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.
Macdonald
P S
PS
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
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M A
MA
Dusting
G J
GJ
D000818:Animals; D001688:Biological Products; D002417:Cattle; D002478:Cells, Cultured; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits
D001688:Biological Products; D009569:Nitric Oxide; D011464:Epoprostenol