Objectives: To assess the effect of sildenafil on monocrotaline-induced right ventricular (RV) remodeling and investigate the possible mechanism.
Methods: Rats were subcutaneously injected with monocrotaline to establish an RV remodeling model and then administered sildenafil (25 mg/kg) from days 1 to 28. After 28 days of administration, the RV systolic pressure and the RV hypertrophy index (RVHI) were measured. The morphology of the right ventricle was observed by H&E staining. The ultrastructure of the right ventricle was observed using a transmission electron microscope. The myocardial apoptosis of the right ventricle was evaluated by TUNEL staining. The protein expression of apoptosis-related proteins and PPARs were examined by western blotting.
Key findings: The results indicated that sildenafil decreased the RV systolic pressure and RVHI, and improved the microstructure and ultrastructure of the right ventricle in monocrotaline-induced rats. In addition, sildenafil suppressed myocardial apoptosis and promoted the protein expression of PPARs of the right ventricle in monocrotaline-induced rats.
Conclusion: Sildenafil inhibits RV remodeling in monocrotaline-induced rats, which might be partially mediated by reducing myocardial apoptosis and activating PPARs.
Keywords: myocardial apoptosis; peroxisome proliferator-activated receptors; right ventricular remodelling; sildenafil.
© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.