title: Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice.
abstract: BACKGROUND
  The role of angiotensin II type 2 receptor (AT2) in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1) and AT2 antagonists in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis.
  
  
  METHODS
  We examined effects of the AT1 antagonist (AT1A) olmesartan medoxomil (olmesartan) and the AT2 antagonist (AT2A) PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF).
  
  
  RESULTS
  With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF)-alpha levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF)-beta1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-alpha and monocyte chemoattractant protein (MCP)-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP)-2 level but not TGF-beta1.
  
  
  CONCLUSIONS
  Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.
authors.affiliation: Respiratory 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
authors.forename: Yuko
authors.initials: Y
authors.lastname: Waseda
authors.forename: Masahide
authors.initials: M
authors.lastname: Yasui
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Inuzuka
authors.forename: Hazuki
authors.initials: H
authors.lastname: Takato
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Atsuro
authors.initials: A
authors.lastname: Tagami
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001761:Bleomycin; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D019402:Macrophage Inflammatory Proteins; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D001761:Bleomycin; C073402:PD 123319; C437965:olmesartan; D006909:Hydroxyproline