title: Mechanisms influencing the vasoactive effects of lidocaine in human skin.
abstract: The vasodilator properties of lidocaine are believed to be due mainly to the inhibition of action potentials via sodium channel blocking in vasoconstrictor sympathetic nerves. However, mechanisms involving the vascular endothelium may also play a role, and in this study we investigated the potential influences of nitric oxide release, the cyclo-oxygenase pathway and the beta-adrenoceptors of vascular smooth muscle. Laser Doppler imaging was used to measure microvascular blood flow responses to intradermal injection of lidocaine 2%, with or without the addition of preservatives, in eight healthy, male volunteers. Co-injection of the nitric-oxide-synthase inhibitor Nomega-nitro-L-arginine methyl ester caused a 60% reduction in the response after about 20 min, and this reduction was enhanced with the lidocaine solution containing the preservatives methylhydroxybenzoate and propylhydroxybenzoate. No reduction in response was seen after blocking the cyclo-oxygenase or beta-adrenoceptor pathways. Nitric oxide release contributes to the vasoactivity of lidocaine in human skin.
authors.affiliation: Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, University Department of Anaesthesia, Dundee DD1 9SY, UK. d.j.newton@dundee.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Newton
authors.forename: G A
authors.initials: GA
authors.lastname: McLeod
authors.forename: F
authors.initials: F
authors.lastname: Khan
authors.forename: J J F
authors.initials: JJ
authors.lastname: Belch
mesh_terms: D000328:Adult; D000779:Anesthetics, Local / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008012:Lidocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D011310:Preservatives, Pharmaceutical; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008012:Lidocaine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester