title: Cyclooxygenase inhibition does not alter methacholine-induced sweating.
abstract: Cholinergic agents (e.g., methacholine) induce cutaneous vasodilation and sweating. Reports indicate that either nitric oxide (NO), cyclooxygenase (COX), or both can contribute to cholinergic cutaneous vasodilation. Also, NO is reportedly involved in cholinergic sweating; however, whether COX contributes to cholinergic sweating is unclear. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) were evaluated in 10 healthy young (24 ± 4 yr) adults (7 men, 3 women) at four skin sites that were continuously perfused via intradermal microdialysis with 1) lactated Ringer (control), 2) 10 mM ketorolac (a nonselective COX inhibitor), 3) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME, a nonselective NO synthase inhibitor), or 4) a combination of 10 mM ketorolac + 10 mM l-NAME. At the four skin sites, methacholine was simultaneously infused in a dose-dependent manner (1, 10, 100, 1,000, 2,000 mM). Relative to the control site, forearm CVC was not influenced by ketorolac throughout the protocol (all P > 0.05), whereas l-NAME and ketorolac + l-NAME reduced forearm CVC at and above 10 mM methacholine (all P < 0.05). Conversely, there was no main effect of treatment site (P = 0.488) and no interaction of methacholine dose and treatment site (P = 0.711) on forearm sweating. Thus forearm sweating (in mg·min(-1)·cm(-2)) from baseline up to the maximal dose of methacholine was not different between the four sites (at 2,000 mM, control 0.50 ± 0.23, ketorolac 0.44 ± 0.23, l-NAME 0.51 ± 0.22, and ketorolac + l-NAME 0.51 ± 0.23). We show that both NO synthase and COX inhibition do not influence cholinergic sweating induced by 1-2,000 mM methacholine.
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: McGinn
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Paull
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Stapleton
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Meade
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada gkenny@uottawa.ca.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Kenny
mesh_terms: D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D020910:Ketorolac / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D013546:Sweating / Q000187:drug effects*; D055815:Young Adult
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D020910:Ketorolac
keywords: muscarinic receptor; nitric oxide; prostanoids; sudomotor activity; thermoregulation