Source:http://linkedlifedata.com/resource/pubmed/id/18281381
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2008-4-2
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pubmed:abstractText |
Mitogen-activated protein kinase phosphatase-1 (MKP-1) is essential in limiting the proinflammatory response to lipopolysaccharide (LPS). We hypothesized that Mkp-1(-/-) mice would respond to low-dose LPS with a fall in blood pressure due to augmented expression of inducible nitric oxide (NO) synthase (iNOS). To test this hypothesis, Mkp-1(-/-) mice and their wild-type littermates were treated with 10 microg/kg iv LPS, and mean arterial blood pressure (MAP) and exhaled NO production (exNO) were measured. Tissues were harvested for an assessment of iNOS protein levels. Wild-type mice had no change in MAP or exNO during the experimental period, whereas Mkp-1(-/-) mice had a fall (P < 0.005) in MAP [79 +/- 5% of baseline (BL)] and an increase (P < 0.01) in exNO (266 +/- 50% of BL) after 150 min. The tissue levels of iNOS were greater in Mkp-1(-/-) than in wild-type mice. In additional experiments, 60 min after LPS treatment, Mkp-1(-/-) and wild-type mice were given N(omega)-nitro-l-arginine methyl ester (l-NAME) or aminoguanidine, and MAP and exNO were monitored for 90 min. Treatment with l-NAME prevented the LPS-induced increase in exNO and decrease in MAP but resulted in decreased exNO and elevated MAP in wild-type mice. Aminoguanidine prevented the increase in exNO and the fall in MAP caused by LPS in Mkp-1(-/-) mice, without significantly affecting MAP or exNO in wild-type mice. These results demonstrate that a deficiency of MKP-1 results in an exaggerated hypotensive response to LPS mediated by augmented iNOS expression. We speculate that defects in the Mkp-1 gene may increase susceptibility for the development of septic shock.
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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/Dual Specificity Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Dusp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanidines,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Spermine,
http://linkedlifedata.com/resource/pubmed/chemical/pimagedine,
http://linkedlifedata.com/resource/pubmed/chemical/spermine nitric oxide complex
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0363-6135
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H1621-9
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pubmed:meshHeading |
pubmed-meshheading:18281381-Animals,
pubmed-meshheading:18281381-Blood Pressure,
pubmed-meshheading:18281381-Breath Tests,
pubmed-meshheading:18281381-Disease Models, Animal,
pubmed-meshheading:18281381-Dose-Response Relationship, Drug,
pubmed-meshheading:18281381-Dual Specificity Phosphatase 1,
pubmed-meshheading:18281381-Enzyme Inhibitors,
pubmed-meshheading:18281381-Guanidines,
pubmed-meshheading:18281381-Hypotension,
pubmed-meshheading:18281381-Lipopolysaccharides,
pubmed-meshheading:18281381-Mice,
pubmed-meshheading:18281381-Mice, Inbred C57BL,
pubmed-meshheading:18281381-Mice, Knockout,
pubmed-meshheading:18281381-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:18281381-Nitric Oxide,
pubmed-meshheading:18281381-Nitric Oxide Donors,
pubmed-meshheading:18281381-Nitric Oxide Synthase Type II,
pubmed-meshheading:18281381-Spermine,
pubmed-meshheading:18281381-Time Factors,
pubmed-meshheading:18281381-Up-Regulation
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pubmed:year |
2008
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pubmed:articleTitle |
Deficiency of mitogen-activated protein kinase phosphatase-1 results in iNOS-mediated hypotension in response to low-dose endotoxin.
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pubmed:affiliation |
The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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