Stamler J, Mendelsohn M E, Amarante P, Smick D, Andon N, Davies P F, Cooke J P, Loscalzo J
Division of Vascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Circ Res. 1989 Sep;65(3):789-95. doi: 10.1161/01.res.65.3.789.
Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.
最近的证据表明，内皮源性舒张因子具有一氧化氮的特性。与一氧化氮一样，它抑制血小板功能，并通过提高细胞内环鸟苷酸来介导其作用。在本研究中，我们研究了还原型硫醇在内皮源性舒张因子对血小板作用机制中的作用。牛主动脉内皮细胞在微载体珠上生长，并在使用前用阿司匹林预处理。用缓激肽刺激或暴露于搅拌培养基中的内皮细胞表现出对血小板聚集的剂量依赖性抑制，这种抑制作用可被还原型硫醇N-乙酰半胱氨酸增强。亚甲蓝可减弱内皮细胞介导的血小板抑制作用。内皮细胞对血小板聚集的抑制作用与血小板细胞内环鸟苷酸的升高有关，N-乙酰半胱氨酸可增强这种作用。这些数据表明：1）还原型硫醇N-乙酰半胱氨酸可增强内皮源性舒张因子对血小板的抑制作用；2）这种作用与增加血小板细胞内环鸟苷酸水平有关。
