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.
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.
Authors: Rebecca J Hodges; R Gisli Jenkins; Caroline P D Wheeler-Jones; Danielle M Copeman; Stephen E Bottoms; Geoffrey J Bellingan; Carmel B Nanthakumar; Geoffrey J Laurent; Stephen L Hart; Martyn L Foster; Robin J McAnulty Journal: Am J Pathol Date: 2004-11 Impact factor: 4.307
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Authors: Gerry T M Wagenaar; Rozemarijn M A Sengers; El Houari Laghmani; Xueyu Chen; Melissa P H A Lindeboom; Anton J M Roks; Gert Folkerts; Frans J Walther Journal: Am J Physiol Lung Cell Mol Physiol Date: 2014-06-20 Impact factor: 5.464
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Authors: Vera Ivanova; Olga B Garbuzenko; Kenneth R Reuhl; David C Reimer; Vitaly P Pozharov; Tamara Minko Journal: Eur J Pharm Biopharm Date: 2012-12-08 Impact factor: 5.571
Authors: Gerry T M Wagenaar; El Houari Laghmani; Melissa Fidder; Rozemarijn M A Sengers; Yvonne P de Visser; Louwe de Vries; Rick Rink; Anton J M Roks; Gert Folkerts; Frans J Walther Journal: Am J Physiol Lung Cell Mol Physiol Date: 2013-06-28 Impact factor: 5.464
Authors: M Molina-Molina; A Xaubet; X Li; A Abdul-Hafez; K Friderici; K Jernigan; W Fu; Q Ding; J Pereda; A Serrano-Mollar; A Casanova; E Rodríguez-Becerra; F Morell; J Ancochea; C Picado; B D Uhal Journal: Eur Respir J Date: 2008-05-28 Impact factor: 16.671
Authors: Young H Lee; Yuichiro J Suzuki; Autumn J Griffin; Regina M Day Journal: Am J Physiol Lung Cell Mol Physiol Date: 2008-02-01 Impact factor: 5.464