Arginine Vasopressin Excretion Research Articles

Chronic Exercise Protects against the Progression of Renal Cyst Growth and Dysfunction in Rats with Polycystic Kidney Disease.

ABSTRACTIntroductionPolycystic kidney disease (PKD) is a genetic disorder characterized by the progressive enlargement of renal epithelial cysts and renal dysfunction. Previous studies have reported the beneficial effects of chronic exercise on chronic kidney disease. However, the effects of chronic exercise have not been fully examined in PKD patients or models. The effects of chronic exercise on the progression of PKD were investigated in a polycystic kidney (PCK) rat model.MethodsSix-week-old male PCK rats were divided into a sedentary group and an exercise group. The exercise group underwent forced treadmill exercise for 12 wk (28 m·min−1, 60 min·d−1, 5 d·wk−1). After 12 wk, renal function and histology were examined, and signaling cascades of PKD progression, including arginine vasopressin (AVP), were investigated.ResultsChronic exercise reduced the excretion of urinary protein, liver-type fatty acid–binding protein, plasma creatinine, urea nitrogen, and increased plasma irisin and urinary AVP excretion. Chronic exercise also slowed renal cyst growth, glomerular damage, and interstitial fibrosis and led to reduced Ki-67 expression. Chronic exercise had no effect on cAMP content but decreased the renal expression of B-Raf and reduced the phosphorylation of extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), and S6.ConclusionChronic exercise slows renal cyst growth and damage in PCK rats, despite increasing AVP, with the downregulation of the cAMP/B-Raf/ERK and mTOR/S6 pathways in the kidney of PCK rats.

P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.

P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.

Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus

Familial neurohypophysial diabetes insipidus (FNDI) is a rare disease that is inherited in an autosomal dominant manner. In a previous study, we made a mouse model for FNDI, which showed progressive polyuria accompanied by inclusion bodies in the arginine vasopressin (AVP) neurons formed by aggregates in the endoplasmic reticulum. The present study was conducted to determine whether the activities of AVP neurons are related to the phenotype progression in the FNDI model. In the first experiment, female heterozygous mice were administered either desmopressin (dDAVP) or a vehicle (control) subcutaneously with osmotic minipumps for 30 days. The dDAVP treatment significantly decreased the urine volume, AVP mRNA expression, and inclusion bodies in the AVP neurons. Urine volume in the dDAVP group remained significantly less than the control for 14 days even after the minipumps were removed. In the second experiment, the males were fed either a 0.2% Na or 2.0% Na diet for 6 mo. Urine AVP excretion was significantly increased in the 2.0% Na group compared with the 0.2% Na group for the first 2 mo but gradually decreased thereafter. Throughout the experiments, urine volume increased progressively in the 2.0% Na group but not in the 0.2% Na group. Immunohistochemical analyses revealed that inclusion bodies in the AVP cells had significantly increased in the 2.0% Na compared with the 0.2% Na group. These data demonstrated that activation of AVP neurons could accelerate the aggregate formation as well as the progression of the polyuria in the FNDI model mice.

Plasma concentration and urinary excretion of arginine-vasopressin in primary aldosteronism during the fluid deprivation tests.

Plasma concentration (PAVP) and urinary excretion (UAVP) of arginine-vasopressin were studied in 8 patients with primary aldosteronism (PA) during a 36 hour period of fluid restriction in relation to the disturbances of their maximal renal concentrating capacity. The results in untreated patients suffering from PA were compared with the findings in patients after a successful treatment of PA as well as with the results in 9 control subjects. The reduction of maximal renal concentrating ability in PA before the treatment was accompanied with a high excretion of UAVP and the physiological reaction of PAVP to dehydration. Together with the shift of the regression line of the dependence of UOsm on UAVP to higher values of UAVP this indicates a decrease of the sensitivity of the nephrons to the sufficiently high concentrations of endogenous AVP. The increase of renal AVP clearance in PA participates in the high urinary excretion of AVP. The disturbance of the renal concentrating ability as well as the changes of urinary AVP in PA are mostly reversible. After the successful treatment of PA and the completion of potassium stores in the body as well as the healing of the kaliopenic nephropathy, the maximal renal concentrating capacity and AVP gradually return to values close or equal to those in healthy subjects.

