Investigating the cardio-protective abilities of supplemental L-arginine on parameters of endothelial function in a hypercholesterolemic animal model

J Nutr Sci Vitaminol (Tokyo). 2014;60(3):145-51. doi: 10.3177/jnsv.60.145.


Endothelial dysfunction is now widely recognized as an early marker of cardiovascular disease, making its treatment, or complete avoidance, an emerging, interesting therapeutic target. This study investigated the ability of the highly intriguing amino acid L-arginine to influence endothelial function. Its therapeutic potential is also compared to that of known cardiovascular medications, namely nitroglycerin [a nitric oxide (NO) donor] and enalapril [an angiotensin-converting enzyme (ACE) inhibitor]. Fifty male New Zealand rabbits were included in the study, divided into 5 equal groups: control, hypercholesterolemia (untreated), hypercholesterolemia (+L-arginine), hypercholesterolemia (+enalapril), and hypercholesterolemia (+nitroglycerin). Biochemical investigations included measurement of circulating NOx, malondialdehyde (MDA), and lipid profile markers, as well as dimethylarginine dimethylaminohydrolase (DDAH) and ACE activities. Furthermore, aortic ACE activity and blood platelet aggregation were estimated. A histopathological examination and intimal thickness measurement were also conducted. Compared to the untreated hypercholesterolemic group, all agents were capable of positively influencing MDA levels, platelet aggregation and intimal thickness; however, only the L-arginine group was capable of beneficially and significantly altering both NOx levels and serum and aortic ACE activities. No agents were capable of modulating serum DDAH activity inhibited by hypercholesterolemia. Based on the results of this study, L-arginine appears to be a novel cardio-protective agent, illustrated by its ability to ameliorate the deleterious effects of hypercholesterolemia on endothelial function, in a manner comparable to, and sometimes more potent than, commonly used cardiovascular medications.

MeSH terms

  • Amidohydrolases / blood
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Animals
  • Arginine / administration & dosage*
  • Cardiotonic Agents / pharmacology*
  • Cardiovascular Diseases / prevention & control
  • Dietary Supplements*
  • Disease Models, Animal
  • Enalapril / administration & dosage
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Heart / drug effects
  • Hypercholesterolemia / drug therapy*
  • Male
  • Malondialdehyde / blood
  • Nitric Oxide / blood
  • Nitroglycerin / administration & dosage
  • Oxidative Stress / drug effects
  • Rabbits


  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiotonic Agents
  • Nitric Oxide
  • Malondialdehyde
  • Enalapril
  • Arginine
  • Amidohydrolases
  • dimethylargininase
  • Nitroglycerin