Dissociation of Direct and Indirect Effects of Angiotensin II on the Heart
Bibliographic record
Abstract
33 Cardiac angiotensin II (Ang II), either derived from the circulation or locally synthesized, is often suggested to be involved in the structural adaptations occurring in the heart in hypertension and following myocardial infarction. However, it is debated whether the proven beneficial effects of renin-angiotensin system blockade in these pathologies are related to an inhibition of the direct cardiac actions of the peptide. The objective of the present study was to investigate which of the effects of cardiac Ang II are due to direct stimulation of cardiac cells by Ang II. To test for cardiac specific functions of Ang II, transgenic mice were developed that express an Ang II-releasing fusion protein (J Biol Chem 1997;272:12994-99) exclusively in cardiomyocytes. Blood pressure, heart rate, cardiac and plasma Ang II content, Ang II receptor binding and organ morphology were monitored in transgenic (TG) and non-transgenic littermate mice (control). Cardiac Ang II levels in TG mice were 20-40 fold higher than in hearts of control mice (15±3 pg/100 mg ww). In 3 independent founder lines of TG mice, plasma Ang II concentration was not altered as compared to control (119±20 vs. 127±20 pg/mL). The heart weight to body weight ratio in TG mice (4.0±0.1 mg/g) was not different from controls (3.8±0.1 mg/g), neither was systolic pressure (137±4 and 138±7 mm Hg respectively) or heart rate (618±13 and 662±15 bpm respectively). Microscopic inspection of TG hearts did not reveal any differences with control regarding size and number of cardiomyocytes and organization of extracellular matrix proteins. TG mice had not become less sensitive for Ang II signaling since Ang II receptor number was not altered in TG mice (Bmax = 23±3 fmol/mg protein) as compared to control (22±2 fmol/mg protein). Our data show that very high Ang II levels in hearts of TG mice do not lead to myocardial enlargement or affect cardiovascular physiology. We conclude that elevated Ang II in the heart has no direct effects on cardiac cells and we hypothesize that effects of cardiac Ang II become apparent upon altered hemodynamic loading.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".