Protective Effect of Sitagliptin and Rosuvastatin Combination on Vascular Endothelial Dysfunction in Type-2 Diabetes

Abstract

The present investigation aimed to evaluate the protective effects of sitagliptin, glimepiride, rosuvastatin and their combinations on oxidative stress and endothelial dysfunction in the aortic tissues in fructose-fed type-2 diabetic rats. Sitagliptin (20 mg/kg, p.o.), glimepiride (2 mg/kg, p.o.), rosuvastatin (5 mg/kg, p.o.) and their combinations were administered for 6 w after induction of diabetes by fructose (66%, w/v solution, p.o. for 8 w) in wistar rats. The effects were examined on body weight, serum glucose, triglyceride, cholesterol, blood pressure, heart rate, nitric oxide and antioxidant defensive enzymes. After completion of treatment schedule, the blood pressure was determined by invasive method and vascular reactivity was tested with adrenaline, noradrenaline and phenylephrine. Endothelial dysfunction was determined by acetylcholine and sodium nitroprusside-induced vasorelaxation studies on isolated rat aortas. Long term treatments significantly decreased body weight gain, serum glucose, triglyceride and cholesterol levels; normalize the heart rate, and blood pressure in fructose fed rats. The treatments significantly improved vascular reactivity to catecholamines with reduction in elevated blood pressure in type-2 diabetic rats. The significant improvement in the relaxant response to acetylcholine and sodium nitroprusside was obtained on isolated aortas. All the treatments were effective in restoring defensive antioxidant enzymes. Sitagliptin and rosuvastatin were able to reverse endothelial dysfunction in type-2 diabetes, but better ameliorating potential was found when used in combination.