L-arginine plus atorvastatin for prevention of atheroma formation in genetically hypercholesterolaemic rabbits.
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.
Rasmusen
Carole
C
Laboratory of Biological Nutrition EA 2498, Faculty of Pharmacy, Paris Descartes University, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Moinard
Christophe
C
Martin
Chantal
C
Tricottet
Viviane
V
Cynober
Luc
L
Couderc
Rémy
R
D000818:Animals; D001120:Arginine / Q000097:blood / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D003131:Combined Modality Therapy; D019587:Dietary Supplements; D004435:Eating; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D011758:Pyrroles / Q000627:therapeutic use*; D011817:Rabbits
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D009569:Nitric Oxide; D001120:Arginine; D002784:Cholesterol; D000069059:Atorvastatin