Published online before print December 5, 2005, doi: 10.1161/CIRCULATIONAHA.105.556233
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2005;112:3795-3801.)
© 2005 American Heart Association, Inc.
Vascular Medicine |
Nebivolol Reduces Nitroxidative Stress and Restores Nitric Oxide Bioavailability in Endothelium of Black Americans
From the Department of Biochemistry, Ohio University, Athens, Ohio (L.K., A.M.J., T.M.); Elucida Research, Beverly, Mass (R.P.M., R.F.J.); and Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (R.P.M.). Dr Kalinowski was on sabbatical leave from the University of Gdansk.
Correspondence to Tadeusz Malinski, PhD, Department of Biochemistry, Ohio University, 350 W State St, Athens, OH 45701. E-mail malinski{at}ohiou.edu
Received April 15, 2005; revision received August 8, 2005; accepted September 19, 2005.
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 ß1-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 µmol/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 ß1-selective blockade.
Key Words: cardiovascular diseases • endothelium • nitric oxide • beta-blockers • ethnic groups
This article has been cited by other articles:
 |
|
 |
|
  L. M. Prisant Nebivolol: Pharmacologic Profile of an Ultraselective, Vasodilatory {beta}1-Blocker J. Clin. Pharmacol., February 1, 2008; 48(2): 225 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hallstrom, M. Franz, H. Gasser, M. Vodrazka, S. Semsroth, U. M. Losert, M. Haisjackl, B. K. Podesser, and T. Malinski S-nitroso human serum albumin reduces ischaemia/reperfusion injury in the pig heart after unprotected warm ischaemia Cardiovasc Res, February 1, 2008; 77(3): 506 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mata-Greenwood and D.-B. Chen Racial Differences in Nitric Oxide--Dependent Vasorelaxation Reproductive Sciences, January 1, 2008; 15(1): 9 - 25. [Abstract] [PDF]
|
|
|
|
|
|
G. Peluffo and R. Radi Biochemistry of protein tyrosine nitration in cardiovascular pathology Cardiovasc Res, July 15, 2007; 75(2): 291 - 302. [Abstract] [Full Text] [PDF]
|
|