Abstract 15087: Chronic Inhibition of NADPH Oxidase Improves Coronary Endothelial Function in Mice With Diabetes

Abstract

Introduction:: Endothelial dysfunction is the leading cause for diabetes (DM) related coronary heart disease. Diabetes is associated with NADPH Oxidase (Nox) overproduction and related ROS amplification in endothelial cells and coronary vasculature, which may contribute to coronary endothelial dysfunction. Small conductance calcium-activated-potassium (SK) channels also play a key role in diabetes-induced coronary endothelial dysfunction . Hypothesis: Chronic inhibition of Nox may improve coronary endothelial function/coronary arteriolar relaxation, and SK activator-induced vasodilation in mice with or without diabetes. Methods: Wild type (control), non-diabetic (ND) mice and genetically modified, obesity/type-2 diabetic mice (BKS.Cg- Dock7 m +/+ Lepr db /J) with or with treatment with Nox inhibitor apocynin (n = 4-6/group) were used in the study. In the Nox inhibitor treated group, apocynin (30mg/kg/day, i.p) was applied to the diabetic mice for 4 weeks. Small coronary arteries (70-120μM) isolated for harvested hearts were pre-contracted and examined in the presence or absence of the vasodilatory agents, SNP, ADP, and NS309, respectively. Results: After 4-week treatment with apocynin, endothelium-NO-dependent relaxation responses to ADP, and endothelium-dependent, SK channel activator NS309 in the diabetic mice were significantly increased when compared with that in untreated diabetic mice, respectively (# p<0.05 vs ND Figure ). There were no significant differences in responses to the endothelium-independent vasodilator SNP (P>0.05) among the three groups. Conclusions: Chronic inhibition of Nox appears to improve coronary endothelial function/coronary relaxation and SK channel activity in mice with diabetes.