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J Pharm Pharmacol ; 73(2): 145-151, 2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33793805

RESUMEN

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.


Asunto(s)
Apoptosis/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Citrato de Sildenafil/farmacología , Remodelación Ventricular/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Ventrículos Cardíacos/patología , Etiquetado Corte-Fin in Situ , Monocrotalina , Miocardio/patología , Receptores Activados del Proliferador del Peroxisoma/efectos de los fármacos , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Inhibidores de Fosfodiesterasa 5/farmacología , Ratas , Ratas Sprague-Dawley
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