Related Experiment Video
Updated: Aug 8, 2026
Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
Increased AT2R protein expression but not increased apoptosis during cardioprotection induced by AT1R blockade
Rohit Moudgil1, Sorin Musat-Marcu, Yi Xu
1Department of Medicine, University of Alberta, Edmonton, Canada.
Background:
The angiotensin II type 2 receptor (AT2R) is considered to be antigrowth and to mediate apoptosis in several cell types. Whether AT2R upregulation, associated with angiotensin II type 1 receptor (AT1R) blockade and cardioprotection after ischemia-reperfusion (IR), might not result in increased cardiomyocyte (CM) apoptosis has not been documented.
Objectives:
To determine whether increased AT2R protein expression, during AT1R blockade after acute IR, is associated with no increase in CM apoptosis.
Materials And Methods:
The recovery of left ventricular (LV) mechanical function after acute IR (30 min of ischemia, 40 min of reperfusion) was measured in isolated Langendorff rat hearts following pretreatment with the AT1R antagonist candesartan (CN) (CN 10 nmol/L) for 40 min before ischemia. The authors established with an initial dose-response curve using escalating concentrations of CN that 10 nmol/L abrogated vasoconstriction induced by angiotensin II (0.1 mmol/L). AT1R and AT2R protein expression (Western immunoblot), CM apoptosis (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labelling assay and nuclear morphology) and apoptotic markers (Bax, Bcl-2, caspase-3, p53) were assessed in LV tissue.
Results:
Compared with IR controls, CN improved peak systolic pressure, LV developed pressure and positive dp/dt, and increased AT2R (not AT1R) protein, but did not change the level of apoptosis or the expression of Bax, Bcl-2, caspase-3 or p53. CN also increased AT2R protein after ischemia alone but did not change CM apoptosis or expression of the markers.
Conclusions:
Increased AT2R protein expression during AT1R blockade after IR in the isolated Langendorff rat heart is associated with cardioprotection but no increase in CM apoptosis.
Insights
Angiotensin II type 2 receptor (AT2R) upregulation with AT1R blockade after ischemia-reperfusion (IR) protects the heart without increasing cardiomyocyte apoptosis. This study investigated the link between AT2R and cell death following IR.
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Ischemia-Reperfusion Injury
Background:
- The angiotensin II type 2 receptor (AT2R) is generally considered antigrowth and pro-apoptotic.
- Upregulation of AT2R is observed with angiotensin II type 1 receptor (AT1R) blockade, a strategy known for cardioprotection after ischemia-reperfusion (IR).
- The potential for increased AT2R to induce cardiomyocyte (CM) apoptosis following IR has not been previously documented.
Purpose of the Study:
- To investigate whether elevated AT2R protein expression, induced by AT1R blockade subsequent to acute IR, correlates with a lack of increased CM apoptosis.
- To assess the impact of AT1R blockade on AT2R expression and CM apoptosis in the context of IR.
Main Methods:
- Isolated Langendorff rat hearts underwent 30 minutes of ischemia followed by 40 minutes of reperfusion (IR).
- Hearts were pretreated with candesartan (CN), an AT1R antagonist, at 10 nmol/L.
- Left ventricular mechanical function, AT1R and AT2R protein expression, CM apoptosis, and apoptotic markers (Bax, Bcl-2, caspase-3, p53) were evaluated.
Main Results:
- Candesartan (CN) improved cardiac function (peak systolic pressure, LV developed pressure, +dp/dt) compared to IR controls.
- CN significantly increased AT2R protein expression but not AT1R protein levels.
- No significant changes were observed in CM apoptosis or the expression of apoptotic markers (Bax, Bcl-2, caspase-3, p53) with CN treatment post-IR.
Conclusions:
- Increased AT2R protein expression, resulting from AT1R blockade in an isolated rat heart model after IR, is linked to cardioprotection.
- This AT2R upregulation does not lead to an increase in cardiomyocyte apoptosis.
- The findings suggest a protective role for AT2R in the context of IR under AT1R blockade.
Related Concept Videos
01:17Antihypertensive Drugs: Action of β1 Blockers
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System