deamino-arginine-vasopressin and Inappropriate-ADH-Syndrome

To discuss the management of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) developing after subarachnoid hemorrhage, in a comparative manner in the light of the literature.. Without country or language restrictions, articles with high evidential value found in electronic databases were compared to our patients?. After the literature review, three articles were included for systematic evaluation. Desmopressin was administered to the patients for the treatment of hyponatremia, volume contraction, and negative sodium balance caused by SIADH. However, it was not used for preventing re-bleeding.. To prevent the development of this complication (SIADH), the use of desmopressin, an analogue of vasopressin, is important in routine clinical practice.

Topics: Deamino Arginine Vasopressin; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Subarachnoid Hemorrhage

Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion lie at opposite ends of the spectrum of disordered renal handling of water. Whereas renal retention of water insidiously causes hypotonic hyponatremia in syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus may lead to free water loss, hypernatremia, and volume depletion. Hypernatremia and hyponatremia are associated with worse outcomes and longer intensive care stays. Moreover, pathologies causing polyuria and hyponatremia in patients in intensive care may be multiple, making diagnosis challenging. We provide an approach to the diagnosis and management of these conditions in intensive care patients.

Topics: Antidiuretic Agents; Critical Care; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Male; Practice Guidelines as Topic; Water-Electrolyte Balance

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

Hyponatraemia is a common finding in patients with acute cerebral insults. The main differential diagnosis is between syndrome of inappropriate ADH secretion and cerebral salt wasting. Our aim is to review the topic of hyponatraemia in patients with acute cerebral insults and suggest a clinical approach to diagnosis and management.

Topics: Acute Disease; Algorithms; Brain Diseases; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Fluid Therapy; Humans; Hyponatremia; Hypothalamic Neoplasms; Inappropriate ADH Syndrome; Postoperative Complications; Renal Agents; Sodium

Hyponatremia following acute or chronic central nervous system injury which is due to excessive Na+ loss in the urine without an increase in the body fluid, has been described as Cerebral Salt Wasting Syndrome (CSWS). This syndrome is often confused with dilutional hyponatremia secondary to inappropriate ADH secretion. Accurate diagnosis and management are mandatory for to improve the course of the disease. In this study a patient with CSW Syndrome is presented and the treatment and diagnosis of this syndrome are discussed in view of the literature.

Topics: Adenoma; Adult; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Pituitary Neoplasms; Postoperative Complications; Saline Solution, Hypertonic; Sodium

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

Hypothalamic-pituitary region lymphoma is rare and diabetes insipidus (DI) represents one of the most common endocrine manifestations. We report the first case of hypothalamic lymphoma associated with both the syndrome of inappropriate antidiuresis (SIAD) and DI.. A 64-year-old woman with a history of stage IV large B-cell non-Hodgkin lymphoma, underwent atypical right lung resection for pulmonary nodules. A few days after surgery, the patient presented severe normovolemic hyponatremia and serum hypo-osmolarity, therefore, we suspected a paraneoplastic syndrome (SIAD) related to the lung neoplasm, histologically diagnosed as typical carcinoid. The brain magnetic resonance imaging (MRI) showed a 9 mm lesion in the hypothalamic region that significantly increased one month later with the onset of neurological symptoms. A trans-sphenoidal biopsy showed localization of the large B-cell lymphoma. After surgery, the patient presented with polyuria and polydipsia, so desmopressin therapy was started. In the following days, serum osmolarity and sodium fluctuated between normal and low values, then DI was excluded, and SIAD became more likely. Desmopressin therapy was discontinued and hyponatremia was treated with sodium infusion. Hypothalamic lymphoma was treated with chemotherapy and radiotherapy with substantial shrinkage. The hyponatremia persisted during anticancer treatments and improved only after radiotherapy, confirming paraneoplastic SIAD.. Lymphomas of the hypothalamic region can cause electrolyte imbalance for various causes. The differential diagnosis between SIAD, DI and impaired thirst centers may not be straightforward and the electrolyte disorders must be evaluated step by step in all different stages of the disease.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Mellitus; Electrolytes; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lymphoma; Middle Aged; Sodium

Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na. Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.

