Korean Circ J.  2001 Nov;31(11):1150-1158. 10.4070/kcj.2001.31.11.1150.

Influence of the Angiotensin II AT1 Receptor Antagonist on Reperfusion Injury in Rat Myocardial Ischemia Model

• Nam JH
• Lee JE
• Kim EJ
• Park SJ
• Jin BC
• Park TJ
• Choi JY
• Choi DJ
• Seo BG

• KMID: 1938934
• DOI: http://doi.org/10.4070/kcj.2001.31.11.1150

Abstract

BACKGROUND AND OBJECTIVES
The protective effect of angiotensin converting enzyme (ACE) inhibitor against ischemia/reperfusion injury has been demonstrated in animal models, however the effect of AT1 receptor antagonist is contradictory. The present study was designed to investigate the myocardial protective effects of the AT1 receptor antagonist irbesartan during myocardial ischemia/reperfusion in vivo.
MATERIALS AND METHODS
Sprague-Dawley rats were subjected to a 45-minute left coronary artery ligation followed by a 2-hour re-perfusion. An inert vehicle (group I:n=14) or irbesartan (50 mg/kg/day:group II, n=12) was administered for 3 days before coronary occlusion. The ratio of the myocardial infarct area to the ischemic area at risk was assessed through triphenyltetrazolium chloride staining. Apoptosis was evaluated by analyzing DNA fragmentation and TdT-mediated dUDP nick end labeling staining. Western blot analysis was performed for MAP Kinases (ERK1/2 and p38) and Bcl-2 and Bax.
RESULTS
The ratio of the infarct area to the ischemic area at risk of group II was smaller than that of group I (42.6+/-2.7% vs. 64.1+/-4.6%;p<0.005). Agarose gel electrophoresis revealed discrete DNA laddering in the ischemic zone of group I, however DNA ladder formation was attenuated in group II. The expressions of ERK1 MAPK and Bcl-2 were increased in the ischemic area of group II compared to that of group I.
CONCLUSION
AT1 receptor antagonist was effective in reducing myocardial reperfusion injury in vivo. This effect can at least be partially attributed to the attenuation of cardiomyocyte apoptosis, and this anti-apoptotic effect appears to be related to the increased expression of Bcl-2 and alterations in MAP kinase signaling.

Keyword

Myocardial reperfusion injury; Receptors, angiotensin; Apoptosis; MAP kinase signaling system; Angiotensin II; Irbesartan

MeSH Terms

Angiotensin II*
Angiotensins*
Animals
Apoptosis
Blotting, Western
Coronary Occlusion
Coronary Vessels
DNA
DNA Fragmentation
Electrophoresis, Agar Gel
Ligation
MAP Kinase Signaling System
Models, Animal
Myocardial Infarction
Myocardial Ischemia*
Myocardial Reperfusion Injury
Myocytes, Cardiac
Peptidyl-Dipeptidase A
Phosphotransferases
Rats*
Rats, Sprague-Dawley
Receptors, Angiotensin
Reperfusion Injury*
Reperfusion*
Angiotensin II
Angiotensins
DNA
Peptidyl-Dipeptidase A
Phosphotransferases
Receptors, Angiotensin