Medical College of Wisconsin
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Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors. Hypertension 2007 Mar;49(3):590-6 PMID: 17200437

Pubmed ID

17200437

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.

Author List

Campbell WB, Falck JR

Author

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-33847018482   156 Citations

MESH terms used to index this publication - Major topics in bold

Arachidonic Acids
Biological Factors
Coronary Vessels
Eicosanoids
Endothelium, Vascular
Humans
Muscle, Smooth, Vascular
Vasodilation
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e