Doses Of Arginine Vasopressin Research Articles

Sensitivity of the renal medullary circulation to plasma vasopressin.

Studies were carried out to determine the effects of physiological changes of plasma arginine vasopressin (AVP) on blood flow distribution in the renal cortex and medulla. Acute decerebration was performed so that studies could be carried out within the low physiological range of circulating AVP. Changes of renal cortical and medullary microcirculatory blood flow were measured with implanted optical fibers and laser-Doppler flowmetry, and total renal blood flow was measured with transit-time ultrasonography. During intravenous infusion of increasing doses of AVP, when plasma AVP was increased in steps from 2.9 to 11.2 pg/ml by intravenous infusion, mean arterial pressure (98 +/- 3 mmHg), total renal blood flow (8.2 +/- 0.6 ml. min-1.g kidney-1), and blood flow in the microcirculation of the cortex (2.11 +/- 0.28 V) remained unchanged, whereas that in the renal medulla decreased progressively. Medullary flow was significantly reduced when circulating levels of AVP increased from a control level of 2.8 to 5.0 pg/ml. The reductions of medullary flow were accompanied by parallel increases of urine osmolality. These data indicate that the vessels supplying the renal medullary circulation are sensitive within the range of plasma AVP concentrations observed with moderate water restriction. The medullary circulation exhibits a sensitivity AVP that parallels that found in the medullary collecting ducts.

Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans

There is evidence that intranasal application of peptides is a way to circumvent the blood-brain barrier. This led us to compare the effects of arginine-vasopressin (AVP) on event-related potentials (ERPs) in healthy men (n = 15) after intranasal and after intravenous (i.v.) administration. In a double-blind, crossover study, subjects received on three different occasions 20 IU of AVP intranasally (IN), 1.5 IU of AVP i.v., and saline solution. ERPs were recorded during the subject's performance on a auditory attention task. Plasma concentrations of vasopressin during task performance were enhanced after AVP, with the increase after i.v. administration of AVP exceeding that after AVP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (< 0.01). By contrast, i.v. administration of AVP had no consistent effects on the ERP responses. In supplementary experiments as well, i.v. administration of lower doses of AVP (0.1 and 0.025 IU) did not affect the ERP. Plasma vasopressin concentrations after the 0.025 IU dose in these experiments were comparable to those after intranasal administration of 20 IU AVP. The results provide functional evidence that in the human brain effects of peptides like AVP may be facilitated after IN as compared to i.v. administration.

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.

Control of renal medullary blood flow by vasopressin V1 and V2 receptors.

Experiments were performed in anesthetized renal-denervated rats to determine the contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the regulation of renal medullary blood flow. Renal medullary interstitial infusion of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1) significantly decreased outer medullary blood flow by 15% and inner medullary blood flow by 35%, as measured with implanted optical fibers for laser-Doppler flowmetry. Medullary interstitial infusion of equimolar doses of arginine vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased inner medullary blood flow by only 17%, a decrease significantly less than that during the infusion of the V1 agonist. These results were confirmed in videomicroscopy experiments on the exposed papilla, which demonstrated that the V1 agonist and AVP decreased descending and ascending vasa recta capillary red blood cell velocity and calculated blood flow, with greater decreases during infusion of the V1 agonist. In further laser-Doppler flowmetry studies, stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D-arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present experiments indicate that vasopressin V1 receptor stimulation serves to decrease renal medullary blood flow while V2 receptor stimulation appears to increase renal medullary blood flow; however, the net effect of AVP is to decrease renal medullary blood flow.

Corticotropin-releasing factor alone, but not arginine vasopressin alone, stimulates the release of adrenocorticotropin in the conscious intact sheep

