Inhibition of brain angiotensin-converting enzyme by peripheral administration of trandolapril versus lisinopril in Wistar rats
Bibliographic record
Abstract
BACKGROUND: Peripheral administration of blockers of the renin-angiotensin system (RAS) may affect the RAS in the brain to a variable degree. In the present study, we determined inhibition of angiotensin-converting enzyme (ACE) in the brain after peripheral administration of a lipophilic (trandolapril) versus hydrophilic (lisinopril) ACE inhibitor. METHODS: Trandolapril (0.2, 1, and 5 mg/kg/day, subcutaneously) was compared with lisinopril (2, 10, and 50 mg/kg/day, subcutaneously), each for 6 days. At 4 and 24 h after the last dose, (125)I-351A binding on brain ACE was measured. RESULTS: Trandolapril and lisinopril caused similar inhibition of ligand binding outside the blood-brain barrier (BBB). However, inside the BBB, trandolapril was more effective at low and medium doses (for lisinopril, 28% to 51% inhibition at a dose of 2 mg, 63% to 72% at 10 mg, and 84% to 86% at 50 mg; and for trandolapril, 62% to 68% inhibition at a dose of 0.2 mg, 84% to 87% at 1 mg, and 88% to 93% at 5 mg). In contrast, in the brain structures caudate putamen and globus pallidus, lisinopril inhibited ligand binding better than trandolapril (for lisinopril 30% to 44% at a dose of 2 mg and 71% to 74% at 10 mg, versus for trandolapril 21% to 27% at 0.2 mg and 51% to 63% at 1 mg). At 24 h after the last dose, inhibition by trandolapril persisted more than inhibition by lisinopril both outside and inside the BBB. CONCLUSIONS: These results suggest that peripheral administration of even hydrophilic ACE inhibitors can result in marked inhibition of brain ACE inside the BBB but that different brain structures show variable inhibition.
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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 | 0.000 |
| 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".