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

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-PGE 2 , which was as potent as PGE 2 in dilating the basilar artery. 20-HETE also stimulated AA release and PGE 2 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 PGE 2 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-PGE 2 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 - Nov 24 2006

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Basilar Artery
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Prostaglandins E
Endothelial Cells
Prostaglandins F
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
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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 Lee; Spector, Arthur A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 5, 24.11.2006.

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 Lee ; 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 - 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 Lee

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-PGE 2 , which was as potent as PGE 2 in dilating the basilar artery. 20-HETE also stimulated AA release and PGE 2 and 6-keto-PGF 1α 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 PGE 2 and 6-keto-PGF 1α production by the MBEC, but to a lesser extent than 20-HETE. Whereas the conversion of 20-HETE to 20-OH-PGE 2 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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