| Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition. | |
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MedLine Citation:
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PMID: 18032446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phosphodiesterase (PDE) inhibitors are currently under investigation for the therapy of pulmonary hypertension. The present study was designed to investigate chronic effects of oral pumafentrine, a mixed selective PDE-3/4 inhibitor, in monocrotaline (MCT)-induced pulmonary hypertension in rats. Treatment with pumafentrine (10 mg.kg(-1) daily) from week 4 to 6 after a single injection of MCT (60 mg.kg(-1)) partially reversed pulmonary hypertension and right heart hypertrophy in rats. In addition, small pulmonary arterial muscularisation, media hypertrophy and decrease in lumen area were largely reversed. Inhibition of smooth muscle proliferation under pumafentrine was demonstrated in vivo as was a pro-apoptotic effect of pumafentrine on vascular cells. Moreover, pumafentrine dose-dependently increased cyclic adenosine monophosphate levels and inhibited proliferation of cultured pulmonary arterial smooth muscle cells. In conclusion, oral pumafentrine partially reverses monocrotaline-induced pulmonary hypertension, lung vascular remodelling and right heart hypertrophy in rats. |
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Authors:
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E Dony; Y-J Lai; R Dumitrascu; S S Pullamsetti; R Savai; H A Ghofrani; N Weissmann; C Schudt; D Flockerzi; W Seeger; F Grimminger; R T Schermuly |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-11-21 |
Journal Detail:
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Title: The European respiratory journal Volume: 31 ISSN: 1399-3003 ISO Abbreviation: Eur. Respir. J. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-03 Completed Date: 2008-04-29 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 8803460 Medline TA: Eur Respir J Country: Switzerland |
Other Details:
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Languages: eng Pagination: 599-610 Citation Subset: IM |
Affiliation:
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University of Giessen Lung Centre (UGLC), Klinikstrasse 36, 35392 Giessen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cyclic Nucleotide Phosphodiesterases, Type 3 / drug effects Cyclic Nucleotide Phosphodiesterases, Type 4 / drug effects Disease Models, Animal Hypertension, Pulmonary / chemically induced, drug therapy*, pathology Hypertrophy, Right Ventricular / chemically induced, drug therapy* Lung / drug effects*, pathology Male Monocrotaline / administration & dosage Muscle, Smooth, Vascular / drug effects* Myocytes, Smooth Muscle / drug effects* Naphthyridines / pharmacology* Phosphodiesterase 3 Inhibitors Phosphodiesterase 4 Inhibitors Phosphodiesterase Inhibitors / pharmacology* Rats |
| Chemical | |
Reg. No./Substance:
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0/Naphthyridines; 0/Phosphodiesterase 3 Inhibitors; 0/Phosphodiesterase 4 Inhibitors; 0/Phosphodiesterase Inhibitors; 063D2YI19E/pumafentrine; 315-22-0/Monocrotaline; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 3; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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