Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School, Brown University, 593 Eddy Street, Providence, RI 02903, USA.
Expert Rev Respir Med. 2011 Jun;5(3):315-28. doi: 10.1586/ers.11.38.
Tadalafil is a selective inhibitor of phosphodiesterase type-5 (PDE-5) that was originally developed for the treatment of male erectile dysfunction and recently approved for the treatment of pulmonary arterial hypertension (PAH). The antipulmonary hypertensive effects of nitric oxide and the natriuretic peptides are mediated via increasing intracellular cGMP and enzymatic degradation by PDE-5 is the major route of cGMP inactivation in the lung. Evidence is accruing that PDE-5 activity is increased in pulmonary vascular diseases and may contribute to the pathogenesis of PAH. The longer half-life of tadalafil allows for once-daily dosing as compared with three-times daily dosing for sildenafil, the only other PDE-5 inhibitor currently approved for treatment of PAH. This article reviews the role of cGMP and PDE-5 in PAH, presents the results of recent clinical trials and discusses the role of tadalafil in the treatment of this rare but difficult-to-treat disease.
他达拉非是一种磷酸二酯酶 5（PDE-5）的选择性抑制剂，最初被开发用于治疗男性勃起功能障碍，最近被批准用于治疗肺动脉高压（PAH）。一氧化氮和利钠肽的抗高血压作用是通过增加细胞内 cGMP 来介导的，而 PDE-5 的酶促降解是肺中 cGMP 失活的主要途径。越来越多的证据表明，肺动脉疾病中 PDE-5 的活性增加，可能导致 PAH 的发病机制。与目前唯一被批准用于治疗 PAH 的 PDE-5 抑制剂西地那非相比，他达拉非的半衰期更长，因此可以每天服用一次。本文综述了 cGMP 和 PDE-5 在 PAH 中的作用，介绍了最近临床试验的结果，并讨论了他达拉非在治疗这种罕见但难以治疗的疾病中的作用。
