Responses of human, monkey and dog coronary arteries in vitro to carbocyclic thromboxane A2 and vasodilators.
Carbocyclic thromboxane A2 (cTxA2), a stable analogue of TxA2, and prostaglandin (PG) F2 alpha contracted helical strips of human, monkey and dog coronary arteries in a concentration-dependent manner. Apparent ED50 values for cTxA2 were markedly less (1/58 in humans, 1/373 in monkeys and 1/397 in dogs) than those for PGF2 alpha; maximum contractions induced by cTxA2 and PGF2 alpha relative to those induced by 30 mM K+ were approximately identical in the human and monkey arteries. PGI2 caused a concentration-related relaxation in human and dog coronary arteries maximally precontracted with cTxA2 and in human, monkey and dog coronary arteries partially precontracted with PGF2 alpha. The relaxation response was greatest in the dog arteries and least in the monkey arteries. Contractions induced by cTxA2 or PGF2 alpha and relaxations induced by PGI2 were selectively antagonized by treatment with diphloretin phosphate. Human coronary artery strips contracted with cTxA2 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) A2 appears to be one of the most potent endogenous vasoconstrictors in human coronary arteries, if cTxA2 acts on TxA2 receptors. It is suggested that PGI2, nitroglycerine and verapamil are effective vasodilators in human conduit coronary arteries maximally contracted with cTxA2, although the extent and the duration of vasodilatation induced by these agents were quite different.
D000328:Adult; D000368:Aged; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D015237:Dinoprost; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008251:Macaca; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D013045:Species Specificity; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D011460:Prostaglandins F; D013931:Thromboxanes; D014665:Vasodilator Agents; C024587:thromboxane A2, carbocyclic; C013509:diphloretin phosphate; D013928:Thromboxane A2; D011121:Polyphloretin Phosphate; D015237:Dinoprost; D014700:Verapamil; D011464:Epoprostenol; D005996:Nitroglycerin