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



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


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


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

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