| Project/Area Number |
16591558
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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) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Vascular endothelial call / Vascular smooth muscle cell / Capacitative Ca^<2+> entry / Volatile anesthetics |
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| Research Abstract |
The production of endothelium-derived relaxing factors is triggered by an increase in the intracellular Ca^<2+> concentration of vascular endothelial cells. Capacitative Ca^<2+> entry (CCE) plays an important role in increasing the intracellular Ca^<2+> concentration of vascular endothelial cells. Our present goal was to compare the effect of SEV on CCE in vascular endothelial cells with those of halothane (HAL) and desflurane (DES).
Cultured bovine aortic endothelial cells (BAECs) were plated onto a 40 mm coverslip. The coverslip was placed in a temperature-regulated air-tight chamber on an inverted fluorescence microscope. Changes in intracellular Ca^<2+> concentration ([Ca^<2+>]_i) were measured as the 340/380 ratio in individual fura 2-loaded BAECs. Thapsigargin (10^<-6>M) was used to deplete endoplasmic reticulum Ca^<2+> stores after extracellular Ca^<2+>([Ca^<2+>]_o) was removed. CCE was observed when the Ca^<2+> concentration of the solution in the chamber was switched from Ca^<2
… More
+>-free to 2.2mM. CCE was compared in control (CON) cells and cells pretreated with SEV (3.5%), HAL (1.5%) or DES (10.5%). These comparisons were also performed in cells pretreated with the PKC inhibitor, BIS-1 (3×10^<-6> M.
Restoring [Ca^<2+>]_o (to induce CCE) caused a reproducible, rapid peak increase (186 ±17% of baseline) followed by a sustained increase (160 ±12% of baseline) in [Ca^<2+>]_i, which returned to baseline when [Ca^<2+>]_o was removed. SEV attenuated (p<0.05) CCE (peak : 89±2% ; sustained : 89±3% of control), and PKC inhibition had no effect on this response. HAL also attenuated (p<0.05) CCE (peak : 73±7% ; sustained : 73±8% of control). This attenuation by HAL was partially reversed (p<0.05) by PKC inhibition. DES only attenuated (p<0.05) the peak increase in CCE (peak : 89±3% ; sustained : 98±3% of control).
These results indicate that the potency of the inhibitory effect of the volatile anesthetics on CCE in vascular endothelial cells is ranked as HAL>SEV>DES. The PKC pathway is likely involved only in the HAL-induced attenuation of CCE Less
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