Activation of protease‐activated receptor 2 mediates cutaneous vasodilatation but not sweating: roles of nitric oxide synthase and cyclo‐oxygenase
Bibliographic record
Abstract
New Findings What is the central question of this study? Protease‐activated receptor 2 (PAR2) is located in the endothelial cells of skin vessels and eccrine sweat glands. However, a functional role of PAR2 in the control of cutaneous blood flow and sweating remains to be assessed in humans in vivo . What is the main finding and its importance? Our results demonstrate that in normothermic resting humans in vivo , activation of PAR2 elicits cutaneous vasodilatation partly through nitric oxide synthase‐dependent mechanisms, but does not mediate sweating. These results provide important new insights into the physiological significance of PAR2 in human skin. Protease‐activated receptor 2 (PAR2) is present in human skin, including keratinocytes, endothelial cells of skin microvessels and eccrine sweat glands. However, whether PAR2 contributes functionally to the regulation of cutaneous blood flow and sweating remains entirely unclear in humans in vivo . We hypothesized that activation of PAR2 directly stimulates cutaneous vasodilatation and sweating via actions of nitric oxide synthase (NOS) and cyclo‐oxygenase (COX). In 12 physically active young men (29 ± 5 years old), cutaneous vascular conductance (CVC) and sweat rate were measured at four intradermal microdialysis forearm skin sites that were treated with the following: (i) lactated Ringer's solution (control); (ii) 10 m m N G ‐nitro‐ l ‐arginine (NOS inhibitor); (iii) 10 m m ketorolac (COX inhibitor); or (iv) a combination of both inhibitors. At all sites, a PAR2 agonist (SLIGKV‐NH 2 ) was co‐administered in a dose‐dependent fashion (0.06, 0.18, 0.55, 1.66 and 5 m m , each for 25 min). The highest dose of SLIGKV‐NH 2 (5 m m ) increased CVC from baseline at the control site ( P ≤ 0.05). This increase in CVC associated with PAR2 activation was attenuated by NOS inhibition regardless of the presence or absence of simultaneous COX inhibition (both P ≤ 0.05). However, COX inhibition alone did not affect the PAR2‐mediated increase in CVC ( P > 0.05). No increase in sweat rate was measured at any administered dose of SLIGKV‐NH 2 (all P > 0.05). We show that in normothermic resting humans in vivo , PAR2 activation does not increase sweat rate, whereas it does modulate cutaneous vasodilatation through NOS‐dependent mechanisms.
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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) | 0.000 | 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".