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Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles

BACKGROUND AND OBJECTIVES: Because pulmonary circulation is the primary vascular target of inhaled particulate matter (PM), and nitric oxide is a major vasculoprotective agent, in this study we investigated the effect of various particles on the NO–cyclic guanosine monophosphate (cGMP) pathway in pu...

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Autores principales: Courtois, Arnaud, Andujar, Pascal, Ladeiro, Yannick, Baudrimont, Isabelle, Delannoy, Estelle, Leblais, Véronique, Begueret, Hugues, Galland, Marie Annick Billon, Brochard, Patrick, Marano, Francelyne, Marthan, Roger, Muller, Bernard
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569085/
https://www.ncbi.nlm.nih.gov/pubmed/18941568
http://dx.doi.org/10.1289/ehp.11021
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author Courtois, Arnaud
Andujar, Pascal
Ladeiro, Yannick
Baudrimont, Isabelle
Delannoy, Estelle
Leblais, Véronique
Begueret, Hugues
Galland, Marie Annick Billon
Brochard, Patrick
Marano, Francelyne
Marthan, Roger
Muller, Bernard
author_facet Courtois, Arnaud
Andujar, Pascal
Ladeiro, Yannick
Baudrimont, Isabelle
Delannoy, Estelle
Leblais, Véronique
Begueret, Hugues
Galland, Marie Annick Billon
Brochard, Patrick
Marano, Francelyne
Marthan, Roger
Muller, Bernard
author_sort Courtois, Arnaud
collection PubMed
description BACKGROUND AND OBJECTIVES: Because pulmonary circulation is the primary vascular target of inhaled particulate matter (PM), and nitric oxide is a major vasculoprotective agent, in this study we investigated the effect of various particles on the NO–cyclic guanosine monophosphate (cGMP) pathway in pulmonary arteries. METHODS: We used intrapulmonary arteries and/or endothelial cells, either exposed in vitro to particles or removed from PM-instilled animals for assessment of vasomotricity, cGMP and reactive oxygen species (ROS) levels, and cytokine/chemokine release. RESULTS: Endothelial NO-dependent relaxation and cGMP accumulation induced by acetylcholine (ACh) were both decreased after 24 hr exposure of rat intrapulmonary arteries to standard reference material 1648 (SRM1648; urban PM). Relaxation due to NO donors was also decreased by SRM1648, whereas responsiveness to cGMP analogue remained unaffected. Unlike SRM1648, ultrafine carbon black and ultrafine and fine titanium dioxide (TiO(2)) manufactured particles did not impair NO-mediated relaxation. SRM1648-induced decrease in relaxation response to ACh was prevented by dexamethasone (an anti-inflammatory agent) but not by antioxidants. Accordingly, SRM1648 increased the release of proinflammatory mediators (tumor necrosis factor-α, interleukin-8) from intrapulmonary arteries or pulmonary artery endothelial cells, but did not elevate ROS levels within intrapulmonary arteries. Decreased relaxation in response to ACh was also evidenced in intrapulmonary arteries removed from rats intratracheally instilled with SRM1648, but not with fine TiO(2). CONCLUSION: In contrast to manufactured particles (including nanoparticles), urban PM impairs NO but not cGMP responsiveness in intrapulmonary arteries. We attribute this effect to oxidative-stress–independent inflammatory response, resulting in decreased guanylyl cyclase activation by NO. Such impairment of the NO pathway may contribute to urban-PM–induced cardiovascular dysfunction.
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spelling pubmed-25690852008-10-21 Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles Courtois, Arnaud Andujar, Pascal Ladeiro, Yannick Baudrimont, Isabelle Delannoy, Estelle Leblais, Véronique Begueret, Hugues Galland, Marie Annick Billon Brochard, Patrick Marano, Francelyne Marthan, Roger Muller, Bernard Environ Health Perspect Research BACKGROUND AND OBJECTIVES: Because pulmonary circulation is the primary vascular target of inhaled particulate matter (PM), and nitric oxide is a major vasculoprotective agent, in this study we investigated the effect of various particles on the NO–cyclic guanosine monophosphate (cGMP) pathway in pulmonary arteries. METHODS: We used intrapulmonary arteries and/or endothelial cells, either exposed in vitro to particles or removed from PM-instilled animals for assessment of vasomotricity, cGMP and reactive oxygen species (ROS) levels, and cytokine/chemokine release. RESULTS: Endothelial NO-dependent relaxation and cGMP accumulation induced by acetylcholine (ACh) were both decreased after 24 hr exposure of rat intrapulmonary arteries to standard reference material 1648 (SRM1648; urban PM). Relaxation due to NO donors was also decreased by SRM1648, whereas responsiveness to cGMP analogue remained unaffected. Unlike SRM1648, ultrafine carbon black and ultrafine and fine titanium dioxide (TiO(2)) manufactured particles did not impair NO-mediated relaxation. SRM1648-induced decrease in relaxation response to ACh was prevented by dexamethasone (an anti-inflammatory agent) but not by antioxidants. Accordingly, SRM1648 increased the release of proinflammatory mediators (tumor necrosis factor-α, interleukin-8) from intrapulmonary arteries or pulmonary artery endothelial cells, but did not elevate ROS levels within intrapulmonary arteries. Decreased relaxation in response to ACh was also evidenced in intrapulmonary arteries removed from rats intratracheally instilled with SRM1648, but not with fine TiO(2). CONCLUSION: In contrast to manufactured particles (including nanoparticles), urban PM impairs NO but not cGMP responsiveness in intrapulmonary arteries. We attribute this effect to oxidative-stress–independent inflammatory response, resulting in decreased guanylyl cyclase activation by NO. Such impairment of the NO pathway may contribute to urban-PM–induced cardiovascular dysfunction. National Institute of Environmental Health Sciences 2008-10 2008-05-21 /pmc/articles/PMC2569085/ /pubmed/18941568 http://dx.doi.org/10.1289/ehp.11021 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Courtois, Arnaud
Andujar, Pascal
Ladeiro, Yannick
Baudrimont, Isabelle
Delannoy, Estelle
Leblais, Véronique
Begueret, Hugues
Galland, Marie Annick Billon
Brochard, Patrick
Marano, Francelyne
Marthan, Roger
Muller, Bernard
Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles
title Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles
title_full Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles
title_fullStr Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles
title_full_unstemmed Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles
title_short Impairment of NO-Dependent Relaxation in Intralobar Pulmonary Arteries: Comparison of Urban Particulate Matter and Manufactured Nanoparticles
title_sort impairment of no-dependent relaxation in intralobar pulmonary arteries: comparison of urban particulate matter and manufactured nanoparticles
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569085/
https://www.ncbi.nlm.nih.gov/pubmed/18941568
http://dx.doi.org/10.1289/ehp.11021
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