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
Ja. Santiago et al., 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, European journal of pharmacology, 254(3), 1994, pp. 207-212
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.