Angiotensin‐converting enzyme 2 antagonizes angiotensin II‐induced pressor response and NADPH oxidase activation in Wistar–Kyoto rats and spontaneously hypertensive rats
Bibliographic record
Abstract
New Findings What is the central question of this study? Angiotensin‐converting enzyme 2 (ACE2), an enzyme which converts angiotensin II (Ang II) into angiotensin‐(1–7) [Ang‐(1–7)] and terminates the effects of Ang II, is a negative regulator of activated renin‐angiotensin system (RAS). Cardiac overexpression of ACE2 has shown conflicting results on myocardial fibrosis in contrast to marked anti‐ hypertensive and anti‐remodelling properties. What is the main finding and its importance? Recombinant hACE2 administration attenuates oxidative stress, NADPH oxidase activity and ERK1/2 signalling and high blood pressure confirming its beneficial role in two rat models of hypertension. Angiotensin‐converting enzyme 2 (ACE2), a monocarboxypeptidase capable of metabolizing angiotensin II (Ang II) into angiotensin‐(1–7) [Ang‐(1–7)], has emerged as a potential therapeutic target. We hypothesized that ACE2 is a negative regulator of Ang II‐mediated pathological effectsin vivo. In Wistar–Kyoto (WKY) rats, Ang II infusion (0.1 μg min−1kg−1) induced a pressor response, activation of NADPH oxidase and generation of superoxide in the heart, kidney and blood vessels; these effects were significantly blunted by recombinant human ACE2 (rhACE2; 2 mg kg−1), in association with a lowering of plasma Ang II and elevation of Ang‐(1–7) levels. In the spontaneously hypertensive rat (SHR) model, rhACE2 (2 mg kg−1day−1) delivered over a 14 day period partly corrected the hypertension, the NADPH oxidase activation and the increased superoxide generation in the heart, kidney and blood vessels. Treatment with rhACE2 inhibited Ang II‐mediated phosphorylation of the myocardial extracellular signal‐regulated kinase 1/2 pathway in WKY rats, with congruent results seen in SHR hearts. Hence, rhACE2 is an important negative regulator of the Ang II‐induced pressor response and NADPH oxidase activation and suppresses pathological myocardial signalling, thereby providing a novel therapeutic agent with which to antagonize an activated renin–angiotesin system.
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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".