Receptor subtype for vasopressin-induced release of nitric oxide from rat 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 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 omega-Monomethyl-L-arginine abolished this increase in NO release; however, a similar increase in renal perfusion pressure induced by prostaglandin F2 alpha 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.
Hirata
Y
Y
Second Department of Internal Medicine, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan. hirata-2im@h.u-tokyo.ac.jp
Hayakawa
H
H
Kakoki
M
M
Tojo
A
A
Suzuki
E
E
Nagata
D
D
Kimura
K
K
Goto
A
A
Kikuchi
K
K
Nagano
T
T
Hirobe
M
M
Omata
M
M
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D003900:Desoxycorticosterone; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000145:classification* / Q000378:metabolism; D012076:Renal Agents / Q000378:metabolism / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004791:Enzyme Inhibitors; D010880:Piperidines; D015363:Quinolones; D017483:Receptors, Vasopressin; D012076:Renal Agents; D001127:Arginine Vasopressin; C068644:OPC 21268; C076251:mozavaptan; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D015237:Dinoprost