COMPARATIVE EFFECTS OF N(OMEGA)-NITRO-L-ARGININE AND N(OMEGA)-NITRO-L-ARGININE METHYL-ESTER ON VASODILATOR RESPONSES TO ACETYLCHOLINE, BRADYKININ, AND SUBSTANCE-P

N(omega)-Nitro-L-arginine methyl ester has been reported to have musca rinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, u ndertaken to compare the inhibitory effects of N(omega)-nitro-L-argini ne methyl ester with those of N(omega)-nitro-L-arginine on baseline to ne and on vasodilator responses to acetylcholine, bradykinin, and subs tance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N(omega)-nitro-L-arginine methyl ester a nd N(omega)-nitro-L-arginine in doses of 100 mg/kg i.v. increased base line tone in the mesenteric vascular bed and inhibited mesenteric vaso dilator responses to acetylcholine, bradykinin, and substance P. The i ncrease in mescnteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator a gents following administration of N(omega)-nitro-L-arginine methyl est er and N(omega)-nitro-L-arginine did not differ significantly. The nit ric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechani sms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine hut did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N(omega)-nitro-L-arginine methyl ester and N(omega)-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest tha t the L-arginine analog, N(omega)-nitro-L-arginine, as well as the met hyl ester of N(omega)-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascula r bed of the cat.