Role of nitric oxide and carbon monoxide in N(omega)-Nitro-L-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery.

The current study examined the hypothesis that acetylcholine-induced N(omega)-Nitro-L-arginine methyl ester (L-NAME)-resistant endothelium-dependent relaxations in the chicken carotid artery are mediated by nitric oxide and carbon monoxide. Acetylcholine (1 nM-3 microM) caused a concentration-dependent relaxation (pD(2) 6.81+/-0.05, R(max) 115+/-3%) of the artery segments precontracted with phenylephrine (3 microM). L-NAME (1 mM) decreased the sensitivity (pD(2) 6.44+/-0.06), but not the efficacy (R(max) 108+/-3%) of acetylcholine. It also partially decreased the acetylcholine (3 microM)-stimulated nitrite release. While treatment with N(omega)-Nitro-L-arginine (l-NNA; 1 mM) plus L-NAME (1 mM) decreased the acetylcholine-stimulated nitrite release to the basal level, it moderately inhibited (R(max) 77+/-3%) the maximal relaxation elicited with the muscarinic agonist. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO; 100 microM) a specific scavenger of nitric oxide (NO) plus the two NOS inhibitors further decreased the acetylcholine-evoked relaxation (R(max) 34+/-2%). Although soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM) markedly inhibited the acetylcholine-stimulated increase in tissue cGMP to less than the basal levels, it only decreased the sensitivity, but not the efficacy of the agonist either in the presence or absence of L-NAME (1 mM). Zinc Protoporphyrin-IX (ZnPP; 10 microM), a hemeoxygenase (HO) inhibitor, partially inhibited (R(max) 72+/-3%) the L-NAME-resistant acetylcholine-induced relaxations. A combined treatment of the arterial rings with L-NAME, l-NNA, PTIO and ZnPP nearly abolished (R(max) 7+/-0.9%) the vasodilator responses to acetylcholine. Endothelium removal abolished the relaxation response to acetylcholine. In conclusion, it is suggested that the acetylcholine-induced L-NAME-resistant relaxation is primarily, mediated by NO with a small but significant contribution from endothelium-derived carbon monoxide in the chicken carotid artery.