Myocardial Fibrosis in DOCA-Salt Hypertensive Rats
Bibliographic record
Abstract
BACKGROUND: To test the hypothesis that endothelin-1 contributes to cardiac fibrosis, cardiac collagen deposition was studied in deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats, in which the endothelin system is activated. The effects of the ET(A)-selective endothelin receptor antagonist A-127722 were evaluated. METHODS AND RESULTS: A-127722 (30 mg/kg per day) was administered for 4 weeks. Myocardial fibrosis was evaluated after Sirius red F3BA staining. Systolic blood pressure was 103+/-1.6 mm Hg in unilaterally nephrectomized rats (Uni-Nx), 202+/-3.2 mm Hg in DOCA-salt rats (P:<0.01 versus Uni-Nx), and 182+/-3.1 mm Hg in ET(A) antagonist-treated DOCA-salt rats (P:<0.01 versus DOCA-salt or Uni-Nx). In DOCA-salt rats, interstitial and perivascular collagen density was increased in the subendocardial and midmyocardial regions of the left ventricle (3- to 4-fold, P:<0.05), whereas in subepicardial myocardium, the increase was predominantly perivascular. The ET(A) antagonist prevented cardiac fibrosis in DOCA-salt rats. Procollagen I and III mRNA, which were increased in hearts of DOCA-salt rats, were normalized by ET(A) antagonist treatment. TGF-beta(1) mRNA and TGF-beta(1) protein increased at 1 week in DOCA-salt rats and were lowered in ET(A) antagonist-treated rats. CONCLUSIONS: ET(A) receptor-mediated collagen deposition in hearts of DOCA-salt rats results from increased procollagen synthesis associated with an initial increment in expression of TGF-beta(1). These results support the hypothesis of 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 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".