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eNOS Activation Induced by a Polyphenol-Rich Grape Skin Extract in Porcine Coronary Arteries

eNOS Activation Induced by a Polyphenol-Rich Grape Skin Extract in Porcine Coronary Arteries,10.1159/000194271,Journal of Vascular Research,Socorro Va

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eNOS Activation Induced by a Polyphenol-Rich Grape Skin Extract in Porcine Coronary Arteries   (Citations: 11)
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Background/Aims: Drinking red wine is associated with a decreased mortality from coronary heart diseases. This study examined whether polyphenols contained in a grape skin extract (GSE) triggered the endothelial formation of nitric oxide (NO) and investigated the underlying mechanism. Methods: Vascular reactivity was assessed in organ chambers using porcine coronary artery rings in the presence of indomethacin (a cyclooxygenase inhibitor) and charybdotoxin plus apamin (inhibitors of endothelium-derived hyperpolarizing factor-mediated responses). The phosphorylation level of Src, Akt and endothelial NO synthase (eNOS) were assessed by Western blot analysis, and the formation of reactive oxygen species (ROS) was investigated using dihydroethidine and dichlorodihydrofluorescein. Results: GSE-induced endothelium-dependent relaxations were abolished by NG-nitro-L-arginine (an eNOS inhibitor) and ODQ (a soluble guanylyl cyclase inhibitor), and they were reduced by MnTMPyP, polyethyleneglycol catalase, PP2 (an inhibitor of Src kinase) and wortmannin (an inhibitor of phosphoinositide 3-kinase). GSE caused phosphorylation of Src, which was prevented by MnTMPyP. It also caused phosphorylation of Akt and eNOS, which were prevented by MnTMPyP, polyethyleneglycol catalase, PP2, wortmannin and LY294002. GSE elicited the formation of ROS in native and cultured endothelial cells, which was prevented by MnTMPyP. Conclusions: GSE causes endothelium-dependent NO-mediated relaxations of coronary arteries. This effect involves the intracellular formation of ROS in endothelial cells leading to the Src kinase/phosphoinositide 3-kinase/Akt-dependent phosphorylation of eNOS.
Journal: Journal of Vascular Research - J VASC RES , vol. 46, no. 5, pp. 406-416, 2009
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    • ...31,...

    Ilse P. G. Botden, et al. Daily Red Wine Consumption Improves Vascular Function by a Soluble Gua...

    • ... of the PI3-kinase/Akt pathway in endothelial cells, which, in turn, causes phosphorylation of eNOS at Ser1177 (an activator site) and dephosphorylation of eNOS at Thr495 (an inhibitor site), leading to an increased formation of NO [77] (Fig. 2). The PI3-kinase/ Akt signaling pathway is triggered by the polyphenolinduced intracellular formation of reactive oxygen species predominantly superoxide anions in endothelial cells [5, 68, 77]...
    • ...A similar mechanism of eNOS activation has been observed in response to a grape seed extract [35], grape skin extract [68], purple grape juice [5], strawberry powder rich in polyphenols [36], and epigallocatechin-3-gallate [67], a major flavonoid from the flavan-3-ol subclass found in green tea...
    • ...Additional investigations identified Src kinase as a redox-sensitive mediator, which acts upstream of the PI3kinase/Akt pathway leading to eNOS activation in response to grape-derived polyphenols [5, 6, 68] (Fig. 2). Moreover, Fyn, a member of the Src family, mediated the epigallocatechin gallate-induced PI3-kinase/Akt-mediated activation of eNOS [59]...

    Valérie B. Schini-Kerth, et al. Nutritional improvement of the endothelial control of vascular tone by...

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