de Graaf J C, Banga J D, Moncada S, Palmer R M, de Groot P G, Sixma J J
Department of Hematology, University Hospital Utrecht, The Netherlands.
Circulation. 1992 Jun;85(6):2284-90. doi: 10.1161/01.cir.85.6.2284.
Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation. An inhibitory role on platelet adhesion has been suggested from experiments with washed platelets under static conditions. We have determined whether endothelium-derived and exogenous NO also regulates platelet adhesion in whole blood under flow conditions.
The effect of endothelium-derived NO was studied by the addition of specific inhibitors of NO production, L-N-monomethyl arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO), to a perfusion system in which both endothelial cells and their matrices were present. A concentration-dependent increase in platelet adhesion to the matrix was found with a maximum inhibition at a concentration of 2 mM L-NMMA and 0.1 mM L-NIO. The effect was dependent on the presence of endothelial cells, because no increase in platelet adhesion was observed in their absence. The effect of exogenous NO was tested in a specially devised perfusion system in which the NO was introduced at the site of adhesion by means of a porous membrane on which an extracellular matrix of endothelial cells was present. Inhibition of platelet adhesion by NO was found at all shear rates tested and after all perfusion periods.
These results demonstrate that NO is a potent inhibitor of platelet adhesion under flow conditions and thereby contributes to the regulatory role of vascular endothelial cells on platelet-vessel wall interaction.
一氧化氮（NO）已被确认为内皮衍生舒张因子（EDRF），它除了对血管平滑肌细胞有舒张作用外，还是血小板聚集的强效抑制剂。在静态条件下对洗涤过的血小板进行的实验表明，它对血小板黏附具有抑制作用。我们已确定内皮衍生的NO和外源性NO在流动条件下的全血中是否也调节血小板黏附。
通过向同时存在内皮细胞及其基质的灌注系统中添加NO生成的特异性抑制剂L- N-单甲基精氨酸（L-NMMA）和N-亚氨基乙基-L-鸟氨酸（L-NIO），研究内皮衍生NO的作用。发现血小板对基质的黏附呈浓度依赖性增加，在2 mM L-NMMA和0.1 mM L-NIO浓度时抑制作用最大。该作用依赖于内皮细胞的存在，因为在没有内皮细胞时未观察到血小板黏附增加。在一个专门设计的灌注系统中测试外源性NO的作用，在该系统中，通过存在内皮细胞细胞外基质的多孔膜在黏附部位引入NO。在所有测试的剪切速率下以及所有灌注时间段后均发现NO对血小板黏附具有抑制作用。
这些结果表明，NO在流动条件下是血小板黏附的强效抑制剂，从而有助于血管内皮细胞对血小板 - 血管壁相互作用的调节作用。
