UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase

Abstract

The incidence of hypertension and cardiovascular disease correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are abundant in human skin we hypothesised that exposure to UVA may mobilise NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers irradiation of the skin with 2 Standard Erythemal Doses of UVA lowered BP, with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO-synthase activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labelled with the NO-imaging probe DAF2-DA revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent fashion, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability which may account for the latitudinal and seasonal variations of BP and cardiovascular disease.Journal of Investigative Dermatology accepted article preview online, 20 January 2014.

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ORCID for Bernadette O. Fernandez: orcid.org/0000-0001-6337-0381

ORCID for Martin Feelisch: orcid.org/0000-0003-2320-1158

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