Journal
HYPERTENSION
Volume 49, Issue 3, Pages 590-596Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000255173.50317.fc
Keywords
cytochrome P450 system; endothelium; arachidonic acid; vascular relaxation; endothelium-derived hyperpolarizing factor
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Funding
- NHLBI NIH HHS [HL-51055, HL-37981] Funding Source: Medline
- NIDDK NIH HHS [DK-58145, DK-38266] Funding Source: Medline
- NIGMS NIH HHS [GM-31278] Funding Source: Medline
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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.
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