Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis.
BACKGROUND
The angiotensin system has a role in the pathogenesis of pulmonary fibrosis. This study examines the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in bleomycin induced lung fibrosis and its possible implication in the regulation of prostaglandin E(2) (PGE(2)) synthesis and cyclooxygenase-2 (COX-2) expression.


METHODS
Rats were given a single intratracheal instillation of bleomycin (2.5 U/kg). Losartan (50 mg/kg/day) was administrated orally starting one day before induction of lung fibrosis and continuing to the conclusion of each experiment.


RESULTS
Losartan reduced the inflammation induced by bleomycin, as indicated by lower myeloperoxidase activity and protein content in the bronchoalveolar lavage fluid. Collagen deposition induced by bleomycin was inhibited by losartan, as shown by a reduction in the hydroxyproline content and the amelioration of morphological changes. PGE(2) levels were lower in fibrotic lungs than in normal lungs. Losartan significantly increased PGE(2) levels at both 3 and 15 days. A reduction in COX-2 expression by bleomycin was seen at 3 days which was relieved by losartan.


CONCLUSIONS
The antifibrotic effect of losartan appears to be mediated by its ability to stimulate the production of PGE(2). Losartan, which is already widely used clinically, could be assessed as a new treatment in lung fibrosis.
Molina-Molina
M
M
Servei de Pneumologia, Institut Clínic del Tórax, Hospital Clínic, c/Villarroel 170, Barcelona 08036, Spain. mariamolinamolina@hotmail.com
Serrano-Mollar
A
A
Bulbena
O
O
Fernandez-Zabalegui
L
L
Closa
D
D
Marin-Arguedas
A
A
Torrego
A
A
Mullol
J
J
Picado
C
C
Xaubet
A
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047228:Angiotensin II Type 1 Receptor Blockers; D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin; D051546:Cyclooxygenase 2; D019808:Losartan; D015232:Dinoprostone