Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets.
1 The pharmacological effects of endothelium-derived relaxing factor (EDRF), nitric oxide (NO) and prostacyclin on human and rabbit platelets were examined. 2 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. 3 The anti-aggregating activity of EDRF was potentiated by M&B 22948, a selective inhibitor of cyclic GMP phosphodiesterase, and by superoxide dismutase (SOD) and was inhibited by haemoglobin and Fe2+. 4 Both NO and prostacyclin inhibited platelet aggregation. 5 The anti-aggregatory activity of NO, but not that of prostacyclin, was potentiated by M&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. 6 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.
Radomski
M W
MW
Wellcome Research Laboratories, Beckenham, Kent.
Palmer
R M
RM
Moncada
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009569:Nitric Oxide / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D013552:Swine; D013917:Thrombin / Q000494:pharmacology
D001688:Biological Products; D007202:Indicators and Reagents; D011450:Prostaglandin Endoperoxides, Synthetic; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D011464:Epoprostenol; D013917:Thrombin