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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



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ID: 723927.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice
Authors:Seimetz, M.; Parajuli, N.; Pichl, A.; Bednorz, M.; Ghofrani, H. A.; Schermuly, R. T.; Seeger, W.; Grimminger, F.; Weissmann, N.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:PLoS ONE
Volume:10
Issue / Number:6
Start Page:e0129327
Audience:Not Specified
Abstract / Description:RATIONALE: Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available. Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease. Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice. We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects. Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both. METHODS: C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both. Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar and vascular morphometry) as well as the heart ratio were determined after 6 months of tobacco smoke exposure. In addition, the number of alveolar macrophages in the respective lungs was counted. RESULTS: Preventive treatment with Tadalafil, Piclamilast or a combination of both almost completely prevented the development of emphysema, the increase in lung compliance, tidal volume, structural remodeling of the lung vasculature, right ventricular systolic pressure, and right ventricular hypertrophy induced by cigarette smoke exposure. Single, but not combination treatment prevented or reduced smoke-induced increase in alveolar macrophages. CONCLUSION: Cigarette smoke-induced emphysema and PH could be prevented by inhibition of the phosphodiesterases 4 and 5 in mice.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1932-6203 (Electronic) 1932-6203 (Linking) %R 10.1371/journal.pone.0129327
URL:http://www.ncbi.nlm.nih.gov/pubmed/26058042
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