title: Evidence of a direct cellular protective effect of Rho-kinase inhibitors on endothelin-induced cardiac myocyte hypertrophy.
abstract: 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.
authors: Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Shizuoka 410-2321, Japan.
authors: Shin-ichi
authors: S
authors: Satoh
authors: Koh
authors: K
authors: Kawasaki
authors: Ichiro
authors: I
authors: Ikegaki
authors: Toshio
authors: T
authors: Asano
authors: Hiroaki
authors: H
authors: Shimokawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D002478:Cells, Cultured; D019610:Cytoprotection; D016232:Endothelins / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D016232:Endothelins; D047428:Protein Kinase Inhibitors; C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil