Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation

• Published in: PloS one 2014-11, Vol.9 (11), p.e113716-e113716
• Main Authors: Peng, Xiao Lin, Qu, Wei, Wang, Lin Zhi, Huang, Bin Qing, Ying, Chen Jiang, Sun, Xiu Fa, Hao, Li Ping
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Aorta; Arginine; Biology and Life Sciences; Blotting, Western; Capillary Permeability - drug effects; Cattle; Caveolae; Caveolin; Caveolin 1 - genetics; Caveolin 1 - metabolism; Caveolin-1; Cells, Cultured; Cyclodextrins; Diet; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats - administration & dosage; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Gene Expression Regulation - drug effects; Glucose; Glucose - administration & dosage; Heart; Inhibitors; Kidneys; Kinases; Liver; Male; Medicine and Health Sciences; NG-Nitroarginine methyl ester; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Nutrition; Phosphorylation - drug effects; Polyphenols; Rats; Rats, Wistar; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Stilbenes - pharmacology; Sucrose; Sucrose - administration & dosage; Sugar; β-Cyclodextrin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113716

Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation.