Abstract 530: Enhanced Expression Of Epithelial Sodium Channels (ENaC) Causes Salt-induced Hypertension In Mice Through Inhibition Of The α <sub>2</sub> -isoform Of Na <sup>+</sup> , K <sup>+</sup> -atpase
Bibliographic record
Abstract
Knockout of the Nedd4-2 gene in mice results in overexpression of ENaC on the plasma membrane in kidneys, choroid plexus and brain nuclei. These mice exhibit enhanced pressor responses to CSF [Na + ] and dietary salt-induced hypertension which both can be blocked by central infusion of the ENaC blocker benzamil. Functional studies suggest that ENaC activation in the CNS results in release of endogenous ouabain (EO) and inhibition of the α 2 -isoform of Na + , K + -ATPase. To test this concept more specifically, we studied Nedd4-2 -/- mice expressing the α 2 R/R -isoform of Na + , K + -ATPase. Intracerebroventricular (icv) infusion of Na + -rich aCSF (225 mM Na + at 0.4 μl/min) increased MAP by 10-15 mmHg in wild type mice and by 25-30 mmHg in Nedd4-2 -/- mice, but by only ~5 mmHg in α 2 R/R and in α 2 R/R /Nedd4-2 -/- mice (Fig top panel). Icv infusion of EO-binding Fab fragments also blocked the BP response in Nedd4-2 -/- mice. In Nedd4-2 -/- mice high salt diet increased MAP by 25-30 mmHg, but in α 2 R/R /Nedd4-2 -/- mice by only 5 mmHg (Fig bottom panel). These findings substantiate the concept that enhanced ENaC activity causes salt-induced pressor responses mainly through EO inhibiting the α 2 -isoform of Na + , K + -ATPase in the brain.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".