Source:http://linkedlifedata.com/resource/pubmed/id/17267581
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2007-4-17
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pubmed:abstractText |
Epoxyeicosatrienoic acids (EETs) have been reported to contract intralobar pulmonary arteries (PA) of the rabbit in a cyclooxygenase (COX)-dependent manner. In the present study, we observed that COX-1 and COX-2 isoforms were expressed in freshly isolated PA of healthy rabbits. We examined the hypothesis that both COX isoforms participate in 5,6-EET-induced contraction of rabbit intralobar PA. Selective inhibition of COX-1 with 300 nM 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) prevented 5,6-EET (1x10(-8)-1x10(-5) M)-induced contractions of isolated intralobar rabbit PA rings in a manner similar to that observed with the nonselective cyclooxygenase inhibitor indomethacin at 10 microM. Selective inhibition of COX-2 with either 100 nM 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonyl) thiophene (DUP-697) or 3 microM N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) shifted the EC50 value of 5,6-EET-induced PA contraction to the right but with considerably lower efficacy than SC-560. In rabbit PA, 5,6-EET-induced contraction was primarily dependent on COX-1 activity. Differential metabolism of 5,6-EET by COX-1 and COX-2 does not explain the primary dependence of PA contraction on COX-1 activity because 5,6-EET was metabolized similarly by both COX isoforms. COX-1 and -2 were expressed primarily in PA endothelium where COX-1 expression was dense and uniform, whereas COX-2 expression was sparse and nonuniform. 5,6-EET-induced PA contraction was endothelium-dependent. These results suggest that 5,6-EET-induced contraction is primarily dependent on COX-1 activity.
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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/5,6-epoxy-8,11,14-eicosatrienoic...,
http://linkedlifedata.com/resource/pubmed/chemical/8,11,14-Eicosatrienoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
321
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
446-54
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17267581-8,11,14-Eicosatrienoic Acid,
pubmed-meshheading:17267581-Animals,
pubmed-meshheading:17267581-Cyclooxygenase 1,
pubmed-meshheading:17267581-Cyclooxygenase 2,
pubmed-meshheading:17267581-Immunohistochemistry,
pubmed-meshheading:17267581-Pulmonary Artery,
pubmed-meshheading:17267581-Rabbits,
pubmed-meshheading:17267581-Vasoconstriction
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pubmed:year |
2007
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pubmed:articleTitle |
Cyclooxygenase (COX)-1 and COX-2 participate in 5,6-epoxyeicosatrienoic acid-induced contraction of rabbit intralobar pulmonary arteries.
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pubmed:affiliation |
Department of Pharmacological and Physiological Science, 1402 S. Grand Blvd., St. Louis, MO 63104, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, N.I.H., Extramural
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