Effect of Y-20811, a thromboxane A2 synthetase inhibitor, on the arachidonic acid-induced response in the blood-superfused canine coronary artery

Effects of Y-20811, a thromboxane A2 synthetase inhibitor, on the arachidonic acid (AA)-induced responses were investigated in the isolated canine coronary artery superfused with blood from a donor dog and Krebs-Henseleit solution. When the coronary artery was superfused with Krebs-Henseleit solution, AA did not have any remarkable effect on its tone. In the coronary artery superfused with blood, in contrast, AA (10-100 μg) caused phasic constriction followed by relaxation. After denudation of the endothelium, the contractile response was augmented, and the relaxant effect was abolished. Y-20811 (1 mg/kg, i.v.), administered into the donor dog, inhibited the contraction and augmented the relaxation. Indomethacin (5 mg/kg, i.v.) and aspirin (30 mg/kg, i.v.) also inhibited the AA-induced contraction. However, indomethacin inhibited the relaxation induced by AA (10-100 μg), whereas aspirin inhibited the relaxation induced by a low dose of AA (10-30 μg). These results suggest that Y-20811 inhibits the TXA2-induced contraction and augments the production of the relaxant metabolite of AA in the coronary artery.