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Menk M, Graw JA, von Haefen C, et al. Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury. J Inflamm Res. 2018;11:169-178doi: 10.2147/JIR.S160573.
Menk, M., Graw, J. A., von Haefen, C., Steinkraus, H., Lachmann, B., Spies, C. D., & Schwaiberger, D. (2018). Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury. Journal of inflammation research, 11169-178. https://doi.org/10.2147/JIR.S160573
Menk, Mario, et al. "Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury." Journal of inflammation research vol. 11 (2018): 169-178. doi: https://doi.org/10.2147/JIR.S160573
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. J Inflamm Res. 2018 May 01;11:169-178. doi: 10.2147/JIR.S160573. eCollection 2018. PMID: 29750051; PMCID: PMC5935084.
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J Inflamm Res. 2018 May 01;11:169-178. doi: 10.2147/JIR.S160573. eCollection 2018.

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

Journal of inflammation research

Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger

Affiliations

  1. Department of Anesthesiology and Operative Intensive Care Medicine, Charité - University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany.

PMID: 29750051 PMCID: PMC5935084 DOI: 10.2147/JIR.S160573

Abstract

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: ARDS; AT2 receptor; Compound 21 (C21); acute lung injury; lung failure

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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