Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Univ...

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Autores principales:	Menk M, Graw JA, von Haefen C, Steinkraus H, Lachmann B, Spies CD, Schwaiberger D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	AT2 receptor lung failure ARDS acute lung injury Compound 21 (C21) Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0c0452c5e4494ddca7fab04d21ccd0f3
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spelling	oai:doaj.org-article:0c0452c5e4494ddca7fab04d21ccd0f32021-12-02T09:23:47ZAngiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury1178-7031https://doaj.org/article/0c0452c5e4494ddca7fab04d21ccd0f32018-05-01T00:00:00Zhttps://www.dovepress.com/angiotensin-ii-type-2-receptor-agonist-compound-21-attenuates-pulmonar-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2) receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21) might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9), a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9), and a control group that received mechanical ventilation only (control, n=9). Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6 expressions in the lungs, whereas the expressions of IL-1, IL-10, and IL-4 remained unchanged. During the 240-min observation period, AT2 receptor stimulation did not improve pulmonary gas exchange or lung edema. Conclusion: In this rodent model of acute lung injury after repeated pulmonary lavage, AT2 receptor stimulation attenuates pulmonary inflammation but does not improve gas exchange. Keywords: AT2 receptor, lung failure, ARDS, acute lung injury, Compound 21 (C21)Menk MGraw JAvon Haefen CSteinkraus HLachmann BSpies CDSchwaiberger DDove Medical PressarticleAT2 receptorlung failureARDSacute lung injuryCompound 21 (C21)PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 169-178 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	AT2 receptor lung failure ARDS acute lung injury Compound 21 (C21) Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	AT2 receptor lung failure ARDS acute lung injury Compound 21 (C21) Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Menk M Graw JA von Haefen C Steinkraus H Lachmann B Spies CD Schwaiberger D Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury
description	Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2) receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21) might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9), a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9), and a control group that received mechanical ventilation only (control, n=9). Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6 expressions in the lungs, whereas the expressions of IL-1, IL-10, and IL-4 remained unchanged. During the 240-min observation period, AT2 receptor stimulation did not improve pulmonary gas exchange or lung edema. Conclusion: In this rodent model of acute lung injury after repeated pulmonary lavage, AT2 receptor stimulation attenuates pulmonary inflammation but does not improve gas exchange. Keywords: AT2 receptor, lung failure, ARDS, acute lung injury, Compound 21 (C21)
format	article
author	Menk M Graw JA von Haefen C Steinkraus H Lachmann B Spies CD Schwaiberger D
author_facet	Menk M Graw JA von Haefen C Steinkraus H Lachmann B Spies CD Schwaiberger D
author_sort	Menk M
title	Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury
title_short	Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury
title_full	Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury
title_fullStr	Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury
title_full_unstemmed	Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury
title_sort	angiotensin ii type 2 receptor agonist compound 21 attenuates pulmonary inflammation in a model of acute lung injury
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/0c0452c5e4494ddca7fab04d21ccd0f3
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Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

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