Electron Spin Resonance Characterization of Vascular Xanthine and NAD(P)H Oxidase Activity in Patients With Coronary Artery Disease

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Abstract
Background— Increased inactivation of nitric oxide by superoxide (O 2 ·− ) contributes to endothelial dysfunction in patients with coronary disease (CAD). We therefore characterized the vascular activities of xanthine oxidase and NAD(P)H oxidase, 2 major O 2 ·− -producing enzyme systems, and their relationship with flow-dependent, endothelium-mediated vasodilation (FDD) in patients with CAD. Methods and Results— Xanthine- and NAD(P)H-mediated O 2 ·− formation was determined in coronary arteries from 10 patients with CAD and 10 controls by using electron spin resonance spectroscopy. Furthermore, activity of endothelium-bound xanthine oxidase in vivo and FDD of the radial artery were determined in 21 patients with CAD and 10 controls. FDD was measured before and after infusion of the antioxidant vitamin C (25 mg/min i.a.) to determine the portion of FDD inhibited by radicals. In coronary arteries from patients with CAD, xanthine- and NAD(P)H-mediated O 2 ·− formation was increased compared with controls (xanthine: 12±2 versus 7±1 nmol O 2 ·− /μg protein; NADH: 11±1 versus 7±1 nmol O 2 ·− /μg protein; and NADPH: 12±2 versus 9±1 nmol O 2 ·− /μg protein; each P 200% in patients with CAD (25±4 versus 9±1 nmol O 2 ·− /μL plasma per min; P r =−0.55; P r =0.54; P Conclusions— The present study represents the first electron spin resonance measurements of xanthine and NAD(P)H oxidase activity in human coronary arteries and supports the concept that increased activities of both enzymes contribute to increased vascular oxidant stress in patients with CAD. Furthermore, the present study suggests that increased xanthine oxidase activity contributes to endothelial dysfunction in patients with CAD and may thereby promote the atherosclerotic process.

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