Resveratrol prevents hyperglycemia-induced endothelial dysfunction via activation of adenosine monophosphate-activated protein kinase.
Endothelial dysfunction secondary to persistent hyperglycemia plays a key role in the development of type 2 diabetic vascular disease. The aim of the present study was to examine the protective effect of resveratrol against hyperglycemia-induced endothelial dysfunction. In cultured human umbilical vein endothelial cells (HUVECs), resveratrol (10-100 microM) concentration dependently enhanced phosphorylation of endothelial nitric oxide synthesis (eNOS) at Ser1177 and nitric oxide (NO) production. In addition, resveratrol can increase the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) at Thr172 and suppress high glucose-induced generation of superoxide anion. In mouse aortic rings, resveratrol (1-100 microM) elicited endothelium-dependent vasodilatations and alleviated high glucose-mediated endothelial dysfunction. All these beneficial effects of resveratrol on the endothelium were abolished by pharmacological antagonism of AMPK by compound C. These results provide new insight into the protective properties of resveratrol against endothelial dysfunction caused by high glucose, which is attributed to the AMPK mediated reduction of superoxide level.
Xu
Qiang
Q
Department of Geriatrics, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Hao
Xinzhong
X
Yang
Qihong
Q
Si
Liangyi
L
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019610:Cytoprotection; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004789:Enzyme Activation; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010766:Phosphorylation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation
D000975:Antioxidants; D013267:Stilbenes; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol