Endothelin‐1 Modulates Methacholine‐Induced Cutaneous Vasodilation but not Sweating in Young Human Skin
Bibliographic record
Abstract
The present study investigated the effect of endothelin‐1 (ET‐1) on cholinergic mechanisms of end‐organs (i.e. skin blood vessels and sweat glands) for heat dissipation. We evaluated the hypothesis that ET‐1 attenuates cholinergic cutaneous vasodilation and sweating through a nitric oxide synthase (NOS)‐dependent mechanism. Cutaneous vascular conductance (CVC) and sweat rate were assessed in three protocols. CVC was normalized to maximal CVC (%CVC max ). In Protocol 1 (n = 8), microdialysis forearm skin sites were perfused with lactated Ringer (Control), 40 p M , 4 n M or 400 n M ET‐1. In Protocol 2 (n = 11) sites were perfused with lactated Ringer (Control), 400 n M ET‐1, 10 m M L ‐NNA (a NOS inhibitor) or a combination of 400 n M ET‐1 and 10 m M L ‐NNA. In Protocol 3 (n = 8), only two sites (Control and 400 n M ET‐1) were utilized to assess the influence of ET‐1 on the dilation capacity of vascular smooth muscle cells using a dual administration of sodium nitroprusside (SNP). Methacholine (MCh) was co‐administered in a dose‐dependent manner (0.0125, 0.25, 5, 100, 2000 m M , each for 25 min) at all skin sites. 400 n M ET‐1 significantly attenuated increases in CVC compared to Control in response to 0.25 (40 ± 13 vs. 75 ± 10 %CVC max ) and 5 m M (55 ± 11 vs. 91 ± 11 %CVC max ) MCh (both P < 0.05). A high dose of ET‐1 (400 n M ) co‐infused with L ‐NNA further attenuated CVC relative to the ET‐1 site during 0.25 (23 ± 9 vs. 43 ± 14 %CVC max ), 5 (35 ± 10 vs. 61 ± 12 %CVC max ) and 100 m M (43 ± 12 vs. 70 ± 10 %CVC max ) MCh administration (all P < 0.05). Cutaneous vasodilation in response to SNP was significantly blunted (perfusion units mmHg −1 : 1.66 ± 0.30 vs. 0.80 ± 0.17) after administration of 400 n M ET‐1 ( P < 0.05). Therefore, we show that ET‐1 attenuates cutaneous vasodilation through a NOS‐independent, possibly through a vascular smooth muscle cell‐dependent mechanism, and that methacholine‐induced sweating is not modulated by ET‐1. Support or Funding Information This study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".