Eicosapentaenoic acid (EPA) induces Ca(2+)-independent activation and translocation of endothelial nitric oxide synthase and endothelium-dependent vasorelaxation

FEBS Lett. 2001 Jan 5;487(3):361-6. doi: 10.1016/s0014-5793(00)02351-6.


Eicosapentaenoic acid (EPA), but not its metabolites (docosapentaenoic acid and docosahexaenoic acid), stimulated nitric oxide (NO) production in endothelial cells in situ and induced endothelium-dependent relaxation of bovine coronary arteries precontracted with U46619. EPA induced a greater production of NO, but a much smaller and more transient elevation of intracellular Ca(2+) concentration ([Ca(2+)]i), than did a Ca(2+) ionophore (ionomycin). EPA stimulated NO production even in endothelial cells in situ loaded with a cytosolic Ca(2+) chelator 1,2-bis-o-aminophenoxythamine-N',N',N'-tetraacetic acid, which abolished the [Ca(2+)]i elevations induced by ATP and EPA. The EPA-induced vasorelaxation was inhibited by N(omega)-nitro-L-arginine methyl ester. Immunostaining analysis of endothelial NO synthase (eNOS) and caveolin-1 in cultured endothelial cells revealed eNOS to be colocalized with caveolin in the cell membrane at a resting state, while EPA stimulated the translocation of eNOS to the cytosol and its dissociation from caveolin, to an extent comparable to that of the eNOS translocation induced by a [Ca(2+)]i-elevating agonist (10 microM bradykinin). Thus, EPA induces Ca(2+)-independent activation and translocation of eNOS and endothelium-dependent vasorelaxation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active / drug effects
  • Calcium / metabolism
  • Cattle
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Eicosapentaenoic Acid / pharmacology*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Enzyme Activation / drug effects
  • In Vitro Techniques
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Vasodilation / drug effects*


  • Nitric Oxide
  • Egtazic Acid
  • Eicosapentaenoic Acid
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium