[Effects of atenolol and metoprolol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction in rats].
OBJECTIVE
To compare the beneficial effects of Atenolol and Metoprolol on cardiomyocyte apoptosis and related gene expressions after acute myocardial infarction (AMI) in rats.


METHODS
AMI model was established with the ligation of anterior descending coronary artery in 251 randomly selected female SD rats. Twenty-four hours after operation, the 124 survivors were randomly assigned to AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(-1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham operation group (group S, n = 27) was also established. Two subgroup (48 h subgroup and 4 weeks subgroup) was randomly divided in each group according to the time points. Drugs were given to each treatment group by gastric gavage 24 h after ligation. Cardiomyocyte apoptosis was detected with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry and Western blot analysis.


RESULTS
Compared with AMI control group, myocyte apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01) in group B. Bcl-2 expression was found to increase in myocytes of infarction, border and non-infarcted areas except for non-infarcted area of group A. Changes of the expressions of bax and caspase-3 was not significant. Four weeks after AMI, MAR was found to decrease significantly in scar, border and non-infarcted areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of bcl-2, bax and caspase-3 expressions was found except for a significant decrease of bax expression in non-infarcted area of group A. As indicated by Western blot, no significant change of the expressions of caspase-3, bcl-2 and bax were found in myocytes of group A and group B compared with AMI control group; however, bcl-2/bax ratio significantly increased to the same level of sham-operated group (P < 0.05).


CONCLUSIONS
Both Atenolol and Metoprolol treatment can reduce cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.
Chen
Yue-Feng
YF
Department of Coronary Heart Disease, Cardiovascular Institute and Fuwai Hospital, CAMS and PUMC, Beijing 100037, China.
Yang
Yue-Jin
YJ
Chen
Xi
X
Ruan
Ying-Mao
YM
Sun
Rui-Cheng
RC
Tian
Yi
Y
Zhou
Yan-Wen
YW
Wang
Qing-Zhi
QZ
Si
Wen-Xue
WX
Chen
Ji-Lin
JL
Gao
Run-Lin
RL
Chen
Zai-Jia
ZJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001262:Atenolol / Q000494:pharmacology*; D005260:Female; D008790:Metoprolol / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
D000319:Adrenergic beta-Antagonists; C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001262:Atenolol; D008790:Metoprolol