Abstract 15033: Chronic Inhibition of Mitochondrial Reactive Oxygen Species Protects Against Endothelial SK Channel Dysfunction in Diabetes

Abstract

Introduction: Oxidative stress plays an important role in the development of pathological condition in diabetes. Persistent oxidative stress during diabetes may result in impaired endothelium-independent vasodilation, by reducing small-conductance Ca 2+ -activated K + (SK) channel activity. The mitochondria are main sources of reactive oxygen species (ROS) in diabetes, and mitochondria-targeted antioxidant mito-TEMPO (MT) prevents ROS generation has been found in a variety of disorders. However, few studies are available on the dysfunction of vasodilation and endothelial SK channels in diabetes after a chronic use of MT. Purpose: We investigated the chronic administration of MT on vasodilation in coronary arteries, and endothelial SK channel activity with or without diabetes. Methods: MT (1mg/kg) was applied to diabetic and health mice (n = 6/group) for 1 month. In-vitro relaxation response of pre-contracted arteries was examined in the presence or absence of the vasodilatory agents. Isolated endothelium was studied using whole-cell patch clamp recording SK channels currents. Results: Coronary arteries dilation was decreased in diabetic mice compared with that in health ( p <0.05). After one month treatment with MT, coronary arteries dilation was significantly improved when compared with that in non-treatment diabetic mice ( p <0.05). Interestingly, coronary arteries dilation was no significantly changed in health mice whether to treat with MT or not. Similar changes were seen in patch clamp recording, impaired currents of SK channels in endothelial cells of diabetic mice were significantly improved after chronic treatment with MT ( p <0.05, Fig) and currents of SK channels were no changed in health mice whether to treat with MT or not. Conclusions: MT appears to improve coronary endothelial function/dilation by protection of SK channel activity in diabetes, and administration of MT may be a novel strategy to treat vascular complications in diabetes.