Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats

Ichiro Ikegaki, Tsuyoshi Hattori, Tamami Yamaguchi, Yasuo Sasaki, Shin ichi Satoh, Toshio Asano, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Long-term inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular remodeling in rats. To determine the pathogenic mechanism involved in vascular remodeling, we examined the effects of fasudil, a Rho-kinase inhibitor, on vascular lesion formation. In rats treated with L-NAME at 10 mg/kg/day, vascular remodeling was evident in both large and small coronary arteries at the fourth week. Fasudil (3 mg/kg, p.o., twice daily) markedly prevented the development of vascular remodeling in small coronary arteries. Coronary flow was measured in Langendorff perfused isolated heart preparations. Long-term treatment with L-NAME caused a significant decrease in coronary flow, which was significantly inhibited by fasudil. Fasudil suppressed the structural and functional changes in coronary arteries by chronic blockade of NO synthesis. Thus, the Rho-kinase pathway may be substantially involved in the pathogenesis of vascular remodeling in this rat model.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalEuropean Journal of Pharmacology
Volume427
Issue number1
DOIs
Publication statusPublished - 2001 Sep 7

Keywords

  • Fasudil
  • Hydroxyfasudil
  • Nitric oxide (NO)
  • Remodeling
  • Rho-kinase

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats'. Together they form a unique fingerprint.

Cite this