Mechanisms of direct actions of perioperative drugs on splachnic resistance vessels

围术期药物对内脏阻力血管的直接作用机制

• 批准号: 09470330
• 负责人: AKATA Takashi
• 金额: $ 5.63万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470330/
• 关键词: Volatile anesthetics; Vascular smooth muscle; Vascular endothelium; Intracellular caclium stores; Resistance vessels; Fura-2; Ketamine; Mesenteric arteries; Fura2; 吸入麻酔薬; 細胞内カルシュウム濃度; Fura-2; 細胞内カルシウム濃度

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

异氟烷和七氟烷是目前在日本常用的挥发性麻醉剂，在临床相关浓度下显著影响离体肠系膜阻力动脉对去甲肾上腺素（NE）（一种交感神经递质）的收缩反应。这些麻醉药对去甲肾上腺素引起的收缩反应的作用包括内皮依赖性缩血管和非内皮依赖性扩血管两部分。在内皮存在的情况下，前者占主导地位，后者增强NE反应，而在内皮缺失的情况下，只有后者出现，抑制NE反应。一氧化氮、内皮源性超极化因子、环氧合酶产物、脂氧合酶产物、内皮素-1、血管紧张素II或5-羟色胺不参与其血管收缩作用。异氟醚可刺激内皮细胞释放超氧阴离子，从而增强NE反应。 ...更多信息 h降低细胞内Ca^2+浓度（[Ca^2+]i），抑制肌丝Ca^2+敏感性。[Ca^2+] i降低作用主要是通过抑制电压门控性Ca^2+内流引起的，而其对肌丝Ca^2+敏感性的抑制作用似乎需要完整的细胞膜。氟烷、异呋喃、安氟醚和七氟醚等4种挥发性麻醉药对肠系膜阻力动脉平滑肌细胞内钙库的各种功能，如钙库量、钙摄取或钙释放机制等，具有不同的影响。这些麻醉剂可能通过影响细胞内钙储备而显著影响肠系膜阻力动脉的血管张力或反应性。本文还报道了静脉麻醉剂氯胺酮对离体肠系膜阻力动脉的作用机制。目前正在研究各种卤代挥发性麻醉剂对离体肝动脉和肾动脉的影响。少

项目成果

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)

Takashi Akada：“挥发性吸入麻醉剂对内脏阻力血管的直接影响和机制研究”临床研究基金会年度报告2-10（1999）。

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)

Izumi K、Akata T、Takahashi S：“七氟烷诱导血管平滑肌细胞质游离钙浓度降低的机制。”麻醉学。

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)

Kaoru Izumi、Takashi Akada、Seisuke Takahashi：“离体肠系膜动脉内皮依赖性 NE 收缩反应增强的机制”J Anesth 13（增刊）：。

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)

Izumi K、Akata T、Takahashi S：“七氟醚对孤立肠系膜阻力动脉血管平滑肌的作用，第一部分：内皮的作用。”麻醉学。

赤田 隆、泉 薫、高橋 成輔: "血管平滑筋細胞胞内Ca^<2+>貯蔵部位に対する4つの揮発性吸入麻酔の効" Journal of Anesthesia. 12. 3-P07-6- (1998)

Takashi Akada、Kaoru Izumi 和 Seisuke Takahashi：“四种挥发性吸入麻醉剂对血管平滑肌细胞内 Ca^2+ 储存位点的影响”麻醉杂志 12. 3-P07-6- (1998)。