Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.
In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Naitoh
M
M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Murakami
M
M
Matsumoto
A
A
Ichihara
A
A
Nakamoto
H
H
Yamamura
Y
Y
Saruta
T
T
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D004338:Drug Combinations; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D017483:Receptors, Vasopressin / Q000145:classification / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D001552:Benzazepines; D004338:Drug Combinations; D010880:Piperidines; D015363:Quinolones; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C068644:OPC 21268; C076251:mozavaptan; D003894:Deamino Arginine Vasopressin