Effect of Raloxifene on Pulmonary Artery Remodeling in Chronic Hypoxic Rats

OBJECTIVE To explore effect of raloxifene on pulmonary artery remodeling in chronic hypoxic rats. METHODS Forty rats were divided 5 groups: normal oxygen group (n=8), hypoxia group (n=8), hypoxia+17β-estraiol group (75?mg·kg^-1·d^-1, n=8), normal oxygen+raloxifene group(10 mg·kg^-1·d^-1, n=8) and hypoxia+raloxifene group(10?mg·kg^-1·d^-1, n=8). Pulmonary artery smooth muscle cells (PASMC) were cultured from pulmonary artery in rats. The chronic hypoxic animal and cell models were established by regular exposing the rats to normabaric hypoxic conditions. The contents of proliferating cell and Caveolin-1(Cav-1) protein expressions were detected by immunohistochemical assay. Reactive oxygen species (ROS) was assessed by fluorescent probe assays. RESULTS Compared with rats in normal oxygen group, pulmonary proliferation, medial wall thickness and fully muscularized vessels were significantly enhanced in response to hypoxia (P<0.01). There were marked decreases in hypoxia groups with raloxifene treatment (P<0.05). The concentrations of ROS were significantly higher in hypoxia group than normal oxygen groups (P<0.01). Raloxifene inhibited the ROS concentrations (P<0.05). Cav-1 protein expressions were decreased in hypoxia groups (P<0.01) and were increased with raloxifene treatment (P<0.05). the efficacy of raloxifene to alleviate the pulmonary arterial remodeling was similar to 17β-estraiol. CONCLUSION Raloxifene up-regulates the expressions of Cav-1 protein, decreases ROS productions, and inhibits pulmonary artery PASMC proliferating. Raloxifene has important modulating effects on pulmonary vascular structural remodeling in chronic hypoxic rats.