Topics: Animals; Deamino Arginine Vasopressin; Hyponatremia; Inappropriate ADH Syndrome; Liver; Male; Mice; Sodium; Spermatogenesis; Vasopressins

the identification and minimization of hyponatraemia-inducing medication (HIM) usage is among the effective strategies for preventing hyponatraemia. However, the differential risk of severe hyponatraemia is unknown.. to evaluate the differential risk of severe hyponatraemia associated with newly started and concurrently used HIMs in older people.. a case-control study using national claims databases.. we identified patients aged >65 years with severe hyponatraemia as those hospitalised with a primary diagnosis of hyponatraemia or who had received tolvaptan or 3% NaCl. A 1:20 matched control with the same visit date was constructed. Multivariable logistic regression was performed to assess the association of newly started or concurrently used HIMs comprising 11 medication/classes with severe hyponatraemia after covariate adjustment.. among 47,766,420 older patients, we identified 9,218 with severe hyponatraemia. After adjusting for covariates, all HIM classes were found to be significantly associated with severe hyponatraemia. Compared with persistently used HIMs, newly started HIMs increased the likelihood of severe hyponatraemia for eight classes of HIMs, with the highest increase being observed for desmopressin (adjusted odds ratio: 3.82, 95% confidence interval: 3.01-4.85). Concurrent use increased the risk of severe hyponatraemia compared to that with individually administered HIMs: thiazide-desmopressin (4.86, 3.90-6.07), medications causing the syndrome of inappropriate anti-diuretic hormone secretion (SIADH)-desmopressin (2.65, 2.25-3.11), medications causing SIADH-thiazides (1.87, 1.75-1.98) and combination among medications causing SIADH (1.36, 1.28-1.45).. in older adults, newly started and concurrently used HIMs increased the risk of severe hyponatraemia compared with persistently and singly used HIMs.

Topics: Aged; Case-Control Studies; Databases, Factual; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Thiazides

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

Topics: Antidiuretic Agents; Brain Injuries; Coronavirus Infections; COVID-19; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Disease Management; Fluid Therapy; Humans; Hypernatremia; Hyponatremia; Hypotonic Solutions; Inappropriate ADH Syndrome; Neurosurgical Procedures; Pandemics; Pneumonia, Viral; Postoperative Complications; Practice Guidelines as Topic; Saline Solution; Shock

In the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatremia is limited by onset of vasopressin-escape caused by loss of the water channel aquaporin-2 in the renal collecting duct despite high circulating vasopressin. Here, we use the methods of systems biology in a well-established rat model of SIADH to identify signaling pathways activated at the onset of vasopressin-escape. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts of vasopressin-treated rats at 1, 2, and 4 days after initiation of oral water loading in comparison to time-control rats without water loading. The time-dependent mRNA abundance changes were mapped to gene sets associated with curated canonical signaling pathways and revealed evidence of perturbation of transforming growth factor β signaling and epithelial-to-mesenchymal transition on Day 1 of water loading simultaneous with the initial fall in Aqp2 gene expression. On Day 2 of water loading, transcriptomic changes mapped to Notch signaling and the transition from G0 into the cell cycle but arrest at the G2/M stage. There was no evidence of cell proliferation or altered principal or intercalated cell numbers. Exposure of vasopressin-treated cultured mpkCCD cells to transforming growth factor β resulted in a virtually complete loss of aquaporin-2. Thus, there is a partial epithelial-to-mesenchymal transition during vasopressin escape with a subsequent shift from quiescence into the cell cycle with eventual arrest and loss of aquaporin-2.

Topics: Animals; Aquaporin 2; Cell Proliferation; Cells, Cultured; Cellular Senescence; Deamino Arginine Vasopressin; Disease Models, Animal; Drinking; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Gene Expression Regulation; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Male; Rats, Sprague-Dawley; Receptors, Notch; RNA, Messenger; Sequence Analysis, RNA; Signal Transduction; Systems Biology; Time Factors; Transcription, Genetic; Transcriptome; Transforming Growth Factor beta

The triphasic response of pituitary stalk injury has previously been described in a minority of patients following intracranial surgery, however, this phenomenon can also occur after traumatic brain injury. We present the case of a 20-year-old male who experienced the triphasic response of pituitary stalk injury (central diabetes insipidus, syndrome of inappropriate antidiuretic hormone and central diabetes insipidus again) after striking his head on a concrete curb. His history and presentation highlight the importance of recognising the distinctive symptoms of each individual stage of pituitary stalk injury, and using the appropriate diagnostic tools and therapies to guide further management.

Topics: Antidiuretic Agents; Brain Injuries, Traumatic; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Headache Disorders; Humans; Inappropriate ADH Syndrome; Male; Pituitary Gland; Polyuria; Thirst; Young Adult

Binding of vasopressin to its type 2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin (AQP)2 water channels to the plasma membrane, and water reabsorption from the prourine. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline's mechanism of action, which is poorly understood, is studied here. In mouse cortical collecting duct (mpkCCD) cells, which exhibit deamino-8-D-arginine vasopressin (dDAVP)-dependent expression of endogenous AQP2, demeclocycline decreased AQP2 abundance and gene transcription but not its protein stability. Demeclocycline did not affect vasopressin type 2 receptor localization but decreased dDAVP-induced cAMP generation and the abundance of adenylate cyclase 3 and 5/6. The addition of exogenous cAMP partially corrected the demeclocycline effect. As in patients, demeclocycline increased urine volume, decreased urine osmolality, and reverted hyponatremia in an SIADH rat model. AQP2 and adenylate cyclase 5/6 abundances were reduced in the inner medulla but increased in the cortex and outer medulla, in the absence of any sign of toxicity. In conclusion, our in vitro and in vivo data indicate that demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments.

