Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels

Hideharu Tomita, Kensuke Egashira, Mayuko Kubo-Inoue, Makoto Usui, Masamichi Koyanagi, Hiroaki Shimokawa, Motohiro Takeya, Teizo Yoshimura, Akira Takeshita

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Abstract

We recently showed that chronic inhibition of NO synthesis by N(ω)- nitro-L-arginine methyl ester (L-NAME) causes coronary vascular remodeling (ie, vascular fibrosis and medial thickening) in rats. To test the hypothesis that the inhibition of NO synthesis induces inflammatory changes in the heart, we characterized the inflammatory lesions that occurred during L-NAME administration and determined whether inflammation involved the induction of monocyte chemoattractant protein-1 (MCP-1) in vivo. During the first week of L-NAME administration to Wistar-Kyoto rats, we observed a marked infiltration of mononuclear leukocytes (ED1-positive macrophages) and fibroblast-like cells (α-smooth muscle actin-positive myofibroblasts) into the coronary vessels and myocardial interstitial areas. These inflammatory changes were associated with the expression of proliferating cell nuclear antigen and MCP- 1 (both mRNA and protein). The areas affected by inflammatory changes, as well as the expression of MCP-1 mRNA, declined after longer (28 days) treatment with L-NAME and were replaced by vascular and myocardial remodeling. Our results support the hypothesis that the inhibition of NO synthesis induces inflammatory changes in coronary vascular and myocardial tissues and involves MCP-1 expression. Results also suggest that the early stages of inflammatory changes are important in the development of later- stage structural changes observed in rat hearts.

Original languageEnglish
Pages (from-to)1456-1464
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume18
Issue number9
Publication statusPublished - 1998
Externally publishedYes

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Keywords

  • Endothelium-derived factors
  • Macrophages
  • Monocyte chemoattractant protein-1
  • Nitric oxide
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Tomita, H., Egashira, K., Kubo-Inoue, M., Usui, M., Koyanagi, M., Shimokawa, H., Takeya, M., Yoshimura, T., & Takeshita, A. (1998). Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels. Arteriosclerosis, Thrombosis, and Vascular Biology, 18(9), 1456-1464.