Abstract MP05: Mineralocorticoid And Angiotensin II Type 1 Receptors In The Subfornical Organ Mediate Angiotensin II Hypertension In Rats
Bibliographic record
Abstract
Circulating Ang II increases BP through both peripheral and central mechanisms. Activation of both AT 1 R and MR in the CNS plays a critical role in Ang II-induced hypertension. The subfornical organ (SFO) contains both MR and AT 1 R and can relay the signals of circulating Ang II to downstream nuclei such as the PVN. In this study, we evaluated the effect of intra-SFO infusion of AAV-MR-siRNA or AAV-AT 1a R-siRNA on MR or AT 1 R mRNA expression in the SFO and PVN and Ang II induced hypertension as assessed by telemetry. Two week sc infusion of Ang II at 500 ng/kg/min in Wistar rats on regular salt diet increased BP by 60~65 mmHg. This pressor effect of Ang II was largely prevented by AAV-MR-siRNA or AAV-AT 1 R-siRNA in the SFO (Figure). Ang II increased AT 1 R mRNA expression (1.7± 0.4 vs 0.8 ± 0.04 х10 -1 , p<0.05) in the SFO. Both MR- and AT 1 R-siRNA in the SFO prevented this increase (1.1 ± 0.2х10 -1 and 1.0± 0.3х10 -1 ). In contrast, Ang II decreased MR mRNA expression (3.2 ± 0.2 vs. 4.1 ± 0.2х10 -2 , p<0.05) in the SFO. Both MR- and AT 1 R-siRNA further decreased MR mRNA expression (2.7 ± 0.2 х10 -2 and 2.3 ± 0.3 х10 -2 ). In the PVN, Ang II increased AT 1 R mRNA by ~100% and MR mRNA by ~20%. Only AT 1 R-siRNA in the SFO prevented these increases in the PVN. AAV mediated eGFP fluorescence expression was observed in the SFO but not the PVN. These results suggest that circulating Ang II differentially regulates MR and AT 1 R expression in the SFO. Prevention of Ang II induced AT 1 R up-regulation by knockdown of either AT 1 R or MR suggests a MR dependent regulation of AT 1 R in the SFO. MR-AT 1 R signaling in the SFO appears to play a major role in Ang II-induced hypertension in rats. * p<0.05, vs. baseline values; a: p<0.05, vs. AAV-SCM-siRNA
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 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".