Effects of Rho-kinase inhibitor on vasopressin-induced chronic myocardial damage in rats.
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.
Satoh
Shin ichi
Si
First Laboratory for Pharmacology, Institute of Life Science Research, Asahi Kasei Corporation, 632-1, Mifuku, Ohito-Cho, Tagata-Gun, 410-2321, Japan.
Ikegaki
Ichiro
I
Toshima
Yoshinori
Y
Watanabe
Atsushi
A
Asano
Toshio
T
Shimokawa
Hiroaki
H
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
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