Early lung injury contributes to lung fibrosis via AT1 receptor in rats.
OBJECTIVE
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, hydroxy-proline 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.


CONCLUSIONS
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.
Chen
Fang-ping
FP
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Gong
Li-kun
LK
Zhang
Ling
L
Wang
Hui
H
Qi
Xin-ming
XM
Wu
Xiong-fei
XF
Xiao
Ying
Y
Cai
Yan
Y
Liu
Lin-lin
LL
Li
Xiang-hong
XH
Ren
Jin
J
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000235:genetics; D015227:Lipid Peroxidation; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D014633:Valine