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2000 Fiscal Year Final Research Report Summary

Mechanisms of direct actions of perioperative drugs on splachnic resistance vessels

Research Project

Project/Area Number 09470330
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

AKATA Takashi  KYUSHU UNIVERSITY, Faculty of Medicine, Lecturer, 医学部・附属病院, 講師 (10260382)

Co-Investigator(Kenkyū-buntansha) KANNA Tomoo  KYUSHU UNIVERSITY, Faculty of Medicine, Assistant, 大学院・医学研究院, 助手 (00274465)
NAKASHIMA Mikio  KYUSHU UNIVERSITY, Saga Medical School, Associate Prof., 助教授 (80159061)
Project Period (FY) 1997 – 2000
KeywordsVolatile anesthetics / Vascular smooth muscle / Vascular endothelium / Intracellular caclium stores / Resistance vessels / Fura-2 / Ketamine / Mesenteric arteries
Research Abstract

Isoflurane and sevoflurane, volatile anesthetics now commonly used in Japan, at clinically relevant concentrations significantly influence contractile response to norepinephrine (NE), a sympathetic neurotransmitter, in isolated mesenteric resistance arteries. The action of these anesthetics on contractile response to NE consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the NE response, while in the absence of endothelium, only the latter emerges, inhibiting the NE response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin II, or serotonin are not involved in their vasoconstricting action. Isoflurane may stimulate release of superoxide anions from endothelial cells, thereby enhancing the NE response.
Sevoflurane appears to inhibit vascular smooth muscle contraction by bot … More h reducing the intracellular Ca^<2+> concentration ([Ca^<2+>]i) and inhibiting myofilament Ca^<2+> sensitivity. The [Ca^<2+>]i-reducing effect is mainly caused by inhibition of voltage-gated Ca^<2+> influx, while its inhibitory action on myofilament Ca^<2+> sensitivity seems to require an intact cell membrane. Four volatile anesthetics halothane, isolfurane, enflurane and sevoflurane have differential effects on various functions of intracellular calcium stores of mesenteric resistance arterial smooth muscle cells such as the amount of stored Ca^<2+>, Ca^<2+> uptake, or Ca^<2+>-releasing mechanisms. These anesthetics may significantly influence vascular tone or reactivity of mesenteric resistance arteries through their various effects on the intracellular calcium stores.
Mechanisms of the action of ketamine, an intravenous anesthetic, on isolated mesenteric resistance arteries were also investigated and reported. The effects of various halogenated volatile anesthetics on isolated hepatic and renal arteries are currently under investigation. Less

  • Research Products

    (53 results)

All Other

All Publications (53 results)

