Roles of NADPH NADPH oxidase and mitochondria in flow‐induced vasodilation of human adipose arterioles: ROS ROS ‐induced ROS ROS release in coronary artery disease

摘要

Abstract Objectives H2 O2 contributes toFID of human arterioles. This study is designed to examine the roles of mitochondria andNADPH oxidase in modulating the release ofROS and in mediatingFID . We tested whetherNADPH oxidase contributes to mitochondrialROS generation in arterioles duringCAD .Methods Visceral adipose arterioles obtained from patients with or withoutCAD were cannulated and pressurized for videomicroscopic measurement of arteriolar diameters. Dilator responses andROS production during flow were determined in the presence and absence of theNADPH oxidase inhibitor gp91dstat and the mitochondrial electron transport inhibitor rotenone.Results Both dilation and H2 O2 generation during flow were reduced in the presence of rotenone (13.5?% vs 97? without rotenone) or gp91dstat in patients withCAD , while patients withoutCAD exhibited H2 O2 independent dilations. Mitochondrial superoxide production during flow was attenuated by gp91dstat in arterioles fromCAD patients.Conclusions These findings indicate thatROS produced byNADPH oxidase are an upstream component of the mitochondriadependent pathway contributing to flowdependent H2 O2 generation and dilation in peripheral microvessels from patients withCAD . We conclude that inCAD , both mitochondria andNADPH oxidase contribute toFID through a redox mechanism in visceral arterioles.