title: Effects of Rho-kinase inhibitor on vasopressin-induced chronic myocardial damage in rats.
abstract: The aim of this study was to develop a new model of vasopressin-induced chronic myocardial damage based on sustained ST-segment depression in electrocardiogram (ECG) with progression of myocardial fibrosis in rats. Furthermore, using this model, we examined the prophylactic potential of fasudil, a Rho-kinase inhibitor, against myocardial damage induced by vasopressin. In 10-week old male Donryu rats, intravenous administration of arginine vasopressin (0.5 iu/kg) induced significant ST-segment depression. Two days and one week after the administration of vasopressin, ST-segment depression was -0.19 +/- 0.02 and -0.14 +/- 0.02 mV, respectively. Fasudil (10 and 30 mg/kg, p.o.) significantly attenuated the ST-segment depression induced by vasopressin. One week after the administration of vasopressin, the percent area of myocardial fibrosis in control animals (0.42 +/- 0.11%, p < 0.01) was significantly greater than that in normal animals (0.05 +/- 0.01%). Fasudil (10 and 30 mg/kg) significantly prevented the development of the fibrosis. We present a new model of chronic myocardial damage based on sustained ST-segment depression with progression of myocardial fibrosis in rats, and suggest that this model may be useful to investigate the treatment of chronic angina. Inhibition of Rho-kinase is efficacious in preventing the ECG change and development of fibrosis induced by vasopressin in this model.
authors.affiliation: First Laboratory for Pharmacology, Institute of Life Science Research, Asahi Kasei Corporation, 632-1, Mifuku, Ohito-Cho, Tagata-Gun, 410-2321, Japan.
authors.forename: Shin ichi
authors.initials: Si
authors.lastname: Satoh
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ikegaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Toshima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Asano
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005355:Fibrosis; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D014667:Vasopressins; D054460:rho-Associated Kinases
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D014667:Vasopressins; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil