Cardioprotective effects of angiotensin II type 1 receptor blockade with candesartan after reperfused myocardial infarction: role of angiotensin II type 2 receptor
Bibliographic record
Abstract
To determine whether angiotensin II (Ang II) type 2 (AT2)-receptor activation associated with cardioprotection induced by Ang II type 1 (AT1)-receptor blockade during ischaemia-reperfusion (IR) might be reflected in increased AT 2-receptor, IP3-(1,4,5- inositol trisphosphate type 2) receptor and PKC-ε (protein kinase C-ε) proteins and tissue cGMP (cyclic guanosine monophosphate), we measured in vivo left ventricular (LV) systolic and diastolic function and remodelling (echocardiogram/Doppler) and haemodynamics, and ex vivo infarct size, AT1-/AT 2receptor, IP3-receptor and PKC-ε proteins (immunoblots) and cGMP (enzyme immunoassay) in dogs with reperfused anterior acute myocardial infarction (MI) (90-minute ischaemia, 120-minute reperfusion). Compared with controls (C, n=6) in vivo, candesartan (1 mg/kg i.v. over 30-minute pre-ischaemia, n=6) effectively inhibited the Ang II pressor response (Δ%, -14±22% vs. -80±11, p<0.003) and decreased preload (122±35 vs. -2±16%, p<0.01), improved LV systolic ejection fraction (-29±4 vs. -11±5, p<0.03) and diastolic function (E/A ratio, -25±7 vs. 33±13, p<0.004), decreased the extent of LV asynergy (26±20 vs. -31±10% LV, p<0.05) and limited acute LV remodelling (expansion index 19±6 vs. -3±5, p<0.05; thinning ratio -22±2 vs. -4±2, p<0.0003). Ex vivo, candesartan decreased infarct size (55±2 vs. 27±2% risk, p<0.001) and increased infarct zone (IZ) AT2 -receptor protein by 8-fold (but not AT1-receptor protein), IP3-receptor protein by 12-fold, PKC-ε protein by 5-fold and cGMP by 40%. Cardioprotective effects of AT1-receptor blockade on acute IR injury, LV function, and remodelling may also involve AT 2-receptor activation and downstream signalling via IP3-receptor, PKC-ε and cGMP.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.000 | 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".