Salt-losing nephrogenic diabetes insipidus caused by fetal exposure to angiotensin receptor blocker

The administration of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs) to pregnant women has been reported to cause ACEI/ARB fetopathy, including oligohydramios, pulmonary hypoplasia, renal insufficiency, limb contracture, and fetal hypotension in the child. Most of the patients die or develop end-stage renal failure during the neonatal period. The long-term prognosis of renal dysfunctions of patients with ARB fetopathy has not been reported. We report two pediatric cases, a 6- and 2-year-old boy, respectively, with ARB fetopathy whose renal functions were thoroughly evaluated after recovery from neonatal renal failure. Both patients showed (1) mildly decreased glomerular filtration rate, (2) no significant proximal tubular dysfunctions, and (3) salt-losing nephrogenic diabetes insipidus, while the excretion of arginine vasopressin and urine level of cyclic AMP were increased. The data on these two patients indicate that the administration of ARB to the fetus profoundly impairs the urine concentrating ability, probably due to papillary atrophy and the disturbed formation of the osmotic gradient in the medulla, which have been confirmed in neonatal rats administered with ACEIs or ARBs. ACEIs/ARBs must not be administered to pregnant women.

Pharmacological Closure of Patent Ductus Arteriosus: Effects on Pulse Pressure and on Endothelin-1 and Vasopressin Excretion

Widened pulse pressure is a classic sign of significant left-to-right shunting patent ductus arteriosus (PDA), but little evidence supports this statement in the early life of premature infants with respiratory distress syndrome (RDS) needing nonsteroidal anti-inflammatory drugs (NSAIDs), the pharmacological treatment for PDA. Pulse pressure and urinary endothelin-1 (ET-1) and arginine vasopressin (AVP) vasoactive factors involved in the transitional circulation were measured before and after the NSAIDs treatment of 46 RDS premature infants receiving either ibuprofen (n = 22) or indomethacin (n = 24), with 28 responders and 18 nonresponders to the first NSAIDs course. We found that following pharmacological PDA closure, systolic and diastolic blood pressure significantly increased, maintaining a stable pulse pressure. However, when pharmacological closure failed, the trend (nonsignificant) was for a more consistent increase in systolic than in diastolic blood pressure, which determined a statistically significant widening pulse pressure. In addition, urinary ET-1 excretion rates decreased significantly after PDA closure, whereas persistent more aggressive pharmacological therapy failed. Urinary AVP excretion rates decreased insignificantly after therapy, uninfluenced by the efficacy of the drugs. We concluded that widened pulse pressure is a clinical sign of failed PDA pharmacological closure in RDS premature infants. ET-1 levels remain elevated when NSAIDs fail to interrupt left-to-right PDA shunting that complicates recovery from RDS.

Effects of V2-receptor antagonist tolvaptan and the loop diuretic furosemide in rats with heart failure

Diuretics are frequently required to treat fluid retention in patients with chronic heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohormonal activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor (V2R) and its levels are increased in CHF. This study was conducted to characterize the diuretic effect of tolvaptan, a non-peptide AVP V2R antagonist, and furosemide, a loop diuretic in a rat model of CHF after experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan, and furosemide. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Tolvaptan produces a diuresis comparable to furosemide. Unlike tolvaptan, furosemide significantly increased urinary sodium and potassium excretion. Tolvaptan markedly elevated electrolyte-free water clearance (E-CH2O) or aquaresis to a positive value and increased urinary AVP excretion. In contrast to tolvaptan, furosemide elevated only electrolyte clearance (E-Cosm) but not E-CH2O. The differences in diuretic profile reflected the changes in plasma sodium and hormone levels. Tolvaptan dose dependently elevated plasma sodium concentration, but furosemide tended to decrease it. Furosemide significantly elevated plasma renin activity and aldosterone concentration. On the other hand, tolvaptan did not affect these parameters. Our results suggest that, tolvaptan have a potential medical benefit for the treatment of edematous conditions in CHF by removing excess water from the body without activating the RAAS or causing serum electrolyte imbalances.

