De Caterina R
Istituto di Fisiologia Clinica, CNR, Pisa, Italia.
Cardiology. 1994;84 Suppl 1:29-42. doi: 10.1159/000176443.
Nitrates are the most widely prescribed drug category in ischemic heart disease, being able to prevent and to interrupt episodes of myocardial ischemia, alleviate anginal symptoms, exert favorable effects in acute myocardial infarction. Their vascular actions, on peripheral arteries and veins, as well as on coronary arteries, can explain most of these effects. However, nitrates also exhibit platelet-inhibiting properties, mediated by the same cellular mechanisms operating on smooth muscle cells, i.e., via stimulation of guanylate cyclase and subsequent increase in cytosolic levels of cyclic GMP. When added to platelet suspensions, nitrates inhibit platelet aggregation induced by most stimuli. These in vitro effects usually require high drug concentrations; there is evidence, however, that nitrates may inhibit platelet function also in vivo. Such evidence derives from a) ex vivo studies with platelet aggregometry; b) the appreciation of a synergism between nitrates and prostacyclin; c) the appreciation of a need, for nitrate actions in vivo, of sulfhydryl group donors, such as N-acetylcysteine, and d) from studies on bleeding time. Antiplatelet effects of nitrates may be an explanation for the protection from cardiac death and reinfarction inferred on the basis of a meta-analysis of many studies of nitrates in acute myocardial infarction.
硝酸盐是缺血性心脏病中处方最为广泛的一类药物，能够预防和中断心肌缺血发作，缓解心绞痛症状，在急性心肌梗死中发挥有益作用。它们对外周动脉和静脉以及冠状动脉的血管作用可以解释这些作用中的大部分。然而，硝酸盐还表现出抑制血小板的特性，这是由作用于平滑肌细胞的相同细胞机制介导的，即通过刺激鸟苷酸环化酶并随后增加细胞溶质中环磷酸鸟苷（cGMP）的水平。当添加到血小板悬液中时，硝酸盐可抑制大多数刺激诱导的血小板聚集。这些体外效应通常需要高药物浓度；然而，有证据表明硝酸盐在体内也可能抑制血小板功能。此类证据来自：a）用血小板聚集测定法进行的体外研究；b）对硝酸盐与前列环素之间协同作用的认识；c）对体内硝酸盐作用需要巯基供体（如N-乙酰半胱氨酸）的认识，以及d）对出血时间的研究。硝酸盐的抗血小板作用可能是基于对急性心肌梗死中硝酸盐的许多研究的荟萃分析推断出的预防心源性死亡和再梗死的一种解释。
