Mechanisms of nicotine-induced cutaneous vasodilation and sweating in young adults: roles for KCa, KATP, and KV channels, nitric oxide, and prostanoids

Appl Physiol Nutr Metab. 2017 May;42(5):470-478. doi: 10.1139/apnm-2016-0615. Epub 2017 Mar 22.


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-1 tetraethylammonium (KCa channel blocker), (iii) 5 mmol·L-1 glybenclamide (KATP channel blocker), and (iv) 10 mmol·L-1 4-aminopyridine (KV channel blocker). In protocol 2 (n = 10), 4 sites were infused with (i) lactated Ringer (Control), (ii) 10 mmol·L-1 Nω-nitro-l-arginine (NOS inhibitor), (iii) 10 mmol·L-1 ketorolac (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 KV channel blockers, whereas nicotine-induced increase in sweat rate was reduced by the KCa and KV channel 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-1 atropine 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 KV channels contribute to nicotinic cutaneous vasodilation, (ii) inhibition of COX augments nicotinic cutaneous vasodilation likely through NOS-dependent mechanism(s), and (iii) KCa and KV channels contribute to nicotinic sweating.

Keywords: 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).

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Atropine / pharmacology
  • Female
  • Glyburide / pharmacology
  • Humans
  • Male
  • Nicotine / pharmacology*
  • Nitric Oxide / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / physiology*
  • Prostaglandins / metabolism*
  • Sweating / drug effects*
  • Tetraethylammonium / pharmacology
  • Vasodilation / drug effects*
  • Young Adult


  • Potassium Channel Blockers
  • Potassium Channels
  • Prostaglandins
  • Nitric Oxide
  • Tetraethylammonium
  • Nicotine
  • Atropine
  • 4-Aminopyridine
  • Glyburide