Aortic endothelium-dependent vasodilation function and PI3K-,PKB-,eNOS mRNA expressions in insulin-resistant and type 2 diabetic rats

Objective To observe the changes of aortic endothelium-dependent vasodilation function (EDVR)and expressions of endothelial nitric oxide synthase(eNOS),phosphatidylinositol 3-kinase (PI3K),and protein kinase B(PKB)in insulin-resistance(IR)and type 2 diabetic rats.Methods IR rat model was established by feeding 4-6 week-old male SD rats with high glucose and cholesterol diet for 6 weeks and type 2 diabetes(DM)were induced by intraperitoneal injection with low dose streptozotocin (STZ)to IR rats.Glucose infusion rate(GIR)was determined by euglycemic hyperinsulinemic clamp technique,EDVR by achtylcholine(Ach)-induced vasodilation response in isolated aortic tings,aortic NO concentration by Griess Reaction,activation of eNOS detected by immnohistochemical SP method,mRNA expressions of eNOS-,PI3K-and PKB of aorta were assayed by RT-PCR,aorta ultrastructure observed by electron microscopy.Body weight,fast plasma glucose(FPG),insulin(FINS),triglyceride(TG), cholesterol(TC)were determined and the insulin sensitivity index(ISI)was calculated.Results(1)Body weight,FINS,TG and TC levels were significantly higher while ISI and GIR significantly lower in IR and DM rats than that in normal control rats(P0.05).(2)Aorta EDVR decreased significantly in IR and DM group compared with that in control group(P0.05)and EDVR was also significantly reduced in DM rats than that in IR rats(P0.05).The maximum Ach-induced vasodilation response(EDVR_(max),P0.01) was positively correlated with ISI and negatively correlated with FPG,TG,TC and FINS(P0.01).(3) Aortic NO concentration,the mRNA expressions of eNOS-,PI3K-,and PKB and eNOS immnohistochemical expression in aorta were significantly lower in IR and DM rats compared with normal control rats and the decrease was more pronounced in DM rats(P0.05 vs.IR).(4)Pathologic aortic ultrastructure changes were also visualized in IR and DM rats.Conclusion Our results suggest that reduced NO concentration and expression as well as reduced PI3K-,PKB-,and eNOS mRNA expressions might contributed to the reduced EDVR function and related pathological ultrastructure changes in IR and DM rats.