Angiotensin-converting enzyme inhibitor prevents plasminogen activator inhibitor-1 expression in a rat model with cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis

Makoto Katoh, Kensuke Egashira, Takashi Mitsui, Susumu Chishima, Akira Takeshita, Hiroshi Narita

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Plasminogen activator inhibitor-1 (PAI-1) may participate in the development of cardiovascular remodeling by inhibiting extracellular matrix turnover and fibrinolysis. However, little is known about physiological regulators of PAI-1 in vivo. Angiotensin II has been shown to stimulate PAI-1 in vitro. We previously reported that longterm inhibition of nitric oxide (NO) synthesis with No-nitro-L-arginine methyl ester (L-NAME) causes cardiovascular remodeling (vascular medial thickening and fibrosis) associated with increased tissue angiotensin-converting enzyme (ACE) activity. In the present study, we examined whether treatment with an ACE inhibitor modulates the cardiovascular PAI-1 expression in this model in vivo. Wistar-Kyoto rats were treated with either no drugs, L-NAME (100 mg/kg day), or L-NAME plus the ACE inhibitor imidapril (20 mg/kg day). Marked increases in PAI-1 mRNA and protein levels in the aorta and left ventricle were observed after the first and fourth weeks of PAI-1 treatment. PAI-1 immunoreactivity was increased in the endothelium and the media of the aorta and coronary arteries after treatment of L-NAME. This increase in PAI-1 levels was associated with an increase in ACE activity of the aorta and left ventricle. ACE inhibition with imidapril significantly prevented both the increases in PAI-1 levels and the development of cardiovascular remodeling. These findings suggest that the local renin-angiotensin system regulates PAI-1 expression, and that the increased PAI-1 levels may contribute to the cardiovascular remodeling in this model (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 2000

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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