• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The research regarding the function of cerebral microvasculature using gene-knockout animals and the role of anesthetic drugs

Research Project

Project/Area Number 13470327
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionWakayama Medical University

Principal Investigator

HATANO Yoshio  Wakayama Medical University, School of Medicine, Professor, 医学部, 教授 (70115913)

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)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
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)
KeywordsATP-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
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

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (43 results)

All 2005 2004 2003 2002 2001 Other

All Journal Article (25 results) Publications (18 results)

  • [Journal Article] The inhibitory effects of lidocaine and mexiletine on vasorelaxation mediated by adenosine triphosphate-sensitive K^+ channels and the role of kinases in the porcine coronary artery.2005

    • Author(s)
      Kimoto Y, Kinoshita H, Nakahata K, Dojo M, Hatano Y
    • Journal Title

      Anesthesiology 102

      Pages: 581-587

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular effects of antiarrhythmic drugs and the roles of K^+ Channels.2004

    • Author(s)
      Kinoshita H, Hatano Y
    • Journal Title

      Current Medicinal Chemistry-Cardiovascular and Hematological Agents 2

      Pages: 99-106

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lidocaine impairs vasodilation mediated by adenosine triphosphate-sensitive K^+ channels but not by inward rectifier K^+ channels in parenchymal microvessels of rat cerebral coutex2004

    • Author(s)
      Kinoshita H, Nakahata K, Dojo M, Kimoto Y, Hatano Y
    • Journal Title

      Anesthesia and Analgesia 99

      Pages: 904-909

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of bupivacaine enantiomers and ropivacaine on vasorelaxation mediated by adenosine triphosphate-sensitive K^+ channels in the rat aorta.2004

    • Author(s)
      Dojo M, Kinoshita H, Nakahata K, Kimoto Y, Hatano Y
    • Journal Title

      Anesthesiology 101

      Pages: 251-254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory effect of high concentration of glucose on relaxations to activation of ATP-sensitive K^+ channels in human omental artery.2004

    • Author(s)
      Kinoshita H, Azuma T, Nakahata K, Iranami H, Kimoto Y, Dojo M, Yugo O, Hatano Y
    • Journal Title

      Arterioscler Thromb Vasc Biol 24

      Pages: 1-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular effects of antiarrhythmic drugs and the roles of K+ channels.2004

    • Author(s)
      Kinoshita H, Hatano Y
    • Journal Title

      Current Medicinal Chemistry-Cardiovascular and Hematological Agents 2

      Pages: 99-106

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lidocaine impairs vasodilation mediated by adenosine triphosphate-sensitive K^+ channels but not by inward rectifier K^+ channels in parenchymal microvessels of rat cerebral cortex.2004

    • Author(s)
      Kinoshita H, Nakahata K, Dojo M, Kimoto Y, Hatano Y
    • Journal Title

      Anesthesia and Analgesia 99

      Pages: 904-909

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory effect of high concentration of glucose on relaxations to activation of ATP-sensitive K^+ channels in human omental artery.2004

    • Author(s)
      Kinoshita H, Azma T, Nakahata K, Iranami H, Kimoto Y, Dojo M, Yuge 0, Hatano Y
    • Journal Title

      Arterioscler Thromb Vasc Biol 24

      Pages: 1-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vascular effects of antiarrhythmic drugs and the roles of K+ channels2004

    • Author(s)
      Kinoshita H, Hatano Y
    • Journal Title

      Current Medicinal Chemistry-Cardiovascular and Hematological Agents 2

      Pages: 99-106

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Lidocaine impairs vasodilation mediated by adenosine triphosphate-sensitive K^+ channels but not by inward rectifier K^+ channels in parenchymal microvessels of rat cerebral cortex2004

    • Author(s)
      Kinoshita H, Nakahata K, Dojo M, Kimoto Y, Hatano Y
    • Journal Title

      Anesthesia and Analgesia 99

      Pages: 904-909

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of bupivacaine enantiomers and ropivacaine on vasorelaxation mediated by adenosine triphosphate-sensitive K^+ channels in the rat aorta2004

    • Author(s)
      Dojo M, Kinoshita H, Nakahata K, Kimoto Y, Hatano Y
    • Journal Title

