RT Journal Article
SR Electronic
T1 Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 599
OP 610
DO 10.1183/09031936.00002007
VO 31
IS 3
A1 E. Dony
A1 Y-J. Lai
A1 R. Dumitrascu
A1 S. S. Pullamsetti
A1 R. Savai
A1 H. A. Ghofrani
A1 N. Weissmann
A1 C. Schudt
A1 D. Flockerzi
A1 W. Seeger
A1 F. Grimminger
A1 R. T. Schermuly
YR 2008
UL http://erj.ersjournals.com/content/31/3/599.abstract
AB 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.