AIMTo elucidate the independent or combined effects of endothelin-1 (ET-1) and prostaglandin F2alpha (PGF2alpha) on cardiomyocytes and investigate the relationship between hypertrophy and apoptosis of cardiomyocytes.

METHODSCultured neonatal rat cardiomyocytes were stained with FITC-conjugated phalloidin and eosin to detect the cardiomyocyte hypertrophy evidenced by increased sarcomeric structure and cell size. Cardiomyocytes were stained with Hoechst 33258 to detect apoptotic nuclei showing features of condensation and fragmentation.

RESULTSCardiomyocyte hypertrophy induced by ET-1 or PGF2, shown a dose dependent effect. The area of cardiomyocytes treated by 10 nmol/L or 100 nmol/L of ET-1 for 24 h increased 68% or 84% as compared with control, respectively. The area of cardiomyocytes exposed to 10 nmol/L or 100 nmol/L of PGF2alpha for 24 h increased 28% or 106% as compared with control, respectively. The ET-1 and PGF2alpha had a synergic effect on cardiomyocyte hypertrophy, but not superimposed effect. The area of cardiomyocytes increased 80%, 122%, 96%, and 199% in 10 nmol/L ET-1 plus 10 nmol/L PGF2, 10 nmol/L ET-1 plus 100 nmol/L PGF2alpha, 100 nmol/L ET-1 plus 10 nmol/L PGF2alpha, and 100 nmol/L ET-1 plus 100 nmol/L PGF2alpha group, respectively. There were no changes in apoptotic rate of cardiomyocytes treated by ET-1 or PGF2alpha alone for 48 h. The apoptotic rate of cardiomyocytes also didn't increase in ET-1 plus PGF2alpha treatment for 24 h groups, but significantly increased in ET-1 plus PGF2alpha treatment for 48 h groups. ET-1 or PGF2alpha could induce an increase in apoptotic rate of hypertrophic cardiomyocytes. There was a positive relationship between hypertrophic extent and apoptotic rate in cardiomyocytes.

CONCLUSIONThe cardiomyocytes treated by ET-1 or PGF2alpha alone only show hypertrophy, but treatment of ET-1 plus PGF2alpha for 48 h induces apoptosis of cardiomyocytes.