      Anesthesiology 101

      Pages: 251-254

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibitory effect of high concentration of glucose on relaxations to activation of ATP-sensitive K^+ channels in human omental artery2004

    • Author(s)
      Kinoshita H, Azma T, Nakahata K, Iranami H, Kimoto Y, Dojo M, Yuge O, Hatano Y
    • Journal Title

      Arteriosclerosis, Thromhosis, and Vascular Biology 24

      Pages: 1-6

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The vascular relaxing effects of sevoflurane and isoflurane are more important in hypertensive than in normotensive rats2004

    • Author(s)
      Yu J, Ogawa K, Tokinaga Y, Iwahashi S, Hatano Y
    • Journal Title

      CAN J ANESTH 51:10

      Pages: 979-985

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The inhibitory effects of isoflurane on protein tyrosine phosphorylation-modulated contraction of rat aortic smooth muscle2004

    • Author(s)
      Yu J, Ogawa K, Tokinaga Y, Mizumoto K, Kakutani T, Hatano Y
    • Journal Title

      Anesthesiology 101:6

      Pages: 1325-1331

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mexiletine differentially modulates vasorelaxation mediated by ATP-sensitive K^+ channels in the aortas from normotensive and hypertensive rats.2003

    • Author(s)
      Kimoto Y, Kinoshita H, Nakahata K, Dojo M, Iranami H, Hatano Y
    • Journal Title

      Anesth Analg 96

      Pages: 673-679

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of halothane and isoflurane on acetylcoline-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.2003

    • Author(s)
      Tsukiyama Y, Iranami H, Kinoshita H, Ogawa K, Hatano Y
    • Journal Title

      J Anesth 17

      Pages: 13-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of K^+ channels in vasorelaxation induced by hypoxia and the modulator role of lidocaine in the rat carotid artery.2003

    • Author(s)
      Kinoshita H, Kimoto Y, Nakahata K, Dojo M, Iranami H, Hatano Y
    • Journal Title

      Anesth Analg 97

      Pages: 333-338

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mild hypercapnia induces vasodilation via ATP-sensitive K^+ channels in parenchymal microvessels of the rat cerebral cortex.2003

    • Author(s)
      Nakahata K, Kinoshita H, Hirano Y, Dojo M, Kimoto Y, Iranami H, Hatano Y
    • Journal Title

      Anesthesiology 99

      Pages: 1333-1339

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mexiletine differentially modulates vasorelaxation mediated by ATP-sensitive K+ channels in the aortas from normotensive and hypertensive rats.2003

    • Author(s)
      Kimoto Y, Kinoshita H, Nakahata K, Dojo M, Iranami H, Hatano Y
    • Journal Title

      Anesth Analg 96

      Pages: 673-679

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in perfused rat mesenteric arterial beds.2003

    • Author(s)
      Tsukiyama Y, Iranami H, Kinoshita H, Ogawa K, Hatano Y
    • Journal Title

      J Anesth 17

      Pages: 13-21

    • NAID

      50000769957

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of K^+ Channels in vasorelaxation induced by hypoxia and the modulator role of lidocaine in the rat carotid artery.2003

    • Author(s)
      Kinoshita H, Kimoto Y, Nakahata K, Dojo M, Iranami H, Hatano Y
    • Journal Title

      Anesth Analg 97

      Pages: 333-338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ketamine stereo-selectively affects vasorelaxation mediated by ATP-sensitive K^+ channels in the rat aorta.2002

    • Author(s)
      Dojo M, Kinoshita H, Iranami H, Nakahata K, Kimoto Y, Hatano Y
    • Journal Title

      Anesthesiology 97

      Pages: 882-886

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats.2001

    • Author(s)
      Kinoshita H, Kakutani T, Iranami H, Hatano Y
    • Journal Title

      Jpn J Pharmacol 85

      Pages: 29-33

    • NAID

      10007119312

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mild alkilinization and acidification differentially modify the effects of lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K^+ channels.2001

    • Author(s)
      Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y
    • Journal Title

      Anesthesiology 95

      Pages: 200-206

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cibenzoline has an inhibitory effect on vasorelaxation mediated by adenosine triphosphate-sensitive K^+ channels in the rat carotid artery.2001

