Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition
Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition
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DOI：
10.1183/09031936.00002007
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发表时间：
2008-03-01
影响因子：
24.3
通讯作者：
Schermuly, R. T.
中科院分区：
文献类型：
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作者：
Dony, E.;Lai, Y-J.;Schermuly, R. T.
本研究旨在观察磷酸二酯酶（PDE）抑制剂pumafentrine（10 mg（.）单次注射MCT（60 mg（.）kg（-1）可部分逆转大鼠肺动脉高压和右心肥大。此外，小肺动脉肌化、中膜肥大和管腔面积减少在很大程度上得到逆转。在体内证实了在pumafentrine下的平滑肌增殖的抑制，这是pumafentrine对血管细胞的促凋亡作用。此外，普马芬群剂量依赖性地增加环磷酸腺苷水平并抑制培养的肺动脉平滑肌细胞增殖。总之，口服普马芬群部分逆转了野百合碱诱导的大鼠肺动脉高压、肺血管重塑和右心肥大。
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.