title: The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine.
abstract: 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.
  
  
  CONCLUSIONS
  A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.
authors.affiliation: Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. sj.brinkmann@vumc.nl.
authors.forename: Saskia J H
authors.initials: SJ
authors.lastname: Brinkmann
authors.affiliation: Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. lisaworner@gmail.com.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Wörner
authors.affiliation: Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. n.buijs@vumc.nl.|Department of Surgery, Medical Center Alkmaar, 1815 JD Alkmaar, The Netherlands. n.buijs@vumc.nl.
authors.forename: Nikki
authors.initials: N
authors.lastname: Buijs
authors.affiliation: Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. m.richir@vumc.nl.|Department of Surgery, Medical Center Alkmaar, 1815 JD Alkmaar, The Netherlands. m.richir@vumc.nl.
authors.forename: Milan
authors.initials: M
authors.lastname: Richir
authors.affiliation: Laboratory of Nutrition Biology EA 4466, Faculty of Pharmacy, Paris Descartes University, 75006 Paris, France. remy.couderc@trs.aphp.fr.|Clinical Chemistry Department, Hopital Cochin et Hôtel-Dieu, AP-HP, 75014/75004 Paris, France. remy.couderc@trs.aphp.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.affiliation: Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. pam.vleeuwen@vumc.nl.
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.affiliation: Clinical Chemistry Department, Hopital Cochin et Hôtel-Dieu, AP-HP, 75014/75004 Paris, France. remy.couderc@trs.aphp.fr.|Clinical chemistry Laboratory, Armand Trousseau hospital, AP-HP, 75012 Paris, France. remy.couderc@trs.aphp.fr.
authors.forename: Rémy
authors.initials: R
authors.lastname: Couderc
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D019587:Dietary Supplements; D006937:Hypercholesterolemia / Q000097:blood / Q000628:therapy*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000517:prevention & control*; D011817:Rabbits
chemical_list: D000924:Anticholesteremic Agents; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D002784:Cholesterol; D000069059:Atorvastatin; D019001:Nitric Oxide Synthase
keywords: ADMA; arginine; atherosclerosis; cholesterol; nitric oxide; ratio; statins