Abstract 154: Knockdown of Mineralocorticoid or AT <sub>1</sub> Receptor Gene in the Paraventricular Nucleus Prevents Ang II Induced Hypertension in Rats
Bibliographic record
Abstract
Circulating Ang II activates an aldosterone-MR-AT 1 R pathway in the hypothalamus. To obtain insights into the actual aldosterone-MR- AT 1 R neuronal pathway, the present study examined whether intra-PVN infusion of AAV-AT 1a R-siRNA or AAV-MR-siRNA prevents the Ang II induced increases in AT 1 R and MR expression and BP. Two weeks sc infusion of Ang II at 500ng/kg/min in Wistar rats on regular salt diet increased BP by telemetry by 66 ± 3 mm Hg, and AT 1 R and MR protein in the SFO, SON and PVN. Intra-PVN AT 1a R-siRNA decreased AT 1 R but not MR expression in the PVN by sc Ang II, and MR-siRNA decreased MR but not AT 1 R expression in the PVN. AT 1 R and MR expression in both SFO and SON were not significantly changed by the two AAV-siRNA. Specific knockdown of AT 1 R or MR in the PVN by AAV-siRNA prevented ~80% of the increase in BP induced by sc Ang II. These results suggest that circulating Ang II up-regulates brain Ang II and aldosterone and increases MR and AT 1 R in the SFO, SON and PVN. Prevention of Ang II induced increases in MR but not AT 1 R by knockdown of MR and vice versa suggests an independent regulation of MR and AT 1 R in the PVN. Both AT 1 R and MR in the PVN play a critical role in Ang II-induced hypertension in rats. * p<0.05 versus AAV-SCM alone. a: p<0.05 versus AAV-SCM + Ang II.
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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) | 0.001 | 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 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".