Nebivolol reduces nitroxidative stress and restores nitric oxide bioavailability in endothelium of black Americans

Background-Alterations in endothelial function may contribute to increased susceptibility of black Americans to cardiovascular disease. The ability to pharmacologically reverse endothelial dysfunction in blacks was tested with nebivolol, a beta(1)-selective agent with vasodilating and antioxidant properties. Methods and Results-The effects of nebivolol on endothelial nitric oxide (NO), superoxide (O-2(-)), and peroxynitrite concentration (ONOO-) release were studied in human umbilical vein endothelial cells and iliac artery endothelial cells isolated from age-matched black and white donors. Kinetics and concentrations of NO/O-2(-)/ONOO- were measured simultaneously with nanosensors from single cells and shown to have significant interracial differences. The rate of NO release was approximate to 5 times slower in blacks than in whites (94 versus 505 nmol center dot L-1 center dot s(-1)), whereas the rates of release were faster by approximate to 2 times for O-2(-) and approximate to 4 times for ONOO- (22.1 versus 9.4 nmol center dot L-1 center dot s(-1) for O-2(-) and 810 versus 209 nmol center dot L-1 center dot s(-1) for ONOO-). Pretreatment with 1.0 to 5.0 mu mol/ L nebivolol restored NO bioavailability in endothelial cells from black donors with concurrent reductions in O-2(-) and ONOO- release, similar to levels in the endothelium of whites. The effects of nebivolol were dose-dependent and not observed with atenolol; similar effects were observed with apocynin, an NAD(P)H oxidase inhibitor. Conclusions-Reduced endothelial NO bioavailability in American blacks is mainly due to excessive O-2(-) and ONOO- generation by NAD(P)H and uncoupled endothelial NO synthase. Nebivolol decreased O-2(-) and ONOO- concentrations and restored NO bioavailability in blacks to the level recorded in cells from whites, independently of beta(1)-selective blockade.