Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction.
OBJECTIVE
We sought to determine whether coronary vascular nitric oxide (NO) release in vivo modulates platelet activation.


BACKGROUND
Nitric oxide modulates vasodilator tone and platelet activity via the cyclic guanosine monophosphate (cGMP) pathway, but whether coronary endothelial dysfunction influences platelet activation in humans is unknown.


METHODS
In 26 patients, we measured coronary blood flow, epicardial diameter and coronary sinus platelet cGMP content during intracoronary infusions of acetylcholine (ACH), L-NG monomethyl arginine (L-NMMA) and sodium nitroprusside.


RESULTS
Acetylcholine increased platelet cGMP content (p = 0.013), but its magnitude was lower in patients with endothelial dysfunction; thus, patients with epicardial constriction with ACH had a 7 +/- 6%, p = ns change compared with a 32 +/- 13%, p = 0.05 increase in platelet cGMP in those with epicardial dilation. Similarly, patients with atherosclerosis or its risk factors had a smaller increase (9 +/- 6%) compared with those having normal coronary arteries without risk factors (51 +/- 22%, p = 0.019). L-NG monomethyl 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 produced a similar increase in platelet cGMP content in patients with and without endothelial dysfunction (p = 0.56). The effects of sodium nitroprusside, but not ACH or L-NMMA, were reproduced in vitro.


CONCLUSIONS
Platelet cGMP levels can be modulated by basal and stimulated release of NO. The platelet inhibitory effect of NO is reduced in patients with endothelial dysfunction, which may explain their increased risk from thrombotic events and the improved survival associated with strategies designed to improve vascular function.
Andrews
N P
NP
Cardiology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Husain
M
M
Dakak
N
N
Quyyumi
A A
AA
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D003326:Coronary Circulation / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D003328:Coronary Thrombosis / Q000503:physiopathology; D006152:Cyclic GMP / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006152:Cyclic GMP; D000109:Acetylcholine