title: Tanshinone IIA attenuates hypoxic pulmonary hypertension via modulating KV currents.
abstract: The voltage-gated K(+) (KV) channels play an essential role in the etiology of chronic hypoxic pulmonary hypertension (CH-PH).Tanshinone IIA (TIIA), a major active component of Salvia miltiorrhiza Bunge (S. miltiorrhiza), has many biological protective effects. In the present study, we investigated whether KV channels were responsible for the protective effect of TIIA on CH-PH. In acute hypoxia experiments, the IKV currents of pulmonary artery smooth muscle cells (PASMCs) isolated from healthy rats were determined in the absence or presence of TIIA (5 μg/ml or 25 μg/ml) or 4-AP (1 mM). In chronic hypoxia experiments, rats were challenged by intermittent hypoxia or sustained hypoxia exposure for 4 weeks with or without TIIA (10 mg/kg) treatment. Subsequently, the hemodynamic data and the pathomorphological changes of pulmonary arteries were gathered. The expressions of KV2.1 and KV1.5 in pulmonary arteries were tested by Western blotting and RT-PCR, respectively. PASMCs were detached from intermittent hypoxia or sustained hypoxia exposure rats to evaluate the IKV currents. Results showed that TIIA markedly recovered acute hypoxia-induced the down-regulation of IKV currents in PASMCs. Moreover, TIIA significantly restrained chronic intermittent hypoxia or sustained hypoxia-induced pulmonary artery wall remodeling, accompanied with modulating the expressions of KV2.1 and KV1.5, and reversing the down-regulation of IKV currents. TIIA is thus an attractive potential therapy for CH-PH.
authors.affiliation: Center of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Lianhe
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Manling
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Pengtao
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China; Lung Injury and Repair Center, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: Lizhic@fmmu.edu.cn.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Li
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D045784:Abietanes; D024642:Potassium Channels, Voltage-Gated; C021751:tanshinone
keywords: Chronic hypoxia pulmonary hypertension (CH-PH); Tanshinone IIA (TIIA); The voltage-gated potassium ion (K(V)) channels