| Project/Area Number |
07670863
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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 |
Pediatrics
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| Research Institution | Kobe University |
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Principal Investigator |
YONETANI Masahiko Kobe University, School of Medicine, Assistant, 医学部, 助手 (60221678)
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| Co-Investigator(Kenkyū-buntansha) |
HAJIME Nakamura Kobe University, School of Medicine, Professor, 医学部, 教授 (40030978)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Nitric oxide / Hypoxia / Dopamine / Newborn / Striatum / ドパミン代謝 |
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| Research Abstract |
The present study tests the hypothesis that nitric oxide (NO) will modulate the metabolic responses of the striatal dopaminergic system during hypoxia in newborn. The study was carried out in urethaneanesthetized 7-day-old rats using in vivo microdialysis. Following baseline, rats underwent 60-min hypoxia in 8% O2 and the subsequent 60-min recovery (21% O2). The rats were randomized prior to hypoxia into 3 treatment groups. One group received L-arginine via microdialysis probe at a concentration of 100 muM.Another group received an inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME) at 100 muM.Treatment was administered from 30 min before hypoxia to the end of hypoxia. The control group received normal Ringer's solution throughout the experiment. Samples were collected at 10 min intervals and dialysate dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were studied. In control, DA level increased to 241(]SY.+-。[)37% of baseline by the end of hy
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poxia. DOPAC and HVA levels decreased by 48(]SY.+-。[)3% and 59(]SY.+-。[)4% respectively. Local application of L-arginine or L-NAME alone did not induce significant changes in the basal extracellular dopamine, DOPAC and HVA levels. In L-NAME treated group, maximal increase of DA level induced by hypoxia (142(]SY.+-。[)24%) was significantly lower than those in both control and L-arginine treated group (p<0.05). L-Arginine treated group showed similar increase of dopamine compared to the controls. Treatment with L-NAME also attenuated the accumulation of extracellular dopamine in striatum induced by by high K-depolarization (L-NAME ; 603(]SY.+-。[)116% vs. control : 1,410(]SY.+-。[)307% of spontaneous baseline level, p<0.05). Thses results indicate that inhibition of NO synthesis attenuates hypoxia-induced increase of striatal extracellular DA and may prevent hypoxic injury by reducing oxygen radicals generation from the oxidation of DA.Inhibition of NO synthesis may prevent hypoxic neuronal injury by inhibiting striatal dopamine release and reducing reactive oxygen species which are generated through the oxidation of dopamine. Less
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