title: Contribution of calcium-activated chloride channel to elevated pulmonary artery pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.
abstract: The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University Nanning, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University Nanning, China.
authors.forename: Chuansi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University Nanning, China.
authors.forename: Jianfa
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University Nanning, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Lao
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University Nanning, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Pang
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D018118:Chloride Channels
keywords: Calcium-activated chloride channel; pulmonary arterial hypertension; pulmonary vascular structural remodeling