| Project/Area Number |
11671527
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | NIPPON MEDICAL SCHOOL |
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Principal Investigator |
SAKAMOTO Atsuhiro NIPPON MEDICAL SCHOOL, DEPARTMENT OF ANESTHESIOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (30196084)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | nitric oxide / carbon monoxide / shock / nitric pride synthase / hemeoxygenase / 循環動態 / エンドトキシンショック |
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| Research Abstract |
Using a rat endotoxin shock model, the effects of inducible nitric oxide (iNOS) inhibitor (L-canavanine, CAN) and hemeoxygenase (HO) inhibitor (zinc protoporphyrin, ZPP) on the blood concentration of nitrosyl hemoglobin (NO-Hb) and carboxy-hemoglobin (CO-Hb) were studied. CAN attenuated the endotoxin-induced hypotension and only inhibited the increase in NO-Hb. ZPP also abrogated hypotension, but only inhibited the increase in CO-Hb. The increases in production of iNOS mRNA and HO-1 mRNA detected by reverse transcription-polymerase chain reaction were inhibited by CAN and ZPP, respectively and independently. These data suggest that both inhibition of iNOS pathway and HO-1 pathway are useful for the treatment of hypotension, however, both pathways work on the vascular smooth muscle independently during endotoxin shock. In a working rat heart model, iNOS inhibitor but not non-specific NOS inhibitor attenuated cardiac depression induced by inflammatory cytokines. In a rat vascular ring model, iNOS inhibitor but not non-specific NOS inhibitor attenuated vascular hyporeactivity induced by inflammatory cytokines. These data suggest the circulatory protective role of constitutive NOS during shock.
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