Effect of L-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial cell aging

Biochem Biophys Res Commun. 2006 Jul 7;345(3):1075-82. doi: 10.1016/j.bbrc.2006.05.015. Epub 2006 May 11.


We investigated here the effect of l-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial aging. Endothelial cells were cultured in medium containing 70micromol/L arginine until fourteenth passage. ADMA, dl-homocysteine, and l-arginine were replaced every 48h starting at the fourth passage. ADMA or homocysteine inhibited significantly the population doublings (PD) and accelerated the process of aging. Co-incubation with l-arginine enhanced PD, inhibited senescence associated beta-galactosidase activity, and increased telomerase activity. This effect was associated with an increase in NO synthesis and NO synthase protein expression. Furthermore, l-arginine-induced NO formation was accompanied by a reduction in oxidative stress and an increase in protein expression and enzyme activity of heme oxygenase (HO)-1. The NO synthase inhibitor l-NAME completely abolished the effect of l-arginine on ADMA or homocysteine-accelerated aging. These findings demonstrate that l-arginine prevents the onset of endothelial aging in ADMA or homocysteine-treated cells by increasing NO formation and consequently the induction of HO-1. This might provide a new strategy to delay ADMA or homocysteine-accelerated aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Arginine / pharmacology*
  • Cells, Cultured
  • Cellular Senescence
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology
  • Homocysteine / metabolism*
  • Humans
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Oxidative Stress
  • Telomerase / metabolism
  • Time Factors


  • Homocysteine
  • N,N-dimethylarginine
  • Arginine
  • Telomerase
  • NG-Nitroarginine Methyl Ester