Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory activity, reduces oxidative stress, and inhibits the activity of TGF-β receptor 1 and α-SMA. The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension (PH) in a rat model. PAH was induced by single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index, oxidative stress parameters, and inflammatory markers were performed. Additionally, histopathology of lung and right ventricular tissue, immunohistochemistry, expression of α-SMA, eNOS, TGF- β, and RT-PCR, and an in-vitro (using HUVECs) study were also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress and increase in expression of α-SMA and TGF-β receptor 1 compared to MCT control group rats. In HUVEC's cells, the expression of α-SMA was increased, whereas eNOS decreased after TGF-β exposure and was substantially reversed after pre-treatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the α-SMA/TGF-β/eNOS signaling pathway.

中文翻译：

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贝尼地平单独使用以及联合波生坦和西地那非对大鼠实验模型肺动脉高压的改善作用。

肺动脉高压（PAH）是一种影响肺动脉内皮的持续性疾病。Benidipine 是一种钙通道阻滞剂，具有血管舒张、抗炎活性、减少氧化应激，并抑制 TGF-β 受体 1 和 α-SMA 的活性。本研究旨在探讨贝尼地平单独使用以及与波生坦和西地那非联合使用对野百合碱 (MCT) 诱导的大鼠肺动脉高压 (PH) 的影响。通过单剂量给予大鼠 MCT 诱导 PAH。将动物随机分为不同组，并单独用贝尼地平或与波生坦或西地那非联合治疗。进行了血流动力学参数、富尔顿指数、氧化应激参数和炎症标志物等各种参数。此外，还进行了肺和右心室组织的组织病理学、免疫组织化学、α-SMA、eNOS、TGF-β的表达和RT-PCR以及体外（使用HUVEC）研究。与MCT对照组大鼠相比，贝尼地平及其联合治疗对右心室收缩压升高、右心室肥厚、氧化应激升高以及α-SMA和TGF-β受体1表达增加具有更好的预防作用。在HUVEC细胞中，α-SMA的表达增加，而eNOS在TGF-β暴露后减少，并且在贝尼地平预处理后基本逆转。我们得出结论，贝尼地平及其与波生坦和西地那非的组合通过 α-SMA/TGF-β/eNOS 信号通路对 MCT 诱导的 PAH 表现出有益的作用。