title: Role of nitric oxide in methacholine-induced sweating and vasodilation in human skin.
abstract: The purpose of this study was to determine whether the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) demonstrates significant muscarinic-receptor antagonism during methacholine (MCh)-stimulated sweating in human forearm skin. Three intradermal microdialysis probes were placed in the skin of eight healthy adults (4 men and 4 women). MCh in the range of 0.033-243 mM in nine steps was perfused through a microdialysis probe with and without the presence of the nitric oxide synthase inhibitor L-NAME (10 mM) or the L-arginine analog NG-monomethyl-L-arginine (L-NMMA; 10 mM). Local sweat rate (sweat rate) and skin blood flow (laser-Doppler velocimetry) were measured directly over each microdialysis probe. We observed similar resting sweat rates at MCh only, MCh and L-NAME, and MCh and L-NMMA sites averaging 0.175 +/- 0.029, 0.186 +/- 0.034, and 0.139 +/- 0.027 mg x min(-1) x cm(-2), respectively. Peak sweat rate (0.46 +/- 0.11, 0.56 +/- 0.16, and 0.53 +/- 0.16. mg x min(-1) x cm(-2)) was also similar among all three sites. MCh produced a sigmoid-shape dose-response curve and 50% of the maximal attainable response (0.42 +/- 0.14 mM for MCh only) was shifted rightward shift in the presence of L-NAME or L-NMMA (2.88 +/- 0.79 and 3.91 +/- 1.14 mM, respectively; P < 0.05). These results indicate that nitric oxide acts to augment MCh-stimulated sweat gland function in human skin. In addition, L-NAME consistently blunted the MCh-induced vasodilation, whereas L-NMMA did not. These data support the hypothesis that muscarinic-induced dilation in cutaneous blood vessels is not mediated by nitric oxide production and that the role of L-NAME in attenuating acetylcholine-induced vasodilation may be due to its potential to act as a muscarinic-receptor antagonist.
authors.affiliation: John B. Pierce Laboratory, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Kichang
authors.initials: K
authors.lastname: Lee
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mack
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D013546:Sweating; D013997:Time Factors; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D016210:Methacholine Chloride; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester