Long-term treatment with eicosapentaenoic acid augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilatation in patients with coronary artery disease

J Cardiovasc Pharmacol. 1999 Apr;33(4):633-40. doi: 10.1097/00005344-199904000-00017.


Long-term treatment with eicosapentaenoic acid (EPA) is known to improve impaired endothelium-dependent relaxations of atherosclerotic blood vessels in animals and humans. However, it remains to be determined which mechanisms are involved in this beneficial effect of EPA. In this study, we investigated our hypothesis that EPA improves both nitric oxide (NO)-mediated and non-NO-mediated endothelium-dependent vasodilatation in patients with coronary artery disease. The study included eight patients with documented coronary artery disease. The forearm vascular responses to the endothelium-dependent vasodilator acetylcholine and substance P were examined before and after intraarterial infusion of NG-monomethyl-L-arginine (L-NMMA). Same measurements were repeated after the treatment with EPA (1,800 mg/day) for 6 weeks. The long-term treatment with EPA augmented forearm blood-flow response to both acetylcholine and substance P. Furthermore, acute administration of L-NMMA significantly inhibited the EPA-induced augmented response to acetylcholine but not that to substance P. The forearm vascular response to sodium nitroprusside was unchanged by the EPA treatment. These results indicate that long-term treatment with EPA augments both NO-dependent and non-NO-dependent endothelium-dependent forearm vasodilatation in patients with coronary artery disease. Thus the beneficial effects of EPA appear to extend to non-NO-dependent mechanism(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Aged
  • Coronary Disease / physiopathology*
  • Dose-Response Relationship, Drug
  • Eicosapentaenoic Acid / therapeutic use*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Forearm / blood supply
  • Forearm / physiopathology
  • Humans
  • Lipids / blood
  • Middle Aged
  • Nitric Oxide / pharmacology
  • Regional Blood Flow / drug effects
  • Substance P / metabolism
  • Vasodilation / drug effects*


  • Lipids
  • Nitric Oxide
  • Substance P
  • Eicosapentaenoic Acid
  • Acetylcholine