20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase.
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.
Fang
Xiang
X
Dept. of Medicine, Harbor Hospital Center, 3001 S. Hanover St., Baltimore MD 21225, USA. xiang.fang01@gmail.com
Faraci
Frank M
FM
Kaduce
Terry L
TL
Harmon
Shawn
S
Modrick
Mary L
ML
Hu
Shanming
S
Moore
Steven A
SA
Falck
J R
JR
Weintraub
Neal L
NL
Spector
Arthur A
AA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013687:Telencephalon / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin