Responses of human, monkey and dog coronary arteries in vitro to carbocyclic thromboxane A₂ and vasodilators

Carbocyclic thromboxane A 2 (cTxA 2 ), a stable analogue of TxA 2 , and prostaglandin (PG) F 2α contracted helical strips of human, monkey and dog coronary arteries in a concentration‐dependent manner. Apparent ED 50 values for cTxA 2 were markedly less (1/58 in humans, 1/373 in monkeys and 1/397 in dogs) than those for PGF 2α ; maximum contractions induced by cTxA 2 and PGF 2α relative to those induced by 30 m M K + were approximately identical in the human and monkey arteries. PGI 2 caused a concentration‐related relaxation in human and dog coronary arteries maximally precontracted with cTxA 2 and in human, monkey and dog coronary arteries partially precontracted with PGF 2α . The relaxation response was greatest in the dog arteries and least in the monkey arteries. Contractions induced by cTxA 2 or PGF 2α and relaxations induced by PGI 2 were selectively antagonized by treatment with diphloretin phosphate. Human coronary artery strips contracted with cTxA 2 responded to nitroglycerine with a rapid, transient relaxation and to verapamil with a slowly‐developing, persistent relaxation, as did monkey and dog coronary artery strips. Thromboxane (Tx) A 2 appears to be one of the most potent endogenous vasoconstrictors in human coronary arteries, if cTxA 2 acts on TxA 2 receptors. It is suggested that PGI 2 , nitroglycerine and verapamil are effective vasodilators in human conduit coronary arteries maximally contracted with cTxA 2 , although the extent and the duration of vasodilatation induced by these agents were quite different.