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.
Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. pguo@implad.ac.cn
Peng
P
Guo
Chongming
C
Wu
T
T
Masaki
H
H
Mori
A
A
Nishiyama
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000450:Aldosterone; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D017931:DNA Primers; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control; D006977:Hypertension, Renal / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009392:Nephrectomy; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride
D000959:Antihypertensive Agents; D015415:Biomarkers; D002121:Calcium Channel Blockers; D017931:DNA Primers; D012333:RNA, Messenger; D012965:Sodium Chloride; D000450:Aldosterone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil