Bibliographic record
Abstract
Sympatho-excitatory and pressor responses to aldosterone mediated by MR in the CNS have been well documented.MR activation by aldosterone appears to increase activity in angiotensinergic pathways involving the PVN by enhancing ENaC activity followed by "ouabain" release.This aldosterone-"ouabain" pathway can be activated by increases in CSF [Na+] eg by chronic central infusions of Na+-rich a CSF or in circulating and central angiotensin II.Central infusion of an aldosterone synthase inhibitor, MR blocker or Digibind to bind "ouabain" prevent the sympatho-excitatory and pressor responses to both CSF [Na+] and Ang II, suggesting that the MR activation may be due to an increase in aldosterone locally produced in the CNS.High salt diet increases CSF [Na+] in models of salt-sensitive hypertension such as Dahl S and SHR.The high salt-induced sympatho-excitation and hypertension in these models can be prevented by specific CNS blockade of any of the steps in the cascade from aldosterone synthase to AT1-receptors and appear therefore to be mediated by the Na+-induced activation of the hypothalamic aldosterone-"ouabain" pathway.Post MI, sympathetic hyperactivity and activation of the circulatory/cardiac RAAS contribute to progressive remodeling of the heart and heart failure.Several groups established the critical role of AT1-receptor stimulation in the PVN.Our group established that chronic activation of the hypothalamic aldosterone-"ouabain" pathway is the main mechanism contributing to this persistent AT1-receptor stimulation and thereby to the sympathetic hyperactivity as well as the chronic activation of the circulatory and cardiac RAAS.Considering the above described CNS effects of circulating Ang II, an initial increase in plasma Ang II post MI may activate neurons in circumventricular organs such as the SFO followed by a local increase in aldosterone biosynthesis.Not surprisingly, chronic central blockade of any step in the cascade also prevents a major part of the structural remodeling of the heart post MI and the decrease in LV function.In conclusion, beyond its classical role as a hormone regulating renal Na+-transport, aldosterone exerts profound effects on arteries and the heart.Its central actions are recently emerging, and appear to play a critical role in cardiovascular homeostasis when challenged by high salt intake or decreased cardiac function.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.015 | 0.003 |
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".