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

Long-term treatment with eicosapentaenoic acid (EPA) is known to improve im paired endothelium-dependent relaxations of atherosclerotic blood vessels i n animals and humans. However, it remains to be determined which mechanisms are involved in this beneficial effect of EPA. In this study, we investiga ted our hypothesis that EPA improves both nitric oxide (NO)-mediated and no n-NO-mediated endothelium-dependent vasodilatation in patients with coronar y artery disease. The study included eight patients with documented coronar y artery disease. The forearm vascular responses to the endothelium-depende nt vasodilator acetylcholine and substance P were examined before and after intraarterial infusion of N-G-monomethyl-L-arginine (L-NMMA). Same measure ments 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 acetylc holine but not that to substance P. The forearm vascular response to sodium nitroprusside was unchanged by the EPA treatment. These results indicate t hat long-term treatment with EPA augments both NO-dependent and non-NO-depe ndent endothelium-dependent forearm vasodilatation in patients with coronar y artery disease. Thus the beneficial effects of EPA appear to extend to no n-NO-dependent mechanism(s).