Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors

William B. Campbell, John R. Falck

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

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
JournalHypertension
Volume49
Issue number3 PART 2 SUPPL.
DOIs
StatePublished - Mar 2007

Fingerprint

Arachidonic Acid
Endothelium
Calcium-Activated Potassium Channels
Acids
Vascular Endothelium
Bradykinin
Cytochrome P-450 Enzyme System
Acetylcholine
Arteries
Potassium Channel Blockers
Epoprostenol
Prostaglandin-Endoperoxide Synthases
Vascular Smooth Muscle
Nitric Oxide Synthase
Endothelial Cells
Membranes

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors. / Campbell, William B.; Falck, John R.

In: Hypertension, Vol. 49, No. 3 PART 2 SUPPL., 03.2007, p. 590-596.

Research output: Contribution to journalArticle

Campbell, William B. ; Falck, John R. / Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors. In: Hypertension. 2007 ; Vol. 49, No. 3 PART 2 SUPPL. pp. 590-596.
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