Drug induced inhibition of the cardiac effects of U 46619 as a thromboxane A2-like agonist.

U 46619 (11,9-epoxymethano-PGH2) appears to be a selective and stable thromboxane-like agonist. In isolated preparations the substance (3.10(-9) - 3.10(-6) mol/l) induced an increase of cardiac performance of auricles and a decrease of contraction force and coronary flow of perfused hearts of guinea pigs. Intravenous infusion of U 46619 (10 micrograms/kg/min) to rabbits caused a marked reduction of heart contractility and blood pressure and the death of the animals within 10 minutes. Antianginal drugs, especially dipyridamole, propranolol, trapidil and verapamil, significantly reduced the TXA2 agonistic effects in auricles and anesthetized rabbits. The results indicate that some antianginal drugs inhibit TXA2 effects in the cardiocirculatory system. This may be regarded as an important factor for the therapeutic use of these substances.