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

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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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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-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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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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N2 - 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.

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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