Mechanisms of the paradoxical effect of L-Arginine on glomerulosclerosis in 5/6 nephrectomized rats
| Project/Area Number |
10671014
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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 |
Kidney internal medicine
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
NAKANISHI Takeshi Hyogo College of Medicine, Assistant Professor, 医学部, 助教授 (70217769)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAOKA Keisuke Hyogo College of Medicine, Assistant Professor, 医学部, 助手 (60248135)
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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 |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | 5 / 6 nephrectomized rats / L-arginine / nitric oxide / glomerulosclerosis / interstitial fibrosis / L-Arginine / Nitric oxide(NO) / in situ hybridization / NO合成酵素(NOS) / ecNOS / nNOS / 間質線維化 |
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| Research Abstract |
It has been still controversial whether L-Arginine (L-ARG) ameliorate or aggravate renal function and histopathological changes in several models of renal disease, as L-ARG is the substrate for nitric oxide(NO) synthase as well as the precursor of proline and polyamines which cause renal fibrosis. These ambiguous results might be attributed to the difference in the dose and period of L-ARG administered, and animal model used in each observation. Therefore, we tested the dose-dependent effect of L-ARG on mean blood pressure (MBP), 24 hour urinary excretion of protein (UP), NO metabolites (NOィイD3-(/)2ィエD3+NOィイD3-(/)3ィエD3) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. 5/6 nephrectomized SD rats were divided into 4 groups. 1) L-ARG 0.2g/kg/day (0.2gARG) 2) L-ARG 1g/kg/day (1gARG) 3) L-ARG 2g/kg/day (2gARG) 4) No administration of L-ARG (ARG(-)). Compared with ARG(-) MBP, UP and ADMA were significantly decreased and NOィイD3-(/)2ィエD3+NOィイD3-(/)3ィエD3, cGMP were significantly increased in 0.2gARG. SI and %INT were significantly increased in 2gARG and decreased in 0.2gARG. Small dose of L-ARG ameliorated glomeruiosclerosis and interstitial fibrosis while larger dose did not. SI,%INT and ADMA were inversely correlated with NOィイD3-(/)2ィエD3+NOィイD3-(/)3ィエD3. These data suggested that renal NO synthesis might attenuate glomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decrease in NO.
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Report
(3 results)
Research Products
(2 results)
