Receptor Subtype for Vasopressin-Induced Release of Nitric Oxide From Rat Kidney

Abstract

The vasopressin receptor subtype that causes nitric oxide (NO) release remains controversial. To elucidate this receptor-ligand interaction, we examined the effects of vasopressin receptor antagonists on vasopressin-induced release of NO from isolated perfused rat kidneys by using a sensitive chemiluminescence assay. Vasopressin increased renal perfusion pressure and NO signals in the perfusate in a dose-dependent manner. N G -Monomethyl- l -arginine abolished this increase in NO release; however, a similar increase in renal perfusion pressure induced by prostaglandin F 2α was not associated with the increase in NO release. OPC-21268, a V 1 receptor antagonist, significantly reduced the vasopressin-evoked renal vasoconstriction and NO release, whereas OPC-31260, a V 2 receptor antagonist, had no effects. Moreover, desmopressin, a selective V 2 receptor agonist, did not increase the NO signal. NO release by vasopressin was markedly attenuated in deoxycorticosterone acetate (DOCA)–salt hypertensive rat kidneys compared with control kidneys (10 −10 mol/L vasopressin: +0.8±0.3 versus +6.9±1.4 fmol/min per gram kidney, DOCA versus control; P <.001). Histochemical analysis for renal NO synthase revealed a substantial attenuation of the staining of endothelial NO synthase in DOCA-salt rats. These results directly demonstrate that vasopressin stimulates NO release via the endothelial V 1 receptor in the rat kidney.