20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: Role of cyclooxygenase

Xiang Fang, Frank M. Faraci, Terry L. Kaduce, Shawn Harmon, Mary L. Modrick, Shanming Hu, Steven A. Moore, J. R. Falck, Neal Lee Weintraub, Arthur A. Spector

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid (AA) metabolite synthesized by cytochrome P-450 ω-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-PGF 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-PGF 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.

Original languageEnglish (US)
Pages (from-to)H2301-H2307
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number5
DOIs
StatePublished - Nov 24 2006

Keywords

  • 20-carboxy-arachidonic acid
  • 20-hydroxy-prostaglandin E
  • Cerebral vascular tone
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Fang, X., Faraci, F. M., Kaduce, T. L., Harmon, S., Modrick, M. L., Hu, S., Moore, S. A., Falck, J. R., Weintraub, N. L., & Spector, A. A. (2006). 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: Role of cyclooxygenase. American Journal of Physiology - Heart and Circulatory Physiology, 291(5), H2301-H2307. https://doi.org/10.1152/ajpheart.00349.2006