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. METHODS AND 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.
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. METHODS AND 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: Zora Djuric; Chloe E Bird; Alice Furumoto-Dawson; Garth H Rauscher; Mack T Ruffin; Raymond P Stowe; Katherine L Tucker; Christopher M Masi Journal: Open Biomark J Date: 2008-01-01
Authors: R Preston Mason; Robert F Jacob; Ruslan Kubant; Adam Jacoby; Febee Louka; J Jose Corbalan; Tadeusz Malinski Journal: Br J Clin Pharmacol Date: 2012-07 Impact factor: 4.335
Authors: Jasmina Varagic; Sarfaraz Ahmad; K Bridget Brosnihan; Javad Habibi; Roger D Tilmon; James R Sowers; Carlos M Ferrario Journal: Am J Nephrol Date: 2010-11-02 Impact factor: 3.754