Bhardwaj R, Page C P, May G R, Moore P K
Department of Pharmacology, King's College (KQC), University of London, U.K.
Eur J Pharmacol. 1988 Nov 15;157(1):83-91. doi: 10.1016/0014-2999(88)90474-8.
Carbachol (0.03-10 microM) or histamine (0.06-10 microM) challenge of indomethacin-pretreated rat aortic rings inhibited ADP-induced aggregation of platelets suspended in anticoagulated human whole blood. The maximum inhibition of platelet aggregation achieved with either drug was approximately 50%. No such inhibition was observed in rat aortic rings rubbed to remove endothelial cells or in intact vessels preincubated with nordihydroguaiaretic acid (NDGA, 10 microM), mepacrine (10 microM) or methylene blue (100 microM). Intravenously (i.v.) injected carbachol (0.5-5 micrograms/kg) also inhibited ADP-induced accumulation of 111indium-labelled platelets in the pulmonary circulation of urethane-anaesthetised rats. This effect of carbachol was inhibited by i.v. injected methylene blue (10 mg/kg) but unaffected by indomethacin (3 mg/kg) or hexamethonium (10 mg/kg) suggesting that PGI2 or adrenaline release did not account for the inhibition of platelet activation observed. Similarly, the platelet inhibitory effect of carbachol in vivo was not related to increased pulmonary vascular blood flow (assessed by accumulation of 111indium-labelled erythrocytes) or blood fibrinolytic activity (measured by euglobulin clot bioassay). The present results suggest that endothelium-derived relaxing factor or a like substance inhibits human platelet aggregation in vitro and rat platelet aggregation in vivo.
用卡巴胆碱（0.03 - 10微摩尔）或组胺（0.06 - 10微摩尔）刺激经消炎痛预处理的大鼠主动脉环，可抑制悬浮于抗凝人全血中的血小板由二磷酸腺苷（ADP）诱导的聚集。两种药物对血小板聚集的最大抑制率约为50%。在擦去内皮细胞的大鼠主动脉环或预先用去甲二氢愈创木酸（NDGA，10微摩尔）、米帕林（10微摩尔）或亚甲蓝（100微摩尔）孵育的完整血管中未观察到这种抑制作用。静脉注射卡巴胆碱（0.5 - 5微克/千克）也可抑制乌拉坦麻醉大鼠肺循环中由ADP诱导的111铟标记血小板的聚集。卡巴胆碱的这种作用可被静脉注射的亚甲蓝（10毫克/千克）抑制，但不受消炎痛（3毫克/千克）或六甲铵（10毫克/千克）影响，这表明观察到的血小板活化抑制作用并非由前列环素（PGI2）或肾上腺素释放所致。同样，卡巴胆碱在体内的血小板抑制作用与肺血管血流量增加（通过111铟标记红细胞的聚集评估）或血液纤溶活性（通过优球蛋白凝块生物测定法测量）无关。目前的结果表明，内皮源性舒张因子或类似物质在体外可抑制人血小板聚集，在体内可抑制大鼠血小板聚集。
