Mechanisms of nicotine-induced cutaneous vasodilation and sweating in young adults: roles for K_Ca, K_ATP, and K_Vchannels, nitric oxide, and prostanoids

Abstract

https://mc06.manuscriptcentral.com/apnm-pubs

Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating

“…Consistent with the healthy young individuals of our previous work (Fujii et al., , ), methacholine and nicotine, but not ATP, activated sweating in the present study (Figure ). Regarding the between‐group comparison, methacholine‐induced sweating was similar between groups (Figure a), and this is consistent with recent work showing that local sweating in individuals with T2D was similar to their age‐matched counterparts as assessed during a passive‐ (Kenny, Sigal, & McGinn, ) and exercise‐induced (Fujii et al., ) heat stress.…”

“…Consistent with our previous work (Fujii et al., ), in both groups we observed that nicotinic sweating demonstrates a transient pattern of response. This might indicate rapid desensitization of nicotinic receptors.…”

“…Thus, the lack of cutaneous vasodilatory response with the administration of nicotine at concentrations of 1.2–11 m m in individuals with T2D in the present study might suggest that T2D does not modulate the cholinergic axon reflex. It should be noted that cutaneous vasodilatation elicited by high doses of nicotine (33–100 m m ) occurs independently of muscarinic receptors (Fujii et al., ). Nicotinic receptor activation on cutaneous vascular endothelial cells (Hagforsen, Edvinsson, Nordlind, & Michaëlsson, ) might underpin this vasodilatory response and, based on our results, T2D might not alter endothelial nicotinic receptor function.…”

“…Thereafter, a 10 min baseline measurement was initiated, after which pharmacological agents were administered at the three intradermal forearm skin sites as follows: (i) methacholine (Sigma‐Aldrich, St Louis, MO, USA; muscarinic receptor agonist; five doses: 0.0125, 0.25, 5, 100 and 2000 m m ); (ii) nicotine (MP Biomedicals, Santa Ana, CA, USA; nicotinic receptor agonist; five doses: 1.2, 3.6, 11, 33 and 100 m m ); or (iii) ATP (Cayman Chemical, Ann Arbor, MI, USA; purinergic receptor agonist; five doses: 0.03, 0.3, 3, 30 and 300 m m ). The doses for each of the agents were determined based on our previous work for methacholine (Fujii et al., , ), nicotine (Fujii et al., ) and ATP (Fujii et al., ) administration. Methacholine, nicotine and ATP were all infused in a dose‐dependent manner, with each dose administered for 25 min at a rate of 4.0 μl min −1 .…”

Nicotinic receptors modulate skin perfusion during normothermia, and have a limited role in skin vasodilatation and sweating during hyperthermia

“…During baseline resting in a non‐heat‐stress condition, hexamethonium reduced cutaneous vascular conductance relative to the control site (Figure ) indicating that nicotinic receptors play a role in the regulation of cutaneous vascular tone under this condition. Activation of nicotinic receptors of cholinergic axons can cause cholinergic axon reflex, increasing acetylcholine release from cholinergic nerves, subsequently activating muscarinic receptors of cutaneous vessels and thus cutaneous vasodilatation (Fujii et al., ). Together, these observations lend support to the hypothesis that muscarinic mechanisms primarily explain the contribution of nicotinic receptors to the regulation of cutaneous vascular tone under non‐heat‐stress conditions.…”