Critical role of CNS effects of aldosterone in cardiac remodeling post-myocardial infarction in rats
Bibliographic record
Abstract
BACKGROUND: Oral administration of spironolactone improves cardiac remodeling and its central infusion prevents the increase in sympathetic drive post-myocardial infarction (MI). We hypothesized that central actions of aldosterone contribute to cardiac remodeling post-MI. OBJECTIVE: To compare the effects of intracerebroventricular (icv) infusion and oral administration of spironolactone on cardiac remodeling and left ventricle (LV) dysfunction post-MI in rats. METHODS: Spironolactone was administered orally (80 mg/kg/day) or by icv infusion (100 ng/h), starting 1-3 days post-MI in Wistar rats and continued for 6 weeks. RESULTS: At 6 weeks post-MI, in the rats treated with vehicle, LV peak systolic pressure (LVPSP) and LV dP/dt max were clearly decreased and LV end diastolic pressure (LVEDP) and plasma catecholamines and serum aldosterone increased. All these parameters improved with both oral and icv spironolactone. The MI-induced increases in internal circumferences of LV and right ventricle (RV), and in interstitial and perivascular fibrosis, in both the LV and RV were significantly prevented/inhibited by both oral and icv spironolactone. Laminin, fibronectin and fibrillar collagen (visualized by scanning electron microscopy, SEM) increased in the non-infarcted part of the LV post-MI in the vehicle group, but not/less in rats on oral or icv spironolactone. CONCLUSIONS: Since the magnitude of beneficial effects of icv spironolactone at low doses was largely equal to that achieved with its oral administration at much higher doses, we propose that in addition to other sites of action, aldosterone appears to activate central nervous system (CNS) pathways and thereby influences peripheral mechanisms involved in cardiac remodeling.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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".