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Indomethacin induces contractions in dog coronary arteries likely by inhibiting the intramural synthesis of vasodilating prostaglandins.
We investigated the mechanisms responsible for indomethacin-induced 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 F2 alpha 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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Sakanashi et al. (1980) studied this question.
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