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 beta1-selective agent with vasodilating and antioxidant properties.


RESULTS
The effects of nebivolol on endothelial nitric oxide (NO), superoxide (O2-), 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/O2-/ONOO- were measured simultaneously with nanosensors from single cells and shown to have significant interracial differences. The rate of NO release was &5 times slower in blacks than in whites (94 versus 505 nmol . L(-1).s(-1)), whereas the rates of release were faster by &2 times for O2- and &4 times for ONOO- (22.1 versus 9.4 nmol.L(-1).s(-1) for O2- and 810 versus 209 nmol.L(-1).s(-1) for ONOO-). Pretreatment with 1.0 to 5.0 micromol/L nebivolol restored NO bioavailability in endothelial cells from black donors with concurrent reductions in O2- 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 O2- and ONOO- generation by NAD(P)H and uncoupled endothelial NO synthase. Nebivolol decreased O2- and ONOO- concentrations and restored NO bioavailability in blacks to the level recorded in cells from whites, independently of beta1-selective blockade.
Mason
R Preston
RP
Elucida Research, Beverly, Massachusetts, USA.
Kalinowski
Leszek
L
Jacob
Robert F
RF
Jacoby
Adam M
AM
Malinski
Tadeusz
T
D000328:Adult; D001741:Black or African American; D001578:Benzopyrans / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000209:etiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D007083:Iliac Artery / Q000166:cytology; D009249:NADP / Q000378:metabolism; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D044465:White People
D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D009249:NADP; D052250:Nitric Oxide Synthase Type III