Cardiovascular and Endocrine Responses to 90° Tilt During a 35-Day Saturation Dive to 46 and 37 ATA

Hyperbaria-induced diuresis is accompanied by decreased basal and stimulated release of arginine vasopressin (AVP) and decreased blood volume possibly contributing to the reported orthostatic intolerance. Since hyperosmolality is not a consistent finding, the explanation of blood volume reduction at hyperbaria must involve an osmotic component to the diuresis. Investigations of a possible involvement of atrial natriuretic peptide (ANP) to the hyperbaric diuresis have revealed mixed results. Urinary excretion of electrolytes, AVP, and aidosterone were measured in four male subjects studied at 1 atmosphere absolute (ATA) and at 46 and 37 ATA (0.5 atmospheres pressure O2: 5% N2: remainder He) during a 35-d saturation dive. Also, the supine and 90 degrees tilt-stimulated plasma levels of AVP, plasma renin activity (PRA), and aldosterone, and the suppressed responses of ANP and the cardiovascular responses to tilt were determined at these pressures. Tilt-stimulated levels of PRA were increased two- to threefold and the AVP response was eliminated throughout hyperbaria, except in two episodes of tilt-induced syncope where AVP was elevated 10- to 20-fold. This pattern supports most previous reports. Contrary to some reports, both supine and tilt-suppressed levels of ANP were reduced by about 50% at all three tilt experiments conducted at hyperbaria compared to predive control values. These results suggest an altered ANP response at pressures of 37 ATA or greater, which is consistent with an appropriate ANP response to blood volume reduction and further suggest that the hyperbaric diuresis is not dependent on increased ANP.

Effects of nonpeptide vasopressin V 2 antagonist tolvaptan in rats with heart failure

Similar to other neurohormones that are activated in chronic heart failure (CHF), circulating arginine vasopressin (AVP) is elevated in patients with CHF. The precise role of AVP in the pathophysiology of cardiovascular disease is controversial. AVP is a peptide hormone that contributes to water retention and vasoconstriction in CHF through effects on V 2 and V 1a receptors, respectively. In the present study, the effect of V 2 receptor (V 2R) blockade using tolvaptan was assessed in a rat model of myosin-induced experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan (3 or 10 mg/(kg day)) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Chronic V 2R blockade increased urine volume and urinary AVP excretion and decreased urine osmolality but had no natriuretic effect, and as a result caused increases in plasma osmolality and sodium. High doses of tolvaptan markedly elevated electrolyte-free water clearance. V 2R blockade did not activate the renin–angiotensin system, not influence cardiac remodeling, cardiac function, or survival. The upregulation of aquaporin 2 protein in the kidney of CHF rats was inhibited by the administration of V 2R antagonist. These results suggest that in a rat model of CHF, AVP plays a major role in water retention through the renal V 2R.

Abstract 584: Simultaneous Antagonism of the V2 Receptor with Tolvaptan and Activation of the Natriuretic Peptide A-Receptor with B-Type Natriuretic Peptide: A Novel Strategy to Physiologically Enhance Water and Sodium Excretion Without Adversely Affecting Renal Function in a Canine Model of Congestive Heart Failure

