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

• Published in: Biochemical and biophysical research communications Vol. 424; no. 2; pp. 338 - 340
• Main Authors: Satoh, Shin-ichi, Kawasaki, Koh, Ikegaki, Ichiro, Asano, Toshio, Shimokawa, Hiroaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.07.2012
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Animals; Cardiomegaly - chemically induced; Cardiomegaly - enzymology; Cardiomegaly - prevention & control; Cardiomyocyte hypertrophy; Cells, Cultured; Cytoprotection; Endothelins - pharmacology; Fasudil; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - enzymology; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; rho-Associated Kinases - antagonists & inhibitors; Rho-kinase; Rho-kinase; Cardiomyocyte hypertrophy; Fasudil
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.06.136

► 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.