| 뇌허혈 재관류로 인한 뇌조직 아민 변동과 nitric oxide 및 ?산소유리기와의 관련성 |
| 문준식, 정희선, 김동구, 김경환, 이병철 |
| 연세대학교 신경과. 약리학교실, 한림대학교 신경과 |
| Relationship of the Changes in Biogenic Amines to Nitric Oxide ?and Oxygen Free Radicals During Cerebral Ischemia/Reperfusion
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| Joon Shik Moon, M.D., Hee-Sun Jung, M.S., Dong Goo kim, M.D., Ph.D., Kyung-Hwan Kim, M.D., Ph.D., Byung-Chul Lee, M.D. |
| Department of Neurology, Pharmacology, Yonsei University College of Medicine, Dept of Neurology, Hallym University College of Medicine |
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| Abstract |
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Recently oxygen free radicals and nitric oxide (NO) are known to play an important role in neuronal reperfusion injury. This study was aimed to investigate the role of oxygen f ree radicals and NO during cerebral ischemia/reperfusion, using dimethylthiourea (DMTU) and NG-monomethyl-L-arginine (NMMA), an oxygen f ree radical scavenger and a competitive NOS inhibitor respectively.
In the in vivo experiment, the ischemia/reperfusion-induced changes of cerebral biogenic
amines were examined in Mongolian gerbil (Meriones unguiculatus) pre-treated with
NMMA and/or DMTU. To induce cerebral ischemia/reperfusion, bilateral common
carotid arteries were clamped for 10 minutes and then released for 15 minutes. The
biogenic amines were measured by using HPLC-ECD(High Performance Liquid
Chromatography-Electrochemical detection). To confirm the results from the in vivo
experiments, the effect of NMMA and/or DMTU on [3H]dopamine release from striatal
slices exposed to hypoxia was investigated.
The results are as follows;
1) Ischemia/reperfusion increased the ratio of DOPAC/dopamine and HVA/dopamine as
well as the concentrations of DOPAC and HVA, which were evident only in corpus
striatum.
2) NMMA attenuated the ischemia/reperfusion-induced increase in the ratio of
DOPAC/dopamine in corpus striatum. However, the change of DOPAC or HVA was
minimal.
3) DMTU attenuated the ischemia/reperfusion-induced increase of DOPAC and HVA,
and the ratio ofDOPAC / dopa-
mine and HVA/dopamine in corpus striatum.
4) Simultaneous pre-treatment with NMMA and DMTU attenuated the
ischemia/reperfusion-induced increase of DOPAC and HVA, and the ratio Of
DOPAC/dopamine and HVA/dopamine in corpus striatum. The extent of attenuation
was greater than the single treatment group with NMMA or DMTU.
5) Exposure to hypoxia markedly increased the release of [3H]dopamine in the striatal
slices.
6) The administration of either NMMA or DMTU attenuated the increase of
[3H]dopamine release induced by hypoxia in the striatal slices.
7) The administration of both NMMA or DMTU markedly attenuated the increase of
[3H]dopamine release induced by hypoxia to the extent of the control in the striatal
slices.
These results suggest that oxygen free radicals play an important role in cerebral
ischemia/reperfusion injury, for which NO seems to be responsible.
Key Words : Ischemia, Reperfusion, Biogenic amine, Dopamine, DMTU, NMMA |
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