| Project/Area Number |
12671458
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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 | Fukui Medical University |
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Principal Investigator |
TAKAKURA Ko Fukui Medical University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (40206735)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUDA Satoru Fukui Medical University, Faculty of Medicine, Professor, 医学部, 教授 (30116751)
木下 義和 福井医科大学, 医学部・附属病院, 助手 (20283179)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | peroxynitrite / catecholamine / vasoconstraction / septic shock / nitric oxide / super oxide / absorbance / functional examination / peroxynitrite / dopamine / epinephrine / 敗血症 / ノルアドレナリン / 血圧 |
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| Research Abstract |
Background : Vascular hyporeactivity to chatecholamines limits successful therapy to hypotension in septic shock. Large amounts of nitric oxide (NO) and superoxide anion (O2^<-1>・)are produced in response to bacterial endotoxins and / or inflammatory cytokines. NO reacts with O2^<-1>・ to form the potentially toxic NO metabolite, peroxynitrite (ONOO^<-1>). The purpose of this study was to investigate whether ONOO^<-1> decreases the vasocontractile activity of norepinephrine, dopamine and epinephrine.
Methods : Norepinephrine, dopamine or epinephrine was treated with ONOO^<-1> or 3-morpholinosydonimine-N-ethyl-carbamine (SIN-1, an ONOO^<-1> producer) in a 5 x 10^<-2> M sodium phosphate buffer solution at pH 7.4, and absorbance of the product was measured spectrophotometrically at 295 and 370 nm. Catecholamines pre-treated with ONOO^<-1> were administered to isolated rat thoracic aortas to observe contractions in functional experiments. The rate constant between *orepinephrine and ONOO^<-1
… More
> was determined via a competition assay with cysteine in functional experiments.
Norepinephrine pre-treated with ONOO^<-1> was injected intravenously into anesthetized rats to measure blood pressure.
Result : Norepinephrine pre-treated with ONOO^<-1> was confirmed spectrally as oxidized norepinephrine.
Catecholamines pre-treated with ONOO^<-1>1 decreased its vasocontractile force in an ONOO^<-1> -concentration-dependent manner. The decrease in its force was lower at pre-treatment with ONOO^<-1> in a lower pH buffer. A rate constant for the ONOO^<-1> / norepinephrine reaction was 6 x 10^2 M^<-1>・s^<-1>. Norepinephrine or dopamineincubated with SIN-1 decreased their vasocontractile forces incubation-time-dependently. Administration of norepinephrine pre-treated with ONOO^<-1> into anesthetized rats caused no significant change in arterial blood pressure.
Conclusion : These results indicate that catecholamines were oxidized and deactivated by ONOO^<-1>. This deactivation may, at least in part, account for the hyporeactivities of vasocontraction to catecholamines in septic shock. Less
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