These studies compared the relative potencies of CRF and arginine vasopressin (AVP) as ACTH secretagogues in the sheep. Dose-response curves to CRF (10, 25, 50, and 100 micrograms/h) and AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h) were obtained in five adult sheep, with arterial blood samples taken for CRF, AVP, ACTH, and cortisol measurements to determine the pituitary-adrenal response. It was found that the first dose of CRF increased plasma CRF levels to 444 +/- 79 pg/ml. ACTH levels rose significantly from 28 +/- 5 to 186 +/- 46 pg/ml, with a concurrent rise in cortisol levels from 7 +/- 3 to 44 +/- 9 ng/ml. Although plasma ACTH and cortisol levels remained elevated, higher doses of CRF failed to produce further increases. AVP, at all of the doses studied, did not produce an increase in ACTH levels, although cortisol levels rose significantly by the second dose. In a second series of experiments, animals received a continuous infusion of CRF (10 micrograms/h) alone or in combination with graded doses of AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h for 60 min each). It was found that AVP at the highest dose was able to potentiate the ACTH response to CRF. Lower doses of AVP, which did not stimulate a further increase in ACTH levels were, however, associated with a significant rise in cortisol levels. In conclusion, it was found that although CRF alone was a potent stimulator of ACTH secretion, AVP at the doses studied was not able to elicit an ACTH response in the conscious intact sheep. However, a dose of AVP that was not stimulatory in itself was able to augment the ACTH response to CRF.

V2 Receptor-Mediated Vasodilation in Healthy Humans

Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms: vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor, but the mechanism of AVP-induced vasodilation remains unclear. To determine if the AVP-induced vasodilation in human forearm vessels is mediated by the V2 receptor, we examined the effects of OPC-31260 (a novel vasopressin V2 receptor antagonist) on AVP-induced vasodilation. The brachial artery was cannulated for drug infusions and direct measurement of arterial blood pressure (BP). We measured forearm blood flow (FBF) by a strain-gauge plethysmograph and calculated forearm vascular resistance (FVR). AVP was infused intraarterially (i.a.) at doses of 0.1, 0.2, 0.5, 1.0, and 2.0 ng/kg/min (n = 8). The lower dose of AVP (0.1 ng/kg/min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg/min) decreased, FVR (p < 0.01). Infusion of nitroglycerin (NTG) i.v. doses of 1.7, 3.3, and 10.0 ng/kg/min decreased FVR dose dependently (p < 0.01). OPC-31260 (1.0 micrograms/kg/min) infused i.a. did not alter arterial BP, baseline FVR, or heart rate (HR). OPC-31260 did not affect AVP-induced vasoconstriction but blocked AVP-induced vasodilation completely. OPC-31260 did not affect NTG-induced vasodilation. These results suggest that AVP-induced vasodilation is mediated by the V2 receptor in human forearm resistance vessels.

In vitro Effects of Oxytocin and Vasopressin on Cyclic Nucleotide Production by Bovine Granulosa Cells

The aim of our in vitro experiments was to determine the involvement of cyclic nucleotides in mediating the effects of oxytocin (OT) and arginine vasopressin (AVP) on bovine ovarian cells. The influence of OT and AVP (1–100,000 ng/ ml) on cGMP and cAMP production by bovine granulosa cell cultures was investigated. It was found that OT stimulated cGMP output in a dose-dependent manner. AVP had no marked influence on cGMP release. OT at low to medium range doses of AVP had no significant effects on cAMP, but high doses (10,000 or 100,000 ng/ml) of AVP stimulated cAMP output. The present observations suggest that cGMP may be a mediator of OT action on ovarian cells. It is also possible that high doses of AVP affect bovine ovarian cells through the cAMP-dependent intracellular mechanism.

Arginine vasopressin-induced renal vasodilation mediated by nitric oxide.

The vasoconstrictor vasopressin has been reported to induce paradoxical local vasodilation in the basilar vasculature through stimulation of the endothelium-derived relaxing factor nitric oxide (NO). We investigated the possibility that at subpressor doses, exogenous arginine vasopressin (AVP) might have a similar effect in the kidney. Ten Inactin-anesthetized rats were infused with sequential doses of AVP from 25 to 6,400 microU/min in 30-min increments. Subpressor infusion resulted in progressive renal vasodilation; renal blood flow (RBF) increased significantly going from 14 +/- 6% above basal at 200 microU/min (p < 0.02) to 27 +/- 5% (p < 0.01) at 1,600 microU/min accompanied by a 24 +/- 5% decrease in renal vascular resistance (RVR). At 6,400 microU/min, blood pressure (BP) increased 29 +/- 6 mm Hg and RVR increased. A second group of 8 rats were first given 10 mg/kg b.w. of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) before infusion of AVP. L-NAME increased BP 22 +/- 3 mm Hg (p < 0.001), and decreased RBF 16 +/- 3% (p < 0.005). After L-NAME, no dose of AVP had any further effect on either BP, RBF, or RVR. Continuous infusion of a single subpressor dose of 100 microU AVP resulted in a 26% increase in RBF (from 7.52 +/- 0.68 to 9.49 +/- 0.54 ml/min/g kidney weight, p < 0.001). AVP doubled urinary cyclic guanosine monophosphate excretion, a marker for renal NO synthesis, from 8.51 +/- 1.01 to 17.48 +/- 4.26 pM/min (p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced pulmonary arterial dilation to arginine vasopressin in chronically hypoxic rats.

