Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors

作者：Campbell William B^*; Falck John R

来源：Hypertension, 2007, 49(3): 590-596.

DOI：10.1161/01.HYP.0000255173.50317.fc

• cytochrome P450 system
• endothelium
• arachidonic acid
• vascular relaxation
• endothelium-derived hyperpolarizing factor

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 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.

• 出版日期2007-3