title: Role of nitric oxide and nitric oxide-independent relaxing factor in contraction and relaxation of rabbit blood vessels.
abstract: It has been shown that spontaneous release of nitric oxide (NO) from the vascular endothelium attenuates contractile responses of vascular smooth muscles to norepinephrine, and that acetylcholine-induced relaxation is mediated by the evoked release of NO and endothelium-derived hyperpolarizing factor. Since the involvement of these substances (or factors) in mechanical responses is heterogeneous among blood vessels, we have investigated the role of these substances in agonist-induced contraction and relaxation in 6 rabbit blood vessels. Vascular reactivity for the contractile response to norepinephrine was potentiated after removal of endothelium and by 100 microM N(G)-nitro-L-arginine (L-NA) but not by 80 nM-0.4 microM clotrimazole. This potentiation was most marked in the mesenteric artery among the blood vessels tested, suggesting that the basal release of NO reduced the contractile response of the vascular smooth muscle to norepinephrine in this artery. Acetylcholine-induced relaxation was abolished by removal of the endothelium and was attenuated by L-NA (1-100 microM) in all blood vessels. The attenuation by 100 microM L-NA was most obvious in aorta and vein and least in mesenteric resistance artery in which the acetylcholine-induced, L-NA-resistant relaxation was inhibited by 80 nM-0.4 microM clotrimazole. These results suggested that there is a regional difference in the degree of involvement of NO in acetylcholine-induced relaxation. In mesenteric resistance artery, the NO-independent, clotrimazole-sensitive factor, possibly hyperpolarizing factor may also contribute to the response to acetylcholine at high concentrations.
authors.affiliation: Department of Pharmacology, Nagoya City University Medical School, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Itoh
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003022:Clotrimazole / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D003022:Clotrimazole; D000109:Acetylcholine