Effect of beraprost sodium on HPH rats and expression of oxygen-sensitive K_V channels in pulmonary artery smooth muscle

Objective: To explore the effect of beraprost sodium (BPS) on hypoxia-induced pulmonary artery hypertension (HPH) in rats and the expression of oxygen-sensitive K_V channels in pulmonary artery smooth muscle (PASM). Methods: The HPH model of rats was established by exposing rats to low-pressure and low-oxygen cabin which was auto-modulated for 8h every day. Rats in the BPS group were given an intragastric administration of BPS [300 μg/(kg·d)], while those in the control group and HPH group were given an intragastric administration of 3 ml/kg of 0.9% saline. After 4 weeks, the mean pulmonary artery pressure (mPAP) was measured and right heart ventricle hypertrophy index (RVHI) was calculated; pulmonary artery remodeling was evaluated by HE staining; the expressions of K_V1.2, K_V1.5 and K_V2.1 in the pulmonary artery were detected by Real-time PCR and Western blot. Results: The HPH model was successfully established in rats exposed to chronic hypoxia for 4 weeks. Compared with those in HPH group, mPAP, RVHI and pulmonary artery remodeling were decreased in BPS group [mPAP: (13.48±2.18)mmHg vs. (23.87±2.23)mmHg vs. (17.09±1.20)mmHg; RVHI: 0.28±0.02 vs. 0.46±0.03 vs. 0.36±0.04; % area of medial smooth muscle: 35.72±6.58 vs. 68.52±5.64 vs. 46.58±8.43; P<0.05], and the mRNA and protein expressions of K_V1.2, K_V1.5 and K_V2.1 were increased (relative protein expression level: K_V1.2, 0.78±0.10 vs. 0.15±0.03 vs. 0.57±0.13; K_V1.5, 0.61±0.10 vs. 0.31±0.05 vs. 0.59±0.13; K_V2.1, 0.29±0.05 vs. 0.10±0.02 vs. 0.28±0.07; P<0.05). Conclusion: BPS can improve pulmonary arterial hypertension induced by hypoxia, and upregulate the decreased mRNA and protein expressions of K_V1.2, K_V1.5 and K_V2.1 in pulmonary artery.