Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease

• Published in: Free radical biology & medicine 2005-11, Vol.39 (9), p.1184-1190
• Main Authors: Baldus, Stephan, Köster, Ralf, Chumley, Phillip, Heitzer, Thomas, Rudolph, Volker, Ostad, Mir Abolfazl, Warnholtz, Ascan, Staude, Hans-Jürgen, Thuneke, Felix, Koss, Klaus, Berger, Jürgen, Meinertz, Thomas, Freeman, Bruce A., Münzel, Thomas
• Format: Article
• Language: English
• Subjects: Aged; Allopurinol; Coronary Artery Disease - drug therapy; Coronary Artery Disease - physiopathology; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Enzyme Inhibitors - blood; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Free radicals; Humans; Male; Middle Aged; Oxidative stress; Oxypurinol - blood; Oxypurinol - pharmacology; Oxypurinol - therapeutic use; Perfusion; Purines - blood; Purines - metabolism; Superoxide; Vasoconstriction - drug effects; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - blood
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2005.06.004

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65 ± 8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and nonelevated uric acid levels (233 ± 10 μM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10 −7 to 10 −5 μM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051 ± 0.001 vs 0.019 ± 0.005 μU/mg protein; p