Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease

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Resumé

BACKGROUND AND PURPOSE: We tested the hypothesis that in resistance arteries from cardiovascular disease patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus.

EXPERIMENTAL APPROACH: Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K(+) , the thromboxane A2 analogue U46619 or endothelin-1 (ET-1).

KEY RESULTS: Relaxing effects of Na-nitroprusside were comparable but those of bradykinin (BK) were more potent in the presence of ET-1 compared to K(+) and U46619. BK-induced relaxation was i) abolished by N(ω) -nitro L-arginine methyl ester (L-NAME) in K(+) -contracted arteries, ii) partly inhibited by L-NAME in presence of U46619, iii) not altered by indomethacin, L-NAME plus inhibitors of small and intermediate conductance calcium-activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular reactive oxygen species with CellROX Deep Red was significantly increased in presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone.

CONCLUSIONS AND IMPLICATIONS: In patient resistance arteries exposed to ET-1, involvement of nitric oxide (NO) in responses to an endothelium-dependent vasodilator is replaced by H2 O2 without notable contribution of NADPH oxidases, xanthine oxidase or NO synthases. This might have consequences for endothelial dysfunction in conditions where intra-arterial levels of ET-1 are enhanced. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftBritish Journal of Pharmacology
Vol/bind173
Udgave nummer10
Sider (fra-til)1653-1664
ISSN0007-1188
DOI
StatusUdgivet - 23. feb. 2016

Fingeraftryk

Endothelin-1
Nitric Oxide
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Endothelium-Dependent Relaxing Factors
NG-Nitroarginine Methyl Ester
NADPH Oxidase
Myography
Allopurinol
Xanthine Oxidase
Pericardium
Nitroprusside
Nitric Oxide Synthase
Indomethacin
Reactive Oxygen Species
Peptides

Citer dette

@article{33250144e50042c3952b374ab9064458,
title = "Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease",
abstract = "BACKGROUND AND PURPOSE: We tested the hypothesis that in resistance arteries from cardiovascular disease patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus.EXPERIMENTAL APPROACH: Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K(+) , the thromboxane A2 analogue U46619 or endothelin-1 (ET-1).KEY RESULTS: Relaxing effects of Na-nitroprusside were comparable but those of bradykinin (BK) were more potent in the presence of ET-1 compared to K(+) and U46619. BK-induced relaxation was i) abolished by N(ω) -nitro L-arginine methyl ester (L-NAME) in K(+) -contracted arteries, ii) partly inhibited by L-NAME in presence of U46619, iii) not altered by indomethacin, L-NAME plus inhibitors of small and intermediate conductance calcium-activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular reactive oxygen species with CellROX Deep Red was significantly increased in presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone.CONCLUSIONS AND IMPLICATIONS: In patient resistance arteries exposed to ET-1, involvement of nitric oxide (NO) in responses to an endothelium-dependent vasodilator is replaced by H2 O2 without notable contribution of NADPH oxidases, xanthine oxidase or NO synthases. This might have consequences for endothelial dysfunction in conditions where intra-arterial levels of ET-1 are enhanced. This article is protected by copyright. All rights reserved.",
author = "Leurgans, {Thomas M} and Maria Bloksgaard and Brewer, {Jonathan R} and Bagatolli, {Luis A} and Fredgart, {Maise H} and Kristoffer Rosenstand and Hansen, {Maria L} and Rasmussen, {Lars M} and Akhmadjon Irmukhamedov and {De Mey}, {Jo G R}",
note = "This article is protected by copyright. All rights reserved.",
year = "2016",
month = "2",
day = "23",
doi = "10.1111/bph.13467",
language = "English",
volume = "173",
pages = "1653--1664",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John Wiley & Sons Ltd",
number = "10",

}

TY - JOUR

T1 - Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease

AU - Leurgans, Thomas M

AU - Bloksgaard, Maria

AU - Brewer, Jonathan R

AU - Bagatolli, Luis A

AU - Fredgart, Maise H

AU - Rosenstand, Kristoffer

AU - Hansen, Maria L

AU - Rasmussen, Lars M

AU - Irmukhamedov, Akhmadjon

AU - De Mey, Jo G R

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/2/23

Y1 - 2016/2/23

N2 - BACKGROUND AND PURPOSE: We tested the hypothesis that in resistance arteries from cardiovascular disease patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus.EXPERIMENTAL APPROACH: Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K(+) , the thromboxane A2 analogue U46619 or endothelin-1 (ET-1).KEY RESULTS: Relaxing effects of Na-nitroprusside were comparable but those of bradykinin (BK) were more potent in the presence of ET-1 compared to K(+) and U46619. BK-induced relaxation was i) abolished by N(ω) -nitro L-arginine methyl ester (L-NAME) in K(+) -contracted arteries, ii) partly inhibited by L-NAME in presence of U46619, iii) not altered by indomethacin, L-NAME plus inhibitors of small and intermediate conductance calcium-activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular reactive oxygen species with CellROX Deep Red was significantly increased in presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone.CONCLUSIONS AND IMPLICATIONS: In patient resistance arteries exposed to ET-1, involvement of nitric oxide (NO) in responses to an endothelium-dependent vasodilator is replaced by H2 O2 without notable contribution of NADPH oxidases, xanthine oxidase or NO synthases. This might have consequences for endothelial dysfunction in conditions where intra-arterial levels of ET-1 are enhanced. This article is protected by copyright. All rights reserved.

AB - BACKGROUND AND PURPOSE: We tested the hypothesis that in resistance arteries from cardiovascular disease patients, effects of an endothelium-dependent vasodilator depend on the contractile stimulus.EXPERIMENTAL APPROACH: Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub-maximally contracted by K(+) , the thromboxane A2 analogue U46619 or endothelin-1 (ET-1).KEY RESULTS: Relaxing effects of Na-nitroprusside were comparable but those of bradykinin (BK) were more potent in the presence of ET-1 compared to K(+) and U46619. BK-induced relaxation was i) abolished by N(ω) -nitro L-arginine methyl ester (L-NAME) in K(+) -contracted arteries, ii) partly inhibited by L-NAME in presence of U46619, iii) not altered by indomethacin, L-NAME plus inhibitors of small and intermediate conductance calcium-activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular reactive oxygen species with CellROX Deep Red was significantly increased in presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone.CONCLUSIONS AND IMPLICATIONS: In patient resistance arteries exposed to ET-1, involvement of nitric oxide (NO) in responses to an endothelium-dependent vasodilator is replaced by H2 O2 without notable contribution of NADPH oxidases, xanthine oxidase or NO synthases. This might have consequences for endothelial dysfunction in conditions where intra-arterial levels of ET-1 are enhanced. This article is protected by copyright. All rights reserved.

U2 - 10.1111/bph.13467

DO - 10.1111/bph.13467

M3 - Journal article

C2 - 26914408

VL - 173

SP - 1653

EP - 1664

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 10

ER -