Myocardial ischemia-
reperfusion injury involves
necrosis and apoptosis. The inhibition of
angiotensin-converting enzyme (ACE) has been reported to suppress
infarct size. In this study, it was investigated whether an
ACE inhibitor affected myocardial apoptosis and apoptosis-related
proteins in rats with experimental
myocardial infarction. Anesthetized Sprague-Dawley rats were divided into four groups. Group I underwent 30 minutes of left coronary artery occlusion followed by 24 hours of reperfusion (control group); Group II underwent
oral administration of the
ACE inhibitor quinapril (10 mg/kg/day) before
coronary occlusion (
quinapril group); Group III underwent administration of the
bradykinin B(2)-receptor antagonist
Hoe 140 (250 microg/kg/day, subcutaneously) with
quinapril (
quinapril +
Hoe 140 group); and Group IV underwent administration of
Hoe 140 alone (
Hoe 140 group). After reperfusion, myocardial
infarct size was determined by
triphenyltetrazolium chloride staining. Myocardial apoptosis was detected immunohistologically using
terminal deoxynucleotidyl transferase-mediated nick end labeling staining and
DNA electrophoresis. Myocardial
caspase-3 activation was analyzed by Western blot and the expressions of Bcl-xL and Bax
proteins were detected immunohistochemically.
Quinapril significantly reduced the ratio of
myocardial infarct size in the ischemic area at risk. In addition,
quinapril significantly suppressed the incidence of apoptotic myocytes around the necrotic region (from 18.9 +/- 0.8% to 8.6 +/- 1.0%; P < 0.0001), the intensity of
DNA ladder formation, and the activation of
caspase-3.
Hoe 140 attenuated these protective effects of
quinapril. In the immunohistochemical study, Bax and Bcl-xL were expressed in myocytes, and
ischemia-reperfusion abolished both
proteins in the center region of
ischemia. The Bax staining was equally observed among all groups. However, Bcl-xL staining remained in the ischemic area widely after
quinapril treatment. In addition,
Hoe 140 also depleted this effect of
quinapril. These results suggest that inhibition of ACE reduces
myocardial infarction and apoptosis via the
bradykinin B(2) receptor in part. The antiapoptotic effect of the
ACE inhibitor is attributed to the changing expression of Bcl-xL.