抄録
xAggregation and 14C-arachidonic acid (AA) metabolism of rabbit platelets were studied before and after intravenous injection of a selective thromboxane (TX) synthetase inhibitor, OKY-1581 (1-3mg/kg). Platelet aggregation induced by threshold concentrations of collagen and AA was inhibited for at least 3hr after the injection, but ADP-induced aggregation was not. The inhibitory effect of OKY-1581 injection on platelet TX synthetase was demonstrated by thin-layer radiochromatographic quantitation of lipid products obtained by incubating 14C-AA with washed platelets prepared after the injection: decreased production of TXB2 and hydroxyheptadecatrienoic acid associated with increased prostaglandin H2. When platelet-rich plasma (PRP) was preincubated in aggregometer cuvettes at 37°C or 7min with a rat aortic ring whose cyclo-oxygenase had been inhibited by aspirin injection, ADP-induced aggregation was inhibited in PRP prepared after the injection. This inhibitory effect of the aorta was hardly observed when platelet cyclo-oxygenase had been inhibited by indomethacin. When PRP prepared before the injection was employed, 2 aortic rings were necessary to inhibit platelet aggregation. These results suggested that ADP-induced aggregation was inhibited by prostacyclin which had been generated from platelet-derived prostaglandin endoperoxides by the cyclo-oxygenase-inhibited aortic ring and that the inhibition of platelet TX synthetase by OKY-1581 injection enhanced ex vivo prostacyclin production by the aorta in PRP.
