vasopressin escape (increased urine volume coupled to decreased urine osmolality) coincided temporally with a marked decrease in renal aquaporin-2 (water channel) protein and mRNA expression in renal collecting ducts. This protein reduction was reversible and correlated to decreased water permeability of the collecting duct. Studies examining the mechanisms underlying AQP2 decrease revealed a decrease in V2-receptor mRNA expression and binding, as well as a decrease in cyclic AMP production in response to acute-dDAVP challenge in collecting duct suspensions from these escape animals. Additional studies showed an increase in sodium transporters of the distal tubule. These changes, hypothetically, might help to attenuate the hyponatremia. Future studies are needed to fully elucidate systemic, intra-organ, and cellular signaling responsible for the physiological phenomenon of vasopressin escape.

Topics: Animals; Aquaporins; Carrier Proteins; Deamino Arginine Vasopressin; Diuresis; Kidney; Natriuresis; Rats; Vasopressins; Water-Electrolyte Imbalance

Involvement of AVP in several pathological states is now established and specific modulation of the different AVP receptor subtypes (V1a, V1b and V2) offers new clinical perspectives for treating major diseases. Recent years have marked a turning point with the design and the use of the first nonpeptide vasopressin receptor antagonists expressing various selectively profile. In that field, we report here the characterization of SR 121463A a highly selective, orally-active antagonist of vasopressin V2 receptors in several models in vitro and in vivo. This compound displayed competitive nanomolar affinity for V2 receptors in various species including man and exhibited a highly selective AVP V2 profile. In vitro, SR 121463A potently antagonized AVP-stimulated adenylyl cyclase activity in human kidney preparations (Ki = 0.26 +/- 0.04 nM) without any intrinsic agonistic effect. In normally-hydrated rats, SR 121463A induced dose-dependent powerful and long-lasting aquaresis after intravenous (0.003 to 0.3 mg/kg) or oral (0.03 to 10 mg/kg) administration. The action of SR 121463A is purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In vasopressin-deficient Brattleboro rats, SR 121463A is devoid of any V2 antidiuretic agonist properties. In addition, this compound potently antagonized DDAVP extrarenal V2 effects on hemostasis factor release (FVIII, vW and t-PA) in dogs (ID50 approximately 10 micrograms/kg i.v.). Thus, SR 121463A is the most potent and selective, orally-active V2 antagonist yet described. It is a useful ligand for exploring V2 receptors and the therapeutical usefulness of pure V2 aquaretic agents in several water-retaining diseases and congestive heart failure.

Topics: Adenylyl Cyclases; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Deamino Arginine Vasopressin; Dogs; Heart Failure; Humans; Kidney; Morpholines; Rats; Rats, Inbred BB; Receptors, Vasopressin; Spiro Compounds; Water-Electrolyte Imbalance

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

Ten patients with chronic schizophrenia completed a 3-month double-blind, placebo-controlled trial with a vasopressin analogue. Modest improvement occurred, but several patients also experienced significant fluid and electrolyte imbalance.

Topics: Adolescent; Adult; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Water-Electrolyte Imbalance

The renin-angiotensin-aldosterone and arginine vasopressin-V2 receptor-aquaporin-2 (AQP2) systems converge on the epithelial Na

Topics: Animals; Aquaporin 2; Deamino Arginine Vasopressin; Epithelial Sodium Channels; Hypertension; Mice; Receptors, Vasopressin; Sodium; Water; Water-Electrolyte Imbalance

Water and electrolyte disturbances are common after pituitary surgery and can generally be classified into transient hypotonic polyuria and transient or permanent diabetes insipidus (DI). The prevalence varies in the literature between 31-51% for transient hypotonic polyuria, 5.1-25.2% for transient DI, and 1-8.8% for permanent DI.. The aim of this study was to identify the prevalence of water and electrolyte disturbances with polyuria and the preoperative and postoperative predictive factors in patients undergoing surgery with an extended endoscopic endonasal approach.. The overall prevalence of water and electrolyte disorders was 30.5% (62), and the prevalence of postoperative polyuria was 23.6% (48). The median number of desmopressin doses administered to patients with postoperative polyuria was one dose (interquartile range [IQR] 1-2), and thus the median duration of treatment was 0 days. The median initiation of desmopressin was the second day after surgery (IQR 1-2). The overall prevalence of DI was 6.89%. Among the patients with transient DI, the duration was less than 3 months in three patients (1.47%), and between 3 and 6 months in two (0.98%). Nine patients had permanent DI (4.43%). (4.43%).. The prevalence of electrolyte disturbances in our study was high, although similar to that found in the literature. Most of the cases were transient hypotonic polyuria that resolved within one day. The prevalence of transient DI in our cohort was lower than that described in the literature, while permanent DI was similar.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Pituitary Neoplasms; Polyuria; Postoperative Complications; Retrospective Studies; Water-Electrolyte Imbalance

