Freedman J E, Ting B, Hankin B, Loscalzo J, Keaney J F, Vita J A
Departments of Pharmacology and Medicine, Georgetown University Medical Center, Washington, DC, USA.
Circulation. 1998 Oct 13;98(15):1481-6. doi: 10.1161/01.cir.98.15.1481.
Thrombus formation within a coronary vessel is the acute precipitating event in most acute coronary syndromes. Recently, constitutive nitric oxide synthase (cNOS) has been identified in human platelets, and platelet-derived nitric oxide has been shown to inhibit platelet recruitment after aggregation. However, its role in regulating platelet responses under normal or pathologic conditions has not yet been elucidated.
We examined nitric oxide (NO) production by platelets isolated from 87 patients undergoing coronary angiography, 37 with stable angina and 50 with unstable angina or a myocardial infarction within 2 weeks. After stimulation with 5 micromol/L ADP, platelet aggregation and NO production were simultaneously measured with an NO-selective microelectrode adapted for use in a standard platelet aggregometer. Mean (+/-SEM) platelet-derived NO production was 1.78+/-0.36 pmol/10(8) and 0.26+/-0.05 pmol/10(8) platelets in coronary patients with stable angina and acute coronary syndromes, respectively (P=0. 0001). By logistic regression analysis, heparin treatment (odds ratio 6.6, CI 1.9 to 22.8, P=0.003), lower platelet-NO production (odds ratio 4.0, CI 1.3 to 11.5, P=0.01), and extent of atherosclerosis (odds ratio 1.5, CI 1.1 to 2.0, P=0.02) were independent predictors of an acute coronary syndrome. In the subset of patients with angiographic evidence of atherosclerosis (n=83), logistic regression demonstrated that platelet NO production (odds ratio 3.9, CI 1.3 to 11.1, P=0.01) and heparin treatment (odds ratio 6.4, CI 1.9 to 22.0, P=0.004) were independent predictors of an acute coronary syndrome, whereas extent of atherosclerosis was not.
In summary, aggregating platelets from patients with acute coronary syndromes produce less NO. Since platelet aggregation and thrombus formation are implicated in unstable angina and myocardial infarction, impaired platelet-derived NO production may contribute to the development of acute coronary syndromes.
冠状动脉内血栓形成是大多数急性冠状动脉综合征的急性促发事件。最近，已在人血小板中鉴定出组成型一氧化氮合酶（cNOS），并且血小板衍生的一氧化氮已显示可抑制聚集后血小板的募集。然而，其在正常或病理条件下调节血小板反应中的作用尚未阐明。
我们检测了从87例接受冠状动脉造影的患者中分离出的血小板产生一氧化氮（NO）的情况，其中37例为稳定型心绞痛患者，50例为不稳定型心绞痛患者或在2周内发生心肌梗死的患者。用5 μmol/L ADP刺激后，使用适用于标准血小板聚集仪的NO选择性微电极同时测量血小板聚集和NO产生情况。稳定型心绞痛冠状动脉患者和急性冠状动脉综合征患者血小板衍生的NO平均产生量（±SEM）分别为1.78±0.36 pmol/10⁸和0.26±0.05 pmol/10⁸血小板（P = 0.0001）。通过逻辑回归分析，肝素治疗（比值比6.6，CI 1.9至22.8，P = 0.003）、较低的血小板NO产生量（比值比4.0，CI 1.3至11.5，P = 0.01）和动脉粥样硬化程度（比值比1.5，CI 1.1至2.0，P = 0.02）是急性冠状动脉综合征的独立预测因素。在有动脉粥样硬化血管造影证据的患者亚组（n = 83）中，逻辑回归表明血小板NO产生量（比值比3.9，CI 1.3至11.1，P = 0.01）和肝素治疗（比值比6.4，CI 1.9至22.0，P = 0.004）是急性冠状动脉综合征的独立预测因素，而动脉粥样硬化程度则不是。
总之，急性冠状动脉综合征患者的聚集血小板产生的NO较少。由于血小板聚集和血栓形成与不稳定型心绞痛和心肌梗死有关，血小板衍生的NO产生受损可能促成急性冠状动脉综合征的发生。
