Race-Specific Differences in Endothelial Function: Predisposition of African Americans to Vascular Diseases, Circulation

Background—The prevalence of the endothelium-impaired function disorders, such as hypertension and diabetes mellitus, and the severity of their complications are considerably greater in blacks than whites. Evidence has accumulated that superoxide (O2) production and its interaction with nitric oxide (NO), yielding the strong oxidant peroxynitrite (ONOO), play central roles in vascular pathophysiology. We hypothesized that the differences in endothelial NO/O2/ONOO metabolism may highlight the potential predisposition to endothelial dysfunction and cardiovascular complications prevalent in blacks. Methods and Results—Highly sensitive tandem electrochemical NO/O2/ONOO nanosensors were positioned in single human umbilical vein endothelial cells (HUVECs) isolated from blacks and whites, and the kinetics of NO/O2/ONOO release were recorded in vitro. HUVECs were also analyzed by Western immunoblotting and enzyme activity assays for NAD(P)H-oxidase and endothelial NO synthase (eNOS). Compared with whites, HUVECs from blacks elicited reduced release of bioactive NO with an accompanying increase in the release of both O2 and ONOO. The greater potency of NO production because of eNOS upregulation in HUVECs from blacks is associated with a decrease in the NO bioavailability. This is due to increased NO degradation by excess O2 produced primarily by 2 enzymatic sources: NAD(P)H-oxidase and uncoupled eNOS. Conclusions—Compared with whites, the steady-state NO/O2/ONOO balance in endothelial cells from blacks is kep