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Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E₂ synthesis

¹ Servei de Pneumologia, Institut Clínic del Tórax, Hospital Clínic, Barcelona, Spain
² Servei d’Otorrinolaringologia, Hospital Clínic, Barcelona, Spain
³ Departament Experimental de Patologia IIBB CSIC, IDIBAPS, University of Barcelona, Barcelona, Spain

Correspondence to:
Correspondence to:
Dr M Molina-Molina
Servei de Pneumologia, Institut Clínic del Tórax, Hospital Clínic, c/Villarroel 170, Barcelona 08036, Spain; mariamolinamolina{at}hotmail.com

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 E₂ (PGE₂) 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. PGE₂ levels were lower in fibrotic lungs than in normal lungs. Losartan significantly increased PGE₂ 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 PGE₂. Losartan, which is already widely used clinically, could be assessed as a new treatment in lung fibrosis.

Abbreviations: ACE, angiotensin converting enzyme; ANGII, angiotensin II; AT1, angiotensin type 1 receptor; COX-2, cyclooxygenase-2; HP, hydroxyproline; IPF, idiopathic pulmonary fibrosis; MPO, myeloperoxidase; PGE₂, prostaglandin E₂; TGF-ß, transforming growth factor ß

Keywords: pulmonary fibrosis; cyclo-oxygenase; COX-2; angiotensin II; losartan; prostaglandin E2

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