Endothelin-1-Induced Impairment of Endothelium-Dependent Relaxation in Aortas Isolated from Controls and Diabetic Rats

Kamata, Katsuo; Kanie, Noriyasu; Matsumoto, Takayuki; Kobayashi, Tsuneo

doi:10.1097/01.fjc.0000166241.49453.e9

Cited by 19 publications

(14 citation statements)

References 22 publications

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“…Excess of O 2 •− generation is critically involved in the breakdown of NO associated with endothelial dysfunction in aortic rings from DOCA-salt rats [7,35,36] and rings incubated with ET-1 [8,11,33]. In our experiments, the presence of SOD (superoxide dismutase) in the organ chamber improved the relaxant response induced by ACh in aortic rings exposed to ET-1.…”

Section: Discussionmentioning

confidence: 49%

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

et al. 2010

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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.

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Section: Discussionmentioning

confidence: 49%

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

et al. 2010

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“…ET-1 stimulates the production of ROS in human endothelial and vascular smooth muscle cell cultures [59,60], as well as in isolated vessels [61,62,63]. It is assumed that the main mechanism for the increased production of ROS in hypertension is increased expression of vascular NADPH oxidase [44,64,65,66]. Increased production of ROS in the vascular wall leads to activation of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre-Hypertensive and Hypertensive Patients with Type 2 Diabetes

Kostov

Blazhev

Atanasova

et al. 2016

IJMS

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Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D). In our study, we compared concentrations of ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9 were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar, while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9 in PHTN and HTN were also significantly higher compared to N. An interesting result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower compared to PHTN. In conclusion, we showed that increased production of ET-1 in patients with T2D can lead to long-lasting increases in blood pressure (BP) and clinical manifestation of hypertension. We also demonstrated that increased levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D mainly reflect the early vascular changes in extracellular matrix (ECM) turnover.

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“…ET-1 increased the expression of gp91 phox , the ratelimiting subunit of NADPH oxidase [59], and augmented superoxide production in endothelial cells via the ET B receptor in human endothelial cells [60]. The stimulating effect of ET-1 on superoxide production may also be coupled to the NADPH oxidase subunit p22 phox [61,62]. The stimulation of superoxide is linked to functional effects since ET-1 was demonstrated to impair endothelium- Each subject was investigated after administration of (A) placebo and (B) the dual ET receptor antagonist bosentan.…”

Section: Interference With No and Increased Oxidative Stressmentioning

confidence: 99%

The importance of endothelin-1 for vascular dysfunction in cardiovascular disease

Böhm

Pernow

2007

Cardiovascular Research

424

295

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Endothelin (ET)-1 is a potent vasoconstrictor peptide originally isolated from endothelial cells. Its production is stimulated in a variety of different cell types under the influence of risk factors for cardiovascular disease and during the development of cardiovascular disease. Based on these observations and the biological effects induced by ET-1, including profound vasoconstriction, pro-inflammatory actions, mitogenic and proliferative effects, stimulation of free radical formation and platelet activation, ET-1 has been implicated as an important factor in the development of vascular dysfunction and cardiovascular disease. In the following the pathogenic role of ET-1, the mechanisms underlying the involvement of ET-1 for the development of vascular dysfunction and the potentially beneficial therapeutic effects of selective ET A and dual ET A /ET B receptor antagonists will be discussed. In particular the changes of pathophysiological importance mediated by ET-1 in clinical studies are reviewed. These changes may be of significance for the development of various cardiovascular diseases beyond pulmonary arterial hypertension which is the currently approved indication for ET receptor antagonists.

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Endothelin-1-Induced Impairment of Endothelium-Dependent Relaxation in Aortas Isolated from Controls and Diabetic Rats

Cited by 19 publications

References 22 publications

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

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

Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre-Hypertensive and Hypertensive Patients with Type 2 Diabetes

The importance of endothelin-1 for vascular dysfunction in cardiovascular disease

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