title: Nebivolol reduces nitroxidative stress and restores nitric oxide bioavailability in endothelium of black Americans.
abstract: 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.
authors.affiliation: Elucida Research, Beverly, Massachusetts, USA.
authors.forename: R Preston
authors.initials: RP
authors.lastname: Mason
authors.forename: Leszek
authors.initials: L
authors.lastname: Kalinowski
authors.forename: Robert F
authors.initials: RF
authors.lastname: Jacob
authors.forename: Adam M
authors.initials: AM
authors.lastname: Jacoby
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Malinski
mesh_terms: 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
chemical_list: D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D009249:NADP; D052250:Nitric Oxide Synthase Type III