title: Fasudil reversed MCT-induced and chronic hypoxia-induced pulmonary hypertension by attenuating oxidative stress and inhibiting the expression of Trx1 and HIF-1α.
abstract: Antioxidant therapy attenuates pulmonary hypertension (PH). In the present study, we tested the antioxidant effects of fasudil against PH in rats. Monocrotaline (MCT)-induced and chronic hypoxia-induced PH models of rats were established, and the haemodynamic and pathomorphologic results of three different doses of fasudil (10 mg/kg, 30 mg/kg, and 75 mg/kg per day) were subsequently compared with those of bosentan (30 mg/kg per day). Additionally, the protein expressions of thioredoxin-1 (Trx1) and hypoxia inducible factor-1α (HIF-1α), the content of superoxide dismutase (SOD), and the levels of hydrogen peroxide (H2O2), malonyldialdehyde (MDA), and hydroxy radical (·OH) were investigated. Fasudil effectively reduced the right ventricular systolic pressure (RVSP) and alleviated right ventricle (RV) hypertrophy, as well as the histological changes in the pulmonary arterioles. Moreover, fasudil markedly lessened the expression of Trx1 and HIF-1α, up-regulated the concentration of SOD, and lowered the levels of H2O2, MDA, and ·OH. In conclusion, fasudil is a notably attractive potential therapy for PH.
authors: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Manling
authors: M
authors: Liu
authors: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Yanxia
authors: Y
authors: Wang
authors: Centre of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors: Lianhe
authors: L
authors: Zheng
authors: Department of Information, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors: Wansong
authors: W
authors: Zheng
authors: Tianjin Chase Sun Pharmaceutical Co., Ltd., Tianjin 301700, PR China.
authors: Kai
authors: K
authors: Dong
authors: Tianjin Chase Sun Pharmaceutical Co., Ltd., Tianjin 301700, PR China.
authors: Shuai
authors: S
authors: Chen
authors: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Bo
authors: B
authors: Zhang
authors: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: Lizhic@fmmu.edu.cn.
authors: Zhichao
authors: Z
authors: Li
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D000860:Hypoxia / Q000139:chemically induced / Q000150:complications; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016686:Monocrotaline / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014665:Vasodilator Agents; D008315:Malondialdehyde; D013879:Thioredoxins; D016686:Monocrotaline; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; C049347:fasudil
keywords: Fasudil; Hypoxia inducible factor-1α (HIF-1α); Oxidative stress; Pulmonary hypertension (PH); Thioredoxin-1 (Trx1)