Source:http://linkedlifedata.com/resource/pubmed/id/19380610
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2009-5-21
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| pubmed:abstractText |
We investigated the effect of atorvastatin on cyclooxygenase (COX) contribution to endothelial dysfunction in spontaneously hypertensive rat (SHR) mesenteric resistance arteries. Atorvastatin (10 mg/kg per day, oral gavage) or its vehicle was administered for 2 weeks to male SHR or Wistar-Kyoto rats. Endothelial function of mesenteric arteries was assessed by pressurized myograph. In Wistar-Kyoto rats, relaxation to acetylcholine was inhibited by N(G)-nitro-L-arginine methyl ester and unaffected by SC-560 (COX-1 inhibitor), DuP-697 (COX-2 inhibitor), or ascorbic acid. In SHRs, the response to acetylcholine was attenuated, less sensitive to N(G)-nitro-L-arginine methyl ester, unaffected by SC-560, and enhanced by DuP-697 or SQ-29548 (thromboxane-prostanoid receptor antagonist) to a similar extent. Endothelium-dependent relaxation was normalized by ascorbic acid or apocynin (NADPH oxidase inhibitor), which also restored the inhibition by N(G)-nitro-L-arginine methyl ester. In atorvastatin-treated SHRs, relaxation to acetylcholine was normalized, fully sensitive to N(G)-nitro-L-arginine methyl ester, and not affected by SC-560, DuP-697, SQ 29548, or antioxidants. Dihydroethidium assay showed an increased intravascular superoxide generation in SHRs, which was abrogated by atorvastatin. RT-PCR revealed a COX-2 induction in SHR arteries, which was downregulated by atorvastatin. The release of prostacyclin and 8-isoprostane was higher from SHR than Wistar-Kyoto mesenteric vessels. COX-2 inhibition and apocynin decreased 8-isoprostane without affecting prostacyclin levels. Atorvastatin increased phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS(1177), and inducible NO synthase levels in SHR mesenteric vessels and decreased 8-isoprostane release. In conclusion, COX-2-derived 8-isoprostane contributes to endothelial dysfunction in SHR mesenteric arteries. Atorvastatin restores NO availability by increasing phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS(1177), and inducible NO synthase levels and by abrogating vascular NADPH oxidase-driven superoxide production, which also results in a downregulation of COX-2-dependent 8-isoprostane generation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Heptanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Malondialdehyde,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/atorvastatin
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1524-4563
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| pubmed:author |
pubmed-author:AntonioliLucaL,
pubmed-author:BlandizziCorradoC,
pubmed-author:ColucciRocchinaR,
pubmed-author:DaghiniElenaE,
pubmed-author:Del TaccaMarioM,
pubmed-author:DurantiEmilianoE,
pubmed-author:FornaiMatteoM,
pubmed-author:GhisuNarcisaN,
pubmed-author:GiannarelliChiaraC,
pubmed-author:TaddeiStefanoS,
pubmed-author:VersariDanieleD,
pubmed-author:VirdisAgostinoA
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| pubmed:issnType |
Electronic
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| pubmed:volume |
53
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1008-16
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| pubmed:meshHeading |
pubmed-meshheading:19380610-Analysis of Variance,
pubmed-meshheading:19380610-Animals,
pubmed-meshheading:19380610-Blotting, Western,
pubmed-meshheading:19380610-Cyclooxygenase 1,
pubmed-meshheading:19380610-Cyclooxygenase 2,
pubmed-meshheading:19380610-Disease Models, Animal,
pubmed-meshheading:19380610-Dose-Response Relationship, Drug,
pubmed-meshheading:19380610-Drug Administration Schedule,
pubmed-meshheading:19380610-Endothelium, Vascular,
pubmed-meshheading:19380610-Heptanoic Acids,
pubmed-meshheading:19380610-Male,
pubmed-meshheading:19380610-Malondialdehyde,
pubmed-meshheading:19380610-Mesenteric Arteries,
pubmed-meshheading:19380610-Probability,
pubmed-meshheading:19380610-Prostaglandins,
pubmed-meshheading:19380610-Pyrroles,
pubmed-meshheading:19380610-RNA,
pubmed-meshheading:19380610-Random Allocation,
pubmed-meshheading:19380610-Rats,
pubmed-meshheading:19380610-Rats, Inbred SHR,
pubmed-meshheading:19380610-Rats, Inbred WKY,
pubmed-meshheading:19380610-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19380610-Sensitivity and Specificity,
pubmed-meshheading:19380610-Vasodilation
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| pubmed:year |
2009
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| pubmed:articleTitle |
Atorvastatin prevents endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats: role of cyclooxygenase 2-derived contracting prostanoids.
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| pubmed:affiliation |
Department of Internal Medicine, University of Pisa, Pisa, Italy. a.virdis@med.unipi.it
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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