Korean J Thorac Cardiovasc Surg.  2001 Mar;34(3):203-212.

Attenuation of Reperfusion Injury with Angiotensin AT1 Receptor Blockade in Rat Myocardial Ischemic Mbdel

• Choi JY
• Choi DJ
• Ahn H

Abstract

BACKGROUND: Although AT1 receptor antagonist can protect myocardium against ischemia/reperfusion injury at the cellular level, the in vivo effect and the mechanisms of this effect have not yet been characterized. The present study was designed to examine the myocardial protective effect of irbesartan(an AT1 receptor antagonist) in ischemia-reperfusion model of rats, and to elucidate the role of apoptosis as a biological mechanism mediating reperfusion injury. MATERIAL AND METHOD: An inert vehicle(10% gum arabic: group I, n=14) or irbesartan(50mg/kg/day: group II, n=12) was administered to Sprague-Dawley rats orally every 24 hours for 3 days. Animals were subjected to a 45-minute left coronary artery ligation followed by a 2-hour reperfusion, then the hearts were harvested. The ratio of myocardial infarct area/ischemic risk area was assessed through TTC(triphenyltetrazolium chloride) staining. Degree of apoptosis was evaluated by analyzing the DNA fragmentation attern on agarose gel electrophoresis and TUNEL(TdT-mediated dUDP nick end labeling) staining. Western blot analysis was performed to estimate the expression of the proteins known to regulate apoptosis such as Bcl-2(B-cell lymphoma 2 gene) and Bad, and the MAPKs(mitogen-activated protein kinases) implicated in signal transduction such as ERK (extracellular signal-regulated kinase) and p-38. RESULT: The ratio of infarct area/ischemic area at risk in group II was significantly 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, but DNA ladder formation was attenuated in group II. The expressions of Bcl-2 and ERK1 were higher in ischemic area of group II compared to that of group I.
CONCLUSION
AT1 receptor antagonist, irbesartan, was effective in reducing myocardial reperfusion injury in vivo. This effect can be attributed partially to the attenuation of cardiomyocyte apoptosis, which was suggested by the increased expression of Bcl-2.

Keyword

Myocardial reperfusion injury; Angiotensin II; Cell death

MeSH Terms

Angiotensin II
Angiotensins*
Animals
Apoptosis
Blotting, Western
Cell Death
Coronary Vessels
DNA
DNA Fragmentation
Electrophoresis, Agar Gel
Gum Arabic
Heart
Ligation
Lymphoma
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Myocytes, Cardiac
Negotiating
Rats*
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1*
Reperfusion Injury*
Reperfusion*
Signal Transduction
Angiotensin II
Angiotensins
DNA
Gum Arabic
Receptor, Angiotensin, Type 1