The effect of dipyridamole on vascular cell-derived reactive oxygen species
The effect of dipyridamole on vascular cell-derived reactive oxygen species
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DOI：
10.1124/jpet.105.089987
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发表时间：
2005-11-01
影响因子：
3.5
通讯作者：
Freedman, JE
中科院分区：
文献类型：
--
作者：
Chakrabarti, S;Vitseva, O;Freedman, JE
血小板和血管刺激导致活性氧（ROS）的释放，已知其影响血管反应性和血栓形成。双嘧达莫是一种血管扩张剂和血小板抑制剂，以前已被证明具有直接的抗氧化特性。尚不清楚双嘧达莫对血管细胞源性ROS的抗氧化作用;因此，将双嘧达莫与内皮细胞和血小板孵育，并评估细胞氧化还原状态和内源性ROS的释放。通过DCFDA（2 '，7'-二氯二氢荧光素二乙酸酯）氧化测定，双嘧达莫降低了内皮细胞的细胞内基础ROS生成。孵育的内皮细胞与双嘧达莫也减弱叔丁基过氧化氢诱导的氧化应激。使用氧化还原敏感的荧光染料，双嘧达莫改善细胞活性后，与叔丁基过氧化氢处理。孵育与潘生丁没有改变血小板释放一氧化氮或过氧化氢，但显着衰减超氧化物释放。使用流式细胞术和共聚焦显微镜，双嘧达莫减少血小板ROS的产生。双嘧达莫也抑制血小板可溶性CD 40配体的释放。总之，在治疗相关浓度下，双嘧达莫抑制血小板和内皮细胞中ROS的形成并改善细胞氧化还原状态。这些数据表明，双嘧达莫的氧化还原依赖性对血管细胞有直接影响。
Platelet and vascular stimulation leads to release of reactive oxygen species (ROS) that are known to influence vascular reactivity and thrombosis. Dipyridamole is a vasodilator and platelet inhibitor that has previously been shown to have direct antioxidant properties. The antioxidant effects of dipyridamole on vascular cell-derived ROS are not known; therefore, dipyridamole was incubated with endothelial cells and platelets and cellular redox status and release of endogenous ROS were assessed. Dipyridamole decreased intracellular basal ROS generation from endothelial cells as measured by DCFDA (2',7'-dichlorodihydrofluorescein diacetate) oxidation. Incubation of endothelial cells with dipyridamole also attenuated t-butylhydroperoxide-induced oxidative stress. Using a redox-sensitive fluorescent dye, dipyridamole improved cellular activity after treatment with t-butylhydroperoxide. Incubation with dipyridamole did not alter platelet release of nitric oxide or hydrogen peroxide but significantly attenuated superoxide release. Using flow cytometry and confocal microscopy, dipyridamole decreased platelet ROS generation. Dipyridamole also suppressed platelet-soluble CD40 ligand release. In summary, at therapeutically relevant concentrations, dipyridamole suppresses the formation of ROS in platelets and endothelial cells and improves cellular redox status. These data suggest that the redox-dependent properties of dipyridamole have a direct effect on vascular cells.