Chronic hypoxic exposure elicits pulmonary vascular remodeling and may alter normal pulmonary endothelial function. We examined the vasodilatory response to the receptor-mediated endothelium-dependent dilator arginine vasopressin (AVP), the non-receptor-mediated endothelium-dependent dilator A-23187, and the nitric oxide (NO) donor sodium nitroprusside in lungs isolated from control or chronically hypoxic rats. Lungs were isolated from male Sprague-Dawley rats and perfused with a physiological saline solution containing 4% albumin. Arterial and venous pressures were monitored and microvascular pressure was estimated by double occlusion, allowing assessment of segmental resistances. After equilibration, lungs were constricted with the thromboxane mimetic U-46619. Upon development of a stable pressor response, lungs were dilated with one of the above agents. A series of doses of AVP was administered to separate groups of lungs from control or chronically hypoxic rats. Lungs from chronically hypoxic rats exhibited an augmented dilatory response to AVP compared with control lungs, and this effect was due to enhanced dilation of precapillary segments. The total and segmental vasodilatory responses to A-23187 and sodium nitroprusside were not different between the two groups of lungs, suggesting that chronic hypoxia did not upregulate the enzyme NO synthase or enhance the vascular smooth muscle responsiveness to NO. Thus our data suggest that the augmented total and pulmonary arterial dilation to AVP after chronic hypoxia is most likely due to altered receptor-mediated processes of the hormone.

Effect of dehydration and hyperosmolal hydration on lignocaine and metabolites disposition in conscious rabbits.

1. The present study aimed to investigate the effect of dehydration and hyperosmolal hydration on the disposition of lignocaine and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). 2. Lignocaine was infused to three groups of conscious rabbits: controls, rabbits previously deprived of water for 48 h and rabbits receiving an infusion of 2.5% NaCl. 3. In dehydrated and hyperosmolal-hydrated rabbits, plasma osmolality was 321 +/- 1 and 313 +/- 1 mOsm kg-1, respectively (P < 0.01 compared to controls, 285 +/- 1 mOsm kg-1). In dehydrated animals, baseline values of plasma arginine vasopressin (AVP) concentrations and plasma renin activity (PRA) were higher than in controls, i.e. 12.4 +/- 1.4 pg ml-1 and 15.4 +/- 1.7 ng AI ml-1 h-1 vs. 3.4 +/- 0.2 pg ml-1 (P < 0.01), and 5.1 +/- 0.6 ng AI ml-1 h-1 (P < 0.01), respectively; atrial natriuretic peptide (ANP) decreased from 55 +/- 11 to 32 +/- 4 pg ml-1 (P < 0.05). Compared to controls, hyperosmolal hydration only increased AVP to 15.5 +/- 0.7 pg ml-1 (P < 0.01). 4. Under both experimental conditions, lignocaine plasma concentrations were almost double (P < 0.01) those in controls, due to a lower systemic clearance, e.g. 54 +/- 3 and 59 +/- 1 vs. 96 +/- 5 ml min-1 kg-1, respectively. Plasma levels of MEGX increased (P < 0.01) only in dehydrated animals, although GX plasma concentrations were augmented (P < 0.01) about three fold in both groups of animals. The changes in lignocaine plasma concentrations were correlated with AVP levels (R2 = 0.5168, P<0.001).5. To document the effect of AVP on hepatic plasma flow, another group of rabbits received on separate occasions two doses of AVP (17 and 84 ng kg-1) while receiving an infusion of in docyanine green. AVP reduced hepatic plasma flow from 38.9 +/-2.7 ml min-1 to 19.6 +/-2.5 ml min-1 (P<0.01).The predicted maximal AVP-induced decrease in hepatic plasma flow was 19.6 ml min-1 kg- 1(Emax), and AVP concentration eliciting 50% of Em.. (ED50) was 28.7 pg ml-1.6 It is concluded that both dehydration and hyperosmolal hydration alter the disposition of lignocaine and two of its metabolites.

