Important role of local angiotensin II activity mediated via type I receptor in the pathogenesis of cardiovascular inflammatory changes induced by chronic blockade of nitric oxide synthesis in rats

Makoto Usui, Kensuke Egashira, Hideharu Tomita, Masamichi Koyanagi, Makoto Katoh, Hiroaki Shimokawa, Motohiro Takeya, Teizo Yoshimura, Kouji Matsushima, Akira Takeshita

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

Background - The chronic inhibition of NO synthesis by N(ω)-nitro-L- arginine methyl ester (L-NAME) upregulates the cardiovascular tissue angiotensin II (Ang II)-generating system and induces cardiovascular inflammatory changes in rats. Methods and Results - We used a rat model to investigate the role of local Ang II activity in the pathogenesis of such inflammatory changes. Marked increases in monocyte infiltration into coronary vessels and myocardial interstitial areas, monocyte chemoattractant protein-1 (MCP-1) expression, and nuclear factor-κB (NF-κB, an important redox- sensitive transcriptional factor that induces MCP-1) activity were observed on day 3 of L-NAME administration. Along with these changes, vascular superoxide anion production was also increased. Treatment with an Ang II type 1 receptor antagonist or with a thiol-containing antioxidant, N- acetylcysteine, prevented all of these changes. Conclusions - Increased Ang II activity mediated via the type 1 receptor may thus be important in the pathogenesis of early cardiovascular inflammatory changes in this model. Endothelium-derived NO may decrease MCP-1 production and oxidative stress- sensitive signals by suppressing localized activity of Ang II.

Original languageEnglish
Pages (from-to)305-310
Number of pages6
JournalCirculation
Volume101
Issue number3
DOIs
Publication statusPublished - 2000 Jan 25
Externally publishedYes

Keywords

  • Cells
  • Endothelium-derived factors
  • Nitric oxide
  • Proteins
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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