Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors

William B. Campbell, John R. Falck

Research output: Contribution to journalArticlepeer-review

176 Scopus citations


The endothelium regulates vascular tone through the release of a number of soluble mediators, including NO, prostaglandin I2, and endothelium-derived hyperpolarizing factor. Epoxyeicosatrienoic acids are cytochrome P450 epoxygenase metabolites of arachidonic acid. They are synthesized by the vascular endothelium and open calcium-activated potassium channels, hyperpolarize the membrane, and relax vascular smooth muscle. Endothelium-dependent relaxations to acetylcholine, bradykinin, and shear stress that are not inhibited by cyclooxygenase and NO synthase inhibitors are mediated by the endothelium-derived hyperpolarizing factor. In arteries from experimental animals and humans, the non-NO, non-prostaglandin-mediated relaxations and endothelium-dependent hyperpolarizations are blocked by cytochrome P450 inhibitors, calcium-activated potassium channel blockers, and epoxyeicosatrienoic acid antagonists. Acetylcholine and bradykinin stimulate epoxyeicosatrienoic acid release from endothelial cells and arteries. These findings indicate that epoxyeicosatrienoic acids act as endothelium-derived hyperpolarizing factors and regulate arterial tone.

Original languageEnglish (US)
Pages (from-to)590-596
Number of pages7
Issue number3 PART 2 SUPPL.
StatePublished - Mar 2007


  • Arachidonic acid
  • Cytochrome P450 system
  • Endothelium
  • Endothelium-derived hyperpolarizing factor
  • Vascular relaxation

ASJC Scopus subject areas

  • Internal Medicine


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