Enhanced Expression of Angiotensin II Type 2 Receptor, Inositol 1,4,5-Trisphosphate Receptor, and Protein Kinase Cε During Cardioprotection Induced by Angiotensin II Type 2 Receptor Blockade
Bibliographic record
Abstract
We hypothesized that the cardioprotective effect of angiotensin II type 2 receptor (AT(2)R) blockade with PD 123,319 (PD) on the recovery of left ventricular (LV) mechanical function after ischemia/reperfusion (IR) in the isolated working rat heart is associated with the enhanced expression of AT(2)R protein and mRNA as well as an increase in inositol 1,4,5-trisphosphate type 2 receptor (IP(3)R) and protein kinase Cepsilon (PKCepsilon) proteins. We assessed AT(2)R, angiotensin II type 1 receptor (AT(1)R), IP(3)R, and PKCepsilon protein expression (Western blots) and AT(2)R mRNA levels (Northern blots) in myocardium from isolated working rat hearts that were subjected to global ischemia (30 minutes) followed by reperfusion (30 minutes). Groups of adult rat hearts (n=6) were exposed to no IR, no IR+PD (0.3 micromol/L), IR, and IR+PD. Compared with no IR and no IR+PD, IR decreased (P<0.05) functional recovery and AT(2)R mRNA and protein, as well as AT(1)R mRNA (not protein) and IP(3)R and PKCepsilon proteins. Compared with IR, PD+IR improved LV functional recovery (P<0.05) and markedly increased AT(2)R mRNA and protein (P<0.001). However, PD did not change AT(1)R mRNA or protein. More importantly, PD+IR markedly increased IP(3)R and PKCepsilon proteins. The downregulation of AT(2)R mRNA and protein with IR and their upregulation with PD indicate that the effects of PD are AT(2)R specific. The overall results suggest that the cardioprotective effect of acute PD treatment on LV functional recovery after IR in the isolated working rat heart is specifically due to AT(2)R blockade and is associated with enhanced downstream IP(3)R and PKCepsilon signaling.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".