Role for NADPH/NADH oxidase in the modulation of vascular tone

The endothelium modulates vascular tone by producing vasodilator andvasoconstrictor substances. Of these, the best characterized and potentially most important are nitric oxide (NO.) and O-2(-.). These small molecules exhibit opposing effects on vascular tone and chemically react with each other in a fashion that negates their individual effects and leads to the production of potentially toxic substances, such as peroxynitrite (ONOO-). These dynamic interactions map likely have important implications, altering not only tissue perfusion but also contributing to the process of atherosclerosis, The precise O-2(-.) source within vascular tissue remains to be determined. Recent work demonstrated that in endothelial cells as well as in vascular smooth muscle cells, a membrane-associated NAD(P)H-dependent oxidase represents the most significant O-2(-.) source. Interestingly, this oxidase is activated upon stimulation with angiotensin Ii, suggesting that under all conditions of an activated circulating and/or local renin-angiotensin system endothelial dysfunction secondary to increased vascular O-2(-.) production is expected.