title: [Cigarette smoke exposure induced pulmonary artery pressure increase through inhibiting Kv1.5 and Kv2.1 mRNA expression in rat pulmonary artery smooth muscles].
abstract: OBJECTIVE
  To investigate the effect of cigarette smoke exposure on Kv1.5 and Kv2.1 mRNA expression in rat pulmonary arterial smooth muscle cells (PASMCs), and further to clarify the possible mechanism of cigarette smoking induced pulmonary arterial hypertension.
  
  
  METHODS
  Primary cell culture and animal experiments were used in this study. Rat distal PASMCs were isolated and cultured by collagenase digestion. PASMCs were treated by nicotine 100 nmol/L. After 48 h, Kv1.5 and Kv2.1 mRNA expression were detected by real-time quantitative PCR and compared with the control group. Rat model of chronic exposure to cigarette smoke was established. Thirty-six male SD rats were randomly divided equally into 6 groups: (1) 1 month control group; (2) 1 month cigarette exposure group; (3) 3 month control group; (4) 3 month cigarette exposure group; (5) 6 month control group; (6) 6 month cigarette exposure group. Direct right heart manometry, HE staining and real-time quantitative PCR were used to detect the effect of smoke exposure on rat right ventricular systolic pressure (RVSP), mean pressure (mPAP), right ventricular hypertrophy index [RV/(LV + S)] as well as Kv1.5 and Kv2.1 mRNA expression on pulmonary artery smooth muscle at different time points (1 month, 3 months and 6 months).
  
  
  RESULTS
  The mPAP and RVSP in cigarette smoke exposure 6 month group were (13.08 ± 0.64) mm Hg and (29.73 ± 0.83) mm Hg, slightly higher than those in the control 6 month group [(10.16 ± 0.44) mm Hg and (22.56 ± 0.64) mm Hg] (P < 0.01). The ratio of Kv1.5 mRNA expression in distal pulmonary arteries in 1 month, 3 month, 6 month cigarette exposure group to that in control groups was (52 ± 11)%, (64 ± 19)% and (75 ± 11)% (P < 0.05). The ratio of Kv2.1 mRNA expression in distal pulmonary arteries in 1 month, 3 month, 6 month cigarette exposure groups to that in control groups was (51.0 ± 18.6)%, (78.7 ± 10.1)% and (71.4 ± 2.3)% (P < 0.01); Chronic exposure to cigarette smoke significantly decreased Kv1.5 and Kv2.1 mRNA expression in rat pulmonary arterial smooth muscle at each time point. The ratio of Kv1.5 and Kv2.1 mRNA expression in rat distal PASMCs treated with nicotine (100 nmol/L, 48 h) to control group were (62 ± 14)% (P < 0.05) and (72 ± 15)% (P < 0.01), respectively. Nicotine inhibited Kv1.5 and Kv2.1 mRNA expression in rat distal PASMCs.
  
  
  CONCLUSIONS
  Cigarette smoke exposure may be involved in pulmonary hypertension by downregulating potassium channels Kv1.5 and Kv2.1 mRNA expression in rat pulmonary artery smooth muscles.
authors.affiliation: Guangzhou Medical University, Guangzhou , China.
authors.forename: Chun-yi
authors.initials: CY
authors.lastname: Lin
authors.forename: Li-mei
authors.initials: LM
authors.lastname: Wan
authors.forename: Yu-qin
authors.initials: YQ
authors.lastname: Chen
authors.forename: Huan-tao
authors.initials: HT
authors.lastname: Ou
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Yu-ting
authors.initials: YT
authors.lastname: Liang
authors.forename: Ran
authors.initials: R
authors.lastname: Ma
authors.forename: Wen-ju
authors.initials: WJ
authors.lastname: Lu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*
chemical_list: C496983:Kcna5 protein, rat; C496991:Kcnb1 protein, rat; D051666:Kv1.5 Potassium Channel; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D009538:Nicotine