Mineralocorticoid receptor blockade attenuates proliferative changes in the rat pulmonary artery in monocrotaline-induced pulmonary hypertension

本研究的目的是通过拮抗盐皮质激素受体(MR)信号通路在大鼠肺动脉高压(PAH)小动脉重构中的作用。动物被分为两组：一组接受口服MR拮抗剂治疗，另一组不接受药物治疗。MR拮抗剂治疗可改善未用药组中因RV峰值压升高而导致的RV功能降低和肥大。与未用药组相比，治疗组的PA内侧壁厚度和肌化程度显著降低。与未用药组相比，MR拮抗剂治疗组大鼠肺组织MR、血管紧张素2型受体1a和转化生长因子β1基因表达水平显著降低，提示MR信号在PAH增殖性血管重塑中起一定作用。

The aim of this study was to investigate a role of mineralocorticoid receptor (MR) signaling in the arteriolar remodeling of pulmonary artery hypertension (PAH) by antagonizing MR.PAH was induced by a single subcutaneous injection of monocrotaline in male rats. Animals were divided in two groups: one group treated with oral MR antagonist and the other received no medication. MR antagonist treatment ameliorated increased reduced RV function and hypertrophy caused by elevated peak RV pressure seen in the group with no medication. The treatment group showed significantly less medial wall thickness and muscularization of PA compared to the group with no medication. MR antagonist treatment resulted in significant reduction in the mRNA levels of the MR, angiotensin 2 type 1a receptor and transforming growth factor beta1 in the lungs, when compared to the group with no medication.These results suggest that MR signaling plays a role in the proliferative vascular remodeling of PAH.