Evidence of a direct cellular protective effect of Rho-kinase inhibitors on endothelin-induced cardiac myocyte hypertrophy

► A protective effect of Rho-kinase inhibitor on cardiac hypertrophy was examined. ► Endothelin caused hypertrophy of cultured neonatal rat cardiomyocytes. ► Fasudil, a Rho-kinase inhibitor, significantly prevented cardiomyocyte hypertrophy. ► Fasudil exerts a direct protective effect on cardiac hypertrophy. Using a cellular approach, the present study examined whether fasudil and active metabolite hydroxyfasudil, Rho-kinase inhibitors, exert a direct protective effect on endothelin-induced cardiac myocyte hypertrophy in vitro. Treatment with endothelin (10nM) caused significant hypertrophy of cultured neonatal rat cardiomyocytes by a 21.2% increase in cell surface area. Fasudil (1–10μM) and hydroxyfasudil (0.3–10μM) significantly prevented endothelin-induced cardiomyocyte hypertrophy. The present results suggest that inhibition of cardiac hypertrophy by fasudil is, at least in part, due to direct protection of cardiomyocytes from hypertrophy.