Abstract
Aim:
Angiotensin II is believed to play an important role in tissue repair and remodeling in lungs by the angiotensin type I (AT1) receptor via a number of potential mechanisms. However, the role of the AT1 receptor in early lung injury has not been characterized.
Methods:
Bleomycin-induced pulmonary fibrosis (PF) in rats was utilized to value the treatment with valsartan, an AT1 receptor antagonist, by measurement of body weight, wet weight of the left lung, hydroxyproline content, mRNA expression of collagen I/III, and the degree of fibrosis in lung tissues on d 21. Tissue injury in the early phase was assessed on d 1, 3 and 7 by apoptosis, malondialdehyde content, myeloperoxidase activity, inflammatory cell count and protein content. Angiotensin converting enzyme (ACE) activity and the AT1 receptor in lung tissues were analyzed by biochemistry method and Western blotting, respectively.
Results:
Valsartan ameliorated PF induced by bleomycin in the rats on d 21. After bleomycin was injected intratracheally, increases in the lung AT1 receptor and ACE activity were observed by d 1, 3 and 7. Lung injury deteriorated in the early phase. Valsartan reduced the increase of the AT1 receptor, ACE activity and lung injury induced by bleomycin in the early phase.
Conclusion:
These observations suggest that angiotensin II may play a potent role in early lung injury via the AT1 receptor. AT1 receptor antagonists should be assessed as potential new therapies for fibrotic lung disease.
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Chen, Fp., Gong, Lk., Zhang, L. et al. Early lung injury contributes to lung fibrosis via AT1 receptor in rats. Acta Pharmacol Sin 28, 227–237 (2007). https://doi.org/10.1111/j.1745-7254.2007.00493.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00493.x
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