Subdose of fasudil suppresses myocardial fibrosis in aldosterone-salt-treated uninephrectomized rats.

Rho/Rho kinase (ROCK) pathway plays an important role in pathological cardiovascular conditions. In the present study, the effect of a subdose of fasudil, a selective ROCK inhibitor, on systemic hypertension and myocardium fibrosis induced by aldosterone was investigated in uninephrectomized Sprague-Dawley rats (SD). Treatment with a fasudil (10 mg/kg x day, s.c.) for 5 weeks decreased the activity of ROCK activity for more than 53% as determined by the expression of phosphorylated Myosin phosphatase target subunit 1 (MYPT1). Although this dose of fasudil did not signifantly prevent hypertension, it remarkably alleviated myocardium hypertrophy and fibrosis. The elevated transcriptional expression of transforming growth factors beta1 (TGF-beta1), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and collagen I and III was also decreased. These results demonstrated that fasudil can protect the myocardium from injury by aldosterone at a subhypertensive dose.