Effect of dual inhibition of angiotensin converting enzyme and neutral endopeptidase on blood pressure and resistance arteries of deoxycorticosterone acetate-salt hypertensive rats
Bibliographic record
Abstract
Omapatrilat is a new dual inhibitor of neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). Omapatrilat is an effective antihypertensive in low-renin animal models; however its effects on resistance artery structure and function are unknown. To examine this, we studied the effect of omapatrilat in DOCA-salt hypertensive rats and in comparision with the ACE inhibitor enalapril. Uninephrectomized rats were divided into four groups: 1) Normotensive controls; 2) DOCA-salt group: received DOCA+1%NaCl; 3) DOCA-salt+omapatrilat group: received DOCA+1%NaCl+omapatrilat (40 mg/kg/d for 3 weeks); 4). DOCA- salt +enalapril group: received DOCA+1%NaCl+enalapril (10 mg/kg/d for 3 weeks); Systolic blood pressure was significantly reduced in omapatrilat-treated DOCA-salt rats compared to enalapril-treated or untreated DOCA-salt rats (P<0.05). Small artery relaxation responses to acetylcholine were improved by omapatrilat treatment in DOCA-salt rats. Omapatrilat increased lumen diameter and decreased media width and media/lumen ratio (P<0.05) in DOCA-salt rats. Stiffness of resistance artery wall components (slope of the elastic modulus vs stress curve) was unaltered by omapatrilat. Enalapril had no effect on endothelial function and vascular structure in DOCA-salt rats. In conclusion, dual inhibition of ACE /NEP in DOCA-salt hypertensive rats results in potent anti-hypertensive effects, improved endothelial function and reduction of media/lumen ratio of resistance arteries. NEP inhibition is involved to a large extent in the effect of omapatrilat in this model, since ACE inhibition was ineffective. These actions of omapatrilat may confer protection against the end-organ damage characteristic of severe hypertension.
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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 | 0.000 |
| 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) | 0.001 | 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 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".