| Project/Area Number |
10670668
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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 |
TSUCHIHASHI Takuya Kyushu University, Department of General Medicine, Assistant Professor, 医学部, 講師 (30163827)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Ventrolateral Medulla / Nitric Oxide / Blood Pressure / Spontaneously Hypertensive Rats / Excitatory Amino Acids / Angiotensin II |
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| Research Abstract |
Role of nitric oxide (NO) in the rostral ventrolateral medulla (RVLM) of hypertensive rats was examined.
1. Microinjection of NO donor or L-arginine into the RVLM elicited depressor response, which was significantly greater in spontaneously hypertensive rats (SHR) than in normotensive WKY rats.
2. Intracerebroventricular infusion of L-arginine for 2 weeks failed to alter arterial pressure of SHR.
3. Intracerebroventricular injection of NO donor produced greater depressor response in the rats that were chronically treated with an NO synthase inhibitor L-NAME than in control normotensive rats. Pressor response to L-glutamate or angiotensin II microinjected into the RVLM was augmented in the L-NAME-treated rats.
4. Chronic antihypertensive treatment with oral administration of angiotensin II type 1 receptor antagonist TCV-116 improved the augmented pressor responsiveness to L-glutamate in the RVLM of SHR.
These results suggest that L-arginine-NO system is impaired in the central nervous system, especially in the RVLM, of SHR and hypertensive rats with chronic systemic NO synthase inhibition, which may contribute to the pathogenesis of hypertension in these animal models. However, the deficiency of L-arginine, the substrate of NO, seems unlikely in the central nervous system of SHR. NO may also have an influence on the actions of L-glutamate and angiotensin II in the RVLM. Thus, NO plays an important role in the central cardiovascular regulation and in the pathogenesis of hypertension.
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