This Article Full Text Full Text (PDF) All Versions of this Article: 49/3/590    most recent 01.HYP.0000255173.50317.fcv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Campbell, W. B. Articles by Falck, J. R. Search for Related Content PubMed PubMed Citation Articles by Campbell, W. B. Articles by Falck, J. R. Related Collections Other hypertension Endothelium/vascular type/nitric oxide

(Hypertension. 2007;49:590.)
© 2007 American Heart Association, Inc.

Norvartis Award

Arachidonic Acid Metabolites as Endothelium-Derived Hyperpolarizing Factors

From the Department of Pharmacology and Toxicology (W.B.C.), Medical College of Wisconsin, Milwaukee; and the Department of Biochemistry (J.R.F.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to William B. Campbell, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail wbcamp{at}mcw.edu

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.

Key Words: Cytochrome P450 system • endothelium • arachidonic acid • vascular relaxation • endothelium-derived hyperpolarizing factor

This article has been cited by other articles:

				B. Eichhorn, G. Muller, A. Leuner, T. Sawamura, U. Ravens, and H. Morawietz Impaired vascular function in small resistance arteries of LOX-1 overexpressing mice on high-fat diet Cardiovasc Res, June 1, 2009; 82(3): 493 - 502. [Abstract] [Full Text] [PDF]

				S. Brahler, A. Kaistha, V. J. Schmidt, S. E. Wolfle, C. Busch, B. P. Kaistha, M. Kacik, A.-L. Hasenau, I. Grgic, H. Si, et al. Genetic Deficit of SK3 and IK1 Channels Disrupts the Endothelium-Derived Hyperpolarizing Factor Vasodilator Pathway and Causes Hypertension Circulation, May 5, 2009; 119(17): 2323 - 2332. [Abstract] [Full Text] [PDF]

				A. A. Spector Arachidonic acid cytochrome P450 epoxygenase pathway J. Lipid Res., April 1, 2009; 50(Supplement): S52 - S56. [Abstract] [Full Text] [PDF]

				N. Z. Burger, O. Y. Kuzina, G. Osol, and N. I. Gokina Estrogen replacement enhances EDHF-mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca2+ Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E503 - E512. [Abstract] [Full Text] [PDF]

				K. L. Fife, Y. Liu, K. R. Schmelzer, H.-J. Tsai, I.-H. Kim, C. Morisseau, B. D. Hammock, and D. L. Kroetz Inhibition of Soluble Epoxide Hydrolase Does Not Protect against Endotoxin-Mediated Hepatic Inflammation J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 707 - 715. [Abstract] [Full Text] [PDF]

				K. G. Maier Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Diabetes: Vascular Implications Vascular and Endovascular Surgery, August 1, 2008; 42(4): 305 - 313. [Abstract] [PDF]

				I. C Villar, A. J Hobbs, and A. Ahluwalia Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor J. Endocrinol., June 1, 2008; 197(3): 447 - 462. [Abstract] [Full Text] [PDF]

				E. M. Awumey, S. K. Hill, D. I. Diz, and R. D. Bukoski Cytochrome P-450 metabolites of 2-arachidonoylglycerol play a role in Ca2+-induced relaxation of rat mesenteric arteries Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2363 - H2370. [Abstract] [Full Text] [PDF]

				W. Yang, V. R. Tuniki, S. Anjaiah, J. R. Falck, C. J. Hillard, and W. B. Campbell Characterization of Epoxyeicosatrienoic Acid Binding Site in U937 Membranes Using a Novel Radiolabeled Agonist, 20-125I-14,15-Epoxyeicosa-8(Z)-Enoic Acid J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1019 - 1027. [Abstract] [Full Text] [PDF]

				J. E. Jalil Blood Pressure Reduction, Potassium Channels, and the Endothelium: Insights From L-Serine Hypertension, March 1, 2008; 51(3): 626 - 628. [Full Text] [PDF]

				C. E. Gomez-Sanchez Regulation of Adrenal Arterial Tone by Adrenocorticotropin: The Plot Thickens Endocrinology, August 1, 2007; 148(8): 3566 - 3568. [Full Text] [PDF]