title: Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation.
abstract: 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.
  
  
  RESULTS
  Xanthine- and NAD(P)H-mediated O*.- 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*-/ microg protein; NADH: 11+/-1 versus 7+/-1 nmol O2*-/ microg protein; and NADPH: 12+/-2 versus 9+/-1 nmol O2*-/ microg 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*-/ microL 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.
authors.affiliation: Division of Cardiology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, Atlanta, Ga, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Spiekermann
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.forename: Sergey
authors.initials: S
authors.lastname: Dikalov
authors.forename: Martin
authors.initials: M
authors.lastname: Bredt
authors.forename: Graciela
authors.initials: G
authors.lastname: Gamez
authors.forename: Helma
authors.initials: H
authors.lastname: Tatge
authors.forename: Nina
authors.initials: N
authors.lastname: Reepschläger
authors.forename: Burkhard
authors.initials: B
authors.lastname: Hornig
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
mesh_terms: D000328:Adult; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000503:physiopathology*; D003331:Coronary Vessels / Q000201:enzymology; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D013481:Superoxides; D014969:Xanthine Oxidase; D019255:NADPH Oxidases