Journal article

Publication year: 2008

Pages: 599-610

Journal: European Respiratory Journal

Volume number: 31

Issue number: 3

ISSN: 0903-1936

Open access status: Bronze

DOI Link: https://doi.org/10.1183/09031936.00002007

Publisher: European Respiratory Society

Abstract: 

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.

Harvard Citation style: Dony, E., Lai, Y., Dumitrascu, R., Pullamsetti, S., Savai, R., Ghofrani, H., et al. (2008) Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition, European Respiratory Journal, 31(3), pp. 599-610. https://doi.org/10.1183/09031936.00002007

APA Citation style: Dony, E., Lai, Y., Dumitrascu, R., Pullamsetti, S., Savai, R., Ghofrani, H., Weissmann, N., Schudt, C., Fockerzi, D., Seeger, W., Grimminger, F., & Schermuly, R. (2008). Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition. European Respiratory Journal. 31(3), 599-610. https://doi.org/10.1183/09031936.00002007