Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles

Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles
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DOI:
10.1161/01.res.0000054200.44505.ab
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发表时间:
2003-02-07
影响因子:
20.1
通讯作者:
Gutterman, DD
Gutterman, DD
中科院分区:
医学1区
文献类型:
--
作者:
Miura, H;Bosnjak, JJ;Gutterman, DD

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血流诱导扩张 (FID) 在很大程度上取决于冠状动脉疾病患者的人冠状动脉 (HCA) 中血管平滑肌细胞 (VSMC) 的超极化。动物研究表明,剪切应力会诱导内皮细胞产生过氧化氢 (H2O2),这种过氧化氢被认为是一种内皮源性超极化因子 (EDHF)。我们测试了 H2O2 有助于 HCA 中 FID 的假设。在心脏手术时从人右心耳中切下小动脉(135+/-7 mum,n=71)并用玻璃微量移液器插管。用视频显微镜记录 VSMC 的内径和膜电位随剪切应力、H2O2 或罂粟碱的变化。在一些血管中,使用 2', 7'-二氯荧光素二乙酸酯 (DCFH) 共聚焦显微镜或使用氯化铈电子显微镜直接监测内皮 H2O2 生成到剪切应力的情况。过氧化氢酶抑制 FID(最大扩张百分比;66+/-8 对比 25+/-7%;P
Flow-induced dilation (FID) is dependent largely on hyperpolarization of vascular smooth muscle cells (VSMCs) in human coronary arterioles (HCA) from patients with coronary disease. Animal studies show that shear stress induces endothelial generation of hydrogen peroxide (H2O2), which is proposed as an endothelium-derived hyperpolarizing factor (EDHF). We tested the hypothesis that H2O2 contributes to FID in HCA. Arterioles (135+/-7 mum, n=71) were dissected from human right atrial appendages at the time of cardiac surgery and cannulated with glass micropipettes. Changes in internal diameter and membrane potential of VSMCs to shear stress, H2O2, or to papaverine were recorded with videomicroscopy. In some vessels, endothelial H2O2 generation to shear stress was monitored directly using confocal microscopy with 2', 7'-dichlorofluorescin diacetate (DCFH) or using electron microscopy with cerium chloride. Catalase inhibited FID (%max dilation; 66+/-8 versus 25+/-7%; P