Open AccessEffect of β 2 ‐adrenergic agonist clenbuterol on ischemia/reperfusion injury in isolated rat hearts and cardiomyocyte apoptosis induced by hydrogen peroxide
Author(s) -
LIU Ping,
XIANG Jizhou,
ZHAO Lei,
YANG Lei,
HU Benrong,
FU Qin
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00794.x
Subject(s) - clenbuterol , hydrogen peroxide , agonist , apoptosis , reperfusion injury , ischemia , adrenergic , β2 adrenergic receptor , pharmacology , adrenergic agonist , medicine , myocardial ischemia , chemistry , endocrinology , anesthesia , receptor , biochemistry
Aim: To observe the effect of β 2 ‐adrenergic agonist clenbuterol on ischemia/reperfusion (I/R) injury in isolated rat hearts and hydrogen peroxide (H 2 O 2 )‐induced cardiomyocyte apoptosis. Methods: Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion on a Langendorff apparatus. Cardiac function was evaluated by heart rate, left ventricular end‐diastolic pressure (LVEDP), left ventricular systolic pressure, maximal rise rate of left ventricular pressure (+d p /d t max ), and the coronary effluent (CF). Lactate dehydrogenase (LDH) in the coronary effluent, malondialdehyde (MDA), superoxide dismutase (SOD), and Ca 2+ ‐ATPase activity in the cardiac tissue were measured using commercial kits. The apoptotic cardiomyocyte was detected by terminal deoxynucleotidyl transferase‐mediated digoxigenin‐dUTP nick‐end labeling (TUNEL) assay. Bax/Bcl‐2 mRNA levels and the expression of caspase‐3 were detected by RT‐PCR and immunoblotting, respectively. Cultured newborn rat cardiomyocytes were pre‐incubated with clenbuterol, and oxidative stress injury was induced by H 2 O 2 . Cell viability and cardiomyocyte apoptosis were evaluated by flow cytometry (FCM). Results: In the isolated rat hearts after I/R injury, clenbuterol significantly improved diastolic function (LVEDP and CF) and Ca 2+ ‐ATPase activity. Treatment with clenbuterol increased SOD activity and decreased the MDA level and LDH release compared with the I/R group ( P <0.05). Moreover, clenbuterol decreased apoptosis, which was associated with a reduction in TUNEL‐positive cells, Bax/Bcl‐2 mRNA, and caspase‐3 expression. In H 2 O 2 ‐induced cardiomyocyte injury, clenbuterol increased cell viability and attenuated cardiomyocyte apoptosis. Pre‐treatment with ICI118551 (selective β 2 ‐adrenergic antagonist) decreased these effects compared with the clenbuterol‐treated group ( P <0.05). Conclusion: Clenbuterol ameliorated ventricular diastolic function by enhaning Ca 2+ ‐ATPase activity and reduced oxidative stress and cardiac myocyte apoptosis in an experimental rat model of myocardium I/R. It decreased cardiomyocyte apoptosis induced by H 2 O 2 in vitro. It plays a key role in the cardiac protection against myocardium I/R injury.