Interaction of protease‐activated receptor 2 with chronic angiotensin II‐induced endothelial dysfunction in mice
Bibliographic record
Abstract
Protease‐Activated Receptor 2 (PAR‐2) knockout mice exhibit a different time course in blood pressure response to angiotensin II (AngII). In this study we measured endothelium‐dependent relaxations of mesenteric arteries from PAR‐2 knockout (PAR‐2 ‐/‐) and C57BL/6 mice using wire myographs. Our goal was to test the influence of PAR‐2 ‐/‐ on AngII‐induced endothelial dysfunction. Chronic AngII infusion of C57BL/6 and PAR‐2 ‐/‐ decreased acetylcholine (ACh)‐induced relaxations by ~20 % whereas PAR‐2 agonist (2fly) and sodium nitroprusside relaxations were unchanged relative to saline infusion groups. ACh‐induced relaxations of AngII‐PAR‐2 ‐/‐ arteries, but not AngII‐C57BL/6 arteries, were rescued in the presence of the cyclooxygenases inhibitor indomethacin. In contrast to these effects, indomethacin decreased the sensitivity to ACh in saline‐PAR‐2 ‐/‐ and did not affect either ACh‐ or 2fly‐induced relaxations in saline‐C57BL/6. The sensitivity to 2fly of arteries from AngII‐C57BL/6 was decreased in the presence of indomethacin. A combination of PAR‐2 gene knockout and indomethacin rescued ACh‐induced relaxations of vascular smooth muscle after chronic AngII infusion in mice. Cyclooxygenases contribute to the mechanism of persistent PAR‐2 vasodilation despite endothelial dysfunction and to the mechanism of action for ACh in PAR‐2 ‐/‐ mice. Funding sources: CIHR, IRIF, CFI.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".