  • [Publications] Akata T,Boyle III WA: "Is guanosine-5'-triphophate involved in calcium-activation of contractile proteins in vascular smooth muscle?"Jpn J Pharmacol. 75(1). 1-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries. Part I : role of endothelium."Anesthesiology. 92(5). 1426-1440 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Izumi K,Nakashima M: "The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries. Part II : mechanisms of endothelium-independent vasorelaxation."Anesthesiology. 92(5). 1441-1453 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Nakashima M,Izumi K: "Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle-Investigation in isolated systemic resistance arteries-"Anesthesiology . (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Izumi K,Nakashima M: "Mechanisms of direct inhibitory action of ketamine on vascular smooth muscle in mesenteric resistance arteries."Anesthesiology. (accepted January3,2001).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "Role of endothelium in the action of isoflurane on vascular smooth muscle of isolated mesenteric resistance arteries."Anesthesiology. (accepted February8,2001).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆: "揮発性吸入麻酔薬が内臓抵抗血管に及ぼす直接作用とその機序に関する研究"臨床研究奨励基金年報. 2-10 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,泉薫: "吸入麻酔薬の血管への作用 -特にハロゲン化炭化水素型揮発性吸入麻酔薬が血管平滑筋あるいは血管内皮に及ぼす直接作用に注目して-"循環制御. 21(1). 61-83 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T et al.: "Differential effects of volatile anesthetics on intracellular calcium stores of vascular smooth muscle."Anesthesiology. 87(3A):. A514 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Boyle III WA: "Is activation of G-proteins involved in calcium-activation of contractile proteins in vascular smooth muscle?"Anesthesiology. 87(3A):. A603 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "Mechanisms of sevoflurane-induced reduction of the cytosolic free calcium concentration in vascular smooth muscle."Anesthesiology. 89(3A):. A600 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "Endothelium-dependent vasoconstricting action of sevoflurane in the rat mesenteric resistance artery."Anesthesiology. 89(3A):. A677 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Izumi K.: "Effects of sevoflurane on calcium sensitivity of the contractile apparatus in vascular smooth muscle."Anesthesiology. 91(3A):. A632 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "Persistent vascular hyporesponsiveness to norepinephrine after washout of sevoflurane in isolated rat mesenteric resistance arteries."Anesthesiology. 91(3A):. A649 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "Which endothelium-derived vasoactive mediator is involved in the endothelium-dependent vasoconstricting action of sevoflurane?"Anesthesiology. 91(3A):. A645 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanna T,Akata T et al.: "Sevoflurane stimulates transmembrane calcium influx in pulmonary arterial valvular endothelial cells in situ."Anesthesiology. 91(3A):. A658 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumi K,Akata T,Takahashi S: "The action of isoflurane on vascular smooth muscle of isolated mesenteric arteries"Anesthesiology. 93(3A):. A604 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Nakashima M,Izumi K: "Effects of four inhaled anesthetics on intracellular calcium stores of vascular smooth muscle in small mesenteric arteries."Anesthesiology. 93(3A):. A594 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Izumi K,Nakashima M: "Effects of ketamine on vascular smooth muscle of rat mesenteric arteries."Anesthesiology. 93(3A):. A595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T,Izumi K et al.: "Mechanisms of inhibitory actions of inhalational anesthetics on high K+-induced contraction in splanchnic resistance arteries."Jpn J Pharmacol. 73(suppl.-I):. 202 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 泉薫,赤田隆,高橋成輔: "内臓抵抗血管平滑筋に対する揮発性吸入麻酔薬の効果"J Anesth. 11(suppl.):. 310 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,泉薫,高橋成輔: "摘出内臓抵抗血管平滑筋に対する揮発性吸入麻酔薬のKCl収縮抑制作用のメカニズム"J Anesth. 11(suppl.):. 313 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,泉薫,高橋成輔: "血管平滑筋細胞内Ca2+貯蔵部位に対する4つの揮発性吸入麻酔薬の効果"J Anesth. 12(suppl.):. 577 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 泉薫,赤田隆,高橋成輔: "摘出内臓抵抗血管平滑筋に対するセボフルランの効果"J Anesth. 12(suppl.):. 153 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,漢那朝雄 et al.: "セボフルランによる肺動脈弁内皮細胞内Ca^<2+>濃度上昇作用のメカニズム"循環制御. 20(suppl.):. 49 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,泉薫: "摘出腸間膜小動脈におけるセボフルランの血管平滑筋直接抑制作用のメカニズム"J Anesth. 13(suppl.):. 154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 泉薫,赤田隆,高橋成輔: "摘出腸間膜動脈におけるセボフルランの内皮依存性NE収縮反応増強作用の機序"J Anesth. 13(suppl.):. 