Effect of Combination of Angiotensin-Converting Enzyme Inhibitors and Vitamin D Receptor Activators on Cardiac Oxidative Stress in Diabetic Rats

Abstract

BackgroundThe principle mediator of diabetic myocardial injury is oxidative stress. The aim was to compare the effect of monotherapy with enalapril, angiotensin-converting enzyme inhibitor and paricalcitol (vitamin D receptor activator), to the combined therapy with both drugs on the cardiac oxidant-antioxidant balance in the type 2 diabetic rats. Materials and MethodsA total of 50 male Sprague-Dawley rats were divided into 5 groups, namely the normal control and diabetic, vehicle, enalapril, paricalcitol and paricalcitol and enalapril-treated groups. Enalapril was given at a dose of (25mg/L) in drinking water once daily and paricalcitol was given intraperitoneally (0.8μg/kg/3 × week) for 3 months. Glycemic status, cardiac oxidant-antioxidant parameters and histologic examination were determined. ResultsParicalcitol and combined treatment significantly (P < 0.01) reduced the level of fasting, postprandial blood glucose, homeostatic model assessment-insulin resistance, cardiac malondialdehyde and nitric oxide. Moreover, they significantly (P < 0.01) increased the levels of insulin and c-peptide compared to diabetic control rats. Combined treatment significantly (P < 0.01) raised the level of glutathione, glutathione S-transferase and catalase more than monotherapy. ConclusionThe combination of angiotensin-converting enzyme inhibitors and vitamin D receptor activators has a superior effect on reducing cardiac oxidative stress by raising antioxidant activity than monotherapy in diabetic rats.