| Project/Area Number |
05671274
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | KAGOSHIMA UNIVERSITY |
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Principal Investigator |
YOSHIMURA Nozomu Kagoshima University, School of Medicine, Professor, 医学部, 教授 (60041399)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAO Junko Kagoshima University, School of Medicine, Assistant, 医学部, 助手 (70107879)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Shock / Endotoxin / Nitric oxide / Vascular smooth muscle / Anesthesia / 麻酔薬 |
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| Research Abstract |
We investigated the effects of dopamine and dobutamine on rabbit arteries using tension recording methods. We confirmed that regional differences were apparent in the effects of dopamine on vascular tissues and that dobutamine possessed vasodilating effects. The inhibitory effects of dobutamine on contractions induced by dopamine in the rabbit ear artery suggested a possible clinical benefit of dobutamine for maintaining peripheral circulation during combined use of dopamine and dobutamine.
It has been proposed that endotoxin and some cytokines play a major role in the development of a marked hypotension in septic shock. However, the direct effects of endotoxin on human vascular tissues have not been well clarified. To investigate the effect of endotoxin on human arteries, We studied the effects of endotoxin on norepinephrine(NE)-induced contraction and on the synthesis of cyclic guanosine monophosphate (cGMP) in the human gastroepiploic artery. Endotoxin attenuated the contraction induced by NE in a time-dependent manner in the human gastroepiploic artery with or without endothelium. The maximal attenuation was obtained after a 12 hr application of endotoxin : the inhibition was abolished by 300mM NG-nitro-L-arginine methyl ester (L-NAME) or by 10mM methylene blue (MB), both inhibitors of the nitric oxide(NO)-cGMP pathway. The inhibitory action of endotoxin on the NE-induced contraction was not modified by indomethacin, an inhibitor of cyclooxygenase, but it was prevented by cycloheximide, an inhibitor by protein synthesis. The concentration of cGMP in arteries treated with endotoxin for 12 hr was about 6-fold greater than that in non-treated arteries. L-NAME (300mM) and MB (10mM) both prevented the endotoxin-induced increase in cGMP.These results indicate that, in the human gastroepiploic artery, endotoxin activates the NO-cGMP pathway through an action on inducible nitric oxide synthase(NOS) in the smooth muscle and thus inhibits contraction.
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