Platelet inhibitory effect of nitric oxide in the human coronary circulation: Impact of endothelial dysfunction

OBJECTIVES We sought to determine whether coronary vascular nitric oxide (N O) release in vivo modulates platelet activation. BACKGROUND Nitric oxide modulates vasodilator tone and platelet activity vi a the cyclic guanosine monophosphate (cGMP) pathway, but whether coronary e ndothelial dysfunction influences platelet cGMP content during intracoronar y infusion of acetylcholine (ACH), L-N-G monomethyl arginine (L-NMMA) and s odium nitroprusside. RESULTS Acety;choline increased platelet cGMP content (p = 0.013), but its magnitude was lower in patients with endothelial dysfunction; thus, patient s with epicardial constriction with ACH had a 7 +/- 6%, p = ns change compa red with a 32 +/- 13%, p = 0.05 increase in platelet cGMP in those with epi cardial dilation. Similarly, patients with atherosclerosis or its risk fact ors had a smaller increase (9 +/- 6%) compared with those having normal cor onary arteries without risk factors (51 +/- 22%, p = 0.019). L-N-G monometh yl arginine decreased platelet cGMP content to a greater extent in patients with epicardial dilation with ACH (-15 +/- 7%, p = 0.06) compared to those with constriction (+5 +/- 6% change, p = 0.5). Sodium nitroprusside produc ed a similar increase in platelet cGMP content in patients with and without endothelial dysfunction (p = 0.56). The effect of sodium nitroprusside, bu t not ACH or L-NMMA, were reproduced in vitro. CONCLUSIONS Platelet cGMP levels can be modulated by basal and stimulated r elease of NO. The platelet inhibitory effect of NO is reduced in patients w ith endothelial dysfunction, which may explain their increased risk from th rombotic events and the improved survival associated with strategies design ed to improve vascular function. (C) 2001 by the American College of Cardio logy.