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 L. Weintraub, Arthur A. Spector

Research output: Contribution to journalArticle

35 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 - 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)

Fingerprint Dive into the research topics of '20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: Role of cyclooxygenase'. Together they form a unique fingerprint.

  • Cite this

    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