The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium.
The inhibition of platelet adhesion by nitric oxide (NO) and prostacyclin and their mechanism of action was studied. Platelet adhesion to collagen fibrils and endothelial cell matrix was inhibited completely by NO but only partially by prostacyclin. Adhesion of platelets to endothelial cell monolayers was inhibited by bradykinin. This effect of bradykinin was unaffected by aspirin, and was accounted for by the amounts of NO released by the endothelial cells. Inhibition of platelet adhesion by NO and prostacyclin was potentiated by selective inhibitors of cGMP phosphodiesterase, but not of cAMP phosphodiesterase, indicating that elevation of cGMP regulates platelet adhesion.
Radomski
M W
MW
Wellcome Research Laboratories, Beckenham, Kent, U.K.
Palmer
R M
RM
Moncada
S
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000502:physiology; D006152:Cyclic GMP / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology*; D010793:Phthalazines / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011688:Purinones / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D010793:Phthalazines; D011688:Purinones; D009569:Nitric Oxide; D003094:Collagen; D011464:Epoprostenol; D013482:Superoxide Dismutase; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D013917:Thrombin; C052490:MY 5445; C011145:zaprinast; D006152:Cyclic GMP; D001241:Aspirin