Disequilibrium syndrome (DS) is a central nervous system disorder described in hemodialysis (HD) patients. The authors present 4 cases of elevated blood urea nitrogen (BUN); the first patient passed away from suspected DS, whereas the other 3 patients were identified as having a high risk of developing DS on the basis of their BUN. The authors tried to lower their BUN slowly and prevent rapid correction by different methods. This is the first study in which DS has been studied in patients who are not on HD, and methods are described to identify and prevent DS in such patients. They also review the existing literature on the pathogenesis of DS and highlight the importance of recognizing this syndrome in non-HD patients, while suggesting some innovative ways to prevent it.

Topics: Aged; Antidiuretic Agents; Blood Urea Nitrogen; Cerebellar Ataxia; Deamino Arginine Vasopressin; Disease Management; Female; Fluid Therapy; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Intellectual Disability; Male; Middle Aged; Treatment Outcome; Urethral Obstruction; Urinary Catheterization; Water-Electrolyte Imbalance

Desmopressin (DDAVP) 1-deamino-8-D-arginine vasopressin is used in patients with bleeding disorders, including mild factor VIII deficiency, types 1 and 2 von Willebrand disease, and platelet function defects, undergoing surgeries to help control bleeding. We conducted a retrospective chart review of bleeding disorder patients undergoing inpatient surgery at Toledo Children's Hospital, OH, from 2005 to 2009. Our study population included 107 patients aged 2 to 19 years with platelet function defects and von Willebrand disease. Our study aimed to evaluate the extent of hyponatremia caused by DDAVP and to propose a safe and effective treatment regimen for these patients. The mean change in sodium level before and after DDAVP was statistically significant within each age group. Thirteen patients had second dose of DDAVP withheld, and 11 patients had postoperative sodium levels ≤ 130 mEq/L. There were 2 patients with significant complications: a 6-year-old with postoperative bleeding and a 2-year-old with post-DDAVP tonic-clonic seizures. We conclude that DDAVP causes significant hyponatremia, despite appropriate fluid restrictions. On the basis of our analysis, we recommend monitoring sodium levels before each dose of DDAVP and fluid restriction. These patients should be observed in the hospital setting after DDAVP administration for complications such as seizures and postoperative bleeding.

Topics: Adolescent; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemophilia A; Hemostatics; Humans; Hyponatremia; Intraoperative Period; Postoperative Complications; Postoperative Period; Retrospective Studies; Sodium; von Willebrand Diseases; Water-Electrolyte Imbalance; Young Adult

Arginine vasopressin (AVP) affects kidney function via vasopressin V2 receptors that are linked to activation of adenylyl cyclase (AC) and an increase in cyclic adenosine monophosphate formation. AVP/cyclic adenosine monophosphate enhance the phosphorylation of the Na-K-2Cl cotransporter (NKCC2) at serine residue 126 (pS126 NKCC2) and of the Na-Cl cotransporter (NCC) at threonine 58 (pT58 NCC). The isoform(s) of AC involved in these responses, however, were unknown. Phosphorylation of S126 NKCC2 and T58 NCC, induced by the V2 receptor agonist (1-desamino-8-D-arginine vasopressin) in wild-type mice, is lacking in knockout mice for AC isoform 6 (AC6). With regard to NKCC2 phosphorylation, the stimulatory effect of 1-desamino-8-D-AVP and the defect in AC6(-/-) mice seem to be restricted to the medullary portion of the thick ascending limb. AC6 is also a stimulator of total renal NKCC2 protein abundance in medullary and cortical thick ascending limb. Consequently, mice lacking AC6 have lower NKCC2 expression and a mild Bartter syndrome-like phenotype, including lower plasma concentrations of K+ and H+ and compensatory upregulation of NCC. Increased AC6-independent phosphorylation of NKCC2 at S126 might help to stabilize NKCC2 activity in the absence of AC6. Renal AC6 determines total NKCC2 expression and mediates vasopressin-induced NKCC2/NCC phosphorylation. These regulatory mechanisms, which are defective in AC knockout mice, are likely responsible for the observed mild Bartter syndrome.