Topics: Adenylyl Cyclases; Animals; Anti-Bacterial Agents; Aquaporin 2; Cells, Cultured; Cyclic AMP; Deamino Arginine Vasopressin; Demeclocycline; Disease Models, Animal; Hyponatremia; In Vitro Techniques; Inappropriate ADH Syndrome; Kidney Medulla; Male; Mice; Minocycline; Rats; Rats, Wistar; Vasopressins

Prompt correction of severe hyponatremia is important, but correction also must be limited to avoid iatrogenic osmotic demyelination. Expert opinion recommends that serum sodium level not be increased by more than 10-12 mEq/L in any 24-hour period and/or 18 mEq/L in any 48-hour period. However, inadvertent overcorrection is common, usually caused by the unexpected emergence of a water diuresis.. Quality improvement report.. All 25 patients admitted to a community teaching hospital between October 1, 2008, and September 30, 2011, who were treated for serum sodium level <120 mEq/L with concurrently administered desmopressin and hypertonic saline solution.. Concurrently administered desmopressin (1-2 µg parenterally every 6-8 hours) and hypertonic saline with weight-based doses adjusted to increase the serum sodium concentration by 6 mEq/L, avoiding inadvertent overcorrection of severe hyponatremia.. Rate of correction of hyponatremia, predictability of response to the combination, adverse events related to therapy.. Rate of correction of hyponatremia at 4, 24, and 48 hours; administered dose of 3% saline solution, salt tablets, and potassium; predicted increase in serum sodium level.. Mean changes in serum sodium levels during the first and second 24 hours of therapy were 5.8 ± 2.8 (SD) and 4.5 ± 2.2 mEq/L, respectively, without correction by >12 mEq/L in 24 hours or >18 mEq/L in 48 hours and without a decrease during therapy. There was no significant difference between actual and predicted increases during the first 24 hours. There was no adverse effect associated with therapy.. Without concurrent controls, we cannot be certain that outcomes are improved. Balance studies were not performed.. Combined 3% saline solution and desmopressin appears to be a valid strategy for correcting severe hyponatremia, but studies comparing the regimen with other therapeutic strategies are needed.

Topics: Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Retrospective Studies; Saline Solution, Hypertonic

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

A recent study has revealed that acute and chronic administration of the vasopressin V2 receptor (V2R) agonist dDAVP induced a marked increase of urinary albumin excretion (UAE) in healthy rats and humans (Bardoux P et al. Nephrol Dial Transplant 2003; 18: 497-506). The occurrence of an elevation of UAE among patients with chronic syndromes of inappropriate antidiuresis has not been reported.. We looked for the elevation of UAE in 24-h urine samples of the following patients: nine chronic SIADH patients, two patients with acute post-operative SIADH, three patients of the same family with nephrogenic syndrome of inappropriate antidiuresis (NSAID) and two patients with hyponatraemia due to surdosage of dDAVP in the setting of central diabetes insipidus.. There was no elevation of UAE in our patients (whether they presented with hyponatraemia or not), apart from a patient treated with supra-physiological doses of dDAVP. When she received 80 microg/day of dDAVP, her UAE was 42 mg/day. In this patient, UAE returned to the normal range (21 mg/day) when doses of dDAVP were tapered (20 microg/day).. The present study shows that chronic V2R stimulation generally does not result in a rise in UAE. The discrepancy between our results and those of the above-mentioned study could be explained by a dose-dependent effect of V2R stimulation on UAE.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Antidiuretic Agents; Chronic Disease; Circadian Rhythm; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Incidence; Male; Middle Aged; Mutation; Receptors, Vasopressin

We report a case of a 65 year old Malay lady with long-standing diabetes mellitus, who presented to our institution with a one month history of worsening neck pain and progressive upper and lower limb weakness. She was stable despite severe hyponatraemia which was initially treated as syndrome of inappropriate anti-diuretic hormone (SIADH). This was consistent with her underlying illness which was concluded as cervical tuberculosis (TB) with spinal cord compression. She underwent decompression and bone grafting. Despite continuous treatment her serum sodium levels remained low. There were no other problems with her adrenals or thyroid. A water loading and hypertonic saline perfusion test was performed and supported the diagnosis of reset osmostat. Her serum sodium remained below the normal range and she was discharged well.

