NOS2 南京医科大学(英文版).pdfVIP

17ß-Estradiol Antagonizes the Down-Regulation of ERa/ NOS-3 Signaling in Vascular Endothelial Dysfunction of Female Diabetic Rats 1. 2. 1. 2 2 2 2 Yi Han , Xiaozhen Li , Suming Zhou , Guoliang Meng , Yujiao Xiao , Wen Zhang , Zhuoying Wang , 2 2 2 2 Liping Xie , Zhen Liu , Hui Lu , Yong Ji * 1 Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China, 2 State Key Laboratory of Reproductive Medicine, Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, People’s Republic of China Abstract Previous studies indicated that estrogen could improve endothelial function. However, whether estrogen protects vascular complications of diabetes has yet to be clarified. The study was designed to investigate the action of 17ß-estradiol on vascular endothelium in streptozotocin (STZ)-induced diabetic rats. Ovariectomized female Sprague-Dawley rats were administered with streptozotocin to produce an ovariectomized-diabetic (OVS) model which manifested as dysfunction of aortic dilation and contraction ability. Meanwhile, OVS animals with 17ß-estradiol supplementation significantly improved aortic function. Accordingly, nitric oxide synthase-3 (NOS-3), Akt, PI3K and estrogen receptor a (ERa) protein expression in aorta declined in the OVS group. Such effects were partially restored by estrogen replacement. The presence of 17ß- estradiol similarly counteracted the reduction of cyclic guanosine monophosphate (cGMP), the enhanced expression of inducible NOS (NOS-2) and NO metabolites (nitrite and nit