Nerve‐evoked contraction of isolated resistance arteries is modulated by protease‐activated receptors (1079.16)
Bibliographic record
Abstract
The sympathetic nervous system is a key regulator of arterial diameter and thus blood flow and pressure. Protease‐activated receptors (PARs) are a novel class of G‐protein coupled receptors activated by proteolytic cleavage of the extracellular domain to reveal a tethered ligand. Four sub‐types of PARs have been identified, of which PAR‐1 and PAR‐2 are expressed in the vasculature. Activation of either PAR‐1 or PAR‐2 can evoke endothelium‐dependent relaxation but whether these receptors can modulate nerve‐mediated vascular responses has not been examined. We have investigated whether activators of PAR‐2 can modulate sympathetic nerve‐evoked increases in tone in rat isolated mesenteric resistance arteries. In endothelium‐denuded segments of mesenteric artery, stimulation of peri‐arterial nerves (0.5 to 20 Hz) elicited frequency‐dependent increases in tone which were abolished by either prazosin, an α1‐adrenoceptor antagonist, or tetrodotoxin, an inhibitor of neuronal sodium channels, but were unaffected by depletion of sensory nerves with capsacin. Activation of PAR‐2 by either trypsin, the tethered ligand mimetic peptide fLIGRL or AC 264613, a synthetic PAR‐2 ligand, significantly attenuated nerve‐mediated responses. Increases in tone to bath applied noradrenaline were also attenuated by trypsin and fLIGRL but to a significantly lesser extent than the nerve‐evoked responses. The effects of trypsin on nerve‐evoked increases in tone were prevented by the trypsin inhibitor aprotinin. Thrombin, an activator of PAR‐1 also attenuated nerve‐evoked increases in tone although the effect was significantly less than that seen with PAR‐2 activation. These data indicate that PARs directly modulate nerve‐mediated vasoconstriction of resistance arteries providing a novel mechanism for regulation of sympathetic vascular tone. Supported by HSFC.
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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) | 0.001 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".