TY - JOUR T1 - Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition JF - European Respiratory Journal JO - Eur Respir J SP - 599 LP - 610 DO - 10.1183/09031936.00002007 VL - 31 IS - 3 AU - E. Dony AU - Y-J. Lai AU - R. Dumitrascu AU - S. S. Pullamsetti AU - R. Savai AU - H. A. Ghofrani AU - N. Weissmann AU - C. Schudt AU - D. Flockerzi AU - W. Seeger AU - F. Grimminger AU - R. T. Schermuly Y1 - 2008/03/01 UR - http://erj.ersjournals.com/content/31/3/599.abstract N2 - 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. ER -