Effects of aspirin and dazoxiben upon the peripheral circulation in man

Abstract

Investigation of the effects of drugs that alter prostaglandin synthesis in man may lead to a better understanding of the physiological role of endogenous prostanoids. Aspirin, in doses of 300 mg or higher, inhibits both vascular and platelet cyclo-oxygenase (Hanley et al., 1981; Preston et al., 1981). This enzyme converts arachidonic acid, derived from the cell membrane, into the prostaglandin endoperoxides PGG2 and PGH2. In blood vessels the major metabolite of PGG2 and PGH2 is prostacyclin (prostaglandin I2, PGI2) which is produced by the action of prostacyclin synthetase. This is both a potent vasodilator and an inhibitor of platelet aggregation. In platelets PGG2 and PGH2 are mainly converted by thromboxane synthetase into thromboxane A2 (TxA2). This is a potent vasoconstrictor and stimulator of platelet aggregation. A low dose of aspirin, 40 mg, selectively inhibits platelet cyclo-oxygenase and thus prevents platelet TxA2 synthesis, without affecting vascular PGI2 production (Hanley et al., 1981). Dazoxiben is a selective inhibitor of thromboxane synthetase (Tyler et al., 1981).