Source:http://linkedlifedata.com/resource/pubmed/id/16380531
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2006-1-25
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| pubmed:abstractText |
Arginase, expressed in endothelial cells and upregulated in aging blood vessels, competes with NO synthase (NOS) for l-arginine, thus modulating vasoreactivity and attenuating NO signaling. Moreover, arginase inhibition restores endothelial NOS signaling and l-arginine responsiveness in old rat aorta. The arginase isoform responsible for modulating NOS, however, remains unknown. Because isoform-specific arginase inhibitors are unavailable, we used an antisense (AS) oligonucleotide approach to knockdown arginase I (Arg I). Western blot and quantitative PCR confirmed that Arg I is the predominant isoform expressed in endothelialized aortic rings and is upregulated in old rats compared with young. Aortic rings from 22-month-old rats were incubated for 24 hours with sense (S), AS oligonucleotides, or medium alone (C). Immunohistochemistry, immunoblotting, and enzyme assay confirmed a significant knockdown of Arg I protein and arginase activity in AS but not S or C rings. Conversely, calcium-dependent NOS activity and vascular metabolites of NO was increased in AS versus S or C rings. Acetylcholine (endothelial-dependent) vasorelaxant responses were enhanced in AS versus S or C treated rings. In addition, 1H-oxadiazolo quinoxalin-1-one (10 micromol/L), a soluble guanylyl cyclase inhibitor, increased the phenylephrine response in AS compared with S and C rings suggesting increased NO bioavailability. Finally, l-arginine (0.1 mmol/L)-induced relaxation was increased in AS versus C rings. These data support our hypothesis that Arg I plays a critical role in the pathobiology of age-related endothelial dysfunction. AS oligonucleotides may, therefore, represent a novel therapeutic strategy against age-related vascular endothelial dysfunction.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1H-(1,2,4)oxadiazolo(4,3-a)quinoxali...,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Arginase,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Oxadiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
1524-4563
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
47
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
245-51
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:16380531-Acetylcholine,
pubmed-meshheading:16380531-Aging,
pubmed-meshheading:16380531-Animals,
pubmed-meshheading:16380531-Aorta,
pubmed-meshheading:16380531-Arginase,
pubmed-meshheading:16380531-Arginine,
pubmed-meshheading:16380531-Calcium,
pubmed-meshheading:16380531-Drug Synergism,
pubmed-meshheading:16380531-Enzyme Inhibitors,
pubmed-meshheading:16380531-Male,
pubmed-meshheading:16380531-Nitric Oxide,
pubmed-meshheading:16380531-Nitric Oxide Synthase,
pubmed-meshheading:16380531-Oligonucleotides, Antisense,
pubmed-meshheading:16380531-Oxadiazoles,
pubmed-meshheading:16380531-Phenylephrine,
pubmed-meshheading:16380531-Quinoxalines,
pubmed-meshheading:16380531-Rats,
pubmed-meshheading:16380531-Rats, Wistar,
pubmed-meshheading:16380531-Signal Transduction,
pubmed-meshheading:16380531-Up-Regulation,
pubmed-meshheading:16380531-Vasoconstrictor Agents,
pubmed-meshheading:16380531-Vasodilation,
pubmed-meshheading:16380531-Vasodilator Agents
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| pubmed:year |
2006
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| pubmed:articleTitle |
Knockdown of arginase I restores NO signaling in the vasculature of old rats.
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| pubmed:affiliation |
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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