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

• 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 H2O2, MDA, and OH, and up-regulated the concentration of SOD.

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.