Document Detail


Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition.
MedLine Citation:
PMID:  18032446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-21
Journal Detail:
Title:  The European respiratory journal     Volume:  31     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-03     Completed Date:  2008-04-29     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  599-610     Citation Subset:  IM    
Affiliation:
University of Giessen Lung Centre (UGLC), Klinikstrasse 36, 35392 Giessen, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
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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