L-NAME ANTAGONIZES VASOPRESSIN V-2-INDUCED VASODILATATION IN DOGS

Experiments were per formed in conscious chronically instrumented dogs to study the mechanism of hemodynamic effects mediated by selective vasopressin Vt agonists. In one group of dogs (n = 5) instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter), the infusion of N-G-nitro-L-arginine methyl ester (L-NAME; 20 or 40 mu g.kg(-1).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 Vt 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).min(-1)) at the same time as that of L-NAME (20 mu g.kg(-1).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 Bz 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 Vt agonists in dogs are not mediated by bradykinin release but instead via a V-2-like receptor on endothelial cells that triggers the release of nitric oxide.