Comparative pharmacology of endothelium‐derived relaxing factor, nitric oxide and prostacyclin in platelets

Abstract

The pharmacological effects of endothelium-derived relaxing factor (EDRF), nitric oxide (NO) and prostacyclin on human and rabbit platelets were examined. EDRF is released from porcine aortic endothelial cells, cultured on microcarriers and treated with indomethacin,in sufficient quantities to inhibit platelet aggregation induced by 9,11-dideoxy-9.alpha.,11.alpha.-methano epoxy-prostaglandin F2.alpha. (U46619) and collagen. The anti-aggregating activity of EDRF was potentiated by M and B 22948, a selective inhibitor of cyclic GMP phosphodiesterase, and by superoxide dismutase (SOD) and was inhibited by haemoglobin and Fe2+. Both NO and prostacyclin inhibited platelet aggregation. The anti-aggregatory activity of NO, but not that of prostacyclin, was potentiated by M and B 22948 and by SOD and was inhibited by haemoglobin and Fe2+. Thus NO is a potent inhibitor of platelet aggregation whose activity on platelets mimics that of EDRF. It is likely that the inhibitory effect of NO on platelets represents the action of endogenous EDRF and therefore this substance, together with prostacyclin, is a regulator of platelet-vessel wall interactions.