Atorvastatin modulates the DDAH1/ADMA system in high-fat diet-induced insulin-resistant rats with endothelial dysfunction

Vasc Med. 2012 Dec;17(6):416-23. doi: 10.1177/1358863X12467492.

Abstract

Dimethylarginine dimethyl-aminohydrolase 1 (DDAH1) is a metabolic enzyme for asymmetric dimethylarginine (ADMA), both of which are closely related to endothelial function. Endothelial dysfunction, a main risk factor of cardiovascular diseases, can be attributed to insulin resistance. We aimed to determine the effects of atorvastatin, an endothelium-protective drug, on DDAH1/ADMA in insulin-resistant rats. Insulin resistance in male Sprague-Dawley rats was induced with a high-fat diet for 8 weeks. Some rats received atorvastatin (30 mg/kg/day) for an additional 8 weeks. Insulin-resistant rats exhibited not only decreases in the DDAH activity and aortic expression of DDAH1 and sterol regulatory element-binding protein 1 (SREBP1) but also increases in plasma ADMA levels, all of which were inhibited by atorvastatin. Insulin sensitivity and DDAH activity showed a significant positive correlation. In conclusion, our results suggest that atorvastatin may modulate DDAH1/ADMA to improve endothelial function in insulin-resistant rats; SREBP1 may also play a role in this.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / metabolism*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Arginine / chemistry
  • Arginine / metabolism
  • Atorvastatin
  • Diet, High-Fat*
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / drug effects*
  • Heptanoic Acids / pharmacology*
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Heptanoic Acids
  • Insulin
  • Pyrroles
  • dimethylarginine
  • Arginine
  • Atorvastatin
  • Amidohydrolases
  • dimethylargininase