Effects of arginine vasopressin and 1-desamino-8-D arginine vasopressin on forearm vasculature of healthy subjects and patients with a V2 receptor defect

Lieburg, A.F. van; Knoers, Nine V A M; Monnens, L.A.H.; Smits, P.

doi:10.1097/00004872-199512010-00034

Cited by 29 publications

(22 citation statements)

References 8 publications

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“…However, a number of studies have now well documented the existence of extrarenal V2 receptors, probably located on the vascular endothelium (29). The stimulation of these receptors by V2 agonists results in a significant vasodilation (30,31) that probably accounts for the fall in BP observed in this study (20,22).…”

Section: Discussionsupporting

confidence: 52%

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Bankir

Fernandes

Bardoux

et al. 2005

Journal of the American Society of Nephrology

121

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In addition to its effect on water permeability, vasopressin, through its V2 receptors (AVPR2), stimulates Na reabsorption in the collecting duct by increasing the activity of the amiloride-sensitive sodium channel ENaC. This study evaluated whether dDAVP (a potent AVPR2 agonist) reduces sodium excretion in healthy humans (n ‫؍‬ 6) and in patients with central (C; n ‫؍‬ 2) or nephrogenic (N) diabetes insipidus (DI) as a result of mutations of either the aquaporin 2 gene (AQP2; n ‫؍‬ 3) or AVPR2 (n ‫؍‬ 10). dDAVP was infused intravenously (0.3 g/kg body wt in 20 min), and urine was collected for 60 min before (basal) and 150 min after the infusion. dDAVP markedly reduced both urine flow rate and sodium excretion in healthy individuals. A reduction in sodium excretion was also observed in CDI and NDI-AQP2 patients but not in NDI-AVPR2 patients. The magnitude of the fall in sodium excretion correlated with the rise in urine osmolality and the fall in urine output but not with the simultaneously observed fall in mean BP. These results suggest that the dDAVP-induced antinatriuresis is due to a direct V2 receptor-dependent stimulation of sodium reabsorption in the collecting duct and is not secondary to a hemodynamic effect. In conclusion, this study reveals a potent V2-dependent antinatriuretic effect of vasopressin in humans. The possibility that an inappropriate stimulation of ENaC by vasopressin might lead to significant sodium retention in chronic situations remains to be determined. 16: 192016: -192816: , 200516: . doi: 10.1681 I nappropriate retention of sodium and water by the kidney is thought to be a key factor in several forms of hypertension. Thus, it is important to identify factors that may favor excessive sodium reabsorption by the kidney. Vasopressin is known to promote water conservation by increasing the permeability to water of the collecting ducts (CD), thus allowing osmotically driven water reabsorption along these ducts when dilute distal tubular fluid enters them in the cortex and later when they traverse the hyperosmotic medulla. However, the effect of vasopressin on sodium excretion is less clear. A large number of studies have shown that vasopressin infusion increases sodium excretion in vivo in rats, dogs, and sheep (e.g., references 1-4). This natriuretic effect is difficult to reconcile with the fact that, in vitro, vasopressin stimulates sodium reabsorption in the isolated perfused CD (5,6), in the amphibian bladder (a tissue that shares a number of similarities with the mammalian CD) (7), and in several cell lines issued from these two tissues (8 -10). This effect on sodium reabsorption is inhibitable by amiloride and has been shown to result from activation of the endothelial sodium channel ENaC (11). Moreover, chronic elevation of vasopressin or infusion of its V2 agonist dDAVP (12) has been shown to increase the abundance of mRNA (13) and protein (14) of the ␤ and ␥ subunits of ENaC and to enhance markedly the subsequent functional response (water and sodium reabsorption) to exoge...

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Section: Discussionsupporting

confidence: 52%

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Bankir

Fernandes

Bardoux

et al. 2005

Journal of the American Society of Nephrology

121

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“…However, similar hemodynamic effects of desmopressin administration have been described in patients with central diabetes insipidus, who lack endogenous vasopressin 10,19 and therefore an antagonism of vasopressin on vascular V 1 receptors is unlikely. By contrast, patients with Xlinked nephrogenic diabetes insipidus, who lack the V 2 receptor-mediated renal antidiuretic response to desmopressin, 20 manifest no increase in coagulation factors 10,12 and show no vasodilatation in response to desmopressin, 10,11 thus suggesting that the absence of responses to desmopressin is a consequence of an extrarenal V 2 receptor defect. In the present experiments, desmopressin caused dilatation in the absence of vasopressin and in the presence of selective V 1 receptor antagonists (peptidic and nonpeptidic).…”

Section: Discussionmentioning

confidence: 98%

“…In agreement with the present results, experiments in healthy subjects indicate that L-NMMA, another nitric oxide synthase inhibitor, did not modify the increase in forearm blood flow induced by desmopressin, thus suggesting that the desmopressin-induced vasodilatation is mediated by mechanisms other than endothelial nitric oxide. 11 The involvement of prostanoids in the modulation of the desmopressin dilator response was assessed by pretreatment of the arterial segments with the cyclooxygenase inhibitor indomethacin. The results showed that indomethacin inhibits the desmopressin-induced relaxation, thus suggesting that the effect is largely due to the release of dilating prostaglandins from renal arteries.…”

