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 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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".