Involvement of nitric oxide synthase in the delayed vasodilator response to ultraviolet light irradiation of rat skin in vivo.
1. 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. 2. Local skin blood flow changes were measured in the shaved dorsal skin of anaesthetized male Sprague-Dawley rats with a laser Doppler flow probe. 3. u.v.B irradiation caused delayed onset vasodilation and by 18 h basal blood flow increased by 125 +/- 25% (P < 0.05, n = 12 rats, mean +/- s.e. mean). 4. 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. 5. 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. 6. Topical application of the corticosteroid, clobetasol 17-propionate, immediately after irradiation inhibited the 18 h u.v.B response in a dose-dependent manner. 7. The delayed onset microcirculatory vasodilation 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.
Warren
J B
JB
Department of Applied Pharmacology, National Heart & Lung Institute, London.
Loi
R K
RK
Coughlan
M L
ML
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D002990:Clobetasol / Q000031:analogs & derivatives / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology / Q000528:radiation effects; D012867:Skin / Q000098:blood supply*; D014466:Ultraviolet Rays; D014664:Vasodilation / Q000528:radiation effects*; D019323:omega-N-Methylarginine
D016861:Cyclooxygenase Inhibitors; D019323:omega-N-Methylarginine; D002172:Canavanine; D001120:Arginine; D002990:Clobetasol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin