Increased AT(2)R protein expression but not increased apoptosis during cardioprotection induced by AT(1)R blockade.

Abstract

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 mol/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.

• Authors: Rohit Moudgil, Sorin Musat-Marcu, Yi Xu, Dinender Kumar, Bodh I Jugdutt
• Journal: The Canadian journal of cardiology (Can J Cardiol) Vol. 18 Issue 10 Pg. 1107-16 (Oct 2002) ISSN: 0828-282X [Print] England
• PMID: 12420045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Corrected and Republished Article)

Chemical References

• Benzimidazoles
• Biphenyl Compounds
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Receptors, Angiotensin
• Tetrazoles
• candesartan

Topics

• Analysis of Variance
• Animals
• Apoptosis (drug effects, physiology)
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Culture Techniques
• Disease Models, Animal
• Hemodynamics (drug effects)
• Male
• Myocardial Reperfusion Injury (blood, prevention & control)
• Myocardium (cytology)
• Primary Prevention
• Probability
• Rats
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Receptors, Angiotensin (analysis, drug effects, metabolism)
• Reference Values
• Tetrazoles (pharmacology)
• Ventricular Dysfunction, Left (physiopathology)