Oxytocin augments baroreflex bradycardia in conscious rats

Previous studies have demonstrated augmentation of baroreflex-mediated bradycardia by arginine vasopressin (AVP). However, the specific receptor subtype responsible for mediating this augmentation has not been determined. In the present study, experiments were performed in conscious rats to determine the possible involvement of oxytocin receptors in this response. Infusion of oxytocin at a dose that had no effect on baseline hemodynamic values significantly augmented the bradycardic response to IV bolus doses of methoxamine. Prior treatment with selective antagonists to either oxytocin, V 1 vasopressingergic or V 2 vasopressinergic receptors reversed this enhancement. In a separate set of experiments, baroreflex-mediated bradycardic responses to IV bolus doses of AVP were assessed. Pretreatment with the selective oxytocin receptor antagonist reversed vasopressinergic augmentation of baroreflex sensitivity. Finally, combined vasopressinergic and oxytocinergic stimulation of the baroreflex was assessed. Treatment with both AVP and oxytocin did not augment baroreflex-mediated bradycardia greater than AVP alone. We conclude from these experiments that AVP and oxytocin both augment baroreflex sensitivity, although the receptor type(s) responsible are not clear.

Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels.

Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms; vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor. However, the mechanism of AVP-induced vasodilation is not known. We investigated whether AVP-induced vasodilation is mediated by nitric oxide (NO) in human forearms by examining the effects of L-arginine (a precursor of NO) and NG-monomethyl-L-arginine (L-NMMA, a blocker of NO synthase) on AVP-induced vasodilation. AVP was infused intraarterially at doses of 0.05, 0.1, 0.2, 0.5, and 1.0 ng/kg per min (n = 8). The lower doses of AVP (< or = 0.1 ng/kg per min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg per min) decreased forearm vascular resistance (FVR) (P < 0.01). Intraarterially infused L-arginine at 10 mg/min did not alter arterial pressure, baseline FVR, or heart rate. L-arginine did not alter the magnitude of AVP-induced vasoconstriction at the lower doses, but L-arginine augmented the magnitude of AVP-induced vasodilation at doses of 0.2 (P < 0.05), 0.5 (P < 0.01), and 1.0 (P < 0.05) ng/kg per min. In another group (n = 6), intraarterially infused L-NMMA (4 mumol/min for 5 min) increased baseline FVR without systemic effects, and inhibited acetylcholine-induced vasodilation (P < 0.01). L-NMMA at this dose inhibited AVP-induced vasodilation (P < 0.01) but did not affect vasoconstriction. L-arginine reversed the inhibitory effect of L-NMMA. Our results suggest that the vasodilatory effect of AVP may be mediated by NO in human forearms.

Effect of arginine vasopressin and parathyroid hormone-related protein on renal function in the ovine foetus.

1. The effects of intravenous infusions of arginine vasopressin (AVP), parathyroid hormone-related protein (PTHrP) and AVP+PTHrP on renal function in intact ovine foetuses at 100-125 days of gestation were examined. 2. A low dose of AVP (5.5 +/- 0.9 pmol/h) increased plasma AVP concentrations from 0.6 pmol/L to 2.1 +/- 0.4 pmol/L (mean +/- s.e.m; n = 8). This dose caused a significant reduction in free water clearance (CH2O; P < 0.001), without any significant change in fetal arterial blood pressure, glomerular filtration rate (GFR), or the urinary excretion rates of sodium, calcium or 3',5'-cyclic adenosine monophosphate (cAMP). 3. Infusions of PTHrP (1 nmol/h), with or without 1 nmol bolus dose, significantly increased (P < 0.05) urine osmolality (UOSM), but did not synergize with AVP in reducing CH2O. 4. It is concluded that AVP and PTHrP do not act synergistically on the kidney of the intact ovine foetus.

Vasopressin stimulates cortisol secretion from human adrenocortical tissue through activation of V1 receptors.

