Asymmetric Dimethylarginine and Reduced Nitric Oxide Bioavailability in Young Black African Men

Abstract

Black Africans have a higher incidence of cardiovascular disease than white Europeans. We explored potential mechanisms of this excess risk by assessing endothelium function, inflammatory status (C-reactive protein), oxidative stress (isoprostane-F2α), and plasma asymmetrical dimethyl arginine (ADMA; an endogenous competitive inhibitor of NO synthase) in each ethnic group. Thirty healthy black Africans and 28 well-matched white European male subjects were studied (mean age±SE: 32.2±0.9 and 29.2±1.2 years, respectively; P =0.07). High-resolution ultrasound was used to assess vascular function in the brachial artery by measuring flow mediated dilatation ([percentage of change]; endothelium-dependent function) and glyceryltrinitrate dilatation ([percentage of change]; endothelium-independent function). Blood pressure, fasting lipids, glucose, and estimated glomerular filtration rate levels were similar in both groups. There was no difference in C-reactive protein (black Africans: 0.8±0.1 mg/L; white Europeans: 0.6±0.1 mg/L; P =0.22), isoprostane-F2α (black Africans: 42.9±1.5 pg/mL; white Europeans: 39.2±1.5 pg/mL; P =0.23), and leptin (black Africans: 64.1±10.2 ng/mL; white Europeans: 47.8±9.8 ng/mL; P =0.37) levels between the 2 ethnic groups. However, compared with white Europeans, plasma ADMA levels were significantly higher in black Africans (0.34±0.02 μmol/L and 0.25±0.03 μmol/L; P =0.03). There was no difference in the percentage of glyceryltrinitrate dilatation ( P =0.7), but the percentage of flow-mediated dilatation was significantly lower in black Africans (black Africans: 5.2±0.3; white Europeans: 6.3±0.4; P =0.02). In a stepwise multiple regression model, ADMA level was the only independent determinant of flow-mediated dilatation ( P =0.02). In turn, race was the only independent determinant of ADMA levels ( P =0.03). Our findings indicate that circulating ADMA levels are significantly higher in healthy black African males than in white European males. This may contribute to the lower NO bioavailability and higher incidence of cardiovascular disease seen in black Africans.