Sodium current inhibitor ranolazine ameliorates experimentally induced diabetic cardiomyopathy

Abstract

Ranolazine is an anti-ischemic drug with glucose lowering effect. Our study scrutinized the effect of ranolazine on Streptozotocin (STZ) induced diabetic cardiomyopathy, emphasizing role of Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) pump. STZ induced diabetic rats showed significant hyperglycaemia with weight loss, hyperlipidaemia, increased cardiovascular risk indices as well as atherogenic index of plasma, Left Ventricular (LV) dysfunction, abnormal electrocardiography (ECG) and elevated cardiac biomarkers (CK-MB, LDH and AST). Twelve weeks ranolazine treatment ameliorated diabetes associated biochemical alterations and LV function along with ECG. The diabetic heart showed increased lipid peroxidation and compromised antioxidant defence mechanism which was reversed by ranolazine treatment. Reduced SERCA expressions were recognised in STZ treated diabetic rats. Ranolazine amplified SERCA expressions thus by regulating intracellular calcium homeostasis and keeping diabetic cardiomyopathy at bay. Ranolazine also prevented histological alterations in the heart and pancreas. Our results may open novel avenues for designing treatment strategies using ranolazine against diabetic cardiomyopathy.