ANTIPLATELET AND ANTITHROMBOTIC EFFECTS OF ORGANIC NITRATES
ANTIPLATELET AND ANTITHROMBOTIC EFFECTS OF ORGANIC NITRATES
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DOI：
10.1016/0002-9149(92)90590-u
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发表时间：
1992-09-24
影响因子：
2.8
通讯作者：
LOSCALZO, J
中科院分区：
文献类型：
--
作者：
LOSCALZO, J
有机硝酸盐被认为主要通过扩张冠状动脉血管来缓解心绞痛。然而，有大量证据支持这些药物也具有有效的抗血小板作用。这些化合物中的每一种最终都被代谢成一氧化氮（或其s -亚硝基硫醇同系物），而这种代谢物反过来又是血小板鸟苷酸环化酶的有效激活剂。鸟苷酸环化酶的激活会增加血小板环鸟苷单磷酸（cGMP），并伴有激动剂介导的钙通量的抑制，进而减少纤维蛋白原与糖蛋白IIb/IIIa受体的结合。由于纤维蛋白原结合对于血小板聚集是必不可少的，而不考虑激动剂的作用，其抑制似乎是这些药物损害血小板功能的关键机制。最近认识到血小板依赖性血栓形成过程在急性冠状动脉综合征中所起的作用，表明硝酸盐对血小板的抑制可能提供了这些化合物改善缺血心肌灌注的额外机制。
Organic nitrates are believed to provide relief from angina principally by dilating the coronary vasculature. Substantial evidence exists, however, to support a potent antiplatelet effect for these agents as well. Each of these compounds ultimately is metabolized to nitric oxide (or an S-nitrosothiol congener thereof), and this metabolite, in turn, is a potent activator of platelet guanylate cyclase. Activation of guanylate cyclase increases platelet cyclic guanosine monophosphate (cGMP), and is accompanied by inhibition of agonist-mediated calcium flux, and, in turn, reduction of fibrinogen binding to the glycoprotein IIb/IIIa receptor. Since fibrinogen binding is essential for platelet aggregation regardless of the agonist involved, its inhibition appears to be the critical mechanism by which platelet function is impaired by these agents. The recently recognized role that platelet-dependent thrombotic processes play in acute coronary syndromes suggests that the inhibition of platelets by nitrates may offer an additional mechanism by which these compounds improve perfusion to ischemic myocardium.