Contribution of Endogenous Endothelin-1 and Endothelin-A-receptors to the Hypertensive State of Endothelin-B Heterozygous (+/−) Knockout Mice
Bibliographic record
Abstract
Summary: We observed that heterozygous knockout (+/−, KO) of either endothelin-A- (ETA) or -B- (ETB) receptors significantly reduced the pressor responses to systemically administered endothelin-1 (ET-1) in ETA or ETB (+/−) KO mice when compared to wild-type (WT) mice (data not shown). Also, we observed that basal mean arterial pressure (MAP) is significantly higher in ETB (+/−) (92.7 ± 1.2 mmHg) (n = 53, p < 0.05) but not ETA (+/−) KO mice (70.6 ± 1.8 mmHg) (n = 23) when compared to their anaesthetized WT littermates (70.1 ± 0.7 mmHg) (n = 118). A 90 min treatment with either BQ-123 (10 mg/kg), an ETA-selective antagonist, or BQ-928 (10 mg/kg), a mixed ETA/ETB antagonist, administered intraperitoneally, significantly reduced basal MAP of ETB (+/−) KO mice almost to the level of their WT treated counterparts (94.9 ± 4.9 mmHg) (n = 6) vs (+ BQ-123: 59.7 ± 0.3 mmHg, n = 8); (+ BQ-928: 72.4 ± 2.6 mmHg, n = 5). It is worthy of note that BQ-123 significantly reduced basal MAP in WT mice but to a lesser extent than in ETB (+/−) KO mice (69.6 ± 2.3 mmHg, n = 8) vs (+ BQ-123: 57.3 ± 1.4 mmHg, n = 8). In contrast, the ETB-selective antagonist, BQ-788 (10 mg/kg i.p.), had no significant effect on MAP even after 90 min of treatment (ETB (+/−) KO: (92.3 ± 2.3 mmHg, n = 6) vs (+ BQ-788: 89.7 ± 3.1 mmHg, n = 6); WT: (70.5 ± 3.7 mmHg, n = 7) vs (+ BQ-788: 71.2 ± 2.0 mmHg, n = 6). Therefore heterozygous KO of either ETA- or ETB-receptors significantly alters the phenotypic pressor properties of ET-1. We also suggest that there is less ET clearance in ETB (+/−) KO mice than in WT mice, which can explain the ETA-dependent hypertensive state of the former strain.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.000 | 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".