Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis

Chu Kataoka, Kensuke Egashira, Minako Ishibashi, Shujiro Inoue, Weihua Ni, Ken Ichi Hiasa, Shiro Kitamoto, Makoto Usui, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Amlodipine (a new class of calcium channel antagonist) has been shown to limit the progression of arteriosclerosis and decrease the incidence of cardiovascular events. The mechanisms underlying the beneficial effects of amlodipine, however, remain unclear. Therefore, we hypothesized that amlodipine attenuates the development of arteriosclerosis through the inhibition of inflammation in vivo. Long-term inhibition of nitric oxide (NO) by administration of a NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), to rats induces coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti-inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly inhibited the L-NAME-induced increase in vascular inflammation, oxidative stress, and local ACE and Rho activity and prevented arteriosclerosis. Interestingly, amlodipine prevented the L-NAME-induced increase in MCP-1 receptor CCR2 expression in circulating monocytes. Amlodipine markedly attenuated the high mortality rate at 8 wk of treatment. These data suggest that amlodipine attenuated arteriosclerosis through inhibiting inflammatory disorders in the rat model of long-term inhibition of NO synthesis. The anti-inflammatory effects of amlodipine seem to be mediated not only by the inhibition of local factors such as MCP-1 but also by the decrease in CCR2 in circulating monocytes. Inhibition of the MCP-1 to CCR2 pathway may represent novel anti-inflammatory actions of amlodipine beyond blood pressure lowering.

Original languageEnglish
Pages (from-to)H768-H774
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number2 55-2
DOIs
Publication statusPublished - Feb 2004

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis'. Together they form a unique fingerprint.

Cite this