PMID- 9743235
OWN - NLM
STAT- MEDLINE
DCOM- 19981001
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 18
IP  - 9
DP  - 1998 Sep
TI  - Inhibition of NO synthesis induces inflammatory changes and monocyte 
      chemoattractant protein-1 expression in rat hearts and vessels.
PG  - 1456-64
AB  - We recently showed that chronic inhibition of NO synthesis by 
      N(omega)-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 
      (alpha-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.
FAU - Tomita, H
AU  - Tomita H
AD  - Research Institute of Angiocardiology, Kyushu University Faculty of Medicine, 
      Fukuoka, Japan.
FAU - Egashira, K
AU  - Egashira K
FAU - Kubo-Inoue, M
AU  - Kubo-Inoue M
FAU - Usui, M
AU  - Usui M
FAU - Koyanagi, M
AU  - Koyanagi M
FAU - Shimokawa, H
AU  - Shimokawa H
FAU - Takeya, M
AU  - Takeya M
FAU - Yoshimura, T
AU  - Yoshimura T
FAU - Takeshita, A
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Blood Pressure
MH  - Chemokine CCL2/analysis/*genetics
MH  - Coronary Vessels/*metabolism/pathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/pathology
MH  - Gene Expression/*drug effects
MH  - Heart Rate
MH  - Immunohistochemistry
MH  - Inflammation/*etiology/pathology
MH  - Kidney/pathology
MH  - Leukocytes, Mononuclear/pathology
MH  - Male
MH  - Mesenteric Arteries/pathology
MH  - Myocardium/*metabolism/pathology
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Inbred WKY
EDAT- 1998/09/22 00:00
MHDA- 1998/09/22 00:01
CRDT- 1998/09/22 00:00
PHST- 1998/09/22 00:00 [pubmed]
PHST- 1998/09/22 00:01 [medline]
PHST- 1998/09/22 00:00 [entrez]
AID - 10.1161/01.atv.18.9.1456 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1456-64. doi: 
      10.1161/01.atv.18.9.1456.