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l-Arginine plus atorvastatin for prevention of atheroma formation in genetically hypercholesterolaemic rabbits

  • Carole Rasmusen (a1), Christophe Moinard (a1), Chantal Martin (a2), Viviane Tricottet (a3) (a4), Luc Cynober (a1) (a5) and Rémy Couderc (a1) (a6)...


We investigated the combined effect of dietary supplementation with l-arginine, which is the precursor of NO, and pharmacological treatment with atorvastatin, which is a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, on the development of atherosclerosis in homozygous Watanabe heritable hyperlipidaemic rabbits. Rabbits were fed either standard rabbit chow (group C; n 9) as control, a 1·5 % l-arginine diet (group A; n 9), standard rabbit chow plus atorvastatin (2·5 mg/kg per d) in drinking water (group S; n 8), or standard rabbit chow plus a 1·5 % l-arginine diet with atorvastatin (group SA; n 8). Blood was sampled at 2-week intervals. After 8 weeks (T8), the aorta was harvested for topographic and histological analysis. Only the SA group showed decreases in total area of lesions (21 %) and the area of abdominal lesions (44 %) compared with the control group (P = 0·019). Furthermore, plaques in the SA group were smaller and less thick than those observed in the S group. Unexpectedly, plasma nitrite + nitrate levels were not modified under either the l-arginine diet alone or under l-arginine plus atorvastatin. The present study is the first to demonstrate that diet supplementation with l-arginine associated with a statin (atorvastatin) is more efficient in reducing lesion size than treatment with l-arginine or a statin alone. This is a relatively novel therapeutic approach associating a macronutrient and a drug.

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Corresponding author

*Corresponding author: Dr Rémy Couderc, fax +33 1 53 73 99 52, email


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