Section: Discussionmentioning

confidence: 99%

V2-receptor–mediated relaxation of human renal arteries in response to desmopressin

Medina

Segarra

Vila

et al. 1999

American Journal of Hypertension

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The effects of deamino-8-D-arginine vasopressin (desmopressin), a V 2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10 ؊6 to 3 ؋ 10 ؊6 mol/L), desmopressin (10 ؊11 to 3 ؋ 10 ؊7 mol/L) caused endothelium-dependent relaxation (81% ؎ 4% reversal of the initial contraction in arteries with endothelium; 20% ؎ 4% in arteries without endothelium; P < . A rginine vasopressin promotes reabsorption of water in renal tubular cells through V 2 receptors coupled to adenylate cyclase activation and acts directly on human vascular smooth muscle to produce constriction through V 1 receptor stimulation.1-4 The specific V 2 receptor agonist deamino-8-d-arginine vasopressin (desmopressin) is a synthetic analogue of the natural hormone vasopressin with a strong V 2 antidiuretic effect and minimal V 1 pressor activity.5 Extrarenal actions of desmopressin include coagulation responses such as the release of factor VIIIc and von Willebrand factor, 6 -8 and cardiovascular effects such as increase in heart rate, decrease in mean arterial blood pressure, facial flushing, and increase in forearm blood flow. 9 -11 Whether these effects are mediated by receptors is not clearly established, but studies in humans demonstrate that an extrarenal V 2 receptor could be responsible for the coagulation and hemodynamic responses to desmopressin. 10 -12 Experiments in isolated arteries show that desmopressin induces concentration-dependent relaxation in human cerebral and mesenteric arteries that is prevented by the mixed V 1 -V 2 receptor antagonist desGly-d(CH 2 ) 5 -d-Tyr(Et)ValAVP but not

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“…Moreover, complex specific tissue interactions were shown between V2 and V1a effects, at the epithelial and vascular levels (25). Acute regional vasodilator and hypotensive effects of dDAVP mediated by endothelial V2R and NO production have been reported in healthy humans and animals (15,45,97,101,103).…”

Section: Water Conservation and Blood Pressure: Pathophysiological Obmentioning

confidence: 99%

Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension?

Bankir

Bichet

Bouby

2010

American Journal of Physiology-Renal Physiology

106

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Excessive sodium reabsorption by the kidney has long been known to participate in the pathogenesis of some forms of hypertension. In the kidney, the final control of NaCl reabsorption takes place in the distal nephron through the amiloride-sensitive epithelial sodium channel (ENaC). Liddle's syndrome, an inherited form of hypertension due to gain-of-function mutations in the genes coding for ENaC subunits, has demonstrated the key role of this channel in the sodium balance. Although aldosterone is classically thought to be the main hormone regulating ENaC activity, several studies in animal models and in humans highlight the important effect of vasopressin on ENaC regulation and sodium transport. This review summarizes the effect of vasopressin V2 receptor stimulation on ENaC activity and sodium excretion in vivo. Moreover, we report the experimental and clinical data demonstrating the role of renal ENaC in water conservation at the expense of a reduced ability to excrete sodium. Acute administration of the selective V2 receptor agonist dDAVP not only increases urine osmolality and reduces urine flow rate but also reduces sodium excretion in rats and humans. Chronic V2 receptor stimulation increases blood pressure in rats, and a significant correlation was found between blood pressure and urine concentration in healthy humans. This led us to discuss how excessive vasopressin-dependent ENaC stimulation could be a risk factor for sodium retention and resulting increase in blood pressure. water conservation; antidiuresis; sodium excretion; collecting duct VASOPRESSIN WAS FIRST IDENTIFIED as a pressor hormone and later recognized to be also a potent antidiuretic hormone. Today, these early historical discoveries have been explained by the identification of different receptor types. V1a receptors (V1aR), abundantly expressed in vascular smooth muscle cells, and signaling through calcium and phosphatidylinositol transducer pathways, are responsible for the pressor effects. V2 receptors (V2R), expressed mainly in principal cells of the renal collecting duct (CD), and signaling through cAMP, mediate the antidiuretic actions of the hormone (113).Vasopressin is elevated in some forms of human hypertension (26,92,111) and in animal models of hypertension (see reviews in Refs. 91 and 108). This hormone has long been suspected to play a role in blood pressure control because of its vasoconstrictive effects, well demonstrated in vitro. However, the studies trying to evaluate the contribution of V1aR-dependent effects in hypertension are inconclusive [either in favor of (27,35,70) or against (59, 98)].Excessive sodium reabsorption by the kidney is known to participate in the pathogenesis of some forms of hypertension.Among the genes responsible for monogenic forms of blood pressure disorders identified to date, the majority either mediate renal sodium transport in the distal part of the nephron or are involved in its regulation. Loss of function of the corresponding proteins leads to salt-wasting states with hypotension (48), ...

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Effects of arginine vasopressin and 1-desamino-8-D arginine vasopressin on forearm vasculature of healthy subjects and patients with a V2 receptor defect

Cited by 29 publications

References 8 publications

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

V2-receptor–mediated relaxation of human renal arteries in response to desmopressin

Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension?

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