Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Shizuoka 410-2321, Japan.
Biochem Biophys Res Commun. 2012 Jul 27;424(2):338-40. doi: 10.1016/j.bbrc.2012.06.136. Epub 2012 Jul 4.
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 (1-10 μM) and hydroxyfasudil (0.3-10 μM) 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.
本研究采用细胞水平的方法，探讨 Rho 激酶抑制剂法舒地尔及其活性代谢产物羟法舒地尔是否对内皮素诱导的心肌细胞肥大具有直接的保护作用。结果发现，内皮素（10nM）处理使培养的新生大鼠心肌细胞表面积增加 21.2%，导致明显的心肌细胞肥大；1-10μM 的法舒地尔和 0.3-10μM 的羟法舒地尔可显著抑制内皮素诱导的心肌细胞肥大。本研究结果提示，法舒地尔抑制心肌肥厚至少部分是由于对心肌细胞肥大的直接保护作用。
