Hypoxia modifies the vasodilatory effects of nitroglycerin, prostaglandin E1, and hydralazine on isolated porcine coronary arteries.
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.
Fukuda
S
S
Department of Anesthesiology, Niigata University School of Medicine, Japan.
Sakuma
K
K
Tsukui
A
A
Fujiwara
N
N
Tanaka
T
T
Fujihara
H
H
Toriumi
T
T
Shimoji
K
K
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
D016232:Endothelins; D006830:Hydralazine; D000242:Cyclic AMP; D000527:Alprostadil; D005996:Nitroglycerin; D006152:Cyclic GMP