Treatment with AT1 receptor blocker restores diabetes-induced alterations in intracellular Ca2+ transients and contractile function of rat myocardium

Abstract We investigated the effect of treatment with an angiotensin II receptor blocker, candesartan-cilexetil, on the mechanical and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Contractile activity and electrophysiological properties were measured in papillary muscle and ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 5 mg/kg/day candesartan-cilexetil for 4 weeks. Alterations in the kinetics of contractile activity and intracellular Ca 2+ transients were observed as well as a typical prolongation of action potential duration and significant decrease of potassium currents in diabetic rat heart preparations. Candesartan-cilexetil treatment recovered significantly prolonged action potential and depressed potassium currents in diabetic rats. It was also shown that treatment with AT 1 blocker restored altered kinetics of both the Ca 2+ transients in cardiomyocytes and the contractile activity in papillary muscle strips of diabetic rats. We also showed that incubation of cardiomyocytes from diabetic rats with a protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM) had a similar effect to candesartan treatment on the Ca 2+ transients. Thus, angiotensin II receptor blockade protects the heart from the development of cellular alterations typically related with diabetes, and this action of AT 1 receptors seems to be related with the activity of PKC.