Glomerular endothelial dysfunction in progressive renal diseases and aging kidney and development the novel therapeutic strategy
| Project/Area Number |
15590867
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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 |
KASHIHARA Naoki Kawasaki Medical School, Dept of Medicine, Professor (10233701)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Tamaki Kawasaki Medical School, Dept of Medicine, Professor (30187124)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Reactive Oxygen Species / Oxidative stress / Nitric Oxide / Diabetic nephropathy / Glomerulosclerosis / Endothelial fuction / 高血圧 / アンジオテンシンII / NADPH oxidase |
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| Research Abstract |
Endothelial dysfunction is a well-established pathogenetic mechanism underlying the development of vascular and renal complications in the various forms of renal injuries and aging kidney as well. The aim of this study is to elucidate the pathogenetic mechanism of renal injury and explore the possible mechanism that could underlie endothelial dysfunction in the systemic vasculature in the progressive forms of renal injuries and senescent kidney. We hypothesized that an imbalance between reactive oxygen species (ROS) and nitric oxide (NO) in the vasculature is implicated in both renal injury and macrovascular dysfunction.
We have successfully developed the novel method by which one could observe the generation of ROS and NO in situ. Briefly, under general anesthesia, The rat whole body was perfused by the infusion pump with 37℃ phosphate buffer saline (PBS) at a flow rate of 5ml/min. Once blood had been removed, the whole body was perfused with PBS containing 0.01mmol/L diaminorhodamine-
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4M AM (DAR-4M AM), 0.05mmol/L dichlorodihydrofluorescin diaceate (DCFH-DA), 0.1mmol/L L-Arginine, and 2mmol/L CaCl2 for 10 minutes at a flow rate of 3ml/min. To remove the unreacted reagent and fix tissues, a postperfusion was added with 4% paraformaldehyde containing 0.2mmol/L Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME ; Sigma-Aldrich Japan) for 30 minutes at a flow rate of 5ml/min. Fluorescent images of ROS and NO were obtained with a confocal laser-scanning microscopy TCS-NT (Leica-Microsystems, Tokyo, Japan). The wavelength was as follow ; DAR-4M AM, excitation at 560nm and emission at 575nm ; DCFH-DA, excitation at 490nm and emission at 530nm.
We have discovered increased generation of ROS and deceased baioavailable NO in the renal tissue in the 5/6 nephrectomized rats. Accumulation of nitrotyrosine, a trace of nitrosative stress, was also increased in the renal vasculature and aorta We also found NADPH oxidase activity was implicated in the generation of ROS in this model. Angiotensin receptor blocker inhibited increased productions of ROS and NO, and significantly reduced nitrosative stress Less
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Nitric Oxide2006
Author(s)
柏原直樹、駒井則夫、守田吉孝、冨田奈留也
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Journal Title
分子腎臓病学-分子生物学的アプローチと分子病態生理学 日本臨床 64・増刊号2
Pages: 212-216
Description
「研究成果報告書概要(和文)」より
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