| Project/Area Number |
11671473
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
GANDO Satoshi Hokkido Univ., Grad.School of Med., Prof, 大学院・医学研究科, 教授 (30125306)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Yuichi Hokkaido Univ., Grad.School of Med., As.Prof, 大学院・医学研究科, 助教授 (50156361)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | sepsis / shock / beta-receptor / intracellular signal thansduction pathway / NO / adnylate cyclase / G protein / 陽性変力作用 / NO(一酸化窒素) |
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| Research Abstract |
Because circulatory failure in patients with septic shock is known to be less responsive to catecholamines, we investigated whether the beta-adrenoceptor-linked signaling transduction mechanisms are altered in the heart of a septic animal model. Rabbits were rendered endotoxemic by an intravenous injection of lipopolysaccharide (LPS). The positive intropic effects of isoproterenol was significantly impaired in papillary muscles isolated from septic rabbit compared with those from controls. This impairment of isoproterenol was not prevented by NOS inhibitor (L-NNA). Adenylate cyclase activity stimulated with isoproterenol was markedly reduced in septic myocardium. The contractile and adenylate cyclase reponse to colfosin daropate were unaffectes by sepsis. Radoligand binding experiments revealed no significant alteration in myocardial beta-adrenoceptor density or affinity in sepsis. Determination of cardiac Gs level by Western blotting showed a reduction of approximately 50% in sepsis. The relative content of Gs messenger RNA in septic myocardium also was reduced from the control level. Little change was found in protein and messenger RNA levels of Gi in septic myocardium. The results suggest that the impaired response to beta-adrenoceptor stimulation in the hearts in septic shock may result from a decreased level of Gs protein which occurs at the level of gene expression.
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