Sildenafil reverses the hypertrophy of mice right ventricle caused by hypoxia but does not reverse the changes in the myosin heavy chain isoforms.

Abstract

In this study, we investigated the effect of hypoxia and concomitant sildenafil treatment on MHC isoforms in hypoxia-induced hypertrophied right ventricles. Right ventricular hypertrophy was induced in mice by exposing them to hypoxic stimulus (11% ambient oxygen) in a normobaric chamber for 20 days. 45 mice were used in this study, distributed randomly into three groups: the first group served as a control (CO), the second group was exposed to hypoxia for 20 days without sildenafil treatment (HY), and the third group was given sildenafil orally at a dose of 30 mg.kg^-1.day^-1 plus exposure to hypoxia for 20 days (HS). Relative amounts of MHC isoforms were calculated using two ELISA kits containing antibodies against α and β MHC, and by SDS-PAGE. Compared with the CO group, the HY group showed a significant increase in right ventricle weight/left ventricle plus septum ratio (Fulton's ratio). The HS group showed a significant decrease in Fulton's ratio compared with the HY group, but not with the CO group. Expression of the MHC-β isoform was significantly increased in the HY group compared with the CO group. There was no significant difference in MHC-β between the HY group and the HS group. Plasma atrial natriuretic peptide level was significantly higher in HY group than HS group and did not return to normal after sildenafil treatment. Conclusion: sildenafil reversed the right ventricular hypertrophy induced by hypoxia but did not decrease the expression of MHC-β to normal levels.