PMID- 14592942
OWN - NLM
STAT- MEDLINE
DCOM- 20040309
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 286
IP  - 2
DP  - 2004 Feb
TI  - Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis 
      induced by long-term inhibition of nitric oxide synthesis.
PG  - H768-74
AB  - 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, N(omega)-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.
FAU - Kataoka, Chu
AU  - Kataoka C
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Ishibashi, Minako
AU  - Ishibashi M
FAU - Inoue, Shujiro
AU  - Inoue S
FAU - Ni, Weihua
AU  - Ni W
FAU - Hiasa, Ken-ichi
AU  - Hiasa K
FAU - Kitamoto, Shiro
AU  - Kitamoto S
FAU - Usui, Makoto
AU  - Usui M
FAU - Takeshita, Akira
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031030
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (DNA Primers)
RN  - 0 (Nitrogen Oxides)
RN  - 0 (Vasodilator Agents)
RN  - 11062-77-4 (Superoxides)
RN  - 1J444QC288 (Amlodipine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Amlodipine/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Arteriosclerosis/drug therapy/*physiopathology
MH  - Base Sequence
MH  - Blood Pressure/drug effects
MH  - DNA Primers
MH  - Disease Models, Animal
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/*antagonists & inhibitors
MH  - Nitrogen Oxides/blood
MH  - Peptidyl-Dipeptidase A/drug effects/metabolism
MH  - Polymerase Chain Reaction
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Superoxides/metabolism
MH  - Vasodilator Agents/pharmacology
EDAT- 2003/11/01 05:00
MHDA- 2004/03/10 05:00
CRDT- 2003/11/01 05:00
PHST- 2003/11/01 05:00 [pubmed]
PHST- 2004/03/10 05:00 [medline]
PHST- 2003/11/01 05:00 [entrez]
AID - 00937.2002 [pii]
AID - 10.1152/ajpheart.00937.2002 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2004 Feb;286(2):H768-74. doi: 
      10.1152/ajpheart.00937.2002. Epub 2003 Oct 30.