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

33 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number5
DOIs
StatePublished - 2006
Externally publishedYes

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Basilar Artery
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Dinoprostone
Endothelial Cells
Vasodilation
Dilatation
Cerebrovascular Circulation
Brain
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
NADPH-Ferrihemoprotein Reductase
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Vasoconstriction
Indomethacin
Prostaglandins

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery : Role of cyclooxygenase. / Fang, Xiang; Faraci, Frank M.; Kaduce, Terry L.; Harmon, Shawn; Modrick, Mary L.; Hu, Shanming; Moore, Steven A.; Falck, J. R.; Weintraub, Neal L.; Spector, Arthur A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 5, 2006.

Research output: Contribution to journalArticle

Fang, Xiang ; Faraci, Frank M. ; Kaduce, Terry L. ; Harmon, Shawn ; Modrick, Mary L. ; Hu, Shanming ; Moore, Steven A. ; Falck, J. R. ; Weintraub, Neal L. ; Spector, Arthur A. / 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery : Role of cyclooxygenase. In: American Journal of Physiology - Heart and Circulatory Physiology. 2006 ; Vol. 291, No. 5.
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AU - Fang, Xiang

AU - Faraci, Frank M.

AU - Kaduce, Terry L.

AU - Harmon, Shawn

AU - Modrick, Mary L.

AU - Hu, Shanming

AU - Moore, Steven A.

AU - Falck, J. R.

AU - Weintraub, Neal L.

AU - Spector, Arthur A.

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AB - 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-PGF1α 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-PGF1α 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.

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