Source:http://linkedlifedata.com/resource/pubmed/id/12016270
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2002-5-17
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| pubmed:abstractText |
Endothelium-dependent hyperpolarization and relaxation of vascular smooth muscle are mediated by endothelium-derived hyperpolarizing factors (EDHFs). EDHF candidates include cytochrome P-450 metabolites of arachidonic acid, K(+), hydrogen peroxide, or electrical coupling through gap junctions. In bovine coronary arteries, epoxyeicosatrienoic acids (EETs) appear to function as EDHFs. A 14,15-EET analogue, 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) was synthesized and identified as an EET-specific antagonist. In bovine coronary arterial rings preconstricted with U46619, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET induced concentration-related relaxations. Preincubation of the arterial rings with 14,15-EEZE (10 micromol/L) inhibited the relaxations to 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET but was most effective in inhibiting 14,15-EET-induced relaxations. 14,15-EEZE also inhibited indomethacin-resistant relaxations to methacholine and arachidonic acid and indomethacin-resistant and L-nitroarginine-resistant relaxations to bradykinin. It did not alter relaxation responses to sodium nitroprusside, iloprost, or the K(+) channel activators (NS1619 and bimakalim). Additionally, in small bovine coronary arteries pretreated with indomethacin and L-nitroarginine and preconstricted with U46619, 14,15-EEZE (3 micromol/L) inhibited bradykinin (10 nmol/L)-induced smooth muscle hyperpolarizations and relaxations. In rat renal microsomes, 14,15-EEZE (10 micromol/L) did not decrease EET synthesis and did not alter 20-hydroxyeicosatetraenoic acid synthesis. This analogue acts as an EET antagonist by inhibiting the following: (1) EET-induced relaxations, (2) the EDHF component of methacholine-induced, bradykinin-induced, and arachidonic acid-induced relaxations, and (3) the smooth muscle hyperpolarization response to bradykinin. Thus, a distinct molecular structure is required for EET activity, and alteration of this structure modifies agonist and antagonist activity. These findings support a role of EETs as EDHFs.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/11,12-epoxy-5,8,14-eicosatrienoic...,
http://linkedlifedata.com/resource/pubmed/chemical/14,15-epoxy-5,8,11-eicosatrienoic...,
http://linkedlifedata.com/resource/pubmed/chemical/15-Hydroxy-11 alpha,9...,
http://linkedlifedata.com/resource/pubmed/chemical/5,6-epoxy-8,11,14-eicosatrienoic...,
http://linkedlifedata.com/resource/pubmed/chemical/8,11,14-Eicosatrienoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/8,9-epoxyeicosatrienoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrans,
http://linkedlifedata.com/resource/pubmed/chemical/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Iloprost,
http://linkedlifedata.com/resource/pubmed/chemical/NS 1619,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroprusside,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/bimakalim
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1524-4571
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
17
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| pubmed:volume |
90
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1028-36
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12016270-15-Hydroxy-11 alpha,9...,
pubmed-meshheading:12016270-8,11,14-Eicosatrienoic Acid,
pubmed-meshheading:12016270-Animals,
pubmed-meshheading:12016270-Arachidonic Acid,
pubmed-meshheading:12016270-Benzimidazoles,
pubmed-meshheading:12016270-Benzopyrans,
pubmed-meshheading:12016270-Bradykinin,
pubmed-meshheading:12016270-Cattle,
pubmed-meshheading:12016270-Coronary Vessels,
pubmed-meshheading:12016270-Dihydropyridines,
pubmed-meshheading:12016270-Dose-Response Relationship, Drug,
pubmed-meshheading:12016270-Endothelium, Vascular,
pubmed-meshheading:12016270-Iloprost,
pubmed-meshheading:12016270-Kidney Cortex,
pubmed-meshheading:12016270-Male,
pubmed-meshheading:12016270-Microsomes,
pubmed-meshheading:12016270-Muscle, Smooth, Vascular,
pubmed-meshheading:12016270-Nitroprusside,
pubmed-meshheading:12016270-Rats,
pubmed-meshheading:12016270-Rats, Sprague-Dawley,
pubmed-meshheading:12016270-Structure-Activity Relationship,
pubmed-meshheading:12016270-Vasoconstriction,
pubmed-meshheading:12016270-Vasoconstrictor Agents,
pubmed-meshheading:12016270-Vasodilation
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| pubmed:year |
2002
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| pubmed:articleTitle |
14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries.
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| pubmed:affiliation |
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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