Topics: Adenylyl Cyclases; Animals; Antidiuretic Agents; Bartter Syndrome; Deamino Arginine Vasopressin; Female; Gene Expression Regulation; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Confocal; Phosphorylation; Sodium Chloride Symporters; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Vasopressins; Water-Electrolyte Imbalance

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described entity, linked to gain-of-function mutations (R137C and R137L) in arginine vasopressin (AVP) gene leading to chronic activation of tubular V2 AVP receptor (V2R) and thus free water reabsorption. In addition to collecting duct cells, the V2R is also expressed in endothelial cells, where it mediates the rise in circulating levels of von Willebrand factor (vWF) and coagulation factor VIII (fVIII). Recent in vitro data showed that these mutant receptors are resistant to vasopressin-stimulated cAMP production. We aimed to explore by clinical observations the sensitivity to vasopressin of the R137C-V2R mutant in vivo.. We performed a stimulation test with 1-desamino-D arginin vasopressin (dDAVP) 0·3 μg/kg of bodyweight in three patients (two hemizygous male and one heterozygous female) with NSIAD with R137C mutation and measured on the one hand the levels of vWF and fVIII and the other hand urine osmolality and albumin excretion (UAE).. Whereas the female heterozygous patient displayed normal response to simulation by dDAVP (except for UAE), no increase in vWF, fVIII, urinary osmolality and UAE was observed among hemizygous male patients.. Coherent with in vitro observation in transfected cells, our clinical observations demonstrate that the R137C-V2R mutant is resistant to vasopressin stimulation in its physiological sites of expression.

Topics: Adult; Antidiuretic Agents; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; DNA Mutational Analysis; Factor VIII; Female; Homeostasis; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Mutation; Pedigree; Receptors, Vasopressin; von Willebrand Factor; Water-Electrolyte Imbalance; Young Adult

In a state of chronic arginine vasopressin (AVP)-induced antidiuresis, the antidiuretic efficacy has been attenuated: a phenomenon known as "AVP escape". We compared the experimental SIADH rats with 1-deamino-8-D-AVP (dDAVP)-excess rats. The SIADH rats, but not the dDAVP-excess rats, showed a marked attenuation of urinary concentrating ability. This is closely associated with diminished up-regulation of aquaporin-2 (AQP-2) mRNA and protein expression. The following in vitro study clarified tonicity-response elements in the 5'-flanking region of AQP-2 gene. There are at least more than two hypertonicity-response elements, and a hypotonicity-response element resided at tonicity-response enhancer (TonE) (-570 to -560bp) in the AQP-2 gene. Hypotonicity directly reduced the cAMP-induced AQP-2 promoter activity by mediating JNK kinase. Reduction in transcriptional regulation of AQP-2 under hypotonic state may support the in vivo finding of AVP escape phenomenon in chronic AVP-induced antidiuresis.

Topics: Animals; Aquaporin 2; Arginine Vasopressin; Bucladesine; Deamino Arginine Vasopressin; Disease Models, Animal; Diuresis; Gene Expression Regulation; Genes, Reporter; Heart Failure; Inappropriate ADH Syndrome; Kidney; Luciferases; Promoter Regions, Genetic; Rats; RNA, Messenger; Water-Electrolyte Imbalance

Topics: Adult; Antidiuretic Agents; Brain; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Histiocytosis, Langerhans-Cell; Humans; Magnetic Resonance Imaging; Water-Electrolyte Imbalance

Disturbances of osmoregulation, leading to diabetes insipidus and hyponatraemia are well known complications after surgery in the sella region. This study was performed to examine the prevalence and predictors of polyuria and hyponatraemia after a complete and selective removal of pituitary adenomas was attempted via the transnasal-transsphenoidal approach.. 1571 patients with pituitary adenomas (238 Cushing's disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson's syndrome, and 13 thyrotropinoma) were daily examined within a 10-day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity.. 487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria-hyponatraemia) and triphasic (polyuria-hyponatraemia-polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty-one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing's disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8-fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant.. The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease.

