Mehta J, Mehta P
J Cardiovasc Pharmacol. 1982 Jul-Aug;4(4):688-93. doi: 10.1097/00005344-198207000-00022.
Modification of platelet function and vessel wall prostaglandin synthesis by pharmacologic intervention has attracted considerable attention. We report our observations on the effects of aspirin and dipyridamole alone and their combination on platelet aggregation and vessel wall prostacyclin (PGI2) generation. Although dipyridamole alone had no effects on platelet aggregation, it potentiated the platelet aggregation inhibitory effects of aspirin in vitro in a dose-related fashion. Dipyridamole also enhanced the platelet aggregation inhibitory effect of synthetic PGI2 in vitro. Potentiation of aspirin- and PGI2-induced platelet aggregation inhibition was observed in therapeutic range (5-10 micrograms/ml). In an isolated umbilical vein model dipyridamole stimulated release of PGI2 at much higher concentration (50-100 microgram/ml). Treatment of umbilical vein with aspirin (180 micrograms/ml) for 10 min blocked the spontaneous release of PGI2. In aspirin-treated umbilical vein segments dipyridamole treatment did not cause PGI2 release as in the untreated segments. These experiments suggest that although dipyridamole enhances both aspirin- and PGI2-induced platelet aggregation inhibition in clinically achieved concentrations, much higher levels are necessary for PGI2 release from intact human vessels. Furthermore, aspirin treatment of human vessels may prevent release of PGI2 in response to dipyridamole by blocking cyclooxygenase enzyme.
通过药物干预来改变血小板功能和血管壁前列腺素合成已引起了相当大的关注。我们报告了关于阿司匹林和双嘧达莫单独使用及其联合使用对血小板聚集和血管壁前列环素（PGI2）生成影响的观察结果。尽管单独使用双嘧达莫对血小板聚集没有影响，但它在体外以剂量相关的方式增强了阿司匹林对血小板聚集的抑制作用。双嘧达莫在体外也增强了合成PGI2对血小板聚集的抑制作用。在治疗范围内（5 - 10微克/毫升）观察到阿司匹林和PGI2诱导的血小板聚集抑制作用增强。在离体脐静脉模型中，双嘧达莫在更高浓度（50 - 100微克/毫升）时刺激PGI2释放。用阿司匹林（180微克/毫升）处理脐静脉10分钟可阻断PGI2的自发释放。在经阿司匹林处理的脐静脉段中，双嘧达莫处理不像未处理段那样引起PGI2释放。这些实验表明，尽管双嘧达莫在临床可达到的浓度下增强了阿司匹林和PGI2诱导的血小板聚集抑制作用，但从完整人体血管释放PGI2需要更高的水平。此外，对人体血管进行阿司匹林处理可能通过阻断环氧化酶来阻止对双嘧达莫产生反应时PGI2 的释放。
