Abstract 629: Role of Angiotensin-Converting Enzyme 2 in the Regulation Of Resistance Artery Function
Bibliographic record
Abstract
Background: Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II to Ang-(1-7), which may have a protective role at the level of the cardiovascular system through its action on the Mas receptor. We hypothesized that, in vivo, ACE2 exerts a protective effect on resistance artery function. METHODS: Ten to twelve-week old male ACE2 gene knockout (Ace2-/y) and wild type (WT) mice were implanted with a dummy pump (control) or infused with a subpressor doses of angiotensin II (400 ng/kg/min, s.c.) for 7 days (n=6-8). Systolic blood pressure (SBP) was measured by telemetry. Endothelial function and vessel structure were assessed in 2nd order mesenteric arteries by pressurized myography. Endothelial function was studied as the relaxation response to increasing concentrations of acetylcholine (10-9 to 10-4 M) in the presence or absence of Ang-(1-7) (10-7M). Results: SBP was not significantly different amongst the four groups. The vasodilatory response to acetylcholine was significantly lower in Ace2-/y mice compared to WT (maximal relaxation in response to acetylcholine, mean ± SEM, Ace2-/y: 85 ± 2.2 %, vs WT: 97 ± 1.3 %, P<0.001). Ang II infusion induced a significant decrease in the vasodilatory response to acetylcholine in WT mice by 25% (P<0.05) and ace2-/y mice by 28% (P<0.05), compared to control mice. In Ace2-/y mice, Ang II-induced endothelial dysfunction was blunted by the presence of Ang-(1-7) in the myograph chamber, an effect not observed in WT mice. No significant difference was observed in vascular remodeling between the four groups. Conclusion: These results indicate that genetic absence of ACE2 causes endothelial dysfunction, independent of changes in blood pressure. The data suggest that endogenous ACE2 exerts a protective effect on resistance artery endothelial function, which may be partly mediated by production of Ang-(1-7).
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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) | 0.000 | 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".