Abstract Title:

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

Abstract Source:

Clin Sci (Lond). 2011 Apr 1;120(8):321-33. PMID: 20977430

Abstract Author(s):

Rocío López-Sepúlveda, Manuel Gómez-Guzmán, Maria José Zarzuelo, Miguel Romero, Manuel Sánchez, Ana María Quintela, Pilar Galindo, Francisco O'Valle, Juan Tamargo, Francisco Pérez-Vizcaíno, Juan Duarte, Rosario Jiménez

Article Affiliation:

*Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain.

Abstract:

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 inthe 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 oxidasesubunit 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 phosphorylationof 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 allbiochemical 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.

Study Type : Animal Study

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