Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

Abstract

Objective Alarming increases in hypertension and type 2 diabetes among Africans accentuate the need to identify factors that could serve as targets for prevention or treatment. In Caucasian populations, asymmetric dimethylarginine (ADMA), the predominant endogenous nitric oxide synthase inhibitor, is associated with cardiovascular disease and insulin resistance (IR). ADMA's counterpart, symmetric dimethylarginine (SDMA), originally thought to be inert, was recently also linked with cardiovascular risk. Since little information regarding ADMA or SDMA is available for Africans, our aim was to explore the relationships of ADMA and SDMA with measures of arterial stiffness and IR in Africans and Caucasians from South Africa.

Methods The study consisted of 235 nonsmoking, nondiabetic, nonobese, human immunodeficiency virus-uninfected Africans (n=64) and Caucasians (n=171), aged 20–70 years. We measured blood pressure, pulse wave velocity, ADMA, SDMA, and IR (homeostasis model assessment, HOMA).

Results African and Caucasian men had similar ADMA and SDMA, whereas Caucasian women had higher ADMA and SDMA than African women (P<0.05). African men and Caucasian women indicated strong correlations of ADMA with arterial stiffness (r=0.47, P=0.021; r=0.26, P=0.008), confirmed in multivariate analyses. Caucasian participants showed negative associations between SDMA and HOMA, being strongest in the men (r=−0.41; P=0.002).

Conclusion Our results indicate that ADMA is independently associated with vascular dysfunction in African men and Caucasian women. A strong, independent negative association of SDMA with IR was found only in Caucasian participants. The molecular explanation for this is unclear, but these findings motivate experimental studies that could shed more light on these relationships