Urinary 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.

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.

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.

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.

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.

Urinary concentrating defect in experimental hemochromatosis.

We studied the urinary concentrating capacity in experimental hemochromatosis. Sprague-Dawley rats were randomized into iron (Fe)-loaded (injected sc with 1.2 g elemental iron/kg body weight as iron dextran) and pair-fed control groups. The urinary concentrating ability was studied after 10 months of iron loading. At basal condition, urine osmolality (Uosm) was significantly lower (P < 0.05) in the Fe-loaded rats compared with the control animals despite comparable urinary arginine-vasopressin (AVP) excretion in the two groups. Although 48-h water deprivation resulted in comparable rises in plasma concentration and urinary excretion of AVP in the two groups, maximal Uosm in the Fe-loaded animals was significantly lower than that seen in the control group (P < 0.01). Moreover, the observed urinary concentrating defect could not be corrected by pharmacological doses of exogenous AVP. There was no significant difference in renal chloride, sodium, calcium, or magnesium handling at either basal or sodium depleted states. Histologic studies showed marked iron deposition in the cortex and outer medulla accompanied by mild tubular atrophy particularly in the distal convoluted tubules. Thus, chronic experimental iron overload leads to nephrogenic diabetes insipidus marked by AVP-resistant urinary concentrating defect.

Enhanced renal production of cyclic GMP and reduced free water clearance during sodium nitroprusside infusion in healthy man

A 90-min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (TcGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min-1), free water clearance (from 4.0 to 1.3 ml min-1) and ANP (from 3.3 to 2.5 pmol l-1) and a significant increase in heart rate (from 57 to 64 beats min-1), Ang II (from 11 to 18 pmol l-1), Aldo (from 189 to 308 pmol L-1) and in the tubular secretion of cGMP (TcGMP from 28.8 to 214.4 pmol min-1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between vasopressin and renal concentrating ability in aging rats.

The relationship between arginine vasopressin (AVP) secretion and the age-related change in renal concentrating ability was studied in 10-, 20-, and 30-mo-old conscious rats. In control condition, urine osmolality (Uosmol) was 2,358 +/- 99, 1,919 +/- 87, and 1,135 +/- 173 mosmol/kgH2O (mean +/- SE) and the corresponding plasma AVP concentration 3.1 +/- 1.2, 2.8 +/- 0.7, and 3.3 +/- 0.7 pg/ml at 10, 20, and 30 mo. Urinary AVP excretion and AVP content in the hypothalamus were comparable in the 3 age groups, while the basal AVP pituitary content was significantly higher at 10 than at 20 or 30 mo. Three days of dehydration induced 1) a similar increase in plasma concentration and urinary excretion of AVP in the 3 groups, even though the maximal Uosmol reached by the oldest animals was significantly reduced (3,988 +/- 218, 3,652 +/- 273, and 2,826 +/- 197 mosmol/kgH2O at 10, 20, and 30 mo, respectively) and 2) a similar AVP depletion of the pituitary at 10, 20, and 30 mo and an increase of the AVP content in the hypothalamus at 10 mo but not at 20 and 30 mo. These results suggest that the decrease in renal concentrating ability reported in aging rats is not due to an inappropriate secretion of AVP along the hypothalamo-neurohypophysial axis but is rather related to an impaired responsiveness of the kidney to the antidiuretic hormone.

Chronic intracerebroventricular infusions of endothelin elevate arterial pressure in rats

We investigated the effects of intracerebroventricular infusions of endothelin on cardiovascular and endocrinological responses using conscious, unrestrained rats. Chronic intracerebroventricular infusions of endothelin, 10 pmol/h for 7 days, elevated arterial pressure significantly on days 5, 6 and 7 of the infusion, compared with intracerebroventricular infusions of the vehicle. Heart rate decreased from day 1 of the infusion of endothelin until the end of the experiment. The urinary excretion of norepinephrine increased on day 3 and epinephrine increased on days 3, 4 and 5 of endothelin infusion. The urinary excretion of arginine vasopressin increased on day 5, 6 and 7 of the infusion. These findings suggest that chronic intracerebroventricular infusions of endothelin elicit elevations in arterial pressure and that the initiation of blood pressure rises can be related to sympathetic activation although the actual role for the pressor responses has been played by the released arginine vasopressin.

Chronic intracerebroventricular infusions of endothelin elevate arterial pressure in rats

We investigated the effects of intracerebroventricular infusions of endothelin on cardiovascular and endocrinological responses using conscious, unrestrained rats. Chronic intracerebroventricular infusions of endothelin, 10 pmol/h for 7 days, elevated arterial pressure significantly on days 5, 6 and 7 of the infusion, compared with intracerebroventricular infusions of the vehicle. Heart rate decreased from day 1 of the infusion of endothelin until the end of the experiment. The urinary excretion of norepinephrine increased on day 3 and epinephrine increased on days 3, 4 and 5 of endothelin infusion. The urinary excretion of arginine vasopressin increased on day 5, 6 and 7 of the infusion. These findings suggest that chronic intracerebroventricular infusions of endothelin elicit elevations in arterial pressure and that the initiation of blood pressure rises can be related to sympathetic activation although the actual role for the pressor responses has been played by the released arginine vasopressin.