Background: Water and sodium (Na) retention are hallmarks of congestive heart failure (CHF). While widely employed, conventional diuretics may adversely affect renal function. Therefore, physiological strategies that enhance water and Na excretion while maintaining renal function are a high priority. Arginine vasopressin (AVP) increases water reabsorption after binding to the V2 receptor in the collecting duct (CD). In contrast, B-type natriuretic peptide (BNP) decreases Na reabsorption via activation of the NPR-A receptor also in the CD and at higher doses also in the proximal tubule. We hypothesized that coadministration of the V2-receptor antagonist tolvaptan (TLV) and BNP would mediate a potent diuresis and natriuresis without adversely affecting renal hemodynamics in experimental CHF. We also assessed plasma and urinary excretion of AVP. Methods: Severe CHF was induced in 2 groups of dogs by tachypacing. On day 11 cardiorenal function was assessed. One group received TLV alone (0.1 mg/kg IV bolus; n=6), whereas the other group received infusion of BNP (50 ng/kg/min) in addition to TLV (n=5). Results: Renal hemodynamics were preserved in both groups. TLV alone increased urine flow from 0.07±0.01 to 0.48±0.09 mL/min, while urinary Na excretion (UNaV) remained unchanged. TLV+BNP-50 increased urine flow from 0.17±0.07 to 2.58±0.47 mL/min and UNaV from 1±1 to 77±23 uEq/min while decreasing proximal fractional Na reabsorption (all p<0.05 vs. TLV alone). TLV alone increased plasma aldosterone and distal fractional Na reabsorption, both of which were prevented with BNP-50. In addition, while plasma AVP did not change with TLV or TLV+BNP, urinary AVP excretion markedly increased with TLV+BNP (from 16±5 to 694±196 pg/min) as compared to TLV alone (from 1±1 to 69±23 pg/min). Conclusions: TLV and BNP coadministration enhances aquaresis and natriuresis through proximal and distal tubular actions without changing renal hemodynamics. Further, TLV with BNP uniquely enhances urinary elimination of AVP warranting further study. We conclude from these findings in experimental CHF that simultaneously antagonizing the V2 receptor by TLV and activating the NPR-A receptor with BNP may be a novel and physiologic diuretic and natriuretic strategy in overt CHF.

Increased Water Intake Decreases Progression of Polycystic Kidney Disease in the PCK Rat

Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.

Effects of Prenatal Ethanol and Choline on Urinary Vasopressin Excretion in the Rat

Prenatal ethanol (PE) exposure in rats increases water turnover and reduces arginine vasopressin (AVP) synthesis, storage, and release. Supplemental choline (SC) fed to pregnant rats while consuming alcohol normalizes water balance and AVP of offspring. Markers of fetal alcohol exposure are needed for people with mild symptoms. Lowered urinary AVP excretion (U[AVP]V) could provide a noninvasive diagnostic marker and SC should normalize the reduced U[AVP]V. Pregnant rats were fed one of four liquid diets; a control or an ethanol diet (35% of calories from ethanol) from day (D)7–21 of pregnancy with half of the rats fed SC (223 mg/100 ml liquid diet) from D10–21. At 8 weeks of age the offspring were placed in metabolic cages for 4 days. U[AVP]V was measured on D4. Increased water turnover in PE exposed rats was not accompanied by reduced U[AVP]V, but SC nearly doubled the U[AVP]V regardless of the PE exposure, and normalized water turnover. While these results in rats do not support the use of U[AVP]V as marker for PE exposure, they suggest an AVP mediated mechanism of SC correction of the polydipsia and polyuria. Supported in part by a Research Centers in Minority Institutions award, P20 RR11091.

Snoring as a cause of nocturia in men with lower urinary tract symptoms.

Snoring increases with increasing age and body mass, and repeated periods of hypoxia cause nocturnal polyuria. Accordingly, we examined the occurrence of snoring problems in patients scheduled for transurethral prostatic resection. Of 171 men scheduled for TUR-P, 41 were excluded due to cardiac disease, diabetes, or prostatic malignancy. Of the remaining 130 patients, 12% were troubled by snoring that disturbed their sleep. The severity of their snoring was evaluated by questionnaires, micturition charts, and determination of nocturnal capillary oxygen saturation (SaO(2)) and pulse rate. Plasma levels of cortisol, arginine vasopressin (AVP), and atrial natriuretic peptide (ANP) were measured in the morning and at 2 p.m. Fifteen non-snoring patients also scheduled for TUR-P served as controls. Compared to controls, the snoring patients had a significantly higher body mass index (BMI), voided more frequently, and produced more urine at night. They also had a significantly larger number of hypoxic episodes at night, which, along with low SaO(2) levels, correlated with the nocturnal diuresis. Snorers did not differ significantly from controls in regard to excretion of cortisol and AVP, but they did have higher plasma levels of ANP. We recommend that elderly obese men with urgency at night be questioned about snoring, and that micturition frequency and volume charts be completed before deciding to operate.