It has previously been shown that arginine vasopressin (AVP) exerts a direct stimulatory action on rat adrenocortical cells. In the present study, we have investigated the possible effect of AVP on cortisol secretion by normal human adrenocortical tissue. The occurrence of endogenous AVP in the human adrenal gland has been studied by means of the indirect immunofluorescence technique. The presence of AVP-containing cells was observed in both cortex and medulla. The action of AVP on corticosteroidogenesis has been investigated in vitro using a perifusion system technique coupled to a specific RIA for cortisol. Graded doses of AVP (from 10(-11)-10(-9) M) increased cortisol secretion in a dose-dependent manner (ED50, 4.5 x 10(-11) M). AVP also induced a significant stimulation of cortisol release from acutely dispersed adrenocortical cells. Prolonged administration of AVP (3 h) induced a rapid and transient increase in cortisol output, followed by a gradual decline in cortisol secretion. Repeated pulses of AVP, given at 90-min intervals, resulted in reproducible stimulations of cortisol output. Selective agonists and antagonists have been used to determine the type of receptor involved in the response of adrenocortical cells to AVP. Oxytocin at doses up to 10(-7) M had virtually no effect on cortisol secretion. The stimulatory effect of AVP was blocked by the V1 antagonist [beta-mercapto-beta,beta-cyclopentamethylene propionyl 1, OMe-Tyr2, Arg8]AVP. In contrast, the V2 antagonist [d(CH2)5D-Phe2,Ile4,Ala9-NH2]AVP did not affect the response of the adrenal gland to AVP. The selective V2 agonist [deamino-Cys1,D-Arg8]AVP did not mimic the stimulatory effect of AVP on cortisol secretion. Taken together, these results suggest that AVP, locally released by intracortical cells, may act as a paracrine factor to stimulate adrenal steroidogenesis in man. The effect of AVP on cortisol secretion appears to be mediated through activation of typical V1 receptors.

Acute effect of physiological concentrations of vasopressin on rat renal function.

1. The antidiuretic, pressor and electrolyte transport effects of arginine vasopressin (AVP) were simultaneously evaluated in the anaesthetized water diuretic rat. Increasing concentrations of AVP (7.5, 75 and 750 ng/kg bolus and per h), were used to produce plasma levels which approximate the physiological range (408 +/- 2.4, 35.7 +/- 12.5, 85.2 +/- 16.1 pg/mL respectively). 2. Administration of a minimally effective antidiuretic dose (7.5 ng) increased mean urine osmolality (from 101 +/- 7 to 312 +/- 89 mosmol/kg) without altering mean arterial pressure (MAP), renal plasma flow (RPF) or glomerular filtration rate (GFR). A maximal antidiuretic dose of AVP (75 ng) increased mean urine osmolality to 2002 +/- 109 mosmol/kg and was associated with significant mean increases in MAP (9 mmHg), RPF and GFR (25%) by 30-60 min. A further ten-fold increase in AVP (750 ng) produced a greater increase in MAP (116 +/- 6 to 134 +/- 7 mmHg; P < 0.01) as well as increasing RPF and GFR by 35.5 and 38.9% respectively. 3. Increasing concentrations of AVP also progressively increased the fractional excretion of sodium, potassium and phosphate. However, fractional calcium and magnesium excretion was significantly decreased with maximal and supramaximal concentrations. 4. These studies support evidence that AVP is a pressor hormone in physiological concentrations in baroreceptor intact animals. Its role in renal electrolyte transport is unclear. Measured increases in RPF and GFR with the maximal and supramaximal AVP concentrations appear to be correlated with the increase in MAP.

Stimulation of the pituitary-adrenal axis with a low dose [Arg 8]-vasopressin in depressed patients and healthy subjects

Graded doses arginine-vasopressin (AVP) were administered to depressed patients and control subjects to compare the sensitivity of the pituitary-adrenal system of these subjects for this compound. The plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and ß-endorphin were measured before and after intravenous AVP injection. The hormonal output was taken as a measure of pituitary-adrenal function. In control subjects 3 doses AVP and placebo were used, whereas in patients two doses AVP, a low and high dose, and placebo were tested. All tests were carried out in the afternoon when the pituitary-adrenal system is stable and more susceptible for stimulation. Patients were subdivided into dexamethasone suppressors and nonsuppressors based on their DST status before testing to look for differences among these groups. Control subjects showed no response of the hormones to the lowest dose AVP and a moderate response to the higher doses. Interestingly, depressed patients as compared to controls responded more to the lowest dose AVP in particular with respect to ACTH. DST status did not influence the results. These findings suggest an enhanced sensitivity of the pituitary to low doses AVP in depressed patients. Thus, AVP might play a role in HPA dysfunction in depression.

