Contrasting effects of intervention with ET<sub>A</sub>and ET<sub>B</sub>receptor antagonists in hypertension induced by angiotensin II and high-salt dietThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Bibliographic record
Abstract
Endothelin (ET) receptor antagonists are antihypertensive and renoprotective in angiotensin II (AngII)-induced hypertension if administered when AngII infusion commences, but their effects on established hypertension are poorly understood. We therefore tested the effects of intervening with an ETA (ABT-627) or ETB (A-192621) receptor antagonist after establishing hypertension with AngII (65 ng/min s.c.) plus 8% NaCl diet (AngII-HS) in rats. Prior to administration of ABT-627, AngII-HS and AngII-HS plus ABT-627 groups displayed robust hypertension (mean arterial pressure (MAP), 170 +/- 5 and 165 +/- 5 mm Hg versus 110 +/- 3 mm Hg in normal salt control rats at day 7, P < 0.05). Administering ABT-627 from day 8 of AngII-HS treatment prevented further rises in MAP (168 +/- 5 and 191 +/- 3 mm Hg at day 13 in AngII-HS plus ABT-627 and AngII-HS, P < 0.001), without blunting the significant increases in urinary protein (19-fold), albumin (25-fold), or MCP-1 excretion (6- to 8-fold) or the reduction in creatinine clearance. Administering A-192621 from day 8 mildly exacerbated AngII-HS induced hypertension (P < 0.05 for AngII-HS versus AngII-HS plus A-192621 on days 11 and 12 only) and reduced plasma nitrite/nitrate concentration (P < 0.05), without affecting proteinuria, albuminuria, or creatinine clearance. These results confirm the importance of ETA receptor signaling in maintaining AngII-HS hypertension and suggest that including ETB receptor blockade in therapeutic approaches to treating hypertension would be ineffective or even counterproductive.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".