Effects of Rho-kinase inhibitor on vasopressin-induced chronic myocardial damage in rats

Shin Ichi Satoh, Ichiro Ikegaki, Yoshinori Toshima, Atsushi Watanabe, Toshio Asano, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalLife Sciences
Volume72
Issue number1
DOIs
Publication statusPublished - 2002 Nov 22
Externally publishedYes

Keywords

  • Angina
  • Fasudil
  • Fibrosis
  • Rho-kinase inhibitor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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