MR or AT1R gene silencing in the PVN markedly attenuates Ang II‐induced hypertension in rats
Bibliographic record
Abstract
Functional studies suggest that circulating Ang II activates an aldosterone‐MR‐endogenous ouabain (EO)‐ AT 1 R pathway in the hypothalamus and thereby causes hypertension. The present study examined whether intra‐PVN infusion of AAV‐MR‐siRNA or AAV‐AT 1a R‐siRNA attenuates Ang II‐induced hypertension in rats. Two wks after bilateral intra‐PVN infusion of AAV‐MR‐siRNA (1 μl of 2.5 × 10 10 genomic particles / ml), MR mRNA and protein expression in the PVN were reduced by 56% and 31% (P<0.01), compared with rats infused with AAV‐SCM‐siRNA. In 2nd set of rats, 1 week following bilateral intra‐PVN infusion of AAV‐MR‐siRNA, AAV‐AT 1a R‐siRNA (1 μl of 2.5 × 10 10 genomic particles / ml) or AAV‐SCM‐siRNA, Ang II was infused subcutaneously at 500ng/kg/min. After 2 weeks, AAV‐AT 1a R‐siRNA significantly attenuated, whereas AAV‐MR‐siRNA largely prevented the Ang II‐induced hypertension. These results suggest that MR activation in the PVN plays a major role in Ang II‐induced hypertension, and genetic intervention of MR or AT 1 R production by AAV‐siRNA into specific nuclei provides new insights into the actual pathways of MR‐EO neuromodulation. MAP (mmHg) HR (bpm) AAV‐SCM‐siRNA ( n=5) 113 ± 2 377 ± 8 AAV‐SCM‐siRNA +Ang II ( n=5) 192 ± 7 416 ± 15 AAV‐AT1aR‐siRNA+ Ang II ( n=7) 153 ± 8, 411 ± 12 AAV‐MR‐siRNA + Ang II ( n=7) 121 ± 6 377 ± 12 Data=means± SE. p<0.05, vs. others, p<0.05, vs. AAV‐SCM, p<0.05, vs. AAV‐MR. (Supported by grant # FRN:MOP‐74432 from the Canadian Institutes of Health Research)
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".