Involvement of nitric oxide synthase in the delayed vasodilator response to ultraviolet light irradiation of rat skin in vivo

Abstract

The role of nitric oxide synthase and cyclo‐oxygenase in the skin blood flow response to ultraviolet light B (u.v.B) irradiation was investigated in the rat in vivo. Local skin blood flow changes were measured in the shaved dorsal skin of anaesthetized male Sprague‐Dawley rats with a laser Doppler flow probe. u.v.B irradiation caused delayed onset vasodilatation and by 18 h basal blood flow increased by 125 ± 25% (P < 0.05, n = 12 rats, mean ± s.e.mean). Indomethacin, 3 nmol per site, NG‐nitro‐l‐arginine methyl ester (l‐NAME) 100 nmol per site, but not d‐NAME 100 nmol per site, injected locally 17.5 h after u.v.B irradiation abolished the 18 h increase in blood flow. The nitric oxide synthase inhibitor l‐NAME, NG‐monomethyl‐l‐arginine (l‐NMMA) and canavanine, 10 and 100 nmol per site injected at 17.5 h, suppressed significantly the u.v.B 18 h response in a dose‐dependent manner. The order of potency was l‐NAME > canavanine = l‐NMMA. The effect of l‐NAME was reversed partially by the co‐injection of an excess of l‐arginine. Topical application of the corticosteroid, clobetasol 17‐propionate, immediately after irradiation inhibited the 18 h u.v.B response in a dose‐dependent manner. The delayed onset microcirculatory vasodilatation induced by u.v.B involves both nitric oxide synthase and cyclo‐oxygenase in this in vivo model. Topical corticosteroids may attenuate the response by inhibiting both prostaglandin and nitric oxide synthesis pathways. 1993 British Pharmacological Society