Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress.
Oxidative stress plays an important role in the progression of vascular endothelial dysfunction. The two major systems generating vascular oxidative stress are the NADPH oxidase and the xanthine oxidase pathways. Allopurinol, a xanthine oxidase inhibitor, has been in clinical use for over 40 years in the treatment of chronic gout. Allopurinol has also been shown to improve endothelial dysfunction, reduce oxidative stress burden and improve myocardial efficiency by reducing oxygen consumption in smaller mechanistic studies involving various cohorts at risk of cardiovascular events. This article aims to explain the role of xanthine oxidase in vascular oxidative stress and to explore the mechanisms by which allopurinol is thought to improve vascular and myocardial indices.
George
Jacob
J
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK. j.george@dundee.ac.uk
Struthers
Allan D
AD
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D014527:Uric Acid / Q000378:metabolism*; D014652:Vascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase