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Role for Hydrogen Peroxide in Flow-Induced Dilation of Human Coronary Arterioles

ABSTRACT—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 pr...

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Bibliographic Details
Published in:Circulation research 2003-02, Vol.92 (2), p.e31-e40
Main Authors: Miura, Hiroto, Bosnjak, John J, Ning, Gang, Saito, Takashi, Miura, Mamoru, Gutterman, David D
Format: Article
Language:English
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Summary:ABSTRACT—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 μm, 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
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000054200.44505.AB