Epoxyeicosatrienoic acids and endothelium-dependent responses. Pflugers Arch 2010 May;459(6):881-95
Date
03/13/2010Pubmed ID
20224870Pubmed Central ID
PMC3373596DOI
10.1007/s00424-010-0804-6Scopus ID
2-s2.0-77952889496 (requires institutional sign-in at Scopus site) 214 CitationsAbstract
Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium in response to agonists such as bradykinin and acetylcholine or physical stimuli such as shear stress or cyclic stretch. In the vasculature, the EETs have biological actions that are involved in the regulation of vascular tone, hemostasis, and inflammation. In preconstricted arteries in vitro, EETs activate calcium-activated potassium channels on vascular smooth muscle and the endothelium causing membrane hyperpolarization and relaxation. These effects are observed in a variety of arteries from experimental animals and humans; however, this is not a universal finding in all arteries. The mechanism of EET action may vary. In some arteries, EETs are released from the endothelium and are transferred to the smooth muscle where they cause potassium channel activation, hyperpolarization, and relaxation through a guanine nucleotide binding protein-coupled mechanism or transient receptor potential (TRP) channel activation. In other arteries, EETs activate TRP channels on the endothelium to cause endothelial hyperpolarization that is transferred to the smooth muscle by gap junctions or potassium ion. Some arteries use a combination of mechanisms. Acetylcholine and bradykinin increase blood flow in dogs and humans that is inhibited by potassium channel blockers and cytochrome P450 inhibitors. Thus, the EETs are endothelium-derived hyperpolarizing factors mediating a portion of the relaxations to acetylcholine, bradykinin, shear stress, and cyclic stretch and regulate vascular tone in vitro and in vivo.
Author List
Campbell WB, Fleming IAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Arachidonic Acid
Arteries
Biological Factors
Cytochrome P-450 Enzyme System
Eicosanoids
Endothelium, Vascular
Endothelium-Dependent Relaxing Factors
Epoxide Hydrolases
Heme Oxygenase (Decyclizing)
Humans
Muscle, Smooth, Vascular
Potassium Channel Blockers
Vasodilation