Topics: Aged; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Muscle Weakness; Saline Solution, Hypertonic; Spinal Cord Compression; Tuberculosis, Central Nervous System

Severe hyponatremia is most frequently caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Although the expressional alteration of the kidney-specific apical water channel, aquaporin 2 (AQP2), in the collecting duct has been demonstrated to be involved in the development of hyponatremia and the subsequent physiologic reaction that is resistant to arginine vasopressin (AVP; vasopressin escape) in SIADH, the complete pathogenesis of and the appropriate medical treatment for hyponatremia have yet to be elucidated.. Hyponatremia was induced in male Sprague-Dawley rats by water loading and subcutaneous infusion of 1-deamino-8-D-arginine vasopressin (dDAVP). For the treatment, a selective AVP V(2) receptor antagonist (OPC-31260) and/or a loop diuretic (furosemide) were administered orally. Protein expression of AQP2 and rat bumetanide-sensitive cotransporter (rBSC1) was examined by Western blotting during the hyponatremia and the subsequent treatment.. We noted a markedly high expression of rBSC1 during the development of hyponatremia, and a relatively low expression during vasopressin escape. OPC-31260 administration elevated serum sodium level in a dose-dependent manner. The therapeutic effect, however, declined with increasing number of treatment days, and doses higher than 15 mg/kg/day induced severe toxicity. The physiologic parameters and the alterations of AQP2 and rBSC1 expression during the treatment demonstrated reactions that were completely opposite to those of vasopressin escape. Combination of a furosemide (100 mg/kg/day) and a low dose of OPC-31260 (5 mg/kg/day) additively elevated serum sodium level and sustained the elevated serum sodium level by significantly reducing sodium accumulation in the renal medulla.. AVP-induced alterations of rBSC1 expression, as well as those of AQP2, are involved in the pathogenesis of SIADH. The pharmacologic blockade of AVP stimulus in SIADH limits its therapeutic efficacy by discontinuing the vasopressin escape, and the selective inhibition of rBSC1 complements this limitation.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Aquaporins; Benzazepines; Deamino Arginine Vasopressin; Diuretics; Furosemide; Hyponatremia; Inappropriate ADH Syndrome; Kidney Medulla; Male; Potassium; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Urea; Water

A 30-year-old man known to have a factor-IX deficiency was presented at the emergency department with unexplained coma. After immediate treatment with factor IX, a CT-scan of the brain revealed no intracerebral haemorrhage. However, blood tests showed severe hyponatraemia, low serum osmolarity and high urine-sodium excretion consistent with the Syndrome of Inappropriate Antiduretic Hormone Secretion (SIADH). Therapy with hypertonic saline was instituted resulting in a gradual rise in the serum-sodium concentration. The cause of the hyponatraemia however remained unclear. After repeat history taking the patient mentioned the use of desmopressin for nocturia. Hyponatraemia as a complication of desmopressin use occurs in 8% of adult patients treated for nocturia. Direct availability of a patient's drug history, by means of an electronic record for instance, could avoid unnecessary tests and delay in diagnosis.

Topics: Adult; Coma; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Saline Solution, Hypertonic; Urination Disorders

The syndrome of inappropriate antidiuretic hormone (SIADH) is associated with water retention and hyponatremia. The kidney adapts via a transient natriuresis and persistent diuresis, i.e., vasopressin escape. Previously, we showed an increase in the whole kidney abundance of aldosterone-sensitive proteins, the alpha- and gamma (70-kDa-band)-subunits of the epithelial Na(+) channel (ENaC), and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure via radiotelemetry, aldosterone activity, and cortical vs. medullary ENaC subunit and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) protein abundances in escape. Eighteen male Sprague-Dawley rats (300 g) were sham operated (n = 6) or infused with desmopressin (dDAVP; n = 12, a V(2) receptor-selective analog of AVP). After 4 days, one-half of the rats receiving dDAVP were switched to a liquid diet, i.e., water loaded (WL) for 5-7 additional days. The WL rats had a sustained increase in urine volume and blood pressure (122 vs. 104 mmHg, P < 0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1,658% of the dDAVP group, respectively. NCC and alpha- and gamma-ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. Beta- and gamma-ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11beta-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate Na(+) losses and ameliorate hyponatremia in vasopressin escape.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Aldosterone; Animals; Blood Pressure; Blotting, Western; Deamino Arginine Vasopressin; Diuresis; Electrolytes; Epithelial Sodium Channels; Immunoenzyme Techniques; Immunohistochemistry; Inappropriate ADH Syndrome; Kidney; Male; Natriuresis; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Renal Agents; Sodium Channels; Vasopressins

