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

The endothelium modulates vascular tone by producing vasodilator and vasconstrictor substances. Of these, the best characterized and potentially most important are nitric oxide (NO.) and O2-.. 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 may likely have important implications, altering not only tissue perfusion but also contributing to the process of atherosclerosis. The precise O2-. 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 O2-. source. Interestingly, this oxidase is activated upon stimulation with angiotension II, suggesting that under all conditions of an activated circulating and/or local renin-angiotensin system endothelial dysfunction secondary to increased vascular O2-. production is expected.