347 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 漢那朝雄,泉薫 et al.: "摘出ラット肺動脈弁内皮細胞内カルシウム濃度に及ぼすセボフルランの効果"J Anesth. 13(suppl.):. 347 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,泉薫,中島幹夫: "各種揮発性吸入麻酔薬が血管平滑筋細胞内カルシウム貯蔵部位に及ぼす作用"J Anesth. 14(suppl.):. O-39.1f (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 泉薫,赤田隆,高橋成輔: "摘出内臓抵抗血管におけるノルエピネフリン収縮応答に及ぼすイソフルランの効果"J Anesth. 14(suppl.):. O-079.2 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆,泉薫,中島幹夫: "内臓抵抗血管に対するケタミンの直接作用とその機序(抄録)"J Anesth. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 泉薫,赤田隆,高橋成輔: "内臓抵抗血管においてノルエピネフリン収縮反応に及ぼすハロタンの効果(抄録)"J Anesth. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆: "吸入麻酔薬の血管への作用(教育講演抄録)"循環制御. 20(suppl.):. 23 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 赤田隆: "摘出内臓抵抗血管における揮発性吸入麻酔薬の作用(シンポジウム抄録)"J Anesth. 13(suppl.):. 45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akata T, Boyle Ill WA: "Is guanosine-5'-triphophate involved in calcium-activation of contractile proteins in vascular smooth muscle?"Jpn J Pharmacol. 75. 1-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries Part I : role of endothelium."Anesthesiology. 92. 1426-1440 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K, Nakashima M: "The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries. Part II : mechanisms of endothelium-independent vasorelaxation."Anesthesiology. 92. 1441-1453 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Nakashima M, Izumi K: "Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle-Investigation in isolated systemic resistance arteries-"Anesthesiology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K, Nakashima M: "Mechanisms of direct inhibitory action of ketamine on vascular smooth muscle in mesenteric resistance arteries."Anesthesiology (provisionally accepted January 3). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "Role of endothelium in the action of isoflurane on vascular smooth muscle of isolated mesenteric resistance arteries."Anesthesiology (provisionally accepted February 8). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K: "Volatile anesthetic actions on vascular smooth muscle (review)"Junkan-Seigyo (Circulation Control). 21(1). 61-83 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K, Kanna T, Yamakawa M, Takahashi S: "Differential effects of volatile anesthetics on intracellular calcium stores of vascular smooth muscle."Anesthesiology. 87(3A). A514 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Boyle Ill WA: "Is activation of G-proteins involved in calcium-activation of contractile proteins in vascular smooth muscle?"Anesthesiology. 87(3A). A603 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "Mechanisms of sevoflurane-induced reduction of the cytosolic free calcium concentration in vascular smooth muscle."Anesthesiology. 89(3A). A600 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "Endothelium-dependent vasoconstricting action of sevoflurane in the rat mesenteric resistance artery."Anesthesiology. 89(3A). A677 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K: "Effects of sevoflurane on calcium sensitivity of the contractile apparatus in vascular smooth muscle."Anesthesiology. 91(3A). A632 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "Persistent vascular hyporesponsiveness to norepinephrine after washout of sevoflurane in isolated rat mesenteric resistance arteries."Anesthesiology. 91(3A). A649 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "Which endothelium-derived vasoactive mediator is involved in the endothelium-dependent vasoconstricting action of sevoflurane?"Anesthesiology. 91(3A). A645 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanna T, Akata T, Nakashima M et al.: "Sevoflurane Stimulates transmembrane calcium influx in pulmonary arterial valvular endothelial cells in situ."Anesthesiology. 91(3A). A658 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi K, Akata T, Takahashi S: "The action of isoflurane on vascular smooth muscle of isolated mesenteric arteries."Anesthesiology. 93(3A). A604 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Nakashima M, Izumi K: "Effects of four inhaled anesthetics on intracellular calcium stores of vascular smooth muscle in small mesenteric arteries."Anesthesiology. 93 (3A). A594 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K, Nakashima M: "Effects of ketamine on vascular smooth muscle of rat mesenteric arteries."Anesthesiology. 93 (3A). A595 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akata T, Izumi K, Setoguchi H, Nagata T, Takahashi S: "Mechanisms of inhibitory actions of inhalational anesthetics on high K^+- induced contraction in splanchnic resistance arteries."Jpn J Pharmacol. 73 (suppl.-I). 202 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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