Angiotensin II Type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice
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 Ashcroftas 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.
Conclusion: Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.
Author: Yuko Waseda, Masahide Yasui, Yoriko Nishizawa, Kanako Inuzuka, Hazuki Takato, Yukari Ichikawa, Atsuro Tagami, Masaki Fujimura and Shinji Nakao
Credits/Source: Respiratory Research 2008, 9:43
Published on: 2008-05-23
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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