AIM To investigate the protective effect of phosphodiesterase 5 (PDE5) inhibitor against isoproterenol (Iso)-induced cardiomyocyte hypertrophy in neonatal rats.
METHODS Rat cardiomyocytes were isolated and divided into control (Con) group, isoproterenol (Iso) group and isoproterenol+sildenafil (Iso+Sil) group. The cell viability and lactate dehydrogenation (LDH) were detected by each group. The concentration of Sil in subsequent experimental was determined. Measurement of cardiac atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) mRNA content by RT-PCR, flow cytometry and Western blot were used to detect apoptosis or endoplasmic reticulum stress-related protein glucose-regulated protein 78 (GRP78) and CCAAT enhancer-binding protein homologous protein (CHOP) levels.
RESULTS Compared with the Con group, the cell viability of the Iso group was decreased (P<0.01), and the release of LDH was increased (P<0.05). Compared with the Iso group, a certain concentration of Sil pretreatment could increase cell viability and reduce LDH (P<0.05). The release achieved maximum effect at 5 μmol/L Sil. Compared with the Con group, the Iso group increased the expression of ANP and β-MHC mRNA, up-regulated the apoptosis rate, and increased the protein levels of GRP78 and CHOP. Compared with the Iso group, Sil pretreatment reduced the expression of ANP and β-MHC mRNA, down-regulation of apoptosis rate and inhibition of GRP78 and CHOP protein expression.
Conclusion PDE5 inhibitor Sil effectively inhibits Iso-induced cardiomyocyte hypertrophy in neonatal rats and its mechanism may be related to down-regulation of apoptosis and endoplasmic reticulum stress.
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