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.
Highlights
Vascular hyperpermeability is one of the manifestations of endothelial dysfunction [1]
To ascertain the concentration range of Res on protection of bovine aortic endothelial cells (BAECs) against high Glu injury, we tested the effect of Res (0.01, 0.1, 1.0, 10.0 and 100.0 mM) on the viability of BAECs incubated with high Glu for 24 h with CCK-8 assay
BAECs exposed to high concentration of mannitol were used to determine whether or not the high Glu-induced change in viability was due to the change in osmolarity
Summary
Vascular hyperpermeability is one of the manifestations of endothelial dysfunction [1]. Early intervention of vascular hyperpermeability is an important measure for prevention of diabetes and cardiovascular disease. Resveratrol (Res; 3, 5, 49-trihydroxystilbene) is a polyphenolic phytoalexin found in grapes, red wines and other products. Recent studies show Cav-1 acted on vascular hyperpermeability by inhibiting endothelial nitric oxide synthase (eNOS) [12]. ENOS and NO are considered as major player in the endothelial function, studies provided dubious results about the effect of Res on them. As shown as previously released data, long-term treatment of cultured endothelial cells with red wine polyphenols (RWP, especially Res) significantly enhance eNOS expression and subsequent NO release from endothelial cells against endothelial dysfunction [14, 15]. Napoli et al found consumption of red wine (Res) failed to affect vascular reactivity and NO production in type 2 diabetic patients [16]. Cav-1 was reported to be involved in the anti-cancer activity of Res in a human hepatocellular carcinoma (HCC) model [17], while limited data existed regarding the modulation of Res on endothelial permeability through Cav-1 in vitro and in vivo
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