Mechanisms of nicotine-induced cutaneous vasodilation and sweating in young adults: roles for KCa, KATP, and KVchannels, nitric oxide, and prostanoids.
We evaluated the influence of K+channels (i.e., Ca2+-activated K+(KCa), ATP-sensitive K+(KATP), and voltage-gated K+(KV) channels) and key enzymes (nitric oxide synthase (NOS) and cyclooxygenase (COX)) on nicotine-induced cutaneous vasodilation and sweating. Using intradermal microdialysis, we evaluated forearm cutaneous vascular conductance (CVC) and sweat rate in 2 separate protocols. In protocol 1 (n = 10), 4 separate sites were infused with (i) lactated Ringer (Control), (ii) 50 mmol·L-1tetraethylammonium (KCachannel blocker), (iii) 5 mmol·L-1glybenclamide (KATPchannel blocker), and (iv) 10 mmol·L-14-aminopyridine (KVchannel blocker). In protocol 2 (n = 10), 4 sites were infused with (i) lactated Ringer (Control), (ii) 10 mmol·L-1Nω-nitro-l-arginine (NOS inhibitor), (iii) 10 mmol·L-1ketorolac (COX inhibitor), or (iv) a combination of NOS+COX inhibitors. At all sites, nicotine was infused in a dose-dependent manner (1.2, 3.6, 11, 33, and 100 mmol·L-1; each for 25 min). Nicotine-induced increase in CVC was attenuated by the KCa, KATP, and KVchannel blockers, whereas nicotine-induced increase in sweat rate was reduced by the KCaand KVchannel blockers (P ≤ 0.05). COX inhibitor augmented nicotine-induced increase in CVC (P ≤ 0.05), which was absent when NOS inhibitor was co-administered (P > 0.05). In addition, our secondrary experiment (n = 7) demonstrated that muscarinic receptor blockade with 58 μmol·L-1atropine sulfate salt monohydrate abolished nicotine-induced increases in CVC (1.2-11 mmol·L-1) and sweating (all doses). We show that under a normothermic resting state: (i) KCa, KATP, and KVchannels contribute to nicotinic cutaneous vasodilation, (ii) inhibition of COX augments nicotinic cutaneous vasodilation likely through NOS-dependent mechanism(s), and (iii) KCaand KVchannels contribute to nicotinic sweating.
a Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, ON, Canada.
Naoto
N
Fujii
a Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, ON, Canada.
Jeffrey C
JC
Louie
a Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, ON, Canada.
Brendan D
BD
McNeely
b Laboratory for Exercise and Environmental Physiology, Faculty of Education, Niigata University, Japan.
Tatsuro
T
Amano
c Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Japan.
Takeshi
T
Nishiyasu
a Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, ON, Canada.
Glen P
GP
Kenny
D015761:4-Aminopyridine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism*; D013546:Sweating / Q000187:drug effects*; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D019789:Tetraethylammonium; D009538:Nicotine; D001285:Atropine; D015761:4-Aminopyridine; D005905:Glyburide
K+ channels; canaux K+; canaux ioniques dépendants du ligand; endothelium; endothélium; heat loss responses; hyperpolarisation; hyperpolarization; ligand-gated ion channels; nAChRs; pertes de chaleur; récepteurs nicotiniques neuronaux de l’acétylcholine (nAChRs)