Role of AMP-activated Protein Kinase in NO- and EDHF-mediated Endothelium-dependent Relaxations to Red Wine Polyphenols.
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Date
2015-10
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Abstract
Background: Several epidemiological studies have shown that regular consumption of moderate amounts of
wine, in particular red wine, is associated with a decreased total mortality due, in part, to a reduced risk
of cardiovascular diseases. The protective effect has been attributable to polyphenols, which are potent
vasodilators and have anti-thrombotic properties. Polyphenols have been shown to induce pronounced
endothelium-dependent relaxations of arteries by causing the redox-sensitive PI3-kinase-dependent formation
of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The aim of the present study was
to determine the role of the AMP-activated protein kinase (AMPK) in the red wine polyphenols (RWPs)-
induced endothelial formation of NO and EDHF.
Methods and Results: Vascular reactivity was assessed in organ chambers. Cultured porcine coronary
artery endothelial cells porcine coronary artery segements were used to study the phosphorylation level of
endothelial NO synthase (eNOS) at serine 1177, and AMPK at the Threonine 172 by Western blot analysis
and immunohistochemical staining. RWPs caused endothelium-dependent relaxations in rings from rat aorta
and mesenteric artery, and in those from porcine coronary artery. NO-mediated relaxations to RWPs as
assessed in the presence of indomethacin and charybdotoxin plus apamin, were inhibited by compound C
(an inhibitor of AMPK). Compound C also reduced EDHF-mediated relaxations as assessed in the presence of
indomethacin and NG-nitro L-arginine. In contrast, compound C did not affect endothelium-dependent relaxations
to acetylcholine and those to sodium nitroprusside. Moreover, RWPs induced the phosphorylation of AMPK at
threonine 172 and eNOS at serine 1177 in endothelial cells; these responses were inhibited by compound C.
Conclusion: The present findings indicate that RWPs cause both NO and EDHF-mediated relaxations in
several types of isolated arteries and that these effects are dependent on the activation of the AMP-activated
protein kinase pathway
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Modou Oumy Kane2, Mbaye SENE2, Eric Anselm1, Stéphanie Dal1, Valérie B. Schini-Kerth1 and Cyril Augier1. Role of AMP-activated Protein Kinase in NO- and EDHF-mediated Endothelium-dependent Relaxations to Red Wine Polyphenols. Indian Journal of Physiology and Pharmacology. 2015 Oct-Dec; 59(4): 369-379.