Activation of the right ventricular endothelin (ET) system in the monocrotaline model of pulmonary hypertension: response to chronic ETA receptor blockade
Bibliographic record
Abstract
Although activation of the endothelin (ET) system contributes to pulmonary hypertension, modifications of the cardiopulmonary ET system and its responses to chronic ET receptor blockade are not well known. To investigate this, rats were injected with monocrotaline (60 mg/kg intraperitoneal) or saline, followed with treatment with the selective ETA receptor antagonist LU135252 (LU; 50 mg.kg(-1).day(-1)) or with saline. After 3 weeks, haemodynamics, cardiac hypertrophy, ET-1 levels and cardiopulmonary ET-receptor-binding profile were evaluated. Monocrotaline (n =7) elicited marked pulmonary hypertension and right ventricular hypertrophy compared with controls (n =8). Both variables were substantially attenuated by LU therapy (n =8; P <0.05 for both). After monocrotaline, right ventricular ET-1 levels were more significantly increased than in the left ventricle (+198% compared with +127%; P <0.05). ETB receptor density was augmented (3-fold) in the right ventricle, whereas that of ETA receptors was not affected. LU treatment also significantly attenuated these alterations (P <0.05). In the lungs, ET-1 levels were not increased after monocrotaline, whereas the balance of ETB to ETA receptors was altered, with a trend toward a lower percentage of ETB than in the control rats. LU treatment did not affect these variables in the lungs. Therefore monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy are associated with the up-regulation of ET-1 and ETB receptors in the right ventricle. These alterations are attenuated with the reduction of pulmonary hypertension and right ventricular hypertrophy after chronic blockade of the ETA receptors, supporting the role of the ET system in right ventricular hypertrophy.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".