The aim of this work was to investigate histopathologically the relationship between the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and kidney abnormalities and the therapeutic efficacy of VP-343 ((N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-alqunoxalin-5(1H)-yl]phenyl]-4'-methyl[1,1'-biphenyl]-2-carboxamide], a selective vasopressin V2 receptor antagonist, in an experimental SIADH rat model. In the model, which was prepared by continuously administering 1-desamino-8-D-arginine vasopressin (DDAVP), histopathologic abnormalities, such as dilatation of tubules, basophilic changes in tubules, inflammatory cell infiltration, and mineralization were found in the kidney, accompanied by significant increases in the relative weight of the kidney, lung, liver, adrenal gland, and heart. VP-343 was shown to be effective in protecting the kidney from the histopathologic abnormalities and to normalize the relative weight of the kidney and several common pathophysiologic features, such as hyponatremia, hyposmolarity of plasma, hyperosmolarity of urea, and oligurea, as described previously. These results demonstrate the occurrence of histopathologic abnormalities in the kidney and the efficacy of VP-343 in improving abnormalities in the DDAVP-induced SIADH rat model.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Deamino Arginine Vasopressin; Diuretics; Histocytochemistry; Inappropriate ADH Syndrome; Kidney; Male; Organ Size; Osmolar Concentration; Pyrroles; Quinoxalines; Rats; Rats, Sprague-Dawley; Renal Agents; Sodium; Urodynamics

In a state of chronic arginine vasopressin (AVP) excess, the action of antidiuresis has been attenuated, resulting in some water diuresis. This state has been termed an "AVP escape" phenomenon. The present study was designed to determine what mechanisms underlie this attenuation in renal concentrating ability, which is found in chronic AVP excess, both in the presence and absence of volume expansion.. Two groups of experimental rats were established. One group received solid chow with water ad libitum. The second group received chow, which was offered as a liquid diet. Both groups received subcutaneous administration of 1-deamino-8-D-arginine vasopressin (dDAVP) at 5 ng/h for the entire observation period of one week. Over the course of the observation period, tissue levels of aquaporin-2 (AQP-2) mRNA and protein were measured. Levels of AVP V2 receptor were monitored, both by measuring mRNA levels and by ligand-binding studies using [3H]AVP. Tissue levels of cAMP also were determined.. Experimental rats with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) had severe hyponatremia below 120 mmol/L, and impaired urinary concentrating ability, during the seven-day observation period. In contrast, the dDAVP-excess rats, given solid chow, maintained maximally concentrated urine and normal levels of serum sodium. The down-regulation of AVP V2 receptor function was comparable in the two groups. The maximal binding capacity (Bmax) fell to the nadir on day 2 and was thereafter suppressed at approximately 60% of control rats during the experiment. Up-regulation of AQP-2 mRNA expression was found, but this up-regulation was significantly less in the SIADH rats compared with the dDAVP-excess rats (153.5 +/- 29.8% vs. 323.7 +/- 23.8% on day 7, P < 0.05). This differential response between these two groups was affirmed by measured differences in AQP-2 protein levels, both in tissue and in urinary excretion.. These results indicate that the attenuated regulation of the AQP-2 gene leads to the decrease in urinary concentrating ability in the experimental SIADH rats, suffering from hypervolemic state, compared with the normonatremic rats receiving AVP. Either hypervolemia or hypotonicity may diminish the post-receptor signaling of AVP in renal collecting duct cells, under the chronic AVP excess state found in SIADH.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin; Cyclic AMP; Deamino Arginine Vasopressin; Diuresis; Gene Expression; Hyponatremia; Inappropriate ADH Syndrome; Kidney Concentrating Ability; Kidney Medulla; Male; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Renal Agents; RNA, Messenger; Time Factors

The aim of this work is to investigate the therapeutic efficacy of VP-343 ((N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-a]qunoxalin-5(1H)-yl]phenyl]-4'-methyl[1,1'-biphenyl]-2-carboxamide), a selective vasopressin V2 receptor antagonist, using the experimental SIADH (syndrome of inappropriate secretion of antidiuretic hormone) rat model. In the model, which was accomplished by administering continuously 1-desamino-8-D-arginine vasopressin (DDAVP), serum sodium levels (S(Na)) and serum osmolarity levels (S(Osm)) significantly and remarkably decreased, which was accompanied with hyper-osmolarity of urine and oliguria. VP-343 increased rapidly and dose-dependently S(Na) and S(Osm). VP-343 exhibited marked diuretic action and decreased urine osmolarity dose-dependently. In the SIADH rat model, all serum levels of chloride, calcium, creatinine, total cholesterol, and uric acid decreased when compared with normal levels. VP-343 increased all serum levels of chloride, calcium, and total cholesterol. These results indicate that VP-343 has efficacy to normalize the abnormalities in DDAVP-induced SIADH.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Deamino Arginine Vasopressin; Inappropriate ADH Syndrome; Male; Osmolar Concentration; Pyrroles; Quinoxalines; Rats; Rats, Sprague-Dawley; Renal Agents; Sodium; Urination; Urine

