Andrews N P, Husain M, Dakak N, Quyyumi A A
Cardiology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
J Am Coll Cardiol. 2001 Feb;37(2):510-6. doi: 10.1016/s0735-1097(00)01114-1.
We sought to determine whether coronary vascular nitric oxide (NO) release in vivo modulates platelet activation.
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.
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.
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.
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.
我们试图确定体内冠状动脉血管一氧化氮（NO）释放是否调节血小板活化。
一氧化氮通过环磷酸鸟苷（cGMP）途径调节血管舒张张力和血小板活性，但冠状动脉内皮功能障碍是否影响人类血小板活化尚不清楚。
在26例患者中，我们在冠状动脉内输注乙酰胆碱（ACH）、L-NG单甲基精氨酸（L-NMMA）和硝普钠期间测量冠状动脉血流、心外膜直径和冠状窦血小板cGMP含量。
乙酰胆碱增加血小板cGMP含量（p = 0.013），但其幅度在内皮功能障碍患者中较低；因此，ACH引起心外膜收缩的患者血小板cGMP变化为7±6%，p =无显著性差异，而心外膜扩张患者血小板cGMP增加32±13%，p = 0.05。同样，与无危险因素的正常冠状动脉患者相比，患有动脉粥样硬化或其危险因素的患者增加幅度较小（9±6%）（51±22%，p = 0.019）。与收缩患者相比，L-NG单甲基精氨酸在ACH引起心外膜扩张的患者中使血小板cGMP含量降低的程度更大（-15±7%，p = 0.06）（变化+5±6%，p = 0.5）。硝普钠在有和没有内皮功能障碍的患者中使血小板cGMP含量产生相似的增加（p = 0.56）。硝普钠的作用，但不是ACH或L-NMMA的作用，在体外得到重现。
血小板cGMP水平可通过基础和刺激释放的NO进行调节。在内皮功能障碍患者中，NO的血小板抑制作用降低，这可能解释了他们血栓事件风险增加以及与旨在改善血管功能的策略相关的生存率提高。
