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Am J Physiol Heart Circ Physiol 291: H2301-H2307, 2006. First published June 16, 2006; doi:10.1152/ajpheart.00349.2006
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20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase

Xiang Fang,1 Frank M. Faraci,2,4 Terry L. Kaduce,1 Shawn Harmon,1 Mary L. Modrick,2 Shanming Hu,1 Steven A. Moore,3 J. R. Falck,5 Neal L. Weintraub,2 and Arthur A. Spector1,2

Departments of 1Biochemistry, 2Internal Medicine, 3Pathology, and 4Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa; and 5Department of Biochemistry, University of Texas Southwestern Medical School, Dallas, Texas

Submitted 31 March 2006 ; accepted in final form 12 June 2006

20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid (AA) metabolite synthesized by cytochrome P-450 {omega}-oxidases, is reported to produce vasoconstriction in the cerebral circulation. However, we find that like 14,15-epoxyeicosatrienoic acid (14,15-EET), 20-HETE produces dilation of mouse basilar artery preconstricted with U-46619 in vitro. Indomethacin inhibited the vasodilation produced by 20-HETE but not by 14,15-EET, suggesting a cyclooxygenase (COX)-dependent mechanism. Metabolic studies indicated several mechanisms that may play a role in this process. Mouse brain endothelial cells (MBEC) converted 20-HETE to 20-OH-PGE2, which was as potent as PGE2 in dilating the basilar artery. 20-HETE also stimulated AA release and PGE2 and 6-keto-PGF1{alpha} production in MBEC. Furthermore, the basilar artery converted 20-HETE to 20-COOH-AA, which also produced COX-dependent dilation of the basilar artery. 20-COOH-AA increased AA release and PGE2 and 6-keto-PGF1{alpha} production by the MBEC, but to a lesser extent than 20-HETE. Whereas the conversion of 20-HETE to 20-OH-PGE2 and production of endogenous prostaglandins probably are primarily responsible for vasodilation, the production of 20-COOH-AA also may contribute to this process.

20-hydroxy-prostaglandin E2; 20-carboxy-arachidonic acid; prostaglandins; cerebral vascular tone


Address for reprint requests and other correspondence: X. Fang, Dept. of Medicine, Harbor Hospital Center, 3001 S. Hanover St., Baltimore MD 21225 (e-mail: xiang.fang01{at}gmail.com)




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