title: Mechanisms contributing to the vaso-active effects of prilocaine in human skin.
abstract: We investigated the roles of the endothelial nitric oxide and cyclo-oxygenase pathways in mediating the vasoactivity of prilocaine in the skin. We injected prilocaine 1% intradermally into forearm skin of 10 healthy, male subjects. Nitric oxide synthesis was inhibited at a second site by co-injecting prilocaine with l-NAME 1%. We then repeated the injections while blocking the cyclo-oxygenase pathway with aspirin (4 x 600 mg). We measured blood flow responses to the injections using laser Doppler imaging. We found that, after the traumatic effects of injection had subsided, l-NAME reduced the vascular response to prilocaine by a third (p = 0.012), indicating an influence specifically on the drug response. Aspirin had no effect on the response (p = 0.588). We conclude that the vasoactive effects of prilocaine in human skin are mediated partly through the release of endothelial nitric oxide and, although other mechanisms might also be involved, the cyclo-oxygenase pathway does not appear to play a role.
authors.affiliation: Peripheral Vascular Diseases Research Unit, University Department of Medicine, Dundee DD1 9SY, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Newton
authors.forename: E L
authors.initials: EL
authors.lastname: Sur
authors.forename: F
authors.initials: F
authors.lastname: Khan
authors.forename: G A
authors.initials: GA
authors.lastname: McLeod
authors.forename: J J F
authors.initials: JJ
authors.lastname: Belch
mesh_terms: D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000009:adverse effects / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D004347:Drug Interactions; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007271:Injections, Intradermal; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011318:Prilocaine / Q000009:adverse effects / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D014665:Vasodilator Agents; D011318:Prilocaine; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester