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Simvastatin‐sodium delays cell death of anoxic cardiomyocytes by inhibition of the Na + /Ca 2+ exchanger
Author(s) -
Bastiaanse E.M.Lars,
Atsma Douwe E.,
Kuijpers Marinette M.C.,
Van Der Laarse Arnoud
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)80308-0
Subject(s) - simvastatin , sodium , chemistry , metabolite , myocyte , calcium , pharmacology , intracellular , biochemistry , biophysics , endocrinology , biology , organic chemistry
When incubated under anoxic conditions, cultured neonatal cardiomyocytes undergo cell necrosis. Simvastatin‐sodium, the bioactive metabolite of simvastatin (a potent serum cholesterol‐lowering drug), delayed the anoxia‐induced myocyte necrosis in a dose‐dependent manner. This beneficial effect of simvastatin‐sodium could not be attributed to its cholesterol‐lowering properties. We found that simvastatin‐sodium, at concentrations of 20 and 50 μM, attenuated the rise in intracellular Ca 2+ concentration ([Ca 2+ ] i ) measured with Fura‐2 in anoxic cardiomyocytes. In a test of sarcolemmal Na + /Ca 2+ exchange activity, simvastatin‐sodium attenuated the rise of[Ca 2+ ] i upon incubation in sodium‐free buffer, which normally causes a reversal of Na + /Ca 2+ exchange and cellular calcium overload. The inhibitory action of simvastatin‐sodium on the sarcolemmal Na + /Ca 2+ exchanger could well explain the cardioprotective effect of the drug on myocytes subjected to anoxia.