Mechanisms Underlying Sesamolin-Induced Attenuation of Vascular Dysfunction in Rats With Streptozotocin-Induced Diabetes

Background: Cardiovascular disorders constitute the major causes of morbidity and mortality among diabetic patients.Objectives: The effect of chronic sesamolin administration was studied on aortic reactivity of rats with streptozotocin (STZ)-induced diabetesMaterials and Methods: One week after induction of diabetes, male rats received sesamolin for 7 weeks. The contractile responses to KCl and phenylephrine (PE) and the relaxation response to acetylcholine (ACh) were measured in aortic rings.Results: The maximum contractile response to PE of endothelium-intact aortic rings was significantly lower in sesamolin-treated diabetic rats than in untreated diabetic rats. Removal of the endothelium from the aortic rings abolished this difference. The endothelium-dependent relaxation response to ACh was significantly higher in sesamolin-treated diabetic rats than in untreated diabetic rats. Pretreatment of aortic rings with the nitric oxide synthase inhibitor N(G) -nitro-L-arginine methyl ester (L-NAME) significantly attenuated the observed response. A 2-month course of diabetes also resulted in elevated malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity; sesamolin treatment reversed the increased MDA level and reversed the reduced SOD activityConclusions: We conclude that chronic treatment of diabetic rats with sesamolin can prevent abnormal changes in vascular reactivity via nitric oxide regulation and attenuation of oxidative stress in aortic tissue. Furthermore, endothelial integrity is necessary for sesamolin’s beneficial effect.