NITRIC-OXIDE (NO)-PLATELET INTERACTIONS - INHIBITION IS INDEPENDENT OF THE PROSTANOID AND ADP PATHWAYS

Effects of nitric oxide (NO) on thrombin-induced responses in gel-filt ered, [P-32] Pr (pre)labeled platelets (GFP) were examined. NO did not alter the levels of P-32-labeled polyphosphoinositides in unstimulate d platelets and did not inhibit the forskolin-induced elevation of [P- 32]PLP (phosphatidylinositol Lt-phosphate), which indicates that NO do es not concomitantly increase the level of cAMP in resting human plate lets. In aspirinated platelets NO inhibited thrombin (0.05 U/ml)-induc ed formation of [P-32] phosphatidic acid (PA), secretion of ATP + ADP from the dense granules and secretion of acid glycosidases in a dose-d ependent manner, At 0.2 U/ml of thrombin NO still inhibited these resp onses, although to a lesser degree, In aspirinated platelets in the pr esence of creatine phosphate/creatine phosphokinase (CP/CPK) to remove secreted ADP, increasing concentrations of NO still produced strong i nhibition of [P-32] PA-formation and secretory responses.