Nebivolol improves eNOS function and nitric oxide bioavailability in endothelial cells from African Americans

Abstract

Listen

Translate article

Increased susceptibility of African Americans to cardiovascular disease and its clinical manifestations has been attributed to reduced endothelial function. We tested the ability of nebivolol, a highly selective β1-selective agent with direct vasodilating and antioxidant properties, to impact endothelial activity in African Americans. The effect of nebivolol on endothelial nitric oxide (NO) bioavailability was tested in human umbilical vein endothelial cells (HUVECs) isolated from age-matched African American and White donors with similar CV risk factors, including family history of hypertension and diabetes. Production of NO/O2−/ONOO− was simultaneously recorded using a highly sensitive tandem of electrochemical nanosensors. The results showed significant differences in the kinetics of the initial rates of NO, O2− and ONOO− release between African Americans and Whites: rate of NO release was ∼5 times slower in African Americans compared with Whites (94 vs. 505 nmol/L/s), whereas the rates of release were faster ∼2 times for O2− and ∼4 times for ONOO− (22.1 vs. 9.4 nmol/L/s for O2− and 810 vs. 209 nmol/L/s for ONOO−). Pretreatment with 1.0 mmol/L nebivolol restored NO bioavailability in HUVECs from African Americans with concurrent reductions in O2− and ONOO− release, similar to levels recorded from White donor cells. The effects of nebivolol were reproducible, dose-dependent and not observed with atenolol, but were by a NAD(P)H-oxidase inhibitor. These data demonstrate that loss of NO bioavailability in African Americans is related to eNOS uncoupling and excessive superoxide generation, a process that can be reversed with nebivolol, independently of β1-selective blockade.