Effect of fasudil on hypoxic pulmonary hypertension and right ventricular hypertrophy in rats.

Objective: To investigate whether right ventricular hypertrophy in hypoxic pulmonary hypertension (HPH) rats could be prevented by treatment with Rho kinase inhibitor fasudil. Methods: The rat model of pulmonary hypertension was established by exposing rats to normobaric intermitent hypoxia [(10±0.5)% O2]. Twenty-four Spraque-Dawley male rats were randomly divided into control group, hypoxic model group and hypoxia with fasudil groups (n=8 each). The mean pulmonary arterial pressure (mPAP), and right ventricle hypertrophy index (RVHI) were measured. Ultrastructure of the right ventricular myocardial cells was observed under transmission electron microscope (TEM). –Results: The level of mPAP (31.38±1.98) mmHg and RVHI (0.47±0.03) were significantly higher in the hypoxic model group than (15.25±0.91) mmHg and (0.25±0.02) in control group respectively (P<0.01). Transmission electron microscope (TEM) revealed the model group right ventricular mitochondria increased significantly, swelling, cristae blurred, lost, heart muscle Siming dark band was not clear. The level of mPAP (16.63±1.53) mmHg and RVHI (0.27±0.02) were significantly lower in fasudil treatment group than in model group respectively (P<0.01). After the intervention of fasudil right ventricular myocardial injury was significantly reduced. Conclusions: Fasudil may partly prevent and reverse the development of pulmonary hypertension and right ventricular hypertrophy and myocardial cell injury.