Darkly pigmented individuals are at the greatest risk of hypovitaminosis D, which may result in microvascular endothelial dysfunction via reduced nitric oxide (NO) bioavailability and/or increased oxidative stress and inflammation. We investigated the associations among skin pigmentation (M-index; skin reflectance spectrophotometry), serum vitamin D concentration [25(OH)D], circulating inflammatory cytokine (TNF-α, IL-6, and IL-10) concentrations, and the NO contribution to local heating-induced cutaneous vasodilation (%NO-mediated vasodilation) in a diversely pigmented cohort of young adults. An intradermal microdialysis fiber was placed in the forearms of 33 healthy adults (14 men/19 women; 18-27 yr; M-index, 30-81 AU) for local delivery of pharmacological agents. Lactated Ringer's solution was perfused through the fiber during local heating-induced (39°C) cutaneous vasodilation. After attaining stable elevated blood flow, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibiter) was infused to quantify %NO-mediated vasodilation. Red cell flux was measured (laser-Doppler flowmetry; LDF) and cutaneous vascular conductance (CVC = LDF/MAP) was normalized to maximal (%CVCmax; 28 mM sodium nitroprusside + 43°C). Serum [25(OH)D] and circulating cytokines were analyzed by ELISA and multiplex assay, respectively. M-index was negatively associated with [25(OH)D] (r = -0.57, P < 0.0001) and %NO-mediated vasodilation (r = -0.42, P = 0.02). Serum[25(OH)D] was positively related to %NO (r = 0.41, P = 0.02). Controlling for [25(OH)D] weakened the association between M-index and %NO-mediated dilation (P = 0.16, r = -0.26). There was a negative curvilinear relation between [25(OH)D] and circulating IL-6 (r = -0.56, P < 0.001), but not TNF-α or IL-10 (P ≥ 0.14). IL-6 was not associated with %NO-mediated vasodilation (P = 0.44). These data suggest that vitamin D insufficiency/deficiency may contribute to reduced microvascular endothelial function in healthy, darkly pigmented young adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to hypertension and overt CVD, is commonly observed in otherwise healthy Black adults, although the underlying causes remain unclear. We show that reduced vitamin D availability with increasing degrees of skin pigmentation is associated with reduced microvascular endothelial function, independent of race or ethnicity, in healthy young adults. Greater prevalence of vitamin D deficiency in more darkly pigmented individuals may predispose them to increased risk of endothelial dysfunction.
Keywords: inflammation; melanin; nitric oxide; race; skin blood flow.