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

doi:10.1152/ajpheart.00349.2006

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

Journal article

Peer reviewed

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 and Arthur A Spector

American journal of physiology. Heart and circulatory physiology, Vol.291(5), pp.H2301-2307

11/2006

DOI: 10.1152/ajpheart.00349.2006

PMID: 16782846

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Abstract

20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid (AA) metabolite synthesized by cytochrome P-450 omega-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(1alpha) 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(1alpha) 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.

Endothelium, Vascular - cytology

Vasoconstrictor Agents - pharmacology

Basilar Artery - drug effects

Mice, Inbred C57BL

Cells, Cultured

Indomethacin - pharmacology

Cyclooxygenase Inhibitors - pharmacology

Telencephalon - blood supply

Hydroxyeicosatetraenoic Acids - metabolism

Animals

Endothelium, Vascular - metabolism

Hydroxyeicosatetraenoic Acids - pharmacology

Prostaglandin-Endoperoxide Synthases - metabolism

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology

Mice

Cell Culture Techniques

Vasodilation - drug effects

Vasodilation - physiology

Details

Title: Subtitle: 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase
Creators: Xiang Fang - Dept. of Medicine, Harbor Hospital Center, 3001 S. Hanover St., Baltimore MD 21225, USA. xiang.fang01@gmail.com
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
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.291(5), pp.H2301-2307
Publisher: United States
DOI: 10.1152/ajpheart.00349.2006
PMID: 16782846
ISSN: 0363-6135
eISSN: 1522-1539
Grant note: HL-072845 / NHLBI NIH HHS HL-062984 / NHLBI NIH HHS HL-076684 / NHLBI NIH HHS HL-070860 / NHLBI NIH HHS DK-038226 / NIDDK NIH HHS GM-31278 / NIGMS NIH HHS HL-38901 / NHLBI NIH HHS HL62984 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS
Language: English
Date published: 11/2006
Academic Unit: Stead Family Department of Pediatrics; Pathology; Cardiovascular Medicine; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984040558602771

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