| Project/Area Number |
18590915
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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 | Kawasaki Medical School |
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Principal Investigator |
SASAKI Tamaki Kawasaki Medical School, Nephrology, Professor (30187124)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIHARA Naoki Kawasaki Medical School, Nephrology, Professor (10233701)
HORIKE Hideyuki Kawasaki Medical School, Nephrology, Assistant Professor (10289150)
SEIICHI Mochizuki Kawasaki University of Medical Welfare, Medical Engineering, Professor (60259596)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | CAPD / Nitric oxide(NO) / NO sensor / Oxidative stress / Tetrahydrobionterin(BH_4) / ADMA / tetrahydrobiopterin(BH4) / Asymmetric |
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| Research Abstract |
Nitric oxide (NO) plays a key role in the regulation of vascular tone and controls both local and systemic hemodynamics. Also, dysfunction of the peritoneal membrane has been suggested to be related to abnormal production and/or metabolism of endogenous NO. Tetrahydrobiopterin (BH_4) is a key cofactor to maintain the enzymatic activity of nitric oxide synthase (NOS). A decrease in BH_4 level may cause endothelial NOS uncoupling, resulting in reduced NO synthesis and enhanced superoxide release from NOS. The aim of the present study was thus to measure NO, BH_4 and BH_2 (an oxidized form of BH_4) concentrations in the dialysate effluent of CAPD patients. Eighteen patients with chronic renal failure undergoing peritoneal dialysis at our hospital participated in this study. We directly measured the concentration of NO in the CAPD dialysate using an NO sensor (amiNO-700, Innovative Instruments, Inc., USA). Both BH_4 and BH_2 concentrations were measured using HPLC. NO concentration was significantly higher in the dialysate after 4 hrs CAPD than in the dialysate immediately after an exchange of CAPD solution (8.3±3.2 nM vs. 3.3±0.9 nM; p<0.05). BH_4 concentration was also higher after a 4-hr CAPD than immediately after solution exchange (4.10±4.18 ng/ml vs. 0.29±0.85 ng/ml; p<0.05). BH2 concentration also showed the same trend (0.18±0.24 ng/ml vs. 0.07±0.10 ng/ml; p<0.05). In the CAPD therapy, both NO and BH_4 concentrations increased in the course of time. These results suggest that the bioavailability of peritoneum-derived NO is increased by CAPD therapy due to the increased BH_4 availability.
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