title: Hypoxia modifies the vasodilatory effects of nitroglycerin, prostaglandin E1, and hydralazine on isolated porcine coronary arteries.
abstract: To evaluate the potency of vasodilatory drugs in hypoxia, we studied the effects of nitroglycerin (NTG), prostaglandin E1 (PGE1), and hydralazine on porcine coronary artery constricted with endothelin-1 (ET-1) in both oxygenated and hypoxic conditions. Removal of endothelium potentiated NTG-induced relaxation in oxygenated conditions. Hypoxia potentiated relaxation of endothelium-intact arteries induced by NTG, but not relaxation of endothelium-denuded arteries. These findings suggest that hypoxia may modify endothelial function in NTG-induced relaxation. The relaxation of endothelium-intact and -denuded arteries induced by PGE1 in hypoxia was significantly greater than that in the oxygenated condition. PGE1 significantly increased the content of cyclic AMP in the hypoxic condition; it was much greater than that in the oxygenated condition, suggesting that hypoxia may enhance PGE1-induced relaxation by increasing cyclic AMP levels. Hypoxia attenuated hydralazine-induced relaxation in both endothelium-intact and denuded arteries. Indomethacin and aspirin attenuated hydralazine-induced relaxation in the oxygenated condition, suggesting that cyclooxygenase-related eicosanoid(s) may be involved in hydralazine-induced relaxation. However, indomethacin did not alter relaxation of hypoxic arteries induced by hydralazine. These findings suggest that hypoxia may inactivate cyclooxygenase in hydralazine-induced relaxation. Hypoxia may greatly modify the action of vasodilators on porcine coronary smooth muscle.
authors.affiliation: Department of Anesthesiology, Niigata University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: K
authors.initials: K
authors.lastname: Sakuma
authors.forename: A
authors.initials: A
authors.lastname: Tsukui
authors.forename: N
authors.initials: N
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Fujihara
authors.forename: T
authors.initials: T
authors.lastname: Toriumi
authors.forename: K
authors.initials: K
authors.lastname: Shimoji
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D013552:Swine
chemical_list: D016232:Endothelins; D006830:Hydralazine; D000242:Cyclic AMP; D000527:Alprostadil; D005996:Nitroglycerin; D006152:Cyclic GMP