Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
Pharmacology. 2013;91(3-4):178-84. doi: 10.1159/000346921. Epub 2013 Feb 21.
Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.
肺动脉高压 (PAH) 仍然无法有效治愈，因此仍在寻找新的治疗方法。在野百合碱 (MCT) 诱导的 PAH 大鼠模型中，评估了西地那非 (25mg/kg 体重) 和法舒地尔 (30mg/kg 体重) 单独或联合给药对右心室压力 (RVP)、右心室质量以及几种生物标志物 (HDL-C、BNP、VEGF-A) 正常化的影响。MCT(60mg/kg 体重) 诱导雄性 Wistar 大鼠出现明显的 PAH。21 天后，评估了西地那非或法舒地尔给药后 RVP 显著降低，同时右心室肥厚减轻 - 右心室/左心室加室间隔比值降低 -。与 MCT 处理的大鼠相比，法舒地尔单独或联合西地那非给药可显著降低血浆 BNP 水平。与 MCT 处理的大鼠相比，法舒地尔单独或联合西地那非给药可显著升高 HDL-C 水平。与暴露于 MCT 的大鼠相比，单独给予法舒地尔或西地那非，或联合给予法舒地尔和西地那非，均可显著增加血浆 VEGF-A 水平。
