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

PLoS One. 2014 Nov 24;9(11):e113716. doi: 10.1371/journal.pone.0113716. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Blotting, Western
  • Capillary Permeability / drug effects*
  • Cattle
  • Caveolin 1 / genetics*
  • Caveolin 1 / metabolism
  • Cells, Cultured
  • Diet, High-Fat
  • Dietary Carbohydrates
  • Dietary Fats / administration & dosage
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Gene Expression Regulation / drug effects
  • Glucose / administration & dosage
  • Male
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation / drug effects
  • Rats, Wistar
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stilbenes / pharmacology*
  • Sucrose / administration & dosage

Substances

  • Angiogenesis Inhibitors
  • Caveolin 1
  • Dietary Carbohydrates
  • Dietary Fats
  • Stilbenes
  • Sucrose
  • Nitric Oxide Synthase Type III
  • Glucose
  • Resveratrol

Grants and funding

This work was supported by the National Key Technology R&D Program of the 11th Five year Plan of the People's Republic of China (No. 2008BAI58B06) and the National Natural Science Foundation of China (Grant No. 81172657). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.