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

Abstract

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

Nitric oxide, but not vasopressin V2 receptor-mediated vasodilation, modulates vasopressin-induced renal vasoconstriction in rats

“…Furthermore, V 2 -related renal vasodilation has been reported with desmopressin and, after V 1 receptor antagonist pretreatment, with vasopressin directly infused in vivo into the canine renal artery (Naitoh et al 1993;Aki et al 1994). In rabbit afferent arterioles, desmopressin elicits relaxation mediated by V 2 receptor stimulation (Tamaki et al 1996), as was also reported recently for human renal arteries (Medina et al 1999). However, we were unable to find any renal vasorelaxation linked to V 2 receptor activation in the rat.…”

The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors

“…These clinical observations strongly supported the existence of extrarenal V2Rs, and later studies positively confirmed V2R effects in the endothelium (55,75): the endothelial V2R, activated by desmopressin in high doses and by equivalent blood concentrations of endogenous AVP (56), releases vWF and factor VIII from Weibel-Palade bodies (Fig. 2).…”

“…Extrarenal V2Rs, primarily located in endothelial cells (Fig. 2), have been shown to increase the circulating levels of coagulation factor VIII, vWF, and tissue plasminogen activator (56,75).…”

Vasopressin-V2 Receptor Stimulation Reduces Sodium Excretion in Healthy Humans

“…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).…”