| Project/Area Number |
16591557
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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 |
OGAWA Koji Wakayama Medical University, Department of Anesthesiology, Associate Professor, 医学部, 助教授 (30204077)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUMOTO Kazuhiro Wakayama Medical University, Department of Anesthesiology, Associate Professor, 医学部, 助教授 (50239258)
HATANO Yoshio Wakayama Medical University, Department of Anesthesiology, Professor and Chairman, 医学部, 教授 (70115913)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Angiotensin II / Vascular smooth muscle / Sevoflurane / Isoflurane / Intracellular Ca^<2+> concentration / Protein kinases / プロポフォール / PKC |
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| Research Abstract |
This study was to investigate the effects of volatile anesthetics including sevoflurane and isoflurane on the expression of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), Rho-kinase and tyrosine kinase (TK) induced by angiotensin using Western blotting in isolated rat aorta.
1) Angiotensin II (Ang II) elicited a transient increase in muscle tension and intracellular calcium concentration [Ca^<2+>]1 in isolated rat aorta without endothelium. Western blotting revealed an increase in phosphorylated PKCα in response to Ang II.
2) Sevoflurane inhibited the muscle tension but not [Ca^<2+>]1 in response to Ang II in a concentration-dependent manner. Sevoflurane also attenuated Ang II-induced phosphorylation of PKCα. By contrast, Isoflurane, at clinically relevant concentrations, inhibited both muscle tension and [Ca^<2+>]1, but failed to affect the PKC phosphorylation in response to Ang II,
3) Ang II also stimulated the p44/42 MAPK phosphorylation in rat aorta, which was inhibi
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ted by sevoflurane in a concentration-dependent fashion.
4) GTPγS, a GTP analogue, stimulated Rho/Rho-kinase signaling pathway and induced vasoconstriction which was associated with membrane translocation of RhoA and Rock2. Sevoflurane attenuated both vascular contraction and activation of RhoA and Rock2 induced by GTPγS.
5) Sodium orthovanadate (Na_3VO_4), an inhibitor of protein tyrosine phosphatase, induced a sustained contraction of rat aorta and significant increase in protein tyrosine phosphorylation of a set of substrates including PLC-γ1 and P42 MAPK. Isoflurane suppressed Na_3VO_4-induced vascular contraction and the total density of the Na_3VO_4-induced, tyrosine-phosphorylated substrate bands including PLC-γ1 band and P42 MAPK band in a concentration-dependent manner.
6) Although sevoflurane also attenuated both vascular contraction and protein tyrosine phosphorylation in response to Na3V0.1, the extent induced by sevoflurane was less than that by sevoflurane at equi-potent concentrations.
These results suggested that the ability of volatile anesthetics including sevoflurane and isoflurane to alter the vascular smooth muscle tension appears to be modulated through different combinations of mechanisms, including Ca^<2+>-mediated pathways and Ca^<2+> sensitization, with exact combination depends on the anesthetic agent tested. Less
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