The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

International Journal of Molecular Sciences

Saskia J. H. Brinkmann¹  Elisabeth A. Wörner¹  Nikki Buijs¹  Milan Richir¹  Luc Cynober³  Paul A. M. van Leeuwen¹  Rémy Couderc² 

[1] Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands; E-Mails:;Clinical Chemistry Department, Hopital Cochin et Hôtel-Dieu, AP-HP, 75014/75004 Paris, France; E-Mail:;Laboratory of Nutrition Biology EA 4466, Faculty of Pharmacy, Paris Descartes University, 75006 Paris, France; E-Mail:

关键词: atherosclerosis;    arginine;    ADMA;    ratio;    statins;    nitric oxide;    cholesterol;   

DOI  :  10.3390/ijms160612230

来源: mdpi

【 摘 要 】

Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

【 授权许可】

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