Skin Pigmentation is Negatively Associated with Both Circulating Vitamin D Concentration and Cutaneous Microvascular Endothelial Function

Abstract

Given population disparities in cardiovascular disease (CVD) prevalence, it is imperative to better understand individual characteristics that result in predisposition to the development of hypertension and overt CVD. Skin color is an important determinant of vitamin D status because melanin has an inhibitory effect on UV-B-induced cutaneous vitamin D synthesis. In turn, vitamin D deficiency may result in reduced vascular endothelial function, an antecedent to CVD, via reduced nitric oxide (NO) bioavailability and/or increased oxidative stress. Purpose To investigate the associations between skin pigmentation (M-index, assessed using skin reflectance spectrophotometry), serum vitamin D concentration [25(OH)D], and the NO contribution to local heating-induced cutaneous vasodilation (%NO). We hypothesized that across a wide range of skin pigmentation, M-index would be negatively related to serum [25(OH)D] and %NO, and that serum [25(OH)D] would be positively related to %NO. Methods An intradermal microdialysis fiber was placed in the forearms of 18 healthy adults (9M/9F; 21±2 yrs) with M-indices ranging from 30 to 68 a.u. for local delivery of pharmacological agents. Lactated Ringer's solution was perfused through the microdialysis fiber during local heating (39°C) to induce cutaneous NO-dependent vasodilation. After attaining a stable plateau blood flow, 15mM NG-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibiter) was infused at all sites to directly quantify %NO. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC=LDF/MAP) was expressed as a percentage of maximum (%CVCmax; 28mM sodium nitroprusside+43°C). Serum [25(OH)D] was analyzed via enzyme-linked immunosorbent assay (coefficient of variation=5.5%). Results As hypothesized, M-index was negatively associated with both serum [25(OH)D] (R2=0.43, β=-0.40, p<0.01) and %NO (R2=0.32, β=-0.50, p=0.02). Serum [25(OH)D] was positively associated with %NO (R2=0.21, β=0.67, p=0.055). Conclusions These data suggest that vitamin D plays an important role in promoting healthy endothelial function, and that ensuring adequate vitamin D status may be an effective intervention to mitigate the development of endothelial dysfunction in darkly-pigmented individuals living in relatively low UVR environments.