Angiotensin ll antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice

K. A. Keogh, J. Standing, Garvan M Kane, Andre Terzic, Andrew Harold Limper

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Based on current evidence, transforming growth factor (TGF)-β plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that ngiotensin II can serve as a stimulus for TGF-β-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.

Original languageEnglish (US)
Pages (from-to)708-714
Number of pages7
JournalEuropean Respiratory Journal
Volume25
Issue number4
DOIs
StatePublished - Apr 2005

Fingerprint

Pulmonary Fibrosis
Bleomycin
Angiotensins
Angiotensin II
Losartan
Transforming Growth Factors
Fibrosis
Acute Lung Injury
Angiotensin Receptor Antagonists
Hydroxyproline
Lung Diseases
Collagen
Therapeutics
Kidney
Lung

Keywords

  • Basic mechanisms
  • Bleomycin
  • Interstitial lung disease
  • Losartan
  • Lung fibrosis
  • Mice

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Angiotensin ll antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice. / Keogh, K. A.; Standing, J.; Kane, Garvan M; Terzic, Andre; Limper, Andrew Harold.

In: European Respiratory Journal, Vol. 25, No. 4, 04.2005, p. 708-714.

Research output: Contribution to journalArticle

@article{4b57d976fd3e485faa03968092754299,
title = "Angiotensin ll antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice",
abstract = "Based on current evidence, transforming growth factor (TGF)-β plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that ngiotensin II can serve as a stimulus for TGF-β-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.",
keywords = "Basic mechanisms, Bleomycin, Interstitial lung disease, Losartan, Lung fibrosis, Mice",
author = "Keogh, {K. A.} and J. Standing and Kane, {Garvan M} and Andre Terzic and Limper, {Andrew Harold}",
year = "2005",
month = "4",
doi = "10.1183/09031936.05.00090204",
language = "English (US)",
volume = "25",
pages = "708--714",
journal = "European Respiratory Journal",
issn = "0903-1936",
publisher = "European Respiratory Society",
number = "4",

}

TY - JOUR

T1 - Angiotensin ll antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice

AU - Keogh, K. A.

AU - Standing, J.

AU - Kane, Garvan M

AU - Terzic, Andre

AU - Limper, Andrew Harold

PY - 2005/4

Y1 - 2005/4

N2 - Based on current evidence, transforming growth factor (TGF)-β plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that ngiotensin II can serve as a stimulus for TGF-β-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.

AB - Based on current evidence, transforming growth factor (TGF)-β plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that ngiotensin II can serve as a stimulus for TGF-β-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.

KW - Basic mechanisms

KW - Bleomycin

KW - Interstitial lung disease

KW - Losartan

KW - Lung fibrosis

KW - Mice

UR - http://www.scopus.com/inward/record.url?scp=17244369540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17244369540&partnerID=8YFLogxK

U2 - 10.1183/09031936.05.00090204

DO - 10.1183/09031936.05.00090204

M3 - Article

C2 - 15802347

AN - SCOPUS:17244369540

VL - 25

SP - 708

EP - 714

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 4

ER -