HYPOXIA MODIFIES THE VASODILATORY EFFECTS OF NITROGLYCERIN, PROSTAGLANDIN E(1), AND HYDRALAZINE ON ISOLATED PORCINE CORONARY-ARTERIES

To evaluate the potency of vasodilatory drugs in hypoxia, we studied the effects of nitroglycerin (NTG), prostaglandin E(1) (PGE(1)), 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 PGE(1) in hypoxia was significantly greater than that in the oxygenated condition. PGE(1) 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 PGE(1)-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.