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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2000-12-1
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pubmed:abstractText |
The cytochrome P450-derived epoxyeicosatrienoic acids (EETs) have potent effects on renal vascular reactivity and tubular sodium and water transport; however, the role of these eicosanoids in the pathogenesis of hypertension is controversial. The current study examined the hydrolysis of the EETs to the corresponding dihydroxyeicosatrienoic acids (DHETs) as a mechanism for regulation of EET activity and blood pressure. EET hydrolysis was increased 5- to 54-fold in renal cortical S9 fractions from the spontaneously hypertensive rat (SHR) relative to the normotensive Wistar-Kyoto (WKY) rat. This increase was most significant for the 14,15-EET regioisomer, and there was a clear preference for hydrolysis of 14, 15-EET over the 8,9- and 11,12-EETs. Increased EET hydrolysis was consistent with increased expression of soluble epoxide hydrolase (sEH) in the SHR renal microsomes and cytosol relative to the WKY samples. The urinary excretion of 14,15-DHET was 2.6-fold higher in the SHR than in the WKY rat, confirming increased EET hydrolysis in the SHR in vivo. Blood pressure was decreased 22+/-4 mm Hg (P:<0.01) 6 hours after treatment of SHRs with the selective sEH inhibitor N:, N:'-dicyclohexylurea; this treatment had no effect on blood pressure in the WKY rat. These studies identify sEH as a novel therapeutic target for control of blood pressure. The identification of a potent and selective inhibitor of EET hydrolysis will be invaluable in separating the vascular effects of the EET and DHET eicosanoids.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,3-dicyclohexylurea,
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/8,11,14-Eicosatrienoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/8,9-epoxyeicosatrienoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Eicosanoids,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Urea
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1524-4571
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pubmed:author |
pubmed-author:DraperA JAJ,
pubmed-author:EnglerM MMM,
pubmed-author:GrahamLL,
pubmed-author:GuyH HHH,
pubmed-author:HammockB DBD,
pubmed-author:HuseL MLM,
pubmed-author:KroetzD LDL,
pubmed-author:MorisseauCC,
pubmed-author:NewmanJ WJW,
pubmed-author:ParkesLL,
pubmed-author:YuZZ,
pubmed-author:ZeldinD CDC
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
87
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
992-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11090543-8,11,14-Eicosatrienoic Acid,
pubmed-meshheading:11090543-Animals,
pubmed-meshheading:11090543-Arachidonic Acids,
pubmed-meshheading:11090543-Blood Pressure,
pubmed-meshheading:11090543-Cytosol,
pubmed-meshheading:11090543-Eicosanoids,
pubmed-meshheading:11090543-Enzyme Inhibitors,
pubmed-meshheading:11090543-Epoxide Hydrolases,
pubmed-meshheading:11090543-Epoxy Compounds,
pubmed-meshheading:11090543-Hydrolysis,
pubmed-meshheading:11090543-Hypertension,
pubmed-meshheading:11090543-Kidney Cortex,
pubmed-meshheading:11090543-Male,
pubmed-meshheading:11090543-Microsomes,
pubmed-meshheading:11090543-Microsomes, Liver,
pubmed-meshheading:11090543-Rats,
pubmed-meshheading:11090543-Rats, Inbred SHR,
pubmed-meshheading:11090543-Rats, Inbred WKY,
pubmed-meshheading:11090543-Rats, Sprague-Dawley,
pubmed-meshheading:11090543-Species Specificity,
pubmed-meshheading:11090543-Urea
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pubmed:year |
2000
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pubmed:articleTitle |
Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.
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pubmed:affiliation |
Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, CA, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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