TRPA1 Channel Activation With Cinnamaldehyde Induces Cutaneous Vasodilation Through NOS, but Not COX and KCa Channel, Mechanisms in Humans
Bibliographic record
Abstract
ABSTRACT: Transient receptor potential ankyrin 1 (TRPA1) channel activation induces cutaneous vasodilation in humans in vivo. However, the mechanisms underlying this response remains equivocal. We hypothesized that nitric oxide synthase (NOS) and Ca2+ activated K+ (KCa) channels contribute to the TRPA1 channel-induced cutaneous vasodilation with no involvement of cyclooxygenase (COX). Cutaneous vascular conductance (CVC) in 9 healthy young adults was assessed at 4 dorsal forearm skin sites treated by intradermal microdialysis with (1) 1.985% dimethyl sulfoxide + 0.015% lactated Ringer solution with propylene glycol (vehicle control), (2) 10 mM l-NAME, a nonselective NOS inhibitor, (3) 10 mM ketorolac, a nonselective COX inhibitor, or (4) 50 mM tetraethylammonium, a nonselective KCa channel blocker. Cinnamaldehyde, a TRPA1 channel activator, was administered to each skin site in a dose-dependent manner (2.9%, 8.8%, 26%, and 80%, each lasting ≥30 minutes). Administration of ≥8.8% cinnamaldehyde increased CVC from baseline at the vehicle control site by as much as 27.4% (95% confidence interval of 5.3; P < 0.001). NOS inhibitor attenuated the cinnamaldehyde-induced increases in CVC at the 8.8%, 26%, and 80% concentrations relative to the vehicle control site (all P ≤ 0.05). In contrast, both the COX inhibitor and KCa channel blockers did not attenuate the cinnamaldehyde induced-increases in CVC relative to the vehicle control site for all concentrations (all P ≥ 0.130). We conclude that in human skin in vivo, NOS plays a role in modulating the regulation of cutaneous vasodilation in response to TRPA1 channel activation with no detectable contributions of COX and KCa channels.
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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 | 0.001 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".