Vascular protective actions of the angiotensin receptor blockers valsartan and losartan in STZ-induced diabetic rats

Abstract

Augmentation of angiotensin II (Ang II) signaling with the subsequent overproduction of the reactive oxygen species (ROS) has been documented to be involved in the development of the diabetic cardiovascular complications. This study aimed to assess the potential impact of angiotensin II type 1 (AT1) receptors blockage, with valsartan or losartan, on the progression of the cardiovascular complications associated with diabetes in comparison with the classical antidiabetic drug, metformin. Animals were randomly assigned into one normal group, one group of untreated streptozotocin (STZ) (45 mg/kg)-induced type â€iT diabetic rats, and five groups of STZ diabetic rats that received different daily oral treatments over a six week period as follows: metformin (100 mg/kg), valsartan (7 and 14 mg/kg), and losartan (5 & 10 mg/kg). Systolic blood pressure and heart rate were measured weekly. At the end of the study, blood samples were withdrawn for the estimation of the oxidative stress biomarkers, and histopathological assessments of aorta were conducted as well. The STZ-induced diabetic rats exhibited blood pressure elevation, heart rate reductions, disturbances in the oxidative stress biomarkers, as well as aortic histopathological aberration compared with normal control group. Metformin administration resulted in a non-significant tendency to ameliorate the elevated blood pressure with no effect on the heart rate and partially reversed the disrupted oxidative stress biomarkers. However, treatment with valsartan or losartan abolished the development of hypertension in diabetic rats with no effect on the associated bradycardia, and successfully attenuated the generation of ROS as compared to the diabetic rats. Treatment with metformin, valsartan, and losartan showed ameliorative effects on the aortic histopathological aberrations observed in diabetic rats. In STZ diabetic rats, our data suggest that the beneficial effects afforded by blockage of the AT1 receptor with valsartan or losartan treatments could be in part mediated through a mechanism that may involve inhibition of ROS production.