Original ArticleNiflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In VivoWang, Kai MD*,†; Ma, Jianfa MD*,‡; Pang, Yusheng MD, PhD*; Lao, Jinquan MD*; Pan, Xuanren MD*; Tang, Qiaoyun MD*; Zhang, Feng MD*; Su, Danyan MD*; Qin, Suyuan MD*; Shrestha, Arnav Prasad MD*Author Information *Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; †Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; and ‡Department of Pediatrics, Hangzhou Children's Hospital, Hangzhou, China. Reprints: Yusheng Pang, MD, PhD, Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Autonomous Region 530021, China (e-mail: [email protected]). Supported by the Natural Science Foundation of China (NSFC 81160040) and Guangxi Natural Science Foundation (2013GXNSFAA019177). The authors report no conflicts of interest. K. Wang and J. Ma contributed equally to this work. Received January 27, 2015 Accepted June 19, 2015 Journal of Cardiovascular Pharmacology: October 2015 - Volume 66 - Issue 4 - p 383-391 doi: 10.1097/FJC.0000000000000291 Buy Metrics Abstract Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.