| Project/Area Number |
17591650
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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 |
KAKUTANI Tetsuya Wakayama Medical University, School of Medicine, Assistant Professor (00264896)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Koji Wakayama Medical University, School of Medicine, Associate Professor (30204077)
HATANO Yoshio Wakayama Medical University, School of Medicine, Professor (70115913)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,940,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Angiotensin II / Vascular smooth muscle / Volatile anesthetics / Diabetes Mellitus / Intracellular Ca^<2+> concentration / Protein kinases / 血管収縮性 / カルシウム |
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| Research Abstract |
This study was to investigate both the mechanism of enhanced vascular contractility in diabetes mellitus and the effects of volatile anesthetics including sevoflurane and isoflurane on the expression of various protein kinase or the intracellular signal pathway.
1) The contraction of isolated rat aorta without endothelium induced by angiotensin II was enhanced in diabetic group compared with non-diabetic group. Sevoflurane inhibited the mnsrle tension in concentration-dependent manner, but isoflurane did not.
2) Sevoflurane attenuated angiotensin II-induced phosphorylation of protein kinase C, which was examined by Western blotting, but not intracellular calcium concentration. This result suggests that sevoflurane would inhibit calcium sensitization of vascular contraction pathway.
3) Angiotensin H and phenylephrine transiently stimulated the phosphorylation of MLC, CPI-17, MYPT1/Thr853, and /Thr696.
4) Volatile anesthetics, both sevoflurane and isoflurane, inhibited the phosphorylation of MLC stimulated by angiotensin II and phenylephrine in concentration-dependent manner.
5) Sevoflurane attenuated vascular smooth muscle tension induced by vasopressin, which was associated with Rho kinase phosphorylation.
6) Reactive oxygen radicals affected the NO-soluble guanylate cyclase (sGC) -cGMP pathway by the desensitization of sGC activity, which was exaggerated by sevoflurane exposure, particularly in hyperoxic condition.
These results suggested that that the ability of volatile anesthetics including sevoflurane and isoflurane to alter the vascular smooth muscle tension through different combination of mechanisms, including the vasclular contraction pathway such as protein kinase phospholyration and calcium sensitization, or the relaxation pathway such as NO-soluble guanylate cyclase (sGC) -cGMP pathway, which was also affected by diabetic condition.
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