title: Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.
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.
authors.affiliation: *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.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Jianfa
authors.initials: J
authors.lastname: Ma
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Pang
authors.forename: Jinquan
authors.initials: J
authors.lastname: Lao
authors.forename: Xuanren
authors.initials: X
authors.lastname: Pan
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Danyan
authors.initials: D
authors.lastname: Su
authors.forename: Suyuan
authors.initials: S
authors.lastname: Qin
authors.forename: Arnav Prasad
authors.initials: AP
authors.lastname: Shrestha
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009544:Niflumic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D018118:Chloride Channels; D009544:Niflumic Acid