Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: role of NADPH oxidase

Clinical Science - Tập 120 Số 8 - Trang 321-333 - 2011
R López-Sepúlveda1, Manuel Gómez‐Guzmán1, María José Zarzuelo Romero1, Miguel Romero1, Manuel Sánchez1, Ana María Quintela1, Pilar Galindo1, Francisco O’Valle2, Juan Tamargo3, Francisco Pérez‐Vizcaíno3, Juan Duarte1, Rosario Jiménez1
1Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain
2Department of Pathological Anatomy, School of Medicine, University of Granada, Granada, Spain
3Department of Pharmacology, School of Medicine, University Complutense of Madrid and Ciber Enfermedades Respiratorias (CIBERES), 28040 Madrid, Spain

Tóm tắt

RWPs (red wine polyphenols) exert antihypertensive effects and improve endothelial function by reducing the plasma levels of ET-1 (endothelin-1) and the subsequent vascular production of O2•− (superoxide anion). Our present study was designed to evaluate whether RWPs act directly in the vascular wall improving endothelial dysfunction and O2•− production induced by ET-1 and to analyse the compounds responsible for these protective effects. We incubated rat isolated aortic rings in the presence or absence of ET-1 (10 nM) and RWPs (10−4 to 10−2 g/l) or catechin (0.2 μM), epicatechin (10 μM) and resveratrol (0.1 μM). ET-1 reduced the relaxant responses to acetylcholine, increased intracellular O2•− production, NADPH oxidase activity and protein expression of NADPH oxidase subunit p47phox. All these changes were prevented by RWPs. The preventive effects of RWPs were unaffected by co-incubation with either ICI-182780, an ER (oestrogen receptor) antagonist, or GW9662, a PPARγ (peroxisome-proliferator-activated receptor γ) antagonist. RWPs inhibited the phosphorylation of the mitogen-activated protein kinase, ERK1/2 (extracellular signal-regulated kinase 1/2), a key regulator of p47phox expression in response to ET-1. When the isolated polyphenols were tested, at the concentrations found in 10−2 g/l RWPs, only epicatechin prevented endothelial dysfunction and all biochemical changes induced by ET-1 in the vascular wall. Taken together, these results indicate that RWPs prevent ET-1-induced vascular O2•− production by reducing overexpression of p47phox and the subsequent increased NADPH oxidase activity, leading to improvement in endothelial function. The effects of RWPs appear to be independent of ER and PPARγ activation and are related to ERK1/2 inhibition.

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Clinical Science

Tập 120 Số 8

321-333

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