The effect of sodium tungstate treatment on altered excitation-contraction coupling of diabetic rat ventricular myocytes

Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts. In this study we investigated the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate.Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for six weeks. Blood glucose levels were found to increase dramatically in diabetic animals. Conversely, body weight, heart weight and plasma insulin levels decreased and tungstate treatment did not reverse any of these parameters. Sarcomere shortening and intracellular Ca2+ [Ca2+]i transients of isolated ventricular myocytes were measured in Fura-2 AM loaded cells. Sodium tungstate treatment improved the peak shortening and the amplitude of [Ca2+]i transients in diabetic cardiomyocytes. However, prolonged time characteristics of neither shortening nor [Ca2+]i transients were reversed after treatment. Significant restoration of suppressed Ito and Iss was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in diabetic or tungstate treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase and xanthine dehydrogenase were also determined to assess whether the effect of tungstate was relevant to oxidative status of heart. Diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate. Although tungstate treatment markedly decreased xanthine oxidase/xanthine dehydrogenase activity, this change was not significant among the different treatment groups.In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca2+]i and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of glycaemia.