Synergistic inhibition of platelet aggregation by endothelium-derived relaxing factor and prostacyclin

The anti-aggregatory effect of endothelium-derived relaxing factor (EDRF) on aggregation of washed, aspirin-treated platelets was compared with that of nitric oxide. Nitric oxide produced a dose-dependent inhibitory effect on PAF-induced aggregation: the antiaggregatory activity was unstable and was completely preventable by pretreating the platelets with haemoglobin (10 mumol/l). Bovine aortic endothelial cells (EC) were grown to confluence on microcarrier beads, pretreated with aspirin (1 mmol/l), and their addition to the platelet cuvette also caused a dose-dependent inhibition of aggregation induced by PAF, thrombin and A23187. The inhibitory effect of the EC on platelet aggregation was partly prevented in the presence of haemoglobin (10 mumol/l). Both nitric oxide and EC showed synergy with prostacyclin, in that the latter potentiated the anti-aggregatory action of both these factors against PAF-induced platelet aggregation. Thus cultured endothelial cells release a non-prostanoid anti-aggregatory factor, which, like nitric oxide, shows a synergistic interaction with prostacyclin and is blocked by haemoglobin. This anti-aggregatory factor has the characteristics of EDRF.