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

Abstract

Objectives: H2O2 contributes to FID of human arterioles. This study is designed to examine the roles of mitochondria and NADPH oxidase in modulating the release of ROS and in mediating FID. We tested whether NADPH oxidase contributes to mitochondrial ROS generation in arterioles during CAD. Methods: Visceral adipose arterioles obtained from patients with or without CAD were cannulated and pressurized for videomicroscopic measurement of arteriolar diameters. Dilator responses and ROS production during flow were determined in the presence and absence of the NADPH oxidase inhibitor gp91ds-tat and the mitochondrial electron transport inhibitor rotenone. Results: Both dilation and H2O2 generation during flow were reduced in the presence of rotenone (13.5±8% vs 97±% without rotenone) or gp91ds-tat in patients with CAD, while patients without CAD exhibited H2O2-independent dilations. Mitochondrial superoxide production during flow was attenuated by gp91ds-tat in arterioles from CAD patients. Conclusions: These findings indicate that ROS produced by NADPH oxidase are an upstream component of the mitochondria-dependent pathway contributing to flow-dependent H2O2 generation and dilation in peripheral microvessels from patients with CAD. We conclude that in CAD, both mitochondria and NADPH oxidase contribute to FID through a redox mechanism in visceral arterioles.