Topics: Acromegaly; Adenoma; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Polyuria; Postoperative Complications; Prevalence; Prolactinoma; Renal Agents; Risk Factors; Water-Electrolyte Imbalance

In a retrospective study, the intra- and early postoperative data of 39 children with 46 operations for craniopharyngioma were analyzed. Diabetes insipidus (DI) occurred in 30 out of 32 cases without preoperative evidence of DI. We observed that all children who did not have a pituitary stalk preserved and 5 out of 7 patients with preserved pituitary stalk developed DI within 18 h of surgery. Short-term inappropriate secretion of antidiuretic hormone (SIADH) occurred in 2 children, but was quickly followed by DI. The time of onset of DI and SIADH did not correlate with sex, age, body weight, location of tumor, or duration or extent of surgery. Parenteral desmopressin was an effective treatment for intra- and postoperative DI. The duration of the clinical effect of desmopressin administration varied in different patients between 4 and 23 h. An approach to the immediate intra- and postoperative management of children with craniopharyngioma is presented.

Topics: Administration, Intranasal; Adolescent; Child; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Fluid Therapy; Humans; Inappropriate ADH Syndrome; Infant; Infant, Newborn; Male; Perioperative Care; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Water-Electrolyte Imbalance

Topics: Anti-Inflammatory Agents, Non-Steroidal; Deamino Arginine Vasopressin; Diuretics; Humans; Isoniazid; Lithium; Methoxyflurane; Phenytoin; Succinylcholine; Tetracycline; Water-Electrolyte Imbalance

A method for maintaining chronic severe hypoosmolality in rats is described utilizing subcutaneous infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine] vasopressin (DDAVP) at rates of 1 or 5 ng/hr via osmotic minipumps in combination with self-ingestion of a concentrated, nutritionally-balanced liquid diet. Using these methods, 97.3% of all rats studied achieved stable levels of severe hyponatremia (plasma [Na+] = 111.6 +/- 0.5 mEq/liter, N = 213), which was sustained for periods of time ranging from two to five weeks. Mortality was low (1.8%) and observable morbidity was not noted over a series of studies encompassing 4,628 rat days of sustained hypoosmolality. Analysis of food intake and body weight revealed no evidence of tissue catabolism at any time with the lower (1 ng/hr) DDAVP infusion rate, and only during the first week with the higher (5 ng/hr) rate. Metabolic balance studies during 13 days of sustained hypoosmolality demonstrated the dilutional nature of the hypoosmolality, and only a limited degree of renal escape from the antidiuretic effects of DDAVP (urine osmolalities 800 to 1200 mOsm/kg H2O). Studies of brain water and electrolyte contents demonstrated complete normalization of brain volume after 14 to 28 days of sustained hypoosmolality, the major part of which (70%) could be accounted for by loss of brain electrolytes. Both natriuresis and kaliuresis occurred during the first five days of hypoosmolality, and were of sufficient magnitude to suggest some degree of adaptation of other body fluid compartments via electrolyte losses as well. These results indicate that rats have substantial capacity to tolerate prolonged severe hypoosmolality with little morbidity and mortality as long as proper attention is paid to their nutritional requirements, and provide further evidence that brain volume regulation likely represents the major adaptive mechanism that allows survival despite sustained hypoosmolality.

Topics: Adaptation, Physiological; Animals; Body Water; Body Weight; Brain; Deamino Arginine Vasopressin; Eating; Male; Osmolar Concentration; Rats; Rats, Inbred Strains; Time Factors; Water-Electrolyte Imbalance

Experimental hyperadiuretism in pregnant rats was induced by applying them daily throughout the pregnancy a synthetic analogue of vasopressin--dDAVP (1-deamino-8-D-arginine vasopressin). It brought about a moderate alteration in the ability to produce hypertonic urine in their offsprings. The osmoregulatory function in the offsprings in the course of fetal development could have been suppressed either by a direct or an indirect effect of dDAVP i.e. by the hypotonicity of mothers' internal environment. There is by now some evidence based on the simultaneous determination of urinary vasopressin and osmolality that the impairment of the osmoregulatory function may be, at least partly, on the renal level.

Topics: Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Kidney; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Water-Electrolyte Imbalance

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: Arginine Vasopressin; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypernatremia; Hypoglycemia; Hyponatremia; Inappropriate ADH Syndrome; Pharmacology; Radioimmunoassay; Vasopressins; Water-Electrolyte Imbalance

Topics: Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Complications; Diabetes Insipidus; Diabetes Mellitus; Humans; Insulin; Male; Water-Electrolyte Imbalance