Abstract P116: Induction of Human Endothelin-1 Overexpression for 3 Months Increases Plasma Aldosterone
Bibliographic record
Abstract
Background: The mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Long-term exposure to endothelial human ET-1 overexpression causes sustained blood pressure elevation via ETA receptors. ET-1 has been shown to stimulate the release of aldosterone from the adrenal cortex. Whether aldosterone plays a role in ET-1 endothelium overexpression-induced BP elevation is still unknown. Methods and Results: Nine to 12-week-old male ieET-1 mice and control ieCre mice expressing a tamoxifen-inducible Cre recombinase (CreER T2 ) under the control of EC-specific Tie2 promoter, were treated with tamoxifen (1 mg/kg/day, SC) for 5 days and studied 3 months later. Plasma aldosterone level measured by ELISA was higher in ieET-1 compared with ieCre mice (1.21±0.14 vs. 0.70±0.09 ng/mL, P <0.05). Sodium and water excretion determined by saline challenge tests done every 2 weeks for 3 months were unaffected by ET-1 overexpression. Reverse transcription-quantitative PCR (RT-qPCR) did not reveal changes in mRNA expression of renin, mineralocorticoid receptor (MR), epithelial sodium channel 1 alpha subunit ( Scnn1a ), TSC22 domain family member 3 ( Rsc22d3 ), serum- and glucocorticoid-induced kinase 1 ( Sgk1 ), and ET type A and B receptors in the kidney or adrenal glands. The mRNA expression of aldosterone synthase ( Cyp11b2 , fold change: 0.52±0.06 vs 1.00±0.16, P <0.01), but not the hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 ( Hsd3b1) and 6 (Hsd3b6) or steroidogenic acute regulatory protein ( Star ), were decreased in the adrenal cortex of ieET-1 compared with ieCre mice. CYP11B2 and HSD3B1 protein levels measured by Western Blotting were unchanged. Treatment of ieET-1 mice with MR antagonist eplerenone (100 mg/kg per day) during the last 2 weeks decreased systolic BP more during the day (128±2 vs. 134±3 mm Hg) than during the night (137±2 vs. 140±2 mm Hg) compared to untreated ieET-1 mice. Conclusions: These results showed that aldosterone contributes at least in part to the BP elevation caused by endothelial human ET-1 overexpression.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 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".