Augmentation of endothelial dependent relaxation in thoracic aorta of streptozotocin induced diabetic rats: Role of Statins

Abstract

Oxidative stress is pathogenetic hypotheses of vascular complication in diabetes by impaired endothelial dysfunction (ED) and antioxidant status. The endothelium is complex organ essential for controlling vascular functions. Vascular endothelium dysfunction leads to pathogenesis of diabetic associated cardiovascular complications. The aim of present study was to evaluate the role of statins in diabetic cardiovascular complications. Hydroxy methyl glutaryl CoA (HMG-CoA) reductase inhibitors (statins) used as lipid lowering began to emerge; such pleiotropic effects include improvement of endothelial dysfunction (ED), increased nitric oxide (NO) bioavailability, antioxidant, anti-inflammatory activities. Hence to evaluate the effect of statins in diabetic vascular complications, we studied the effect of Atorvastatin on acetylcholine responses in thoracic aorta isolated from streptozotocin (STZ, 60 mg kg^-1 i.p.) induced 8 weeks diabetic rats. Acetylcholine induced relaxation response was significantly decreased in aortic strips from diabetic as compared to control rats. Lipid peroxidation was significantly increased while the superoxide dismutase (SOD) and catalase activity were significantly decreased in aorta of diabetic rats with compared to control rats. The systolic, diastolic and mean arterial pressure (MAP) was significantly increased in diabetic rats with compared to control rats. Diabetic rats treated with Atorvastain (20 & 40 mg/kg/day) for 8 weeks selectively restored the endothelial dependent relaxation response of acetylcholine to near the reactivity observed in vessels from control rats. The enhanced lipid peroxidation, systolic, diastolic and MAP and reduced SOD and Catalase activity were significantly restored to control values following Atorvastain treatment. From results we infer that Atorvastain improves diabetes induced endothelial dysfunction by reducing oxidative stress and blood pressure, increasing relaxation responses of acetylcholine. So it could be an ideal intervention in therapy of diabetic associated cardiovascular complications.