Effects of chronic treatment with L-arginine on atherosclerosis in apoE knockout and apoE/inducible NO synthase double-knockout mice.
Arterioscler Thromb Vasc Biol
; 23(1): 97-103, 2003 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-12524231
ABSTRACT
OBJECTIVE:
L-arginine serves as a substrate for the formation of NO by the NO synthase (NOS) enzymes. In some studies, dietary supplementation of L-arginine reduces atherosclerosis through the restoration of NO release and improvement in endothelial function. In the present study, we investigate the effect of L-arginine supplementation on the development of atherosclerosis in a mouse model. METHODS ANDRESULTS:
Apolipoprotein E (apoE) knockout (ko) and apoE/inducible NOS (iNOS) double-ko mice were fed a western-type diet with or without L-arginine supplementation in the drinking water (25 g/L). L-Arginine did not affect the lesion area after 16 weeks or 24 weeks in apoE ko mice. However, L-arginine negates the protective effect of iNOS gene deficiency. In contrast to apoE/iNOS dko mice without arginine supplementation, lesion areas were increased in apoE/iNOS double-ko mice with arginine supplementation at 24 weeks. This was associated with an increase in thiobarbituric acid-reactive malondialdehyde adducts, nitrotyrosine staining within lesions, and a decrease in the ratio of reduced tetrahydrobiopterin to total biopterins.CONCLUSIONS:
Although L-arginine supplementation does not affect lesion formation in the western-type diet-fed apoE ko mice, it negates the protective effect of iNOS gene deficiency in this model. This raises the possibility that L-arginine supplementation may paradoxically contribute to, rather than reduce, lesion formation by mechanisms that involve lipid oxidation, peroxynitrite formation, and NOS uncoupling.
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Database:
MEDLINE
Main subject:
Apolipoproteins E
/
Arginine
/
Arteriosclerosis
/
Tyrosine
/
Nitric Oxide Synthase
/
Disease Models, Animal
Language:
En
Journal:
Arterioscler Thromb Vasc Biol
Year:
2003
Type:
Article
Affiliation country:
United States