Brain Amiloride-Sensitive Phe-Met-Arg-Phe-NH <sub>2</sub> –Gated Na <sup>+</sup> Channels and Na <sup>+</sup> -Induced Sympathoexcitation and Hypertension
Bibliographic record
Abstract
Dietary and cerebrospinal fluid (CSF) Na(+) may act through brain amiloride-sensitive, Phe-Met-Arg-Phe-NH(2) (FMRFamide)-gated Na(+) channels (FaNaChs) to cause sympathoexcitation and hypertension. We hypothesized that FaNaChs cause sympathoexcitation via the activation of brain "ouabain" and the brain renin-angiotensin system. In conscious Wistar rats, intracerebroventricular (ICV) infusion of Na(+)-rich (0.3 mol/L) artificial CSF (aCSF) and ICV injection of angiotensin II or ouabain increase renal sympathetic nerve activity (RSNA), blood pressure (BP), and heart rate (HR). ICV benzamil, an amiloride analogue, did not affect baseline values and blocked the responses to ICV infusions of Na(+)-rich aCSF but not ICV angiotensin II or ouabain. ICV FMRFamide also increased RSNA, BP, and HR. Blocking brain "ouabain" with ICV antibody Fab fragments abolished the responses to both ICV FMRFamide and Na(+)-rich aCSF. In conscious spontaneously hypertensive rats (SHR) on a high salt intake for 6 weeks, prolonged ICV but not intravenous infusion of benzamil at 10 to 20 microg/h significantly decreased RSNA, BP, and HR in a dose-related manner. The extent of these responses was significantly smaller in SHR on regular salt intake. These findings suggest that benzamil-blockable brain FaNaChs represent the major mechanism through which a small increase in CSF Na(+) by ICV Na(+)-rich aCSF in Wistar rats or high salt intake in SHR initiates sympathoexcitation and hypertension. Enhanced Na(+) entry through FaNaChs appears to activate brain "ouabain" and the brain renin-angiotensin system and, thereby, increases the sympathetic outflow. Brain FaNaChs appear to contribute to the worsening of hypertension in SHR on a high salt diet and, to a small extent, to the maintenance of hypertension in SHR on a regular salt diet.
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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 | 0.000 | 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) | 0.001 | 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".