TY - JOUR
T1 - 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery
T2 - Role of cyclooxygenase
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 Lee
AU - Spector, Arthur A.
PY - 2006
Y1 - 2006
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.
KW - 20-carboxy-arachidonic acid
KW - 20-hydroxy-prostaglandin E
KW - Cerebral vascular tone
KW - Prostaglandins
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U2 - 10.1152/ajpheart.00349.2006
DO - 10.1152/ajpheart.00349.2006
M3 - Article
C2 - 16782846
AN - SCOPUS:33751188531
SN - 0363-6135
VL - 291
SP - H2301-H2307
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -