title: Nitric oxide and human skin blood flow responses to acetylcholine and ultraviolet light.
abstract: Nitric oxide (NO) is a potent endogenous vasodilator of large blood vessels but its role in the physiological and pathological control of the human microcirculation is not known. This study was designed to assess whether NO contributes to the control of blood flow in the human skin microcirculation in vivo. Local changes in blood flow were measured in the forearm skin microcirculation of normal volunteers. The responses to agents injected intradermally were assessed with a laser Doppler flow probe. NO was generated in local areas of skin by the injection of the NO donor, sodium nitroprusside. Endogenous NO was generated by the injection of acetylcholine and the exposure of skin to ultraviolet light (UVB) to stimulate the constitutive and inducible forms of nitric oxide synthase (NOS), respectively. The skin microvasculature was comparatively insensitive to exogenous NO derived from the NO donor sodium nitroprusside, being 10,000-fold more sensitive to the vasodilator prostaglandin PGE2 (P < 0.001). However, the rapid onset, dose-dependent local vasodilation caused by acetylcholine was blocked by the NOS inhibitor NG-monomethyl-L-arginine, L-NMMA (P < 0.05), but not by the cyclooxygenase inhibitor indomethacin. The delayed local blood flow response to UVB was attenuated by either L-NMMA or indomethacin (P < 0.05 in each case). The UVB response was abolished by a combination of L-NMMA and indomethacin or by local, topical corticosteroid treatment (P < 0.01 in each case). This study indicates that NO increases blood flow in the human microcirculation in vivo. NOS inhibition attenuated both the rapid blood flow response to acetylcholine and the delayed response to UVB. Both NOS and cyclooxygenase contributed to the erythema response to UVB, and dual inhibition of both enzymes would explain the mechanism of action of the corticosteroid in this model of inflammation.
authors.affiliation: Department of Applied Pharmacology, National Heart and Lung Institute, London, U.K.
authors.forename: J B
authors.initials: JB
authors.lastname: Warren
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000098:blood supply*; D014466:Ultraviolet Rays; D019323:omega-N-Methylarginine
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine