Source:http://linkedlifedata.com/resource/pubmed/id/19047580
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2009-1-23
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| pubmed:abstractText |
We examined the possibility that continuous activation of the human brain renin-angiotensin system causes cognitive impairment, using human renin (hRN) and human angiotensinogen (hANG) gene chimeric transgenic (Tg) mice. Cognitive function was evaluated by the shuttle avoidance test once a week from 10 to 20 weeks of age. The avoidance rate in wild-type mice gradually increased. In contrast, the avoidance rate in chimeric hRN/hANG-Tg mice also increased; however, no further increase in avoidance rate was observed from 14 weeks of age, and it decreased thereafter. Cerebral surface blood flow was markedly reduced in 20-week-old hRN/hANG-Tg mice. Superoxide anion production in the brain was already higher in 10-week-old hRN/hANG-Tg mice and further increased thereafter with an increase in NADPH oxidase activity. Moreover, expression of p47(phox) and Nox4 in the brain of hRN/hANG-Tg mice also increased. Administration of an angiotensin II type 1 receptor blocker, olmesartan (5.0 mg/kg per day), attenuated the increase in blood pressure and ameliorated cognitive decline with enhancement of cerebral surface blood flow and a reduction of oxidative stress in hRN/hANG-Tg mice. On the other hand, hydralazine (0.5 mg/kg per day) did not improve the decrease in avoidance rate, and did not influence cerebral surface blood flow or oxidative stress in hRN/hANG-Tg mice, in spite of a similar reduction of blood pressure to that by olmesartan. Moreover, we observed that treatment with Tempol improved impaired cognitive function in hRN/hANG-Tg mice. These results suggest that continuous activation of the brain renin-angiotensin system impairs cognitive function via stimulation of the angiotensin II type 1 receptor with a decrease in cerebral surface blood flow and an increase in oxidative stress.
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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/Angiotensin II Type 1 Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensinogen,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic N-Oxides,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Nox4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Renin,
http://linkedlifedata.com/resource/pubmed/chemical/Spin Labels,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/neutrophil cytosolic factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/olmesartan,
http://linkedlifedata.com/resource/pubmed/chemical/tempol
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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 |
53
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
356-62
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| pubmed:meshHeading |
pubmed-meshheading:19047580-Angiotensin II Type 1 Receptor Blockers,
pubmed-meshheading:19047580-Angiotensinogen,
pubmed-meshheading:19047580-Animals,
pubmed-meshheading:19047580-Antioxidants,
pubmed-meshheading:19047580-Blood Pressure,
pubmed-meshheading:19047580-Brain,
pubmed-meshheading:19047580-Cognition,
pubmed-meshheading:19047580-Cyclic N-Oxides,
pubmed-meshheading:19047580-Imidazoles,
pubmed-meshheading:19047580-Male,
pubmed-meshheading:19047580-Mice,
pubmed-meshheading:19047580-Mice, Transgenic,
pubmed-meshheading:19047580-NADPH Oxidase,
pubmed-meshheading:19047580-Oxidative Stress,
pubmed-meshheading:19047580-Receptor, Angiotensin, Type 1,
pubmed-meshheading:19047580-Regional Blood Flow,
pubmed-meshheading:19047580-Renin,
pubmed-meshheading:19047580-Renin-Angiotensin System,
pubmed-meshheading:19047580-Spin Labels,
pubmed-meshheading:19047580-Superoxides,
pubmed-meshheading:19047580-Tetrazoles
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| pubmed:year |
2009
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| pubmed:articleTitle |
Continuous activation of renin-angiotensin system impairs cognitive function in renin/angiotensinogen transgenic mice.
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| pubmed:affiliation |
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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