L-NAME antagonizes vasopressin V2-induced vasodilatation in dogs.
Experiments were performed in conscious chronically instrumented dogs to study the mechanism of hemodynamic effects mediated by selective vasopressin V2 agonists. In one group of dogs (n = 5) instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter), the infusion of NG-nitro-L-arginine methyl ester (L-NAME; 20 or 40 micrograms.kg-1 x min-1) prevented or significantly inhibited the increase in cardiac output, heart rate and systemic conductance induced by injections of 1-desamino-8-D-arginine vasopressin (DDAVP, desmopressin) and 4-valine-8-D-arginine vasopressin (VDAVP), two selective V2 agonists. L-NAME infusion did not modify the aortic adenosine 3',5'-cyclic monophosphate increase induced by DDAVP infusion. In a second group of dogs similarly prepared (n = 4), the administration of L-arginine (10 mg.kg-1 x min-1) at the same time as that of L-NAME (20 micrograms.kg-1 x min-1) completely prevented the hemodynamic effects of L-NAME and restored the response to DDAVP administration. In a third group of dogs (n = 4), the infusion of a bradykinin B2 antagonist, at a rate that significantly inhibited the cardiac output, heart rate, and blood pressure responses to bradykinin, did not modify the hemodynamic response to DDAVP infusion. We conclude that the hemodynamic effects of selective V2 agonists in dogs are not mediated by bradykinin release but instead via a V2-like receptor on endothelial cells that triggers the release of nitric oxide.
Liard
J F
JF
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects*; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D014667:Vasopressins; D001127:Arginine Vasopressin; D009569:Nitric Oxide; C016180:argipressin, Val(4)-; D001120:Arginine; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester