Acute ultraviolet radiation exposure attenuates nitric oxide-mediated vasodilation in the cutaneous microvasculature of healthy humans.

5-methyltetrahydrofolate (5-MTHF) is important for nitric oxide (NO)-mediated cutaneous microvascular vasodilation. Ultraviolet B (UVB) radiation may deplete 5-MTHF, either directly or via production of reactive oxygen species (ROS), decreasing NO-mediated vasodilation. We hypothesized that 1) acute UVB exposure would attenuate NO-dependent cutaneous vasodilation, 2) local perfusion of 5-MTHF or ascorbate (ASC; anti-oxidant) would augment NO-dependent vasodilation after UVB, and 3) darker skin pigmentation would be UVB-protective. Three intradermal microdialysis fibers placed in each forearm of 21 healthy young adults (23±1 yr; 8M/13F) locally delivered lactated Ringer's (control), 5mM 5-MTHF, or 10mM ASC. One arm was UVB-exposed (300mJ/cm2), the other served as non-exposed control (CON). Following UVB exposure, a standardized local heating (42˚C) protocol induced cutaneous vasodilation. After attaining a plateau blood flow, 15mM NG-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibiter) was infused at all sites to quantify the NO contribution. 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). UVB attenuated NO-mediated vasodilation compared to CON (23.1±3.6 vs 33.9±3.4 %; p=0.001). Delivery of 5-MTHF or ASC improved NO-mediated vasodilation versus lactated Ringer's in the UVB-exposed arm (MTHF: 30.1±4.8 vs 23.1±3.8 %; p=0.03; ASC: 30.9±4.3 vs 23.1±3.8 %; p=0.02). Neither treatment affected the response in the non-exposed arm (p≥0.09). Skin pigmentation (M-index) was not predictive of the UVB response (p≥0.34). These data suggest that acute UVB exposure attenuates NO-mediated vasodilation via direct and/or ROS-induced reductions in 5-MTHF, independent of skin pigmentation.