Abstract:
:Endothelial cells release several compounds, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF), that mediate the vascular effects of vasoactive hormones. The identity of EDHF remains unknown. Since arachidonic acid causes endothelium-dependent relaxations of coronary arteries through its metabolism to epoxyeicosatrienoic acids (EETs) by cytochrome P450, we wondered if the EETs represent EDHFs. Precontracted bovine coronary arteries relaxed in an endothelium-dependent manner to methacholine. The cytochrome P450 inhibitors, SKF 525A and miconazole, significantly attenuated these relaxations. They were also inhibited by tetraethylammonium (TEA),an inhibitor of Ca2+-activated K+ channels, and by high [K+]0 (20 mmol/L). Methacholine also caused hyperpolarization of coronary smooth muscle (-27 +/- 3.9 versus -40 +/- 5.1 mV), which was completely blocked by SKF 525A and miconazole. In vessels prelabeled with [3H] arachidonic acid, methacholine stimulated the release of 6-ketoprostaglandin F1alpha, 12-HETE, and the EETs. Arachidonic acid relaxed precontracted coronary arteries, which were also blocked by TEA, charybdotoxin, another Ca2+-activated K+ channel inhibitor, and high [K+]0. 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET relaxed precontracted coronary vessels (EC50, 1 X 10(-6) mol/L). The four regioisomers were equally active. TEA, charybdotoxin, and high [K+]0 attenuated the EET relaxations. 11,12-EET hyperpolarized coronary smooth muscle cells from -37 +/- 0.2 to -59 +/- 0.3 mV. In the cell-attached mode of patch clamp, both 14,15-EET and 11,12-EET increased the open-state probability of a Ca2+-activated K+ channel in coronary smooth muscle cells. This effect was blocked by TEA and charybdotoxin. These data support the hypothesis that the EETs are EDHFs.
journal_name
Circ Resjournal_title
Circulation researchauthors
Campbell WB,Gebremedhin D,Pratt PF,Harder DRdoi
10.1161/01.res.78.3.415subject
Has Abstractpub_date
1996-03-01 00:00:00pages
415-23issue
3eissn
0009-7330issn
1524-4571journal_volume
78pub_type
杂志文章abstract:RATIONALE:Diabetes mellitus increases cardiovascular disease risk in humans and remains elevated despite cholesterol-lowering therapy with statins. Consistent with this, in mouse models, diabetes mellitus impairs atherosclerosis plaque regression after aggressive cholesterol lowering. MicroRNA 33 (miR33) is a key negat...
journal_title:Circulation research
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更新日期:1977-10-01 00:00:00
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更新日期:2000-06-09 00:00:00
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更新日期:1990-03-01 00:00:00
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更新日期:2015-08-14 00:00:00
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pub_type: 杂志文章
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更新日期:1983-02-01 00:00:00
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更新日期:1988-03-01 00:00:00
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更新日期:1999-02-05 00:00:00
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更新日期:1986-02-01 00:00:00
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更新日期:1975-06-01 00:00:00
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更新日期:2003-11-14 00:00:00
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更新日期:1983-05-01 00:00:00
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更新日期:1990-10-01 00:00:00
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更新日期:2016-04-15 00:00:00
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更新日期:2004-04-30 00:00:00
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更新日期:2008-05-23 00:00:00