Bidirectional regulation of renal hemodynamics by activation of PAR<sub>1</sub>and PAR<sub>2</sub>in isolated perfused rat kidney
Bibliographic record
Abstract
Proteinase-activated receptors (PARs) are activated by either serine proteinases or synthetic peptides corresponding to the NH2-terminal tethered ligand sequences that are unmasked by proteolytic cleavage. Although PARs are highly expressed in the kidney, their roles in regulating renal function are not known. In the present study, we evaluated the impact of PAR activation on renal hemodynamics using PAR1- and PAR2-activating peptides (TFLLR-NH2 and SLIGRL-NH2) and proteinases (thrombin and trypsin) as PAR agonists in the isolated perfused rat kidney preparation. PAR1 activation resulted in renal vasoconstriction and a marked reduction in the glomerular filtration rate (GFR). In contrast, PAR2 activation caused vasodilation, partially reversing the vasoconstriction induced by TFLLR-NH2 and ANG II and increasing GFR that had been prereduced by ANG II. The vasoconstrictor actions of PAR1 activation were abolished by protein kinase C inhibition. The PAR2-induced vasodilation was only partially blocked by NG-nitro-l-arginine methyl ester, suggesting both nitric oxide-dependent and -independent mechanisms. Although PAR4 mRNA was detected in renal parenchyma, the PAR4-activating peptide AYPGKF-NH2 had no effect on renal perfusion flow rate. We conclude that PAR1 and PAR2 play bidirectional roles in the regulation of renal hemodynamics.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".