Vascular superoxide production by NAD(P)H oxidase - Association with endothelial dysfunction and clinical risk factors

Superoxide anion plays important roles in vascular disease states. Increase d superoxide production contributes to reduced nitric oxide (NO) bioactivit y and endothelial dysfunction in experimental models of vascular disease. W e measured superoxide production by NAD(P)H oxidase in human blood vessels and examined the relationships between NAD(P)H oxidase activity, NO-mediate d endothelial function, and clinical risk factors for atherosclerosis, Endo thelium-dependent vasorelaxations and direct measurements of vascular super oxide production were determined in human saphenous veins obtained from 133 patients with coronary artery disease and identified risk factors. The pre dominant source of vascular superoxide production was an NAD(P)H-dependent oxidase. Increased vascular NAD(P)H oxidase activity was associated with re duced NO-mediated vasorelaxation, Furthermore, reduced endothelial vasorela xations and increased vascular NAD(P)H oxidase activity were both associate d with increased clinical risk factors for atherosclerosis, Diabetes and hy percholesterolemia were independently associated with increased NADH-depend ent superoxide production. The association of increased vascular NAD(P)H ox idase activity with endothelial dysfunction and with clinical risk factors suggests an important role for NAD(P)H oxidase-mediated superoxide producti on in human atherosclerosis. The full text of this article is available at http://www.circresaha.org.