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Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors Campbell WB; Falck JRHypertension 2007[Mar]; 49 (3): 590-6The 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.|Arachidonic Acids/*metabolism[MESH]|Biological Factors/*metabolism[MESH]|Coronary Vessels/*metabolism[MESH]|Eicosanoids/metabolism[MESH]|Endothelium, Vascular/*physiology[MESH]|Humans[MESH]|Muscle, Smooth, Vascular/*metabolism[MESH]|Vasodilation/physiology[MESH] |
