Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects

Free Radic Res. 2003 May;37(5):529-36. doi: 10.1080/1071576031000083170.

Abstract

Hypercholesterolemia is linked to endothelial dysfunction and enhancement of the endogenous inhibitor of NO synthase. The statins have lipid-lowering and pleiotropic properties, which could exert protective effects on the endothelium in hypercholesterolemia. The association of L-arginine with simvastatin could promote a further improvement on endothelial function in this condition. Thus, we investigated whether simvastatin, with or without supplementation with L-arginine, could improve endothelium-dependent vasodilation. In this study, 25 hypercholesterolemic subjects were treated according to the following protocol: washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20 mg/day) + L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen at random for evaluation of vascular function by high resolution ultrasonography of the brachial artery. In subjects treated with simvastatin plus L-arginine, an increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations of NO metabolites nitrite + nitrate (NOx: 34%), S-nitrosothiols (RSNO: 42%), total cholesterol (25%), low density lipoprotein (LDL)-cholesterol (36%) and the LDL-cholesterol/high density lipoprotein (HDL-cholesterol ratio (34%). Simvastatin, associated or not to L-arginine, did not affect ADMA levels and endothelium-dependent vasodilation. Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium-dependent vasodilation in hypercholesterolemia.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use
  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Arginine / pharmacology
  • Arginine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Female
  • Free Radicals / blood
  • Humans
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / physiopathology
  • Lipids / blood
  • Male
  • Middle Aged
  • Nitrates / blood
  • Nitric Oxide / blood
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / blood
  • Nitrites / blood
  • S-Nitrosothiols / blood
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use*
  • Time Factors
  • Vasodilation / drug effects*

Substances

  • Anticholesteremic Agents
  • Free Radicals
  • Lipids
  • Nitrates
  • Nitrites
  • S-Nitrosothiols
  • Nitric Oxide
  • N,N-dimethylarginine
  • Arginine
  • Simvastatin
  • Nitric Oxide Synthase