CHANGES IN CORONARY VASCULAR-RESISTANCE ASSOCIATED WITH PROLONGED HYPOXIA IN ISOLATED RAT HEARTS - POSSIBLE ROLE OF PROSTAGLANDINS

Hypoxia caused an initial dilatation in the coronary circulation of perfused male rat hearts but within 15 minutes the coronary vessels became strongly constricted. In hearts from very young (30 days) animals only dilatation was seen. Physiological levels of progesterone in the perfusate prevented the constriction whereas estradiol and testosterone had little effect. Blockade of adrenergic alpha receptors or angiotensin receptors did not prevent the constriction. Two structurally different inhibitors of prostaglandin synthesis, indomethacin and aspirin, and three drugs which can interfere with prostaglandin action, chloroquine, procaine, and propranolol blocked the constriction. Thromboxane A2, a product of PG synthesis, had been reported to be a coronary vasoconstrictor but four drugs which inhibit thromboxane A2 synthesis, dipyridamole, benzydamine, N-0164 and imidazole were not able to prevent the hypoxia-induced constriction. This form of hypoxic coronary constriction seems not to be related to α-adrenergic, angiotensin or thromboxane A2 effects. It may depend on some other product of the prostaglandin pathway. © 1979.