(Hypertension. 1997;29:58.)
© 1997 American Heart Association, Inc.
Research Articles (Issue 1, Part 1) |
The Second Department of Internal Medicine (Y.H., H.H., M.K., A.T., E.S., D.N., K.K, A.G., M.O.) and Faculty of Pharmaceutical Sciences (K.K., T.N., M.H.), University of Tokyo (Japan).
Correspondence to Yasunobu Hirata, MD, The Second Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. E-mail hirata-2im@h.u-tokyo.ac.jp
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. NG-Monomethyl-L-arginine abolished this increase in NO release; however, a similar increase in renal perfusion pressure induced by prostaglandin F2
was not associated with the increase in NO release. OPC-21268, a V1 receptor antagonist, significantly reduced the vasopressin-evoked renal vasoconstriction and NO release, whereas OPC-31260, a V2 receptor antagonist, had no effects. Moreover, desmopressin, a selective V2 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 V1 receptor in the rat kidney.
Key Words: endothelium hormone antagonists desoxycorticosterone nitric oxide
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