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

Background: The 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 Methods: A 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 (25 mg/L) in drinking water once daily and paricalcitol was given intraperitoneally (0.8 g/kg/3 x week) for 3 months. Glycemic status, cardiac oxidant-antioxidant parameters and histologic examination were determined. Results: Paricalcitol 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. Conclusion: The 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.