PMID- 10912772
OWN - NLM
STAT- MEDLINE
DCOM- 20001115
LR  - 20191025
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 23
IP  - 4
DP  - 2000 Jul
TI  - Pravastatin attenuates cardiovascular inflammatory and proliferative changes in a 
      rat model of chronic inhibition of nitric oxide synthesis by its 
      cholesterol-lowering independent actions.
PG  - 353-8
AB  - Recent studies suggest that some of the beneficial effects of 
      3-hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitors such as pravastatin 
      may be through their cholesterol-lowering independent effects on the blood 
      vessels. We have recently reported that chronic inhibition of nitric oxide (NO) 
      synthesis with N(omega)nitro-L-arginine methyl ester (L-NAME) increases systolic 
      blood pressure and induces coronary vascular inflammatory changes in rats. We 
      designed this study to investigate whether treatment with pravastatin attenuates 
      such proarteriosclerotic changes through their cholesterol-lowering independent 
      effects. Several groups of Wistar-Kyoto rats were studied: the control group, L 
      group received L-NAME in their drinking water (100 mg/kg per day) and L+Px group 
      received L-NAME plus pravastatin (50, 100 or 250 mg/kg per day). We observed 
      marked increases in monocyte infiltration into the coronary arteries, 
      proliferative cell nuclear antigen-positive cells, and monocyte chemoattractant 
      protein-1 (MCP-1) expression in the heart on day 3 after L-NAME administration 
      began. Treatment with pravastatin did not affect serum cholesterol levels or 
      systolic blood pressure but did reduce the L-NAME induced inflammatory and 
      proliferative changes. Pravastatin also attenuated the MCP-1 gene expression 
      induced by L-NAME. In summary, pravastatin inhibited the inflammatory and 
      proliferative changes in the coronary vessels through their 
      cholesterol-independent effects in this model, which may provide an insight into 
      the mechanisms of anti-inflammatory or anti-arteriosclerotic actions of 
      pravastatin.
FAU - Egashira, K
AU  - Egashira K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Ni, W
AU  - Ni W
FAU - Inoue, S
AU  - Inoue S
FAU - Kataoka, C
AU  - Kataoka C
FAU - Kitamoto, S
AU  - Kitamoto S
FAU - Koyanagi, M
AU  - Koyanagi M
FAU - Takeshita, A
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Animals
MH  - Anticholesteremic Agents/*pharmacology
MH  - Blood Pressure/drug effects
MH  - Chemokine CCL2/genetics
MH  - Cholesterol/blood
MH  - Coronary Vessels/*drug effects/pathology
MH  - Gene Expression/drug effects
MH  - Male
MH  - Nitric Oxide/*antagonists & inhibitors/biosynthesis
MH  - Pravastatin/*pharmacology
MH  - RNA, Messenger/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Systole
MH  - Time Factors
MH  - Vasculitis/*pathology/physiopathology
EDAT- 2000/07/27 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/07/27 11:00
PHST- 2000/07/27 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/07/27 11:00 [entrez]
AID - 10.1291/hypres.23.353 [doi]
PST - ppublish
SO  - Hypertens Res. 2000 Jul;23(4):353-8. doi: 10.1291/hypres.23.353.