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 NG-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·min−1·cm−2, respectively. Peak sweat rate (0.46 ± 0.11, 0.56 ± 0.16, and 0.53 ± 0.16. mg·min−1·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.