Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats

Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pha...

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Main Authors:	Brégeon, Fabienne, Xeridat, Francois, Andreotti, Nicolas, Lepidi, Hubert, Delpierre, Stéphane, Roch, Antoine, Ravailhe, Sylvie, Jammes, Yves, Steinberg, Jean-Guillaume
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152549/

id	pubmed-3152549
recordtype	oai_dc
spelling	pubmed-31525492011-08-19 Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats Brégeon, Fabienne Xeridat, Francois Andreotti, Nicolas Lepidi, Hubert Delpierre, Stéphane Roch, Antoine Ravailhe, Sylvie Jammes, Yves Steinberg, Jean-Guillaume Research Article Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pharmacological activation of the alpha 7 nicotinic receptors (α7-nAChR) could down regulate intracellular mediators involved in lung cell inflammatory response to stretch. Our aim was to test in vivo the protective effect of the pharmacological activation of the α7-nAChR against ventilator-induced lung injury (VILI). Anesthetized rats were ventilated for two hours with a high stretch ventilation mode delivering a stroke volume large enough to generate 25-cmH2O airway pressure, and randomly assigned to four groups: pretreated with parenteral injection of saline or specific agonist of the α7-nAChR (PNU-282987), or submitted to bilateral vagus nerve electrostimulation while pre-treated or not with the α7-nAChR antagonist methyllycaconitine (MLA). Controls ventilated with a conventional stroke volume of 10 mL/kg gave reference data. Physiological indices (compliance of the respiratory system, lung weight, blood oxygenation, arterial blood pressure) and lung contents of inflammatory mediators (IL-6 measured by ELISA, substance P assessed using HPLC) were severely impaired after two hours of high stretch ventilation (sham group). Vagal stimulation was able to maintain the respiratory parameters close to those obtained in Controls and reduced lung inflammation except when associated to nicotinic receptor blockade (MLA), suggesting the involvement of α7-nAChR in vagally-mediated protection against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased lung injury and lung IL-6 and substance P contents, and nearly abolished the increase in plasmatic IL-6 levels. Pathological examination of the lungs confirmed the physiological differences observed between the groups. In conclusion, these data suggest that the stimulation of α7-nAChR is able to attenuate VILI in rats. Public Library of Science 2011-08-08 /pmc/articles/PMC3152549/ /pubmed/21857926 http://dx.doi.org/10.1371/journal.pone.0022386 Text en Brégeon et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Brégeon, Fabienne Xeridat, Francois Andreotti, Nicolas Lepidi, Hubert Delpierre, Stéphane Roch, Antoine Ravailhe, Sylvie Jammes, Yves Steinberg, Jean-Guillaume
spellingShingle	Brégeon, Fabienne Xeridat, Francois Andreotti, Nicolas Lepidi, Hubert Delpierre, Stéphane Roch, Antoine Ravailhe, Sylvie Jammes, Yves Steinberg, Jean-Guillaume Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats
author_facet	Brégeon, Fabienne Xeridat, Francois Andreotti, Nicolas Lepidi, Hubert Delpierre, Stéphane Roch, Antoine Ravailhe, Sylvie Jammes, Yves Steinberg, Jean-Guillaume
author_sort	Brégeon, Fabienne
title	Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats
title_short	Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats
title_full	Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats
title_fullStr	Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats
title_full_unstemmed	Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats
title_sort	activation of nicotinic cholinergic receptors prevents ventilator-induced lung injury in rats
description	Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pharmacological activation of the alpha 7 nicotinic receptors (α7-nAChR) could down regulate intracellular mediators involved in lung cell inflammatory response to stretch. Our aim was to test in vivo the protective effect of the pharmacological activation of the α7-nAChR against ventilator-induced lung injury (VILI). Anesthetized rats were ventilated for two hours with a high stretch ventilation mode delivering a stroke volume large enough to generate 25-cmH2O airway pressure, and randomly assigned to four groups: pretreated with parenteral injection of saline or specific agonist of the α7-nAChR (PNU-282987), or submitted to bilateral vagus nerve electrostimulation while pre-treated or not with the α7-nAChR antagonist methyllycaconitine (MLA). Controls ventilated with a conventional stroke volume of 10 mL/kg gave reference data. Physiological indices (compliance of the respiratory system, lung weight, blood oxygenation, arterial blood pressure) and lung contents of inflammatory mediators (IL-6 measured by ELISA, substance P assessed using HPLC) were severely impaired after two hours of high stretch ventilation (sham group). Vagal stimulation was able to maintain the respiratory parameters close to those obtained in Controls and reduced lung inflammation except when associated to nicotinic receptor blockade (MLA), suggesting the involvement of α7-nAChR in vagally-mediated protection against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased lung injury and lung IL-6 and substance P contents, and nearly abolished the increase in plasmatic IL-6 levels. Pathological examination of the lungs confirmed the physiological differences observed between the groups. In conclusion, these data suggest that the stimulation of α7-nAChR is able to attenuate VILI in rats.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152549/
_version_	1611469827631742976

Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in Rats

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