論文 - 詳細
| RRC ID | 11801 |
|---|---|
| 著者 | Inaba S, Iwai M, Furuno M, Tomono Y, Kanno H, Senba I, Okayama H, Mogi M, Higaki J, Horiuchi M. |
| タイトル | Continuous activation of renin-angiotensin system impairs cognitive function in renin/angiotensinogen transgenic mice. |
| ジャーナル | Hypertension |
| Abstract |
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. |
| 巻・号 | 53(2) |
| ページ | 356-62 |
| 公開日 | 2009-2-1 |
| DOI | 10.1161/HYPERTENSIONAHA.108.123612 |
| PII | HYPERTENSIONAHA.108.123612 |
| PMID | 19047580 |
| MeSH | Angiotensin II Type 1 Receptor Blockers / pharmacology Angiotensinogen / genetics Angiotensinogen / metabolism* Animals Antioxidants / pharmacology Blood Pressure / physiology Brain / blood supply* Brain / metabolism* Cognition / physiology* Cyclic N-Oxides / pharmacology Imidazoles / pharmacology Male Mice Mice, Transgenic NADPH Oxidase 4 NADPH Oxidases / metabolism Oxidative Stress / physiology Receptor, Angiotensin, Type 1 / metabolism Regional Blood Flow / physiology Renin / genetics Renin / metabolism* Renin-Angiotensin System / physiology* Spin Labels Superoxides / metabolism Tetrazoles / pharmacology |
| IF | 7.713 |
| 引用数 | 79 |
| WOS 分野 | PERIPHERAL VASCULAR DISEASE |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC01122 RBRC01123 |