Fasudil reversed MCT-induced and chronic hypoxia-induced pulmonary hypertension by attenuating oxidative stress and inhibiting the expression of Trx1 and HIF-1α

Highlights • The antioxidant effects of fasudil against MCT-induced and chronic hypoxia-induced pulmonary hypertension in rats were tested. • The haemodynamic and pathomorphologic results of three different doses of fasudil were compared with those of bosentan. • Fasudil markedly lessened the protei...

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Veröffentlicht in:	Respiratory physiology & neurobiology 2014-09, Vol.201, p.38-46
Hauptverfasser:	Liu, Manling, Wang, Yanxia, Zheng, Lianhe, Zheng, Wansong, Dong, Kai, Chen, Shuai, Zhang, Bo, Li, Zhichao
Format:	Artikel
Sprache:	eng
Schlagworte:	1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use Analysis of Variance Animals Disease Models, Animal Dose-Response Relationship, Drug Fasudil Gene Expression Regulation - drug effects Hemodynamics - drug effects Hydrogen Peroxide - metabolism Hypertension, Pulmonary - drug therapy Hypertension, Pulmonary - etiology Hypoxia - chemically induced Hypoxia - complications Hypoxia inducible factor-1α (HIF-1α) Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Male Malondialdehyde - metabolism Medical Education Monocrotaline - toxicity Oxidative stress Oxidative Stress - drug effects Pulmonary hypertension (PH) Pulmonary/Respiratory Rats Rats, Sprague-Dawley Superoxide Dismutase - metabolism Thioredoxin-1 (Trx1) Thioredoxins - metabolism Vasodilator Agents - pharmacology Vasodilator Agents - therapeutic use
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Zusammenfassung:	Highlights • The antioxidant effects of fasudil against MCT-induced and chronic hypoxia-induced pulmonary hypertension in rats were tested. • The haemodynamic and pathomorphologic results of three different doses of fasudil were compared with those of bosentan. • Fasudil markedly lessened the protein expression of Trx1 and HIF-1α induced by MCT and chronic hypoxia. • Fasudil effectively reduced the levels of H2 O2 , MDA, and OH, and up-regulated the concentration of SOD.
ISSN:	1569-9048 1878-1519
DOI:	10.1016/j.resp.2014.06.001