Enhanced or Repressed Pressor Responses to Endothelin-1 or IRL-1620, respectively, in eNOS Knockout Mice
Bibliographic record
Abstract
Nitric oxide (NO) has been shown to be a physiological antagonist of the potent pressor agent endothelin-1, a transcriptional and post-transcriptional repressor of the production of this particular peptide as well as an endogenous modulator of vascular resistance in several animal species as well as in man. The aim of the present study was to assess the hemodynamic properties of endothelin-1 in endothelial NO synthase knockout mice (eNOS (-/-) KO). Ketamine- xylazine anesthetized eNOS (-/-) KO mice show a significantly higher mean arterial pressure (+25.7 +/- 4.3 mmHg, n = 10) than their wild-type congeners (C57BL/6 background). eNOS (-/-) KO mice, when subjected to systemically administered endothelin-1 or the selective endothelin-B agonist IRL-1620 (1 nmol/kg, each), responded by markedly enhanced and reduced pressor responses (systolic, diastolic and mean arterial pressure), respectively, when compared with wild-type mice. Surprisingly, plasma levels of immunoreactive endothelin are not significantly different in endothelial nitric oxide synthase knockout mice and wild-type mice. Our results suggest that chronic repression of endothelial nitric oxide synthase affects in opposite fashion the functionality of endothelin-A and endothelin-B receptor-dependent responses. The increase in mean arterial pressure afforded in endothelial nitric oxide synthase knockout mice does not appear to involve an increase in production of endogenous endothelin in vivo.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".