Nephrogenic diabetes insipidus associated with hemochromatosis

Although hemochromatosis is one of the most common genetic disorders in humans, the clinical information on iron-induced renal impairment is limited. We describe the clinical features of nephrogenic diabetes insipidus (NDI) observed in a case of hemochromatosis. A 57-year-old diabetic man was admitted to the hospital with a 6-month history of persistent polyuria, which had been sustained after glycemic optimization with insulin therapy and resulted in hepatic coma. Despite sufficient basal excretion of arginine vasopressin, impaired urinary concentrating capacity was observed, which could not be corrected by supraphysiologic doses of exogenous arginine vasopressin. Histochemical investigations showed widely distributed iron deposition in hepatocytes and moderately increased iron deposits in the tubular epithelium of distal urinary tubules and collecting ducts, suggesting that iron deposition resulting from hemochromatosis leads to NDI. This may be the first case report of NDI associated with hemochromatosis in humans. More attention should be paid to latent NDI as another complication of hemochromatosis. © 2002 by the National Kidney Foundation, Inc.

Urinary Excretion of Aquaporin-2 Water Channel During Pregnancy

BACKGROUND: In healthy primiparas the total body water content increases by about 8 liters within the last trimester, with a consequent reduction in plasma arginine-vasopressin (AVP) levels. The aim of the present study was to investigate the effect of normal pregnancy on urinary excretion of AQP2, a vasopressin sensitive water channel.METHODS: Forty-five healthy pregnant primiparas (specify mean age and range) with a physiological single-fetus pregnancy were studied during weeks 12, 24 and 36 of pregnancy and then for 3 to 5 days postpartum. The control group consisted of 14 age-matched women in the early follicular phase of the menstrual cycle (day 5 or 6). The behavior of plasma AVP, ANP, oxytocin, urinary 6-keto-PGF1α (a metabolite of prostacyclin) and urinary AQP-2 excretion were evaluated in all subjects.RESULTS: Plasma ANP and oxytocin, and urinary AQP-2 and 6kPGF1α excretion increased during all three trimesters, with the highest peaks at the 36^th week. In the postpartum period, these values markedly decreased. No statistically significant changes were found in plasma AVP levels throughout the study period.CONCLUSIONS: Our findings suggest that a non-AVP factor present in pregnancy plays a role in the control of the excretion of AQP-2 water channels.

Aquaretic and hormonal effects of a vasopressin V 2 receptor antagonist after acute and long-term treatment in rats

A single oral administration of 1-[4-( N- tert-butylcarbamoyl)-2-methoxybenzene sulfonyl]-5-ethoxy-3-spiro-[4-(2-morpholinoethoxy)cyclohexane]indol-2-one SR121463 (0.3–3 mg/kg), a vasopressin non-peptide V 2 receptor antagonist, to rats induced dose-dependent aquaresis which was accompanied by Na +, K +, aldosterone and arginine vasopressin excretion over 6 h after dosing. However, no solute excretion was observed over 24 h. As a result of aquaresis, hemoconcentration and increases in plasma angiotensin II and adenocorticotrophin hormone were seen with 3 mg/kg at 2 h after dosing. Chronic treatment with SR121463 (3 mg/kg/day×28 days) induced a marked aquaresis associated with aldosterone and vasopressin excretion. After a week of treatment, urine volume and aldosterone excretion were reduced (∼40%) and then stabilised, while urine vasopressin excretion remained almost constant throughout the study. There were no changes in arterial pressure, plasma osmolality, plasma sodium concentration, or in number and affinity of liver vasopressin V 1A and kidney V 2 receptors 24 h after the last treatment. These results indicate that SR121463 is a potent aquaretic agent and might be useful for the chronic management of water-retaining diseases in humans.