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

In animal models of the syndrome of inappropriate antidiuresis (SIADH), sustained administration of vasopressin and water results in free-water retention and progressive hyponatremia for several days, which is then followed by escape from the vasopressin-induced antidiuresis. With the onset of vasopressin escape, water excretion increases despite sustained administration of vasopressin, allowing water balance to be re-established and the serum sodium to be stabilized at a steady, albeit decreased, level. Studies from our laboratories have investigated whether this escape phenomenon can be attributed to altered regulation of aquaporin water channels. After four-day pre-treatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic minipump, rats were divided into control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load) groups. A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating escape from antidiuresis. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semi-quantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. Additional studies have indicated that the observed down-regulation of aquaporin-2 expression also occurs in the renal cortex as well as the inner and outer medullas, and can be reversed simply by water restriction despite maintenance of hyponatremia. Our results therefore suggest that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent and osmolality-independent decrease in aquaporin-2 water channel expression in the renal collecting duct. Similar mechanisms likely contribute to the phenomenon of escape from antidiuresis seen clinically in patients with SIADH as well.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Deamino Arginine Vasopressin; Disease Models, Animal; Diuresis; Drinking Behavior; Gene Expression Regulation; Inappropriate ADH Syndrome; Kidney; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transcription, Genetic; Urine

In hyponatremia related to syndrome of inappropriate antidiuretic hormone (SIADH), hypouricemia is explained primarily by the high uric acid clearance rate that results from the decrease in tubular uric acid reabsorption. This modification of tubular handling of uric acid is considered to be induced by the increase in the "effective vascular volume". This study was designed to determine if V1-receptor stimulation participates in the development of a high uric acid clearance rate as in SIADH, in which the antidiuretic hormone acts on V1 and V2 receptors. Therefore, the urate clearance rate was measured in seven volunteers with 1-desamino-8-D-arginine vasopressin (dDAVP)-induced hyponatremia, with dDVAP stimulating exclusively the V2 receptors (Group I), and in six patients with SIADH (Group II) during both normo- and hyponatremia. As expected, in both groups, the serum uric acid concentration decreased during hyponatremia, but did so to a larger extent in the patients with SIADH (-53% versus -29%, P < 0.02). Despite similar levels of hyponatremia (126 +/- 5 mmol/L and 125 +/- 5.5 mmol/L), of hypoproteinemia (64 +/- 5 g/L and 63 +/- 5 g/L) and of salt excretion (FENa, 0.66 +/- 0.28% and 0.73 +/- 0.25%), the urate clearance (8.3 +/- 3.3 mL/min) and the fractional excretion of filtered uric acid (5.7 +/- 2%) in Group I were not significantly different during hyponatremia than during normonatremia (6.4 +/- 1.5 mL/min and 5.4 +/- 0.9%). On the other hand, in Group II, both parameters were increased (17.8 +/- 2.9 mL/min and 19.6 +/- 5.3%; P < 0.001) and both values were higher than in the dDAVP-induced hyponatremia (P < 0.01). Additionally, the administration of a potent V1-receptor agonist (triglycyl-lysine-vasopressin) in a patient with central diabetes insipidus with preexisting dDAVP-induced hyponatremia produced a rapid increase of urate clearance. Because dDAVP acts only on the V2 receptors, these data suggest that the higher urate clearance observed during hyponatremia related to SIADH is not only the consequence of an increased "effective vascular volume," but that V1-receptor stimulation also contributes to it, by a mechanism that remains to be determined.

Topics: Adult; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Proximal; Lypressin; Male; Metabolic Clearance Rate; Natriuresis; Receptors, Vasopressin; Sodium; Terlipressin; Uric Acid

Rats were infused with a selective agonist of vasopressin V2 receptors (1-desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and severe (plasma [Na+] = 106-112 mmol/l) hyponatremia. Whole body water and electrolyte contents were analyzed after 1, 7, and 14 days of hyponatremia to assess the relative contributions from water retention and sodium depletion to hyponatremia of varying duration and severity. Body water of the hyponatremic rats was significantly increased over normonatremic control rats after 1 and 7 days; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water, but the 5 ng/h DDAVP-infused rats returned to levels not significantly different from controls. Body Na+ and Cl- both decreased significantly after 1 day of hyponatremia, and these decreases were sustained for 14 days; measured decreases were significantly greater in the more hyponatremic rats compared with the less hyponatremic rats. Body K+ of the 1 ng/h DDAVP-infused rats was not different from control rats, but significant K+ decreases occurred in the 5 ng/h DDAVP-infused rats after 7 and 14 days. Analysis of the measured plasma Na+ concentrations vs. those predicted by the changes in body water and sodium showed that both water retention and sodium losses were necessary to predict the final plasma [Na+]. However, the relative contribution from each varied with the duration of induced hyponatremia: acutely, water retention was the major cause of decreased plasma [Na+], but sodium depletion became predominant with longer periods of sustained hyponatremia.

