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

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 O(2)(•-) (superoxide anion). Our present study was designed to evaluate whether RWPs act directly in the vascular wall improving endothelial dysfunction and O(2)(•-) 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 O(2)(•-) 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 O(2)(•-) 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.

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

“…O 2 Ϫ is derived from several sources in the endothelium, including eNOS (14,62), mitochondria (27), xanthine oxidase (64), and NADPH oxidase (5). NADPH oxidase-derived ROS increase with age in animals (25) and humans (11) and are associated with decreases in endothelial function in large conduit arteries (11,28). In contrast, our present data show that inhibition of NADPH oxidase-derived ROS impaired endothelium-dependent vasodilation in skeletal muscle arterioles from all groups (Fig.…”

Nutritional recommendations for individuals with Flammer syndrome

“…Polyphenols in wine lower the susceptibility of LDL lipids to oxidation [34] and improve endothelial dysfunction [35,36] impairment which leads to damage to vascular cells and the surrounding tissue. Wine polyphenols affect endothelial function by stimulating the production of endothelial nitric oxide synthase (eNOS) and thus increasing the production of nitric oxide (NO) which induces vasodilation [37].…”

“…Wine polyphenols affect endothelial function by stimulating the production of endothelial nitric oxide synthase (eNOS) and thus increasing the production of nitric oxide (NO) which induces vasodilation [37]. In addition, wine polyphenols inhibit the synthesis of the potent vasoconstrictor endothelin-1 [35]. In experimental models, flavonoids in wine prevented the initiation of atherosclerotic plaque development [38,39].…”

The role of endothelin-1 and new therapeutic approaches in sepsis and septic shock

“…Bu peptit intravenöz verildiğinde başlangıçta kan damarlarının dilatasyonuna ardın-dan uzun süren konstriksiyona yaparak iç organlarda iskemi ve endotel işlevinde bozukluğa neden olmaktadır. Oluştur-duğu bu değişikliklerle çok miktarda ROT açığa çıkmasını sağlamaktadır (82)(83)(84).…”