Arachidonic Acid Metabolites as Endothelium-Derived Hyperpolarizing Factors

W. B. Campbell, J. R. Falck
2007 Hypertension  
The endothelium regulates vascular tone through the release of a number of soluble mediators, including NO, prostaglandin I 2 , 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
more » ... tress 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. (Hypertension. 2007;49[part 2]:590-596.)
doi:10.1161/01.hyp.0000255173.50317.fc pmid:17200437 fatcat:rxt7nsl6tjfl3otprw77wf6h3m