Topics: Animals; Body Water; Body Weight; Chlorides; Deamino Arginine Vasopressin; Disease Models, Animal; Hyponatremia; Inappropriate ADH Syndrome; Male; Potassium; Rats; Rats, Sprague-Dawley; Sodium

We conducted a retrospective analysis of the cases of 122 children operated on for various brain tumors, to determine the incidence and natural history of postoperative diabetes insipidus (DI), and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Abnormalities of water homeostasis were observed in 15 patients (12%). DI, with or without SIADH, was observed in 10 patients (8%), while SIADH alone was seen in five (4%). DI was permanent in five subjects (50%), whereas SIADH resolved completely in all affected individuals. Parenteral desmopressin (dDAVP) was an effective mode of therapy in the postoperative period. The effect did not correlate with a dosage strictly based on body weight.

Topics: Adolescent; Age Distribution; Brain Neoplasms; Child; Child, Preschool; Craniotomy; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Inappropriate ADH Syndrome; Infant; Male; Postoperative Complications; Sex Distribution; Treatment Outcome; Water

The present study was undertaken to determine whether the non-peptide V2 antidiuretic hormone (ADH) antagonist 5-dimethylamino-1[4-(2- methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (OPC-31260) normalized hyponatremia in rats with an experimental syndrome of inappropriate secretion of ADH (SIADH). Rats were administered V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) subcutaneously at a rate of 5 ng/hr using an osmotic minipump and a 40 ml/day liquid diet. Serum sodium levels (SNa) and serum osmolality (SOsm) markedly decreased to 119 mEq/liter and 249 mOsm/kg H2O, respectively, 48 hours after the start of dDAVP administration. Hyponatremia persisted in a similar magnitude during the observation period of 14 days. On days 7 to 13 OPC-31260, administered 5 mg/kg per day orally, promptly raised SNa and SOsm to 134 mEq/liter and 282 mOsm/kg H2O in half a day, respectively, followed by the normalization of SNa and SOsm during the rest of the observation period. The cease of administration of OPC-31260 again decreased SNa and SOsm in rats receiving dDAVP. In contrast, SNa and SOsm were within the normal values in rats receiving 0.15 M NaCl, a vehicle for dDAVP, in the presence or absence of OPC-31260. The administration of OPC-31260 promptly caused marked water diuresis on day 7 in the hyponatremic rats receiving dDAVP, namely 5 mg/kg OPC-31260 markedly increased urinary volume and decreased UOsm. These results indicate that there is dilutional hyponatremia in rats receiving dDAVP and 40 ml/day liquid diets, and that OPC-31260 is an effective therapeutic for hyponatremia associated with dDAVP-induced SIADH.

Topics: Animals; Benzazepines; Deamino Arginine Vasopressin; Hyponatremia; Inappropriate ADH Syndrome; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Sodium; 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

The mechanisms responsible for the natriuresis encountered in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are not fully understood. The present study explores the role of atrial natriuretic factor (ANF). Eight subjects unable to excrete ingested free water normally (three patients with SIADH and five healthy humans after intranasal administration of desmopressin) underwent a standard oral water loading test. Plasma ANF level and urinary sodium excretion increased during water retention, whereas plasma aldosterone value decreased later. The increment of urinary sodium excretion rate was significantly correlated with that of plasma ANF. In two patients with hyponatremia due to SIADH, plasma ANF levels were increased during the hyponatremic phase of their condition and decreased under water restriction. In one of them, marked natriuresis was observed when the plasma ANF level was high. It is concluded that secretion of ANF is acutely and chronically stimulated during water retention in SIADH and that ANF may be in part responsible for the natriuresis encountered in inappropriate antidiuresis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Deamino Arginine Vasopressin; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Natriuresis; Renin-Angiotensin System; Water; Water-Electrolyte Balance

