Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors.
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.
Campbell
William B
WB
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. wbcamp@mcw.edu
Falck
John R
JR
D001095:Arachidonic Acids / Q000378:metabolism*; D001685:Biological Factors / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
D001095:Arachidonic Acids; D001685:Biological Factors; D015777:Eicosanoids; C067410:endothelium-dependent hyperpolarization factor