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Published ahead of print on May 5, 2005, doi:10.1164/rccm.200502-296OC
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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 358-363, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200502-296OC

Original Article

Inhaled Iloprost Reverses Vascular Remodeling in Chronic Experimental Pulmonary Hypertension

Ralph Theo Schermuly, Hüseyin Yilmaz, Hossein Ardeschir Ghofrani, Kathrin Woyda, Soni Pullamsetti, Andreas Schulz, Tobias Gessler, Rio Dumitrascu, Norbert Weissmann, Friedrich Grimminger and Werner Seeger

Department of Internal Medicine, Justus Liebig University Giessen, Giessen; and Schering Deutschland, Berlin, Germany

Correspondence and requests for reprints should be addressed to Ralph Theo Schermuly, Ph.D., Zentrum für Innere Medizin, Justus Liebig Universität Giessen, Klinikstrasse 36, 35392 Giessen, Germany. E-mail: ralph.schermuly{at}innere.med.uni-giessen.de

Rationale: Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH. Objectives: The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats. Methods: Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 µg · kg–1 · day–1, or underwent sham nebulization with saline. Results: After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed. Conclusions: We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.

Key Words: iloprost • monocrotaline • pulmonary hypertension • remodeling




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