Myocardial fibrosis in DOCA-salt hypertensive rats: effect of endothelin ETA receptor antagonism
Bibliographic record
Abstract
Cardiovascular remodeling associated with hypertension is characterized by increase of cardiomyocyte volume and changes in extracellular matrix, particularly collagen deposition. To test the hypothesis that endothelin-1 contributes to fibrosis of the heart in some models of experimental hypertension, we studied cardiac collagen in deoxycorticosterone acetate-salt hypertensive rats (DOCA-salt), in which the endothelin system is activated, and the effect of the ETA-selective endothelin receptor antagonist, A-127722. A-127722 (30 mg/kg per day) was administered for 4 weeks to DOCA-salt rats. Cardiac fibrosis was evaluated after Sirius Red F3BA staining of paraffin embedded sections. Systolic blood pressure was 103 ± 1.6 mmHg in unilaterally nephrectomized rats (UniNx), 202 ± 3.2 mmHg in DOCA-salt (p < 0.01 vs UniNx) and 182 ± 3.1 mmHg in ETA-treated DOCA-salt (p < 0.01 vs DOCA-salt or UniNx). In DOCA-salt, collagen density was significantly increased in the subendocardial (4-fold, P < 0.01) and midmyocardial regions (3-fold, P < 0.05) but not in the subepicardial myocardium of the left ventricle. The administration of ETA-receptor antagonist to DOCA-salt normalized collagen to baseline value. Subendocardial and midmyocardial collagen density was significantly increased in DOCA-salt hypertensive rats. Both were corrected by ETA receptor antagonism, although blood pressure was only slightly lower and cardiac hypertrophy was unaffected in treated rats. This suggests a role for endothelin-1 in cardiac collagen deposition in mineralocorticoid hypertension, which may have pathophysiological and pharmacological implications in hypertensive heart disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".