title: Role of nitric oxide and carbon monoxide in N(omega)-Nitro-L-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery.
abstract: 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.
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India.
authors: Marie Dennis Marcus
authors: MD
authors: Leo
authors: Yeshavanth K B
authors: YK
authors: Siddegowda
authors: Dinesh
authors: D
authors: Kumar
authors: Surendra K
authors: SK
authors: Tandan
authors: Kochiganti V H
authors: KV
authors: Sastry
authors: Vellanki Ravi
authors: VR
authors: Prakash
authors: Santosh K
authors: SK
authors: Mishra
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002248:Carbon Monoxide / Q000502:physiology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D002645:Chickens; D004730:Endothelium, Vascular / Q000502:physiology; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D002248:Carbon Monoxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester