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

We evaluated the influence of K + channels (i.e., Ca 2+ -activated K + (K Ca ), ATP-sensitive K + (K ATP ), and voltage-gated K + (K V ) 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 (K Ca channel blocker), (iii) 5 mmol·L −1 glybenclamide (K ATP channel blocker), and (iv) 10 mmol·L −1 4-aminopyridine (K V channel blocker). In protocol 2 (n = 10), 4 sites were infused with (i) lactated Ringer (Control), (ii) 10 mmol·L −1 N ω -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 K Ca , K ATP , and K V channel blockers, whereas nicotine-induced increase in sweat rate was reduced by the K Ca and K V 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) K Ca , K ATP , and K V channels contribute to nicotinic cutaneous vasodilation, (ii) inhibition of COX augments nicotinic cutaneous vasodilation likely through NOS-dependent mechanism(s), and (iii) K Ca and K V channels contribute to nicotinic sweating.