    • Author(s)
      Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y
    • Journal Title

      Anesth Analg 93

      Pages: 282-286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kinoshita H, Kakutani T, Iranami H, Hatano Y: "The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats."Jpn J Pharmacol. 85. 29-33 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y: "Mild alkilinization and acidification differentially modify the effects of lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K+ channels."Anesthesiology. 95. 200-206 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y: "Cibenzoline has an inhibitory effect on vasorelaxation mediated by adenosine triphosphate-sensitive K+ channels in the rat carotid artery."Anesth Analg. 93. 282-286 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] Dojo M, Kinoshita H, Iranami H, Nakahata K, Kimoto Y, Hatano Y: "Ketamine stereo-selectively affects vasorelaxation mediated by ATP-sensitive K+ channels in the rat aorta."Anesthesiology. 97. 882-886 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimoto Y., Kinoshita H., Nakahata K., Dojo M., Iranami H., Hatano Y.: "Mexiletine differentially modulates vasorelaxation mediated by ATP-sensitive K+ channels in the aortas from normotensive and hypertensive rats."Anesth Analg. 96. 673-679 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kinoshita H, Kimoto Y, Nakahata K, Dojo M, Iranami H, Hatano Y: "The role of K+ Channels in vasorelaxation induced by hypoxia and the modulator role of lidocaine in the rat carotid artery."Anesth Analg. 97. 333-338 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakahata K, Kinoshita H, Hirano Y, Dojo M, Kimoto Y, Iranami H, Hatano Y: "Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K+ channels in parenchymal microvessels of the rat cerebral cortex."Anesthesiology. 99. 1333-1339 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kinoshita H, Ishikawa T, Hatano Y: "Role of K^+ channels in augmented relaxations to sodium nitroprusside induced by mexiletine in rat aortas"Anesthesiology. 92(3). 813-820 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa K, Yamada S.Mizumoto K, I Iranami H, Hatano Y: "Inhibitory effects of halothane, isoflurarie, sevoflurane, and pentobarbital on the constriction induced by I hypocapnia and bicarbonate in isolated canine cerebral arteries"Jounal Neurosurg Anesthesiology. 12(2). 99-106 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Dojo M, Kinoshita H, Iranami H, Nakahata K, Kimoto Y, Hatano Y: "Ketamine stereo-selectively affects vasorelaxation mediated by ATP-sensitive K^+ channels in the rat aorta"Anesthesiology. 97. 882-886 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kinoshita H, Kakutani T, Iranami H, Hatano Y: "The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats"Jpn J Pharmacol. 85. 29-33 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y: "Mild alkilinization and acidification differentially modify the effects of lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K^+ channels"Anesthesiology. 95. 200-206 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y: "Cibenzoline has an inhibitory effect on vasorelaxation mediated by adenosine triphosphate-sensitive K^+ channels in the rat carotid artery"Anesth Analg. 93. 282-286 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kinoshita H, Ishikawa T, Hatano Y: "Role of K^+ channels in augmented relaxations to sodium nitroprusside induced by mexiletine in rat aortas"Anesthesiology. 92(3). 813-820 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogawa K, Yamada S, Mizumoto K, Iranami H, Hatano Y: "Inhibitory effects of halothane, isoflurane, sevoflurane, and pentobarbital on the constriction induced by hypocapnia and bicarbonate in isolated canine cerebral arteries"Jounal Neurosurg Anesthesiology. 12(2). 99-106 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kinoshita H, Iwahashi S, Kakutani K, Mizumoto K, Iranami H, Hatano Y: "The role of endothelium-derived nitric oxide in relaxation to levcromakarim in the rat aorta"Japanese Journal of Pharmacology. 81. 362-366 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kinoshita H, Ishikawa T, Hatano Y: "Differential effects of lidocaine and mexiletine on relaxations to ATP-sensitive K^+ channel openers in rat aortas"Anesthesiology. 90(4). 1165-1170 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogawa K.Yamamoto M, Mizumoto K, Hatano Y: "Volatile anesthestics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries"Canadian Jounal of Anesthesia. 44(4). 426-432 (1997)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi