Mechanisms of nicotine-induced cutaneous vasodilation and sweating in young adults: roles for K<sub>Ca</sub>, K<sub>ATP</sub>, and K<sub>V</sub> channels, nitric oxide, and prostanoids
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".