Losartan attenuates bleomycin-induced pulmonary fibrosis in rats.
BACKGROUND
In addition to regulating blood pressure and body fluid homeostasis, the renin-angiotensin system is also involved in lung fibrogenesis.


OBJECTIVE
To study the effect of losartan, an angiotensin II antagonist, on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.


METHODS
Pulmonary fibrosis was induced in SD rats by intratracheal instillation of bleomycin (5 mg x kg(-1)). Subsequently, the rats received daily losartan (3, 9 and 27 mg x kg(-1)) or prednisone (20 mg x kg(-1)) orally. Six rats in each group were sacrificed 14 and 21 days after intratracheal instillation. Hydroxyproline, superoxide dismutase (SOD), and malondialdehyde (MDA) levels in lung tissues were determined by spectroscopy. The levels of TGF-beta1 in serum were measured by ELISA. Histological changes in the lungs were evaluated by hematoxylin-eosin stain, and scored.


RESULTS
Rat body weight evidently decreased while the indices of lung and hydroxyproline contents in lung tissue were significantly increased 14 and 21 days after intratracheal bleomycin instillation. Inflammatory cell infiltration and fibrotic scores were more prominent in the model group compared to the sham group. Losartan (3, 9 and 27 mg.kg(-1), i.g.) apparently attenuated the degree of pulmonary fibrosis. Further study showed that losartan significantly increased SOD levels while it decreased MDA contents in lung homogenates. Serum TGF-beta1 levels of pulmonary fibrosis rats were also decreased by losartan.


CONCLUSIONS
Losartan had an inhibitory effect on bleomycin-induced pulmonary fibrosis, and its effect may be associated with its anti-free radicals and the reduction in TGF-beta1.
Yao
Hong Wei
HW
Zhejiang Respiratory Drug Research Laboratory, Food and Drug Administration of China, Zhejiang University School of Medicine, Hangzhou, China. yhgwei@hotmail.com
Zhu
Jian Ping
JP
Zhao
Meng Hui
MH
Lu
Yuan
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D015430:Weight Gain / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000903:Antibiotics, Antineoplastic; D005938:Glucocorticoids; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D019808:Losartan; D006909:Hydroxyproline; D011241:Prednisone