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Trimetazidine improved Ca 2+ handling in isoprenalinemediated myocardial injury of rats
Author(s) -
Meng Dan,
Feng Lin,
Chen XiangJian,
Yang Di,
Zhang JiNan
Publication year - 2006
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.032615
Subject(s) - trimetazidine , cardiology , medicine
Dysregulation of intracellular Ca 2+ homeostasis plays an important role in mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve intracellular Ca 2+ handling in myocardial injury of rats. The control group received saline only (10 ml kg −1 day −1 , i.p .) for 7 days. In a second group, isoprenaline (ISO; 5 mg kg −1 day −1 , s.c .) was administered to rats for 2 days to induce an acute injury of the myocardium. In a third group, treatment with TMZ (10 mg kg −1 day −1 , i.p. ) was initiated 1 day before ISO administration and continued for 7 days ( n = 7 rats in each group). Histopathological evaluation showed that TMZ prevented ISO‐induced myocardial damage. TMZ preserved the ATP levels and decreased the maleic dialdehyde (MDA) content in the hearts compared with ISO‐treated rats. The diastolic [Ca 2+ ] i measured by loading with fura‐2 AM in isolated cardiomyocytes was increased significantly in ISO‐treated rats compared to the control animals. TMZ prevented the rise of diastolic [Ca 2+ ] i and the depression of caffeine‐induced Ca 2+ transients caused by ISO administration. The reduction in sarcoplasmic reticulum (SR) Ca 2+ content in the heart cells and in cardiac SR Ca 2+ ‐ATPase activity in ISO‐treated rats was abolished by TMZ, although there were no differences in SR Ca 2+ ‐ATPase protein levels between the control, ISO and ISO + 7 mz‐treated rats. In addition, TMZ prevented the reduction in sarcolemmal L‐type Ca 2+ current density in the heart cells induced by ISO treatment. These results demonstrate that the treatment of rats with TMZ inhibited the increase of diastolic [Ca 2+ ] i and prevented the decrease of SR Ca 2+ content, SR Ca 2+ ‐ATPase activity and L‐type Ca 2+ current density in cardiomyocytes in ISO‐mediated myocardial injury of rats. These changes in Ca 2+ handling could help to explain the favourable action of TMZ in myocardial injury.