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Epoxyeicosatrienoic acids and endothelium-dependent responses

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Abstract

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.

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Acknowledgments

The authors thank Dr. Kathryn Gauthier for her comments and help with the figures and Ms. Gretchen Barg for her secretarial assistance. Support was provided by a grant from the National Heart, Lung and Blood Institute (HL-51055) and by the Deutsche Forschungsgemeinschaft (Exzellenzcluster 147 “Cardio-Pulmonary Systems”).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    William B. Campbell

  2. Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Theodor Stern-Kai 7, 60590, Frankfurt, Germany

    Ingrid Fleming

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  1. William B. Campbell
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Correspondence to William B. Campbell.

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Campbell, W.B., Fleming, I. Epoxyeicosatrienoic acids and endothelium-dependent responses. Pflugers Arch - Eur J Physiol 459, 881–895 (2010). https://doi.org/10.1007/s00424-010-0804-6

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  • DOI: https://doi.org/10.1007/s00424-010-0804-6

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