Simvastatin‐sodium delays cell death of anoxic cardiomyocytes by inhibition of the Na⁺/Ca²⁺ exchanger

Abstract

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 microM, attenuated the rise in intracellular Ca2+ concentration ([Ca2+]i) measured with Fura-2 in anoxic cardiomyocytes. In a test of sarcolemmal Na+/Ca2+ exchange activity, simvastatin-sodium attenuated the rise of [Ca2+]i upon incubation in sodium-free buffer, which normally causes a reversal of Na+/Ca2+ exchange and cellular calcium overload. The inhibitory action of simvastatin-sodium on the sarcolemmal Na+/Ca2+ exchanger could well explain the cardioprotective effect of the drug on myocytes subjected to anoxia.