Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers

Experimental models have indicated prothrombotic effects of inhibition of n itric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well est ablished. We therefore investigated the effects of systemic inhibition of N O synthesis by N-G-monomethyl-L-arginine (L-NMMA) and of NO inhalation on p latelet function in vivo. On two occasions, L-NMMA (13.5 mg/kg) or saline i nfusion was administered to 14 healthy volunteers in a double-blind cross-o ver study. After a 30 min infusion of L-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions . Measurements included filtragometry ex viv0 (reflecting platelet aggregab ility), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma beta-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation mar kers (thrombin fragment 1+2 and thrombin-antithrombin complexes) in plasma, and bleeding time. L-NMMA increased blood pressure and decreased heart rat e. Na inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P < 0.001). Neither L-NMMA nor N O influenced filtragometry readings or flow-cytometric determinations of pl atelet fibrinogen binding and P-selectin expression. Furthermore, plasma be ta-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by L-NMMA compared with placebo, but was increased by approximate to 25% during NO in halation (P < 0.01), whether NO synthesis had been inhibited or not. The pr olongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circ ulating platelets are not influenced by endogenous or inhaled NO, presumabl y due to the rapid inactivation of NO in the blood. This does not exclude p ossible effects of endothelial NO in the interface between the blood and th e vessel wall.