| Project/Area Number |
12470318
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Nagoya University |
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Principal Investigator |
SHIMADA Yasuhiro Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50028669)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Naohisa Aichi Medical University, Professor, 医学部, 教授 (80109321)
KIMURA Tomomasa Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50161568)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥12,000,000 (Direct Cost: ¥12,000,000)
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| Keywords | neurogenic pulmonary edema / pulmonary vascular permeability / nitric oxide / vagus nerve / fibrin-induced pulmonary edema |
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| Research Abstract |
It has been suggested that sympathetic overactivity associated with central nervous system (CNS) diseases mediates neurogenic pulmonary edema (NPE). But the exact mechanism is still unknown. In this study, we have obtained the following results.
1. Fibrinogen and thrombin injected into the cisterna magna of rats induces NPE (fibrin-induced pulmonary edema : FIPE). Neuropeptide Y (NPY) was measured using enzyme-linked immunoassay. NPY was found in the alveolar macrophages and edema fluids in cases of FIPE but was almost absent in hydrostatic edema. Pharmacological studies revealed that NPY Y_3 receptors were found to be associated with pulmonary vascular permeability.
2. By using a rat endothelial cell (RAEC) monolayer cultures, endothelial permeability was measured. NPY did not influence permeability of RAEC cultured in the ambient air but increased permeability dose-dependently in hypoxic condition (5% oxygen). Pharmacological studies revealed that Y_3 receptor of REAC was related with this increase in permeability in hypoxic condition.
3. It has been reported that nitric oxide (NO) has different effects between CNS and peripheral tissues relating to the development of pulmonary edema. In the FIPE, injection of NO inhibitor in the 4^<th> ventricle of rat brain accelerated the development of pulmonary edema when the vagus nerve was intact, but was unchanged when the vagus was severed. When arginine was injected, NPE was unchanged in the vagus-intact rats, but was decreased in the vagus-severed rats.
4. Inhibition of FIPE by previous unilateral left-vagotomy was related with increased levels of brain NO synthase (bNOS) in the nucleus tractus solitarii of rats.
5. L-glutamate in the medulla oblongata inhibited NPE by accelerating NO synthesis.
We are now in the process of cloning NPY Y_3 receptor, and this will greatly accelerate the development of drugs for the treatment of NPE.
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