Enzyme-independent NO stores in human skin: quantification and influence of UV radiation

Nitric oxide (NO) has many functions in the skin, including the mediation of inflammation and antimicrobial defense, wound healing, regulation of keratinocyte homeostasis, and regulation of apoptosis following UV radiation. NO is synthesized by a family of NO synthase enzymes, but its rapid release following UV exposure suggests the existence of preformed stores. NO can be converted into nitrite or nitrosothiols that are stable until cleaved by UV to release NO. Using dermal microdialysis, suction blister epidermal samples, and sweat collection, we demonstrated cutaneous concentrations of total NO-related products of 12+/-5.97 microM, 0.03+/-0.03 micromol mg(-1) epidermal protein, and 22+/-9.34 microM, respectively. The predominant oxyanion was nitrate (60-75%) followed by nitrite. S-Nitrosothiols were barely detectable. Serum total NO-related products correlated directly with those of the upper dermis and sweat (R(2)=0.62 and 0.3, respectively). UVA irradiation (10 mW cm(-2)) increased the yield of NO-related products by microdialysis, peaking after 30 minutes. Dialysis with noradrenaline abrogated this rise. Both the skin and the dermal vasculature contain biologically significant stores of NO, particularly nitrite, which can be directly mobilized by UVA irradiation. The level of circulating NO-related products probably determines skin-bound stores.