RECEPTOR SUBTYPE FOR VASOPRESSIN-INDUCED RELEASE OF NITRIC-OXIDE FROMRAT-KIDNEY

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 vasopr essin-induced release of NO from isolated perfused rat kidneys by usin g a sensitive chemiluminescence assay. Vasopressin increased renal per fusion pressure and NO signals in the perfusate in a dose-dependent ma nner. N-G-Monomethyl-L-arginine abolished this increase in NO release; however, a similar increase in renal perfusion pressure induced by pr ostaglandin F-2 alpha was not associated with the increase in NO relea se. OPC-21268, a V-1 receptor antagonist, significantly reduced the va sopressin-evoked renal vasoconstriction and NO release, whereas OPC-31 260, 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 ki dneys (10(-10) mol/L vasopressin: +0.8+/-0.3 versus +6.91+/-1.4 fmol/m in per gram kidney, DOCA versus control; P<.001). Histochemical analys is for renal NO synthase revealed a substantial attenuation of the sta ining of endothelial NO synthase in DOCA-salt rats. These results dire ctly demonstrate that vasopressin stimulates NO release via the endoth elial V-1 receptor in the rat kidney.