Fukuda S, Sakuma K, Tsukui A, Fujiwara N, Tanaka T, Fujihara H, Toriumi T, Shimoji K
Department of Anesthesiology, Niigata University School of Medicine, Japan.
J Cardiovasc Pharmacol. 1994 May;23(5):852-8. doi: 10.1097/00005344-199405000-00024.
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.
为评估血管舒张药物在缺氧状态下的效力，我们研究了硝酸甘油（NTG）、前列腺素E1（PGE1）和肼苯哒嗪在有氧和缺氧条件下对用内皮素-1（ET-1）收缩的猪冠状动脉的影响。在有氧条件下，去除内皮会增强NTG诱导的舒张作用。缺氧增强了NTG诱导的内皮完整动脉的舒张，但未增强内皮剥脱动脉的舒张。这些发现表明，缺氧可能会改变NTG诱导舒张时的内皮功能。缺氧时PGE1诱导的内皮完整和内皮剥脱动脉的舒张明显大于有氧条件下的舒张。PGE1在缺氧条件下显著增加环磷酸腺苷（cAMP）的含量；其增加幅度远大于有氧条件下，这表明缺氧可能通过增加cAMP水平来增强PGE1诱导的舒张。缺氧减弱了肼苯哒嗪诱导的内皮完整和内皮剥脱动脉的舒张。吲哚美辛和阿司匹林在有氧条件下减弱了肼苯哒嗪诱导的舒张，提示环氧化酶相关的类花生酸可能参与了肼苯哒嗪诱导的舒张。然而，吲哚美辛并未改变缺氧时肼苯哒嗪诱导的动脉舒张。这些发现表明，缺氧可能使肼苯哒嗪诱导舒张时的环氧化酶失活。缺氧可能会极大地改变血管舒张剂对猪冠状动脉平滑肌的作用。