Vasopressin-induced suppression of renal sympathetic outflow depends on the number of baroafferent inputs in rabbits.

We tested the hypothesis that the inhibitory action of arginine vasopressin (AVP) on renal sympathetic nerve activity (RSNA) is related to the number of baroreceptor stations. The role of baroreceptor afferents was determined by comparing the effects of AVP on the baroreflex function curves [mean arterial pressure (MAP) vs. %RSNA] obtained in intact conscious rabbits with those obtained in rabbits with one carotid sinus and one aortic nerve intact (1CSN + 1AoN) and in rabbits with only a single carotid sinus nerve intact (1CSN). Baroreflex curves were obtained by relating %RSNA to MAP during ramp increases and decreases in MAP. MAP was increased with phenylephrine and decreased with caval occlusion. In the intact state (n = 7), AVP infusions (0.4, 1.5, and 3.0 mU.kg-1 x min-1) produced dose-dependent reduction in the maximum %RSNA (97 +/- 1 to 85 +/- 6, 68 +/- 6, and 57 +/- 5%, respectively) at minimum MAP and the gain of the baroreflex curve (5.7 +/- 0.2 to 3.9 +/- 0.2, 3.2 +/- 0.3, and 2.2 +/- 0.2 mmHg, respectively) and shifted the midrange of the curves (72 +/- 3 to 68 +/- 4, 68 +/- 2, and 63 +/- 3 mmHg, respectively). However, in the 1CSN + 1AoN state (n = 6), the medium dose of AVP (1.5 mU.kg-1 x min-1) did not significantly alter the maximum %RSNA, the gain of the curve, or the midrange of the curve. The highest dose of AVP (3.0 mU.kg-1 x min-1) still reduced the maximum %RSNA (98 +/- 3 to 75 +/- 3) and the gain of the curve (4.1 +/- 0.4 to 2.7 +/- 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Further studies on the anti-nociceptive effect of vasopressin.

The possible interactions of pathways which mediate anti-nociception when stimulated by alpha 2-adrenoceptor agonists and arginine vasopressin (AVP) were investigated. Yohimbine, an alpha 2-antagonist, failed to modify the anti-nociceptive response of AVP. However, clonidine pretreatment, in sub-effective and effective doses, potentiated the anti-nociceptive response of a sub-effective dose of AVP. This potentiation was attenuated by yohimbine and completely antagonized by naloxone. These studies suggest that pathways related to the opioidergic system and those stimulated by alpha 2-agonists may be utilized by AVP in eliciting the anti-nociceptive response.

Age-associated decrease in vasopressin-induced renal water transport: a role for adenylate cyclase and G protein malfunction.

Aging is associated with a decline in renal concentrating ability in response to dehydration-induced arginine vasopressin (AVP) release. To examine target tissue sensitivity, cortical collecting tubules (CCT) were individually microdissected from young (3 months), middle-aged (2-3 years) and old (4-5.5 years) rabbits and subjected to in vitro perfusion analysis and tissue culture of defined epithelial monolayers. Osmotic fluid transport was compared with adenylate cyclase activity and an age-associated decline in both parameters detected in response to increasing doses of AVP. [3H]-AVP binding was unchanged in CCT epithelia of different ages, excluding receptor alterations as the underlying mechanism. Also, hydraulic conductivity measurements of isolated young and old CCT were not significantly different, excluding post-cAMP events as a major mechanism of reduced sensitivity. Effects of cholera toxin and forskolin on hydraulic conductivity and adenylate cyclase activity showed a dramatic decrease in the ability of these compounds to elicit a response in CCT epithelia from old rabbits. It was concluded that alterations in Gs proteins and the catalytic unit of adenylate cyclase-were responsible for the age-associated decline in CCT response to AVP.