| Project/Area Number |
11670689
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
HIROOKA Yoshitaka Kyushu Univ, Dept of Cardiovasc Med, Assist Prof, 医学部・附属病院, 助手 (90284497)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKI Toshihiro Kyushu Univ, Dept of Cardiovasc Med, Assist Prof, 医学部・附属病院, 助手 (80311843)
田川 辰也 日本学術新興会, 特別研究員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | nitric oxide / angiotensin / heart failure / gene transfer / blood pressure / heart rate / sympathetic nervous system / brain |
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| Research Abstract |
1. Heart failure (HF) was induced by an aortocaval shunt in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of HF.Urinary catecholamine excretion and maximal renal sympathetic nerve activity (SNA) were greater in rats with HF than in the control rats. Microinjection of an angiotensin type 1 (AT1) receptor antagonist into the nucleus tractus solitarius (NTS) was performed. The arterial pressure and renal SNA were reduced by an AT1 receptor antagonist to a greater degree in HF rats than in the control rats. The expression of angiotensin converting enzyme mRNA in the medulla was greater in the HF rats than in the control rats. These results suggest that activation of the renin-angiotensin system in the NTS contributes to an enhanced SNA in HF.
2. Adenovirus vectors encoding either endothelial nitric oxide synthase (eNOS)(AdeNOS) or β-galactocidase were transfected into the NTS in vivo. In the AdeNOS-treated rats, the local expression of eNOS protein and by
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increased production of nitrite and nitrate in the NTS measured by in vivo microdialysis. Blood pressure and heart rate, monitored by the use of a radiotelemetry system in a conscious state, were significantly decreased in the AdeNOS-treated group at day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion also was decreased at day 7 after the gene transfer in the AdeNOS-treated group. Our results indicate that overexpression of eNOS in the NTS decreases blood pressure, heart rate, and SNA in conscious rats.
3. HF was induced by coronary ligation in the mouse. These mice exhibited a left ventricular dilatation and a reduced left ventricular systolic function by echocardiography. In addition, urinary norepinephrine excretion for 24 hours was greater in these mice than in the control mice. Furthermore, neuronal NOS expression was reduced in the HF mice by Western blot analysis as compared with that in the control mice. We are transfecting eNOS into the brain stem in the HF mice. Less
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