Influence of the Angiotensin II AT1 Receptor Antagonist on Reperfusion Injury in Rat Myocardial Ischemia Model.
10.4070/kcj.2001.31.11.1150
- Author:
Jung Hee NAM
1
;
Ji Eun LEE
;
Eun Ji KIM
;
Seong Ji PARK
;
Byung Cheol JIN
;
Tae Jun PARK
;
Jun Young CHOI
;
Dong Ju CHOI
;
Bong Gwan SEO
Author Information
1. Department of Interenal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea. djchoi@nongae.gsnu.ac.kr
- Publication Type:Original Article
- Keywords:
Myocardial reperfusion injury;
Receptors, angiotensin;
Apoptosis;
MAP kinase signaling system;
Angiotensin II;
Irbesartan
- MeSH:
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*
- From:Korean Circulation Journal
2001;31(11):1150-1158
- CountryRepublic of Korea
- Language:Korean
-
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.
