Abstract
BackgroundThe 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.MethodsWe 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).ResultsWith olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF)-α 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)-β1. 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-α 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-β1.ConclusionBoth AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.
Highlights
The role of angiotensin II type 2 receptor (AT2) in pulmonary fibrosis is unknown
We examined the involvement of AT2 in pulmonary fibrosis by evaluating the influence of AT1 antagonist (AT1A) and AT2 antagonist (AT2A) in a mouse model of BLM-induced pulmonary fibrosis, with the goal of clarifying the differences in the roles of angiotensin II type 1 receptor (AT1) and AT2 in pulmonary fibrosis
Cell components and cytokine levels in bronchoalveolar lavage fluid (BALF) Effect of olmesartan On day 7, total cell, lymphocyte, and neutrophil counts were lower in the mice treated with both BLM and 1 mg/ kg olmesartan than in the group treated with BLM alone (Table 1)
Summary
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. It is known that the renin-angiotensin system (RAS) has a variety of actions in vivo. A classical action of this system includes contraction of the blood vessels and increase in intravascular volume, both of which are involved in eleva-. The RAS is active in the vascular system and in various tissues. Renin converts angiotensinogen into angiotensin I (AI), and angiotensin-converting enzymes (ACE) convert AI into angiotensin II (AII). AII is the center of activity of the RAS. Angiotensin receptor blockers (ARBs), which are often used as depressor drugs, are selective AT1 antagonists (AT1As) [3]
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