Administration of urea to patients with the syndrome of inappropriate antidiuresis (SIAD) is thought to ameliorate hyponatremia by both producing an osmotic diuresis and diminishing ongoing natriuresis. The present study evaluated these effects in a rat model of SIAD utilizing dilutional hyponatremia induced by continuous infusion of 1-deamino-[8-D-arginine] vasopressin. Following 48 hours of sustained hyponatremia, separate groups of rats were then refed with either: (1) 5% dextrose alone, (2) a 20% protein chow, (3) an isocaloric protein deficient (0%) chow, or (4) the isocaloric protein-deficient chow supplemented with oral urea. Our results demonstrate that rats refed a 20% protein diet significantly improved their plasma [Na+] as compared to rats refed protein deficient diets, and this improvement was accompanied by decreases in natriuresis despite an increased glomerular filtration rate and an unchanged negative free water clearance. Identical effects were observed in rats refed a protein deficient diet but supplemented with oral urea, suggesting that urea generation from catabolism of dietary protein is responsible for the effect of protein refeeding to decrease urinary sodium excretion. Both the protein and urea refed rats had significantly higher inner medullary urea contents and concentrations compared to rats refed protein-deficient diets and also to rats studied immediately before protein refeeding, supporting the hypothesis that urea and dietary protein decrease natriuresis in patients with SIAD in association with increased inner medullary urea concentrations.

Topics: Animals; Blood Urea Nitrogen; Deamino Arginine Vasopressin; Dietary Proteins; Inappropriate ADH Syndrome; Kidney Medulla; Male; Natriuresis; Rats; Rats, Inbred Strains; Sodium; Urea

Our purpose was to investigate a method of prolonged desmopressin (DDAVP) infusion in a free roaming rat to better understand the SIADH (syndrome of inappropriate antidiuretic hormone secretion) syndrome in man. DDAVP was infused for 2 weeks from implanted self-powered osmotic minipumps. At the end of that time, plasma DDAVP and urine osmolality were both significantly elevated in experimental as compared with control animals. However, hyponatremia and hypoosmolality, which are characteristic in the SIADH, did not develop. Our observations suggest that inappropriate high antidiuretic hormone levels do not necessarily lead to the SIADH either by urine sodium loss or by water retention if animals decrease water intake.

Topics: Animals; Deamino Arginine Vasopressin; Drinking; Female; Inappropriate ADH Syndrome; Infusion Pumps; Osmolar Concentration; Rats; Rats, Inbred Strains; Sodium; Vasopressins; Water-Electrolyte Balance

A new rat model of the Schwartz--Bartter syndrome was created by the administration of 1-deamino-8-D-arginine vasopressin together with a forced water intake. The treatment led to water retention, hypernatriuria, marked hyponatraemia (in 4-5 days) and severe cerebral oedema. These changes could be prevented by the simultaneous administration of [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid)- 2-o-ethyltyrosine-4-valine] arginine vasopressin. The observations indicate that this vasopressin antagonist analogue might be of use in the future as an effective drug against the Schwartz--Bartter syndrome.

Topics: Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Disease Models, Animal; Inappropriate ADH Syndrome; Male; Rats; Vasopressins; Water Intoxication

An experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was developed using continuous subcutaneous infusions of arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (DDAVP) in conscious unrestrained rats drinking 5% dextrose solution. Retention of both ingested water and endogenously generated free water from tissue catabolism was the primary determinant of hyponatremia using either AVP or DDAVP infusions. Natriuresis occurred transiently following water expansion but only slightly further lowered plasma [Na+]. Cessation of antidiuretic infusion resulted in free water excretion with correction of plasma [Na+]. Erythrocyte cell volume was significantly increased in hyponatremic animals and intracellular [K+] and [Na+] both decreased equivalently, consistent with dilution of intracellular fluid by retained water. This model of SIADH differs significantly from those previously described, in that escape from the hydroosmotic effect of AVP and DDAVP does not occur in the absence of high urinary flow rates. The observed results using this model suggest that the retained water in SIADH primarily resides intracellularly following isotonic equilibration of extracellular fluid volume.

Topics: Animals; Arginine Vasopressin; Body Water; Deamino Arginine Vasopressin; Disease Models, Animal; Erythrocyte Count; Hyponatremia; Inappropriate ADH Syndrome; Male; Potassium; Rats; Rats, Inbred Strains; Rodent Diseases; Sodium

Topics: Adult; Arginine Vasopressin; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Humans; Inappropriate ADH Syndrome; Male; Water Intoxication

Topics: Arginine Vasopressin; Body Water; Chlorpropamide; Deamino Arginine Vasopressin; Diabetes Complications; Diabetes Insipidus; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Polyuria; Time Factors; Vasopressins

Topics: Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Complications; Diabetes Insipidus; Diabetes Mellitus; Humans; Inappropriate ADH Syndrome; Male; Middle Aged

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