Treprostinil (Orenitram) is a potent DP1, IP and EP2 agonist (EC50: 0.6/1.9/6.2 nM).

EP3:68.9 nM (EC50), EP2:6.2 nM (EC50), DP1:0.6 nM (EC50), IP:1.9 nM (EC50)

Treprostinil对IP、EP2和DP1受体具有高亲和力（Ki分别为32、3.6和4.4 nM），对EP1和EP4受体的亲和力低，而对EP3、FP和TP受体的亲和力更低。IP、DP1和EP2受体的激活都可以导致人类肺动脉的血管舒张[1]。Treprostinil抑制培养的内皮集落形成细胞的存活率。经Treprostinil预处理的间充质干细胞的条件培养基能刺激内皮集落形成细胞的增殖[2]。

Treprostinil在提高小鼠和人类造血干细胞以及祖细胞内cAMP水平方面极为有效[2]。与安慰剂相比，Treprostinil能够保护窦状内皮细胞层并在移植后早期减少血小板沉积。在安慰剂组中，肝组织血流显著受损，而Treprostinil能维持接近正常水平的血流[3]。Treprostinil治疗显著增加了在无毛小鼠体内Matrigel植入的内皮群落形成细胞与间充质干细胞共同形成血管的能力。VEGF-A基因在间充质干细胞中的沉默也阻断了Treprostinil的促血管生成效果[4]。与常氧小鼠相比，Treprostinil治疗显著减少了细胞的招募。Treprostinil还降低了右心室收缩压并略微减少了血管重塑，但未能逆转右心室肥厚[5]。

Human or murine hematopoietic stem and progenitor cells are incubated in the presence of vehicle or the combination of 10 μM Treprostinil and 30 μM forskolin at 37°C for 1 hour and 24 hours. After washing with phosphate-buffered saline at 4°C, cells are stained for externalized phosphatidylserine with the apoptosis kit [2].

Male Lewis rats weighing 200-300 g are used in the study. Donor animals receive treprostinil or placebo 24 h before hepatectomy and the corresponding recipient animal receive a similar treatment until the time of sacrifice. The surgeon is blinded to treatment. Recipients are sacrificed at 1, 3, 6, 24 and 48 h post-transplantation to examine the early events after IRI. Treprostinil (100 ng/kg/min) or placebo is administered subcutaneously via an Alzet implantable osmotic pump. This dose is selected to achieve a steady-state plasma concentration in the range of 5-20 ng/mL [3]. . Bone marrow transplanted (BMT) mice are divided into five different groups with each group consisting of 6 to 10 mice. One group of mice is exposed to hypoxia (10% inspired oxygen fraction) in a normobaric chamber whereas the second group (control BMT) of animals are placed in a normoxic chamber with a normal oxygen environment (21% inspired O2 fraction) for 28 days. Sham group mice receive saline treatment whereas two other groups of mice receive Treprostinil infusions of different dose levels (14 ng/kg and 70 ng/kg per minute) and are exposed to hypoxia for 4 weeks. For comparison, human infusion rates in PAH therapy vary from 10 to 60 ng/kg per min[5].