Clinical/Translational Research Whole Body UVA Irradiation Lowers Systemic Blood Pressure by Release of Nitric Oxide From Intracutaneous Photolabile Nitric Oxide Derivates

Rationale: Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO. Objective: Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunteers because of cutaneous nonenzymatic NO formation. Methods and Results: As detected by chemoluminescence detection or by electron paramagnetic resonance spectroscopy in vitro with human skin specimens, UVA illumination (25 J/cm 2) significantly increased the intradermal levels of free NO. In addition, UVA enhanced dermal S-nitrosothiols 2.3-fold, and the subfraction of dermal S-nitrosoalbumin 2.9-fold. In vivo, in healthy volunteers creamed with a skin cream containing isotopically labeled 15 N-nitrite, whole body UVA irradiation (20 J/cm 2) induced significant levels of 15 N-labeled S-nitrosothiols in the blood plasma of light exposed subjects, as detected by cavity leak out spectroscopy. Furthermore, whole body UVA irradiation caused a rapid, significant decrease, lasting up to 60 minutes, in systolic and diastolic blood pressure of healthy volunteers by 11؎2% at 30 minutes after UVA exposure. The decrease in blood pressure strongly correlated (R 2 ‫)47.0؍‬ with enhanced plasma concentration of nitrosated species, as detected by a chemiluminescence assay, with increased forearm blood flow (؉26؎7%), with increased flow mediated vasodilation of the brachial artery (؉68؎22%), and with decreased forearm vascular resistance (؊28؎7%). Conclusions: UVA irradiation of human skin caused a significant drop in blood pressure even at moderate UVA doses. The effects were attributed to UVA induced release of NO from cutaneous photolabile NO derivates. A part from its effects on stroke, renal failure, and peripheral arterial disease, systemic arterial hypertension is a major risk factor for cardiovascular complications, including coronary artery disease, heart failure and sudden cardiac death. 1,2 Interestingly, mean systolic and diastolic pressures and the prevalence of hypertension vary throughout the world. Many data suggest a linear rise in blood pressure at increasing distances from the equator. Similarly, blood pressure is higher in winter than summer. 3 Previously, it has been hypothesized that reduced epidermal vitamin D 3 photosyn-thesis associated with decreased UV light intensity at distances from the equator, alone or when coupled with decreased dietary calcium and vitamin D, may be associated with reduced vitamin D stores and increased parathyroid hormone secretion. 4 These changes may stimulate growth of vascular smooth muscle and enhance its contractility by affecting intracellular calcium, adrenergic responsiveness, and/or endothelial function. Thus, UV light intensity and …