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

K. A. Keogh, J. Standing, G. C. Kane, A. Terzic, Andrew H. Limper

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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
Issue number4
StatePublished - Apr 2005


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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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