Modulation of genetic hypertension by short-term AVP V1A or V2 receptor antagonism in young SHR.

To characterize the role of arginine vasopressin (AVP) V(1A) or V2 receptors and the possible interaction with the renin-angiotensin system in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR), young male SHR were treated from 6 to 10 wk of age with AVP V(1A) receptor blockade, angiotensin-converting enzyme (ACE) inhibition, combination of V(1A) receptor blockade and ACE inhibition, V2 receptor blockade, and vehicle. Treatments were then withdrawn, and systolic blood pressure (SBP) was measured until 19 wk of age. At both 10 and 19 wk of age, SBP was significantly reduced with V(1A) receptor blockade, ACE inhibition, and combined treatment compared with vehicle treatment, although no treatment normalized SBP to levels of Donryu normotensive rats. Throughout the experimental period, no significant additive effects were observed with combined treatment. At 10 wk of age, plasma AVP concentration and 24-h urinary AVP excretion were increased with AVP V2 receptor blockade. At 19 wk of age, SBP was significantly higher in rats previously treated with V2 receptor blockade (233 +/- 3 mmHg) than with vehicle (221 +/- 2 mmHg) (P < 0.01). Left ventricular mass was significantly reduced in rats previously treated with ACE inhibition or combined treatment. These results suggest that AVP (via V(1A) receptors) and angiotensin II contribute to the pathogenesis of SHR hypertension, whereas the AVP V2 receptor may be involved in preventing the full expression of the hypertension, in male SHR.

Role of urinary arginine vasopressin in the sodium excretion in patients with chronic renal failure.

Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FE(Na)). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FE(ET-1) correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FE(AVP) is the major dependent determinant for FE(Na) (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FE(Na) in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure.

Role of Urinary Arginine Vasopressin in the Sodium Excretion in Patients With Chronic Renal Failure

Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FENa). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FEET-1 correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FEAVP is the major dependent determinant for FENa (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FENa in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure. Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FENa). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FEET-1 correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FEAVP is the major dependent determinant for FENa (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FENa in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure.

Restraint vs. hindlimb suspension on fluid and electrolyte balance in rats.

To determine the effect of hindlimb suspension on body fluid volume, salt and water balance, and relevant hormones, two series of experiments were performed in an experimental protocol including periods of isolation (7 days), horizontal attachment (7 days), and suspension (14 days). 1) During the first experiment, water and electrolyte balance, arginine vasopressin (AVP), and guanosine 3',5'- cyclic monophosphate (cGMP) were determined in urine, atrial natriuretic peptide in plasma and atria, and renin concentration and AVP in plasma in 30 rats. 2) During the second experiment, blood volume and extracellular fluid volume were measured by a dilution technique (Evans blue and sodium thiocyanate) in another 30 rats. We observed a pronounced and early effect of horizontal attachment on the renal variables. After 48 h, diuresis (49%), natriuresis (44%), kaliuresis (36%), osmotic load (39%), creatinine (28%), and AVP excretion (155%) were significantly increased in attached rats (P < 0.05). There was no short-term (24-h) effect of suspension on urine flow and Na+, K+, creatinine, and AVP excretion, but the urine cGMP decreased significantly (45%; P < 0.05). Significant decreases in natriuresis, kaliuresis, urine creatinine, and osmotic load occurred in the suspension group 7 days after suspension. After the 14-day tail suspension, plasma volume and extracellular fluid volume measured in suspended rats were not different from isolated rat values, whereas plasma volume increased by 15% (P < 0.05) in the attached rats. Plasma immunoreactive plasma atrial natriuretic levels of suspended rats were significantly reduced by 35% vs. isolated rats (P < 0.001) and by 18% vs. attached rats (P < 0.05). By using this experimental protocol, the physiological alterations revealed that suspension produced some acute and long-term effects, but the fixation to the suspension device, restraint, and confinement have their own influence on fluid distribution and renal function.