EFFECTS OF GENERAL ANESTHETICS ON INTRACELLULAR CALCIUM CONCENTRATION AND NITRIC OXIDE PRODUCTION OF VASCULAR ENDOTHELIUM

全身麻醉药对血管内皮细胞内钙浓度和一氧化氮生成的影响

• 批准号: 13671607
• 负责人: OGAWA Koji
• 金额: $ 1.6万
• 依托单位: WAKAYAMA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671607/
• 关键词: VASCULAR ENDOTHELIUM; INTRACELLULAR CALCIUM CONCENTRATION; ENDOTHELIUM-DEPENDENT RELAXATION; ANESTHETICS

An elevation of intracellular Ca^<2+> concentration ([Ca^<2+>]_i) is essential for nitric oxide (NO) production in vascular endothelium. The first goal of this study to elucidate the change in endothelial [Ca^<2+>]_i and NO production induced by receptor-dependent and -independent endothelial activators. The second goal was to investigate the effects of anesthetics on the relationship between [Ca^<2+>]_i and NO production.Bovine aortic endothelial cells were loaded with fluorescence Ca^<2+> indicator, fura-2/AM (5μM). Fluorescence measurements were performed at excitation wavelength of 340 and 380 nm and an emission wavelength of 510nm. The 340/380 fluorescence ratio (R340/380) was used as an indicator of [Ca^<2+>]_i.Bradykinin (10nM) elicited a rapid increase in endothelial [Ca^<2+>]_i followed by a gradual decline to a sustained plateau above the resting level. The initial phase was likely caused by intracellular Ca^<2+> release, and the sustained phase was caused by Ca^<2+> influx. In contrast to bradykinin, receptor-independent agonist, A23187 (100nM) induced a monophasic increase in endothelial [Ca^<2+>]_i. Intravenous anesthetics, ketamine (100μM) and etomidate(100μM) attenuated increases in [Ca^<2+>]_i at the peak and sustained phases in response to bradykinin. Neither ketamine nor etomidate altered A23187-induced [Ca^<2+>]_i transient.Ketamine and etomidate selectively attenuated receptor-mediated endothelium-dependent vasorelaxation by inhibiting of the endothelial [Ca^<2+>]_i transient in response to receptor activation.

细胞内Ca~(2+)浓度升高是血管内皮细胞产生一氧化氮(NO)所必需的。本研究的第一个目标是阐明受体依赖和非依赖的内皮激活剂诱导的内皮细胞内[Ca^&lt；2+&gt；]_i和NO产生的变化。第二个目标是研究麻醉药对[Ca^&lt；2+&gt；]i与NO产生关系的影响。用荧光指示剂Fura-2/AM(5μM)标记牛主动脉内皮细胞。荧光测量的激发波长为340和380 nm，发射波长为510 nm。用340/380荧光比值(R340/380)作为[Ca^&lt；2+&gt；]_i的指示剂。缓激肽(10 Nm)可引起内皮细胞[Ca^&lt；2+&gt；]_i迅速升高，随后逐渐下降至高于静息水平的持续平台。起始期可能是细胞内Ca~(2+)释放所致，而持续期可能是由Ca~(2+)内流引起的。与受体非依赖性激动剂缓激肽不同，A23187(100 Nm)引起内皮细胞[Ca~(2+)]_i单相升高，静脉麻醉药氯胺酮(100μM)和依托咪酯(100μM)可减弱缓激肽引起的峰值和持续期[Ca~(2+)]_i升高。氯胺酮和依托咪酯均不改变A23187诱导的[Ca^&lt；2+&gt；]_i瞬变。氯胺酮和依托咪酯通过抑制受体激活的内皮[Ca^&lt；2+&gt；]_i瞬变而选择性地减弱受体介导的内皮依赖性血管松弛。

项目成果

小川幸志, 畑埜義雄: "麻酔薬の血管作用"臨床麻酔. 26. 377-388 (2002)

Koushi Okawa，Yoshio Hatano：“麻醉剂的血管作用”临床麻醉 26. 377-388 (2002)。

Maeda H, Iranami H, Yamamoto M, Ogawa K, Morikawa K, et al.: "Halothane but not isoflurane attenuates 1L-1β induced nitric oxide synthase in vascular smooth muscle"Anesthesiology. 95. 492-499 (2001)

Maeda H、Iranami H、Yamamoto M、Okawa K、Morikawa K 等人：“氟烷而非异氟烷会减弱血管平滑肌中 1L-1β 诱导的一氧化氮合酶”麻醉学。

Kinoshita H, Iranami H, Kimoto Y, Dojo M, Hatano Y: "Mild alkalization and acidification differentially modify the effects of lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K^+ channels"Anesthesiology. 95. 200-206 (2001)

Kinoshita H、Iranami H、Kimoto Y、Dojo M、Hatano Y：“轻度碱化和酸化不同地改变了利多卡因或美西律对 ATP 敏感 K^ 通道介导的血管舒张的影响”麻醉学。

Ogawa K, Tanaka S, Murray PA: "Propofol potentiates phenylephrine-induced contraction via cyclooxygenase inhibition in pulmonary artery smooth muscle"Anesthesiology. 94. 833-839 (2001)

Okawa K、Tanaka S、Murray PA：“异丙酚通过抑制肺动脉平滑肌中的环氧合酶来增强去氧肾上腺素诱导的收缩”麻醉学。

Ogawa K, Hatano Y: "Vascular effects of anesthetics"J Clinical Anesthesia (Japan). 26. 377-388 (2002)

小川 K、波多野 Y：“麻醉剂的血管效应”J 临床麻醉（日本）。