| Project/Area Number |
15591919
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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 |
Emergency medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
OKAJIMA Kenji Kumamoto University, Graduate School of Medical sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (60152295)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIBA Mitsuhiro Kumamoto University, University Hospital, Instructor, 医学部附属病院, 助手 (90315292)
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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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | CGRP / tumor necrosis factor / capsaicin sensitive sensory neurons / prostacyclin / Septic shock / Nitric oxide / iNOS / endotoxin / CGRP / カプサイシン知覚神経 |
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| Research Abstract |
Systemic blood pressure was decreased and lasma levels of TNF-alpha and lung iNOS level were increased by LPS administration in rats. LPS administration also increased CGRP release from capsaicin sensitive sensory neurons thereby increased plasma levels. To determine whether the intrinsic CGRP contributes to pathogenesis of septic shock, we examined effect of capsazepin, chemical denervation factor, on rat LPS-induced shock model. Plasma CGRP levels were decreased and TNF-alpha levels and iNOS activity in lung were increased by capsazepin pretreatment. LPS-induced shock was worsen by capsazepin. CGRP8-37, an antagonist of CGRP, also increased TNF-alpha and iNOS activity thereby worsen LPS-induced shock. In contrast, exogenous administration of CGRP improved septic shock induced by LPS administration. These results indicated that CGRP released from capsaicin sensitive sensory neurons prevents pathogenesis of shock. This effect of CGRP to prevent shock was cancelled by indomethacin, an inhibitor of cyclooxgenase, suggesting that this protective effect of CGRP is mediated by prostacyclin production.
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