Indomethacin-Induced Contractions of Dog Coronary Arteries

Abstract
We investigated the mechanisms responsible for indomethacininduced contractions of coronary arteries. In isolated dog hearts perfused through the coronary circulation with blood under constant pressure, an intracoronary injection of 1 mg of indomethacin decreased coronary blood flow without significant changes in myocardial contractile force and heart rate. Indomethacin (10-8-10-5 M) caused concentration-dependent contractions of isolated dog coronary arterial strips. These contractions were significantly inhibited by calcium-free solution, diltiazem, nifedipine, prostaglandin E1, arachidonic acid, and phospholipase A2, but not by phenoxybenzamine, atropine, or oleic acid. Propranolol and prostaglandin F2α*** tended to enhance the contractions. The results indicate that indomethacin contracts dog coronary arteries through inhibition of intramural synthesis of vasodilating prostaglandins.

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