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

Abstract

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-F2␣), and plasma asymmetrical dimethyl arginine (ADMA; an endogenous competitive inhibitor of NO synthase) in each ethnic group. 1 This in part may be explained by an increased prevalence and severity in blacks of some risk factors for atherosclerosis. In particular, in black subjects, essential hypertension has a higher prevalence, earlier onset, and is associated with more severe end-organ damage, including left ventricular hypertrophy, renal failure, and stroke. 1 However, conventional risk factors for cardiovascular disease do not account for all of this increased risk. A recent study demonstrated that black ethnicity is a strong and independent risk factor for the development of peripheral arterial disease, which was not explained by higher levels of diabetes, hypertension, or body mass index. 2 The mechanisms underlying this ethnic predisposition to cardiovascular dysregulation remain unresolved.A number of studies have demonstrated that black subjects have endothelial dysfunction, 3-5 a key step in the initiation/ progression of atherosclerotic vascular disease. A hallmark of endothelial cell dysfunction is a reduction in the bioavailability of the antiatherosclerotic signaling molecule NO. 6 Longitudinal studies have demonstrated that a reduction in NO bioavailability is a predictor of accelerated atherosclerosis. 7,8 NO is generated by a family of NO synthases from L-arginine in a reaction that requires oxygen, reduced nicotinamideadenine dinucleotide phosphate, and essential cofactors, including tetrahydrobiopterin. NO bioavailability is principally determined by a reduction in its biosynthesis and/or inactivation by reactive oxygen species. Asymmetric dimethylargi-

Ethnicity-specific differences in L-arginine status in South African men

“…The results of our analysis are consistent with previously described interactions of these mechanisms in an epidemiological context. 19,29,33,58,59 In addition, our results contribute to an understanding of the metabolic role of L-arginine in the differential prevalence of hypertension in Africans and Caucasians.…”

“…31,33 --36 Profiles of several other cardiovascular risk factors in the two ethnic groups also differ. For example, Melikian et al 33 reported that in a small study on black Africans (n ¼ 30) living in Europe, ethnicity predicted serum concentrations of ADMA. A decrease in the relative availability of NO may diminish endothelial function, potentially contributing to the higher prevalence of hypertension and cardiovascular disease.…”

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

“…The strong relationship between ADMA and arterial stiffness observed in the African men could point to a different vascular mechanism in the development of cardiovascular disease previously seen in black African men (1,7). It is well known that compared to Caucasians, Africans disclose larger increases in aortic and peripheral PWV after smoking (30), they show no changes in the peripheral arterial response to exercise compared to Caucasians who show significant reductions (31), and their peripheral muscular arteries show increased PWV with diabetes, with no change in Europeans (32).…”

“…Furthermore, the increasing incidence of diabetes (5) in Africa will aggravate the severity of renal and cardiac damage caused by any given blood pressure (BP) level (1). Although a high prevalence of known modifiable risk factors for atherosclerotic disease and hypertensive heart disease is detected in black South African individuals (6), these conventional risk factors do not account for all of their increased risk (7). It is therefore imperative to identify additional markers that might explain their increased risk and may contribute to the early detection and prevention of vascular and metabolic abnormalities.…”

“…Owing to its inhibitory effect on NO synthase, ADMA has been implicated in the impairment of NO generation in a variety of cardiovascular diseases (16). Melikian et al (7) have indicated that ADMA levels were significantly higher in Africans compared to Europeans and they suggested that this may contribute to higher incidence of cardiovascular disease in black Africans. ADMA therefore seems to be a suitable candidate for the early detection of cardiovascular and metabolic disease in Africans.…”