title: Nicotinic receptor activation augments muscarinic receptor-mediated eccrine sweating but not cutaneous vasodilatation in young males.
abstract: What is the central question of this study? Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors. Although each receptor can independently induce cutaneous vasodilatation and eccrine sweating, it remains to be elucidated whether the two receptors interact in order to mediate these responses. What is the main finding and its importance? We show that although nicotinic receptor activation does not modulate muscarinic cutaneous vasodilatation, it lowers the muscarinic receptor agonist threshold at which onset for eccrine sweating (augmentation of muscarinic eccrine sweating) occurs in young men in normothermic resting conditions. These results provide new insights into the physiological significance of nicotinic receptors in the regulation of cutaneous perfusion and eccrine sweating. Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors; each is known independently to induce cutaneous vasodilatation and eccrine sweating in humans. However, it is not known whether the two receptors interact in order to mediate cutaneous vasodilatation and eccrine sweating. In 10 young men (27 ± 6 years old), cutaneous vascular conductance and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with either lactated Ringer's solution (control) or three different concentrations of nicotine (0.1, 1 and 10 mm), a nicotinic receptor agonist. Co-administration of methacholine, a muscarinic receptor agonist, was performed at all skin sites in a dose-proportional fashion (0.0125, 0.25, 5, 100 and 2000 mm, each for 25 min). Administration of nicotine alone caused dose-dependent transient increases in cutaneous vascular conductance and sweat rate (all P ≤ 0.05), which thereafter returned to pre-nicotine levels, except that a portion of transient responses remained with continuous administration of 10 mm nicotine (both P ≤ 0.05). Cutaneous vascular conductance was increased by administration of ≥0.25 mm methacholine at the control site, and this response was likewise observed in the presence of co-administration of all doses of nicotine used (all P ≤ 0.05). Sweat rate at the control site was increased by administration of ≥0.25 mm methacholine, but the lowest dose of methacholine (0.0125 mm) was able to increase sweat rate in the presence of 10 mm nicotine (P ≤ 0.05). We conclude that nicotinic receptor activation lowers the muscarinic receptor agonist threshold for eccrine sweating (augmentation of muscarinic sweating) but does not affect muscarinic cutaneous vasodilatation in young men in normothermic resting conditions.
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: Jeffrey C
authors.initials: JC
authors.lastname: Louie
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: McNeely
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: My-An
authors.initials: MA
authors.lastname: Tran
authors.affiliation: Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Glen P
authors.identifier: 0000-0001-8683-6973
authors.initials: GP
authors.lastname: Kenny
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D004439:Eccrine Glands / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D017551:Microdialysis / Q000379:methods; D018721:Muscarinic Agonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012146:Rest / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D013542:Sweat / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013546:Sweating / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D016210:Methacholine Chloride; D009538:Nicotine; D000109:Acetylcholine
keywords: acetylcholine receptors; intradermal microdialysis; thermoregulation