Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

Thomas M Leurgans, Maria Bloksgaard, Akhmadjon Irmukhamedov, Lars P. Riber, Jo G R De Mey*

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Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K + or the TxA 2 analogue U46619 and by H 2O 2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H 2O 2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K +, the TXA 2 analogue U46619 or ET-1. Effects of the NO donor Na-nitroprusside (SNP) and of exogenous H 2O 2 were recorded in the absence and presence of inhibitors of cyclooxygenases, NO synthases and small and intermediate conductance calcium-activated K + channels. During contractions induced by either of the three stimuli, the potency of SNP did not differ and was not modified by the inhibitors. In vessels contracted with ET-1, the potency of H 2O 2 was on average and in terms of interindividual variability considerably larger than in K +-contracted vessels. Both differences were not statistically significant in the presence of inhibitors of mechanisms of endothelium-dependent vasodilatation. In resistance arteries from patients with cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing responses to NO or H 2O 2. Furthermore, the candidate endothelium-derived relaxing factor H 2O 2 also acts as an endothelium-dependent vasodilator.

OriginalsprogEngelsk
TidsskriftBasic & Clinical Pharmacology & Toxicology
Vol/bind122
Udgave nummer1
Sider (fra-til)74–81
ISSN1742-7835
DOI
StatusUdgivet - jan. 2018

Fingeraftryk

Endothelin-1
Hydrogen Peroxide
Nitric Oxide
Endothelium-Dependent Relaxing Factors
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Single Nucleotide Polymorphism
Smooth Muscle
Muscle
Myography
Complement Factor H
Calcium-Activated Potassium Channels
Cyclooxygenase Inhibitors
Pericardium
Nitroprusside
Bradykinin
Vasodilation
Nitric Oxide Synthase
Surgery
Endothelium

Citer dette

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title = "Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1",
abstract = "In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K + or the TxA 2 analogue U46619 and by H 2O 2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H 2O 2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K +, the TXA 2 analogue U46619 or ET-1. Effects of the NO donor Na-nitroprusside (SNP) and of exogenous H 2O 2 were recorded in the absence and presence of inhibitors of cyclooxygenases, NO synthases and small and intermediate conductance calcium-activated K + channels. During contractions induced by either of the three stimuli, the potency of SNP did not differ and was not modified by the inhibitors. In vessels contracted with ET-1, the potency of H 2O 2 was on average and in terms of interindividual variability considerably larger than in K +-contracted vessels. Both differences were not statistically significant in the presence of inhibitors of mechanisms of endothelium-dependent vasodilatation. In resistance arteries from patients with cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing responses to NO or H 2O 2. Furthermore, the candidate endothelium-derived relaxing factor H 2O 2 also acts as an endothelium-dependent vasodilator.",
keywords = "Aged, Cardiovascular Diseases/physiopathology, Coronary Vessels/drug effects, Endothelin-1/metabolism, Endothelium, Vascular/drug effects, Female, Humans, Hydrogen Peroxide/pharmacology, Male, Muscle, Smooth, Vascular/drug effects, Nitric Oxide/pharmacology, Nitroprusside/pharmacology, Pericardium/physiopathology, Vasodilation/drug effects, Vasodilator Agents/pharmacology",
author = "Leurgans, {Thomas M} and Maria Bloksgaard and Akhmadjon Irmukhamedov and Riber, {Lars P.} and {De Mey}, {Jo G R}",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = "1",
doi = "10.1111/bcpt.12843",
language = "English",
volume = "122",
pages = "74–81",
journal = "Basic & Clinical Pharmacology & Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",
number = "1",

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TY - JOUR

T1 - Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

AU - Leurgans, Thomas M

AU - Bloksgaard, Maria

AU - Irmukhamedov, Akhmadjon

AU - Riber, Lars P.

AU - De Mey, Jo G R

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

PY - 2018/1

Y1 - 2018/1

N2 - In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K + or the TxA 2 analogue U46619 and by H 2O 2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H 2O 2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K +, the TXA 2 analogue U46619 or ET-1. Effects of the NO donor Na-nitroprusside (SNP) and of exogenous H 2O 2 were recorded in the absence and presence of inhibitors of cyclooxygenases, NO synthases and small and intermediate conductance calcium-activated K + channels. During contractions induced by either of the three stimuli, the potency of SNP did not differ and was not modified by the inhibitors. In vessels contracted with ET-1, the potency of H 2O 2 was on average and in terms of interindividual variability considerably larger than in K +-contracted vessels. Both differences were not statistically significant in the presence of inhibitors of mechanisms of endothelium-dependent vasodilatation. In resistance arteries from patients with cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing responses to NO or H 2O 2. Furthermore, the candidate endothelium-derived relaxing factor H 2O 2 also acts as an endothelium-dependent vasodilator.

AB - In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K + or the TxA 2 analogue U46619 and by H 2O 2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H 2O 2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K +, the TXA 2 analogue U46619 or ET-1. Effects of the NO donor Na-nitroprusside (SNP) and of exogenous H 2O 2 were recorded in the absence and presence of inhibitors of cyclooxygenases, NO synthases and small and intermediate conductance calcium-activated K + channels. During contractions induced by either of the three stimuli, the potency of SNP did not differ and was not modified by the inhibitors. In vessels contracted with ET-1, the potency of H 2O 2 was on average and in terms of interindividual variability considerably larger than in K +-contracted vessels. Both differences were not statistically significant in the presence of inhibitors of mechanisms of endothelium-dependent vasodilatation. In resistance arteries from patients with cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing responses to NO or H 2O 2. Furthermore, the candidate endothelium-derived relaxing factor H 2O 2 also acts as an endothelium-dependent vasodilator.

KW - Aged

KW - Cardiovascular Diseases/physiopathology

KW - Coronary Vessels/drug effects

KW - Endothelin-1/metabolism

KW - Endothelium, Vascular/drug effects

KW - Female

KW - Humans

KW - Hydrogen Peroxide/pharmacology

KW - Male

KW - Muscle, Smooth, Vascular/drug effects

KW - Nitric Oxide/pharmacology

KW - Nitroprusside/pharmacology

KW - Pericardium/physiopathology

KW - Vasodilation/drug effects

KW - Vasodilator Agents/pharmacology

U2 - 10.1111/bcpt.12843

DO - 10.1111/bcpt.12843

M3 - Journal article

C2 - 28686356

VL - 122

SP - 74

EP - 81

JO - Basic & Clinical Pharmacology & Toxicology

JF - Basic & Clinical Pharmacology & Toxicology

SN - 1742-7835

IS - 1

ER -