UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase.
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.
Department of Dermatology, University of Edinburgh, Edinburgh, UK.
Donald
D
Liu
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Bernadette O
BO
Fernandez
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
Alistair
A
Hamilton
BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Ninian N
NN
Lang
Leithmount Surgery, Edinburgh, UK.
Julie M C
JMC
Gallagher
BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
David E
DE
Newby
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK. Electronic address: m.feelisch@soton.ac.uk.
Martin
M
Feelisch
Department of Dermatology, University of Edinburgh, Edinburgh, UK; MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK. Electronic address: r.weller@ed.ac.uk.
Richard B
RB
Weller
D001794:Blood Pressure / Q000528:radiation effects*; D003198:Computer Simulation; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D005542:Forearm / Q000098:blood supply; D064368:Healthy Volunteers; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D008297:Male; D008955:Models, Cardiovascular; D009566:Nitrates / Q000008:administration & dosage / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000008:administration & dosage / Q000097:blood; D012039:Regional Blood Flow / Q000528:radiation effects; D012307:Risk Factors; D012621:Seasons; D012867:Skin / Q000098:blood supply* / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014664:Vasodilation / Q000528:radiation effects*; D014807:Vitamin D / Q000378:metabolism; D055815:Young Adult
D009566:Nitrates; D009573:Nitrites; D014807:Vitamin D; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase