title: Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.
abstract: OBJECTIVE
  The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction.
  
  
  METHODS
  Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio.
  
  
  RESULTS
  HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio.
  
  
  CONCLUSIONS
  This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: El-Awady
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Suddek
mesh_terms: D000376:Agmatine / Q000627:therapeutic use*; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000008:administration & dosage; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D008055:Lipids; D009569:Nitric Oxide; D000376:Agmatine; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase
keywords: agmatine; hypercholesterolemia; nitric oxide; rabbits; vascular endothelial dysfunction