| Project/Area Number |
13470327
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
HATANO Yoshio Wakayama Medical University, School of Medicine, Professor, 医学部, 教授 (70115913)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Koji Wakayama Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (30204077)
MIZUMOTO Kazuhiro Wakayama Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (50239258)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥11,300,000 (Direct Cost: ¥11,300,000)
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| Keywords | ATP-sensitive K^+ channels / Lidocaine / Inward rectifier K^+ channels / Hypertension / Neuronal nitric oxide synthase / Isoflurane / Cerebral intraparenchymal arterioles / 神経型一酸化窒素合成酵素 / 揮発性麻酔薬 / ノックアウトマウス / 脳微小血管 / 高炭酸ガス / 局所麻酔薬 / グリベンクラミド |
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| Research Abstract |
Intraparenchymal arterioles (ID:5-10 μm) in the rat or mouse brain slices were located within the neuronal tissue, and their internal diameters were continuously monitored with the live computerized videomicroscopy. Changes of intraluminal diameter in cerebral microvessels were recorded on computer image files and then analyzed using the image software.
During contraction to prostaglandin F_<2_α>, hypercapnia (PCO_2=50 mmHg) induced vasodilation, which is abolished by an ATP-sensitive K^+ channel antagonist glibenclamide. Levcromakalim and KCl produced the vasodilation of the cerebral parenchymal arterioles, which is abolished by glibenclamide or an inward rectifier K^+ channel antagonist BaCl_2, respectively. Lidocaine inhibited the dilation produced by levcromakalim, but not by KCl. Therefore, in cerebral parenchymal arterioles, ATP-sensitive K^+ channels play a major role in vasodilator responses produced by mild hypercapnia. In addition, lidocaine appears to reduce vasodilation medi
… More
ated by ATP-sensitive K^+ channels, but not by inward rectifier K^+ channels.
Addition of KCl induced vasodilation of normotensive (5 to 10 mM) and hypertensive (5 to 15 mM) rat cerebral arterioles, whereas BaCl_2 completely abolished the vasodilation in both strains. In arterioles of hypertensive rats, vasodilator responses to KCl were augmented compared with those in normotensive rat arterioles. Thus, in cerebral parenchymal arterioles, the vasodilator response via inward rectifier K^+ channels appears to be augmented in chronic hypertension.
Isoflurane simultaneously dilated intraparenchymal arterioles in brain slices from normal as well as neuronal nitric oxide synthase knockout mice, indicating that activity of neuronal nitric oxide synthase may not mediate the cerebral vasodilator effect of this anesthetic.
Above results indicate that K^+ channels contribute to vascular function of cerebral parenchymal arterioles and that neuronal nitric oxide synthase may not play a role in vasodilator effect induced by some anesthetics. Less
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