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Updated: Jul 5, 2026

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
06:03

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis

Published on: May 9, 2025

Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice

Yuko Waseda1, Masahide Yasui, Yoriko Nishizawa

  • 1Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan. yuko_m@med3.m.kanazawa-u.ac.jp

Respiratory Research
|May 27, 2008
PubMed
Abstract

Insights

Both angiotensin II type 1 receptor (AT1) and type 2 (AT2) antagonists reduced pulmonary fibrosis in a mouse model. These treatments affected inflammatory cell counts and cytokine levels, indicating distinct roles in lung injury.

Area of Science:

  • Pulmonary Medicine
  • Pharmacology
  • Immunology

Background:

  • The role of the angiotensin II type 2 receptor (AT2) in pulmonary fibrosis remains unclear.
  • This study investigates the impact of AT1 and AT2 antagonists on bleomycin-induced pulmonary fibrosis.

Purpose of the Study:

  • To evaluate the therapeutic effects of AT1 and AT2 antagonists in a mouse model of pulmonary fibrosis.
  • To elucidate the mechanisms by which these antagonists influence fibrotic processes and inflammation.

Main Methods:

  • Mice with bleomycin-induced pulmonary fibrosis were treated with an AT1 antagonist (olmesartan) or an AT2 antagonist (PD-123319).
  • Pulmonary fibrosis was assessed using pathological scoring and hydroxyproline content.
  • Cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF) were analyzed.

Main Results:

  • Olmesartan significantly reduced lung fibrosis score, hydroxyproline levels, and inflammatory cell counts (lymphocytes, neutrophils, macrophages) and cytokines (TNF-alpha, TGF-beta1) in BALF.
  • PD-123319 also reduced lung fibrosis score and hydroxyproline levels, with significant reductions in BALF inflammatory cells and cytokines (TNF-alpha, MCP-1, MIP-2), but not TGF-beta1.
  • Both treatments demonstrated efficacy in mitigating pulmonary fibrosis, albeit through potentially different pathways.

Conclusions:

  • Both AT1 and AT2 receptors play a role in promoting interstitial pneumonia and pulmonary fibrosis.
  • The antagonists exert their effects through distinct mechanisms, highlighting the complexity of the renin-angiotensin system in lung disease.

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