2003 Fiscal Year Final Research Report Summary
The role of Nitric oxide synthase andCytochrome P450 enzyme on the inhibitory effect of sevoflumae on vascular relaxation
| Project/Area Number |
14571463
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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 | Wakayama Medical University |
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Principal Investigator |
MIZUMOTO Kazuhiro Wakayama Medical University, Department of Medicine, assistant professor, 医学部, 講師 (50239258)
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| Co-Investigator(Kenkyū-buntansha) |
HATANO Yoshio Wakayama Medical University, Department of Medicine, Professor, 医学部, 教授 (70115913)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Sevoflurane / Nitric Oxide / Cytochrome P450 |
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| Research Abstract |
<Isometric Force tension Recordings>
After obtaining the various results as control, we checked both the Ach-induced relaxation of the rings pretreated with chlorzoxasone, a specific substrate of CYP450-2E1 and that of the rings from the rats to which CYP450-2E1 was induced by feeding with the water containing ethanol. From these results, the interaction between sevoflurane and CYP450-2E1 is suggested to be included in the mechanism underlying sevoflurane-induced inhibition of endothelium dependent vascular relaxation.
<The measurement of nitric oxide synthase activity by Radioimmunoassay>
The activity of nitric oxide synthase was tested with the method of measuring the conversion of radiolabelled L-arginine to L-citrulline. Sevoflurane did not affect the conversion L-arginine to L-citrulline which suggests that sevoflurane has no effect on nitric oxide synthase activity.
<The confirmation of CYP450-2E1 induction with RT-PCR>
The rings from the rats treatment with ethanol drinking were assured to overexpress CYP450-2E1 mRNA with the method of competitive RT-PCR.
<The nitric oxide assay with chemoluminescence>
After loading DAF FM-DA, nitroc oxide sensitive luminescence into the cultured bovine aortic endothelial cells, we tested the effect of sevoflurane on the intensity induced by bradykinin with or without the treatment of CYP450-2E1 induction. Under the treatment of CYP450-2E1 induction, the sevoflurane-induced inhibition of intensity was abolished.
From these findings, it is suggested that CYP450-2E1 is one of the mediators producing Ach-induced endotherium dependent vascular relaxation, and sevoflurane expresses the inhibitory effect on the relaxation th* interference to the activity of CYP450-2E1 inside endothelial cells.
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