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

Liu, D., Fernandez, B. O., Hamilton, A., Lang, N. N. , Gallagher, J. M.C., Newby, D. E., Feelisch, M. and Weller, R. B. (2014) UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. Journal of Investigative Dermatology, 134(7), pp. 1839-1846. (doi: 10.1038/jid.2014.27) (PMID:24445737)

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Abstract

The incidence of hypertension and cardiovascular disease (CVD) 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 hypothesized that exposure to UVA may mobilize NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers, irradiation of the skin with two standard erythemal doses of UVA lowered blood pressure (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 (NOS) activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labeled with the NO-imaging probe diaminofluorescein 2 diacetate revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent manner, 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 CVD.

Item Type:Articles
Additional Information:The work was funded by Foundation for Skin Research, and Chest Heart Stroke Scotland (RBW), the Clare Wand Fund (JMCG), and the Faculty of Medicine, University of Southampton (MF).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Newby, Professor David and Lang, Professor Ninian
Authors: Liu, D., Fernandez, B. O., Hamilton, A., Lang, N. N., Gallagher, J. M.C., Newby, D. E., Feelisch, M., and Weller, R. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of Investigative Dermatology
Publisher:Elsevier
ISSN:0022-202X
ISSN (Online):1523-1747
Published Online:20 February 2014

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