Circulation. 2003;107:1383-1389
Published online before print March 3, 2003, doi: 10.1161/01.CIR.0000056762.69302.46
Published online before print March 3, 2003, doi: 10.1161/01.CIR.0000056762.69302.46
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(Circulation. 2003;107:1383.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Electron Spin Resonance Characterization of Vascular Xanthine and NAD(P)H Oxidase Activity in Patients With Coronary Artery Disease
Relation to Endothelium-Dependent Vasodilation
From the Division of Cardiology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, Atlanta, Ga (S.S., U.L., S.D., G.G., D.G.H.); Abteilung Kardiologie und Angiologie (S.S., U.L., H.T., N.R., B.H., H.D.) and Institut für Pathologie (M.B.), Medizinische Hochschule Hannover, Hannover, Germany.
Correspondence to Burkhard Hornig, MD, Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl Neuberg Str 1, 30625 Hannover, Germany. E-mail Hornig.Burkhard{at}MH-Hannover.DE
Background— Increased inactivation of nitric oxide by superoxide (O2·-) 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 O2·--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 O2·- 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 O2·- formation was increased compared with controls (xanthine: 12±2 versus 7±1 nmol O2·-/µg protein; NADH: 11±1 versus 7±1 nmol O2·-/µg protein; and NADPH: 12±2 versus 9±1 nmol O2·-/µg protein; each P<0.05). Endothelium-bound xanthine oxidase activity was increased by >200% in patients with CAD (25±4 versus 9±1 nmol O2·-/µL plasma per min; P<0.05) and correlated inversely with FDD (r=-0.55; P<0.05) and positively with the effect of vitamin C on FDD (r=0.54; P<0.05).
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.
Key Words: endothelium • free radicals • xanthine oxidase • NADPH oxidase • coronary disease
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