title: Alleviation of hyperglycemia induced vascular endothelial injury by exenatide might be related to the reduction of nitrooxidative stress.
abstract: We will investigate the effects of exenatide on vascular endothelial injury and nitrooxidative stress in hyperglycemia both in vivo and in vitro and explore the role of nitrooxidative stress in endothelium-protective action of exenatide. Healthy male Wistar rats were randomly divided into 4 groups: control, diabetes mellitus (DM) model, low dose of exenatide treatment, and high dose of exenatide treatment. In vitro study showed that, compared with control group, the DM rats exhibited a lowered endothelium-dependent relaxation and damaged structural integrity of thoracic aortas, and there was a significant increase in plasma nitrotyrosine concentration. These parameters were improved after treatment with either low dose or high dose of exenatide for 45 days. In vitro study showed that exendin-4 (the active ingredient of exenatide) attenuated HUVECs injury induced by high glucose, with improving cell viability and attenuating cell apoptosis. Exendin-4 also significantly alleviated the increased malondialdehyde (MDA), nitrotyrosine content, and inducible nitric oxide synthase (iNOS) expression induced by high glucose in HUVECs. In conclusion, this study demonstrates that exenatide treatment can alleviate the vascular endothelial injury, as well as attenuating the nitrooxidative stress in hyperglycemia, implying that the endothelium-protective effect of exenatide might be related to the reduction of nitrooxidative stress.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men Wai, Fengtai District, Beijing 100069, China ; Nursing Department, Peking University Shougang Hospital, No. 9 Jinyuanzhuang Street, Shijingshan District, Beijing 100144, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Street, Xicheng District, Beijing 100050, China.
authors.forename: Chun-ling
authors.initials: CL
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men Wai, Fengtai District, Beijing 100069, China.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Xiong
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomenxiang, Dongcheng District, Beijing 100730, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomenxiang, Dongcheng District, Beijing 100730, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomenxiang, Dongcheng District, Beijing 100730, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomenxiang, Dongcheng District, Beijing 100730, China.
authors.forename: Si-yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men Wai, Fengtai District, Beijing 100069, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D018376:Cardiovascular Abnormalities / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries; D000077270:Exenatide; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D010455:Peptides; D014688:Venoms; D009569:Nitric Oxide; D000077270:Exenatide; D052247:Nitric Oxide Synthase Type II