Blockade of brain mineralocorticoid receptors or Na<sup>+</sup> channels prevents sympathetic hyperactivity and improves cardiac function in rats post-MI
Bibliographic record
Abstract
In rats post-myocardial infarction (MI), sympathetic hyperactivity can be prevented by blockade of brain mineralocorticoid receptors (MR). Stimulatory responses to central infusion of aldosterone can be blocked by benzamil and therefore appear to be mediated via Na+ channels, presumably epithelial Na+ channels (ENaC), in the brain. To evaluate this concept of endogenous mineralocorticoids in Wistar rats post-MI, we examined effects of blockade of MR and Na+ channels in the brain. At 3 days after coronary artery ligation, intracerebroventricular infusions were started with spironolactone (400 ng.kg(-1).h(-1)) or its vehicle, or with benzamil (4 microg.kg(-1).h(-1)) or its vehicle, using osmotic minipumps. Rats with sham ligation served as control. After 4 wk, in conscious rats, mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded at rest and in response to air-jet stress, intracerebroventricular injection of the alpha2-adrenoceptor agonist guanabenz, and intravenous infusion of phenylephrine and nitroprusside for baroreflex function. MI size was similar among the four groups of rats (approximately 31%). In rats treated post-MI with vehicles, cardiac function was decreased, sympathetic reactivity was enhanced, and baroreflex function was impaired. Blockade of brain Na+ channels or brain MR similarly prevented sympathetic hyperactivity and impairment of baroreflex function and improved cardiac function. These findings suggest that in rats post-MI, increased binding of endogenous agonists to MR increases ENaC activity in the brain and thereby leads to sympathetic hyperactivity and progressive left ventricular dysfunction.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| 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".