The vasopressin response to severe birth asphyxia

Serial measurements of urinary arginine vasopressin (AVP) were made in six severely birth asphyxiated newborn infants. In five infants serial plasma concentrations were also evaluated. There was a strong negative correlation between plasma AVP and plasma osmolality in these infants ( r = −0.52, P = 0.0012). In neither the individual babies nor the group as a whole was there a significant correlation between plasma AVP and the urinary excretion of AVP even if the latter was standardised for creatinine content. Normal development at follow up was only observed in two asphyxiated infants who had consistently low urinary arginine vasopressin levels in the first days of life. Infants with consistently high urinary vasopressin concentrations either died or were severely abnormal in their subsequent development.

Effects of Sodium Intake, Furosemide, and Infusion of Atrial Natriuretic Peptide on the Urinary and Metabolic Clearances of Arginine Vasopressin in Normal Subjects*

Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have important influences on water and electrolyte metabolism, and studies on the interactions between these hormones may have important implications. We have investigated the effects of sodium intake, furosemide, and infusion of ANP on the urinary and metabolic (nonurinary) clearances of AVP in hydrated normal subjects. On a high sodium diet there was an increase in urine volume, sodium excretion, osmolal clearance, plasma ANP concentration, and urinary clearance and fractional excretion of AVP, with a decrease in PRA. The infusion of furosemide increased urine volume, sodium excretion, osmolal clearance, and PRA, but decreased circulating ANP levels and urinary clearance and fractional excretion of AVP. Since there was a positive correlation between circulating ANP and urinary clearance of AVP in these experiments, we infused human alpha ANP in physiological amounts and found increases in the urinary and metabolic (nonurinary) clearances of AVP. The changes in urinary clearance of AVP in all three experiments occurred even in relation to creatinine clearance. These observations demonstrate that urinary clearance of AVP does not correlate with urine volume, sodium or solute excretion, or PRA. The observations support a physiological role for ANP in modulating the renal action of AVP, probably at the level of the renal tubules, and indicate a need for caution when using plasma or urinary AVP as an indicator of AVP release from the neurohypophysis.

Determination and Characterization of Arginine-Vasopressin in Extracted and Unextracted Urine and Its Urinary Excretion in Normal Children and Adolescents

Arginine-vasopressin (AVP) was measured by radioimmunoassay in extracted and unextracted urine using two different antisera. The specificity of the assay was confirmed by high-performance liquid chromatography. By the use of a high specific antiserum, AVP can reliably be measured in unextracted urine. Measurements with a less specific antiserum revealed higher concentrations, probably due to nonspecific binding. The extraction of AVP by the use of octadecasilyl-silica columns is unable to separate the intact hormone from substances interfering with the assay. The urinary AVP excretion in 34 normal children and adolescents ranged between 3.5 and 120 ng/m2/24 h with a mean of 39.1 +/- 29.9 ng/m2/24 h.

Interrelationship between urinary kallikrein and arginine-vasopressin in man.

Physiological saline solution was infused in 9 normal subjects and 6 patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected (i.m.). Urine was collected every 30 min fraction. The urinary excretion of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) was significantly lower in patients with DI than in normal subjects, without showing the differences of plasma renin activity (PRA), plasma aldosterone concentration (PAC), creatinine clearance (Ccr) and blood pressure between the two groups, except a marked water-diuresis in DI. The urinary excretion of KAL-A correlated positively with the urinary excretion of AVP. AVP administration significantly increased the urinary excretion of KAL-A. After overnight fasting, an acute oral water-loading was carried out for 15 min in 6 normal subjects. Concomitant with a significant suppression of the level of plasma AVP from the first 30 min, a slight, but significant, decrease in urinary excretion of KAL-A was observed in the first 30 min fraction after loading, compared with the control period. Afterwards, the urinary excretion of KAL-A increased prominently with an increase in urine flow. KAL-A in the urine decreased promptly from the first 30 min fraction and then gradually until 120 min after loading. Urine volume and free-water markedly increased except the first 30 min fraction, compared with the control period. Thus it is suggested that AVP is one of factors which actually regulate the secretion of renal kallikrein in man.

Inter-relationship between urinary kallikrein-kinins and arginine vasopressin in man.

1. Physiological saline solution was infused in nine normal subjects and six patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected intramuscularly. Urine was collected in 30 min fractions before and after AVP administration. 2. The urinary excretions of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) and immunoreactive kinins (i-kinins) were significantly lower in patients with DI than in normal subjects before AVP administration, while there were no differences in plasma renin activity, plasma aldosterone concentration, creatinine clearance and blood pressure between the two groups, except for a marked water diuresis in patients with DI. The urinary excretion of KAL-A and i-kinins correlated positively with the urinary excretion of AVP. 3. AVP administration increased both plasma AVP and urinary excretion of AVP to similar levels in both groups. As a result, urine volume decreased to a greater degree in patients with DI than in normal subjects. In contrast, the urinary excretions of KAL-A and i-kinins were increased by AVP administration, with a greater response in normal subjects than in the patients with DI. 4. After overnight fasting, acute water loading was carried out orally for 15 min in six normal subjects. At 30 min plasma AVP was suppressed by water loading to almost the basal level found in patients with DI. Urinary excretions of KAL-A and i-kinins in the first 30 min fraction after loading were also suppressed to the basal level in patients with DI. Later, the urinary excretion of KAL-A increased together with the increase in urine flow. Urine volume and free water clearance markedly increased except in the first 30 min fraction, compared with the control period.(ABSTRACT TRUNCATED AT 250 WORDS)