Study on mechanism of niflumic acid inhibiting the involvement of transmembrane protein 16A in pulmonary artery hypertension induced by high pulmonary blood flow

Objective: To explore the role and potential mechanism of niflumic acid (NFA), a calcium-activated chloride channel (CaCCs) inhibitor, and transmembrane protein 16A (TMEM16A) in the pulmonary artery hypertension (PAH) induced by high pulmonary blood flow. Methods: Forty SD rats were randomly divided into normal group, sham group, model group and model+NFA group. The sham group was used vascular clamp to clamp the abdominal aorta for 15 minutes, the model group was used abdominal aorta-inferior vena cava fistulation to establish a left-to-right shunt PAH model, and the model+NFA group was given NFA by gavage daily after fistulation. After feeding for 12 weeks, the mean pulmonary artery pressure and pulmonary artery tension of rats were measured, and the expression of TMEM16A in pulmonary artery smooth muscle cells (PASMCs) of each group was detected by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Results: The contraction rate of pulmonary artery ring, TMEM16A mRNA and protein expression levels in the model group and model+NFA group were significantly higher than those in the normal group (P＜0.05). Compared with the model group, the TMEM16A mRNA and protein expression level in the model+NFA group was down-regulated and the contraction rate of pulmonary artery ring was decreased (P＜0.05). Conclusion: PAH induced by high pulmonary blood flow is related to the high expression of TMEM16A. NFA can reduce pulmonary artery tension and inhibit the overexpression of TMEM16A.