Effects of halothane, an inhalational anesthetics, on endothelium-dependent hyperpolarization in canine coronary arteries

吸入麻醉剂氟烷对犬冠状动脉内皮依赖性超极化的影响

• 批准号: 06671534
• 负责人: NAKASHIMA Mikio
• 金额: $ 1.34万
• 依托单位: SAGA MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06671534/
• 关键词: EDHF; halothane; gap-junction; inhalation anesthetics; endothelium; coronary artery; NO; bradykinin; EDHF(内皮由来過分極因子); 血管平滑筋; P-450; K-チャンネル; アラキドン酸; 冠(状)動脈; 一酸化窒素(NO); 内皮依存性過分極反応; ハロセン; NO

The present study was designed to determine whether or not halothane, an inhalation al anesthetic, which could inhibit electrical coupling between endothelium and smooth muscle through gap junction, could inhibit endothelium-dependent hyperpolarization of vascular smooth muscle in caninecoronary arteries. The membrane potential of smooth muscle cells was measured by glass capillary microelectrodes. In the presence of in domethacin and N^G-nitro-L-arginine (NLA), the resting membrane potential wasabout-50 mV,and was not affected by treatment with perindoprilat, an angiotensin converting enzyme in hibitor. In the presence of both in domethacin and NLA,bradykinin evoked transient and concentration-dependent hyperpolarizations only in tissues with endothelium, which were augmented by perindoprilat. Halothane did not inhibit membrane hyperpolarization to bradykinin. In higher concentration (10^<-4> M), halothane and heptanol (another inhalational an esthetic) caused depolarization of the membrane, but did not inhibit hyperpolarization to bradykinin. The present findings indicate that endothelium-dependent hyperpolarization in smooth muscle cells does not result from an electrical communication between the endothelium and the underlying smooth muscles, and suggest the existence of endothelium-derived hyperpolarizing factor EDHF.

氟烷是一种通过间隙连接抑制内皮与平滑肌电偶联的吸入性麻醉剂，本研究旨在探讨氟烷是否能抑制犬冠状动脉血管平滑肌内皮依赖性超极化。用玻璃毛细管微电极测定平滑肌细胞的膜电位。在吲哚美辛和N^ g -硝基- l -精氨酸（NLA）存在的情况下，静息膜电位约为-50 mV，并且不受血管紧张素转换酶抑制剂perindoprilat的影响。在吲哚美辛和NLA同时存在的情况下，缓激肽仅在有内皮的组织中引起短暂的和浓度依赖性的超极化，perindoprilat增强了这种超极化。氟烷对缓激肽的超极化无抑制作用。在较高浓度（10^<-4> M）下，氟烷和庚醇（另一种吸入性和审美性）引起膜去极化，但不抑制缓激肽的超极化。目前的研究结果表明，平滑肌细胞中的内皮依赖性超极化不是由内皮和下层平滑肌之间的电通信引起的，并表明存在内皮衍生的超极化因子EDHF。

项目成果

中島幹夫 他: "一酸化窒素と血管内皮依存性過分極因子" 臨床麻酔.19. 69-73 (1995)

Mikio Nakajima 等人：“一氧化氮和血管内皮依赖性超极化因子”临床麻醉.19-73 (1995)。

Desta,B.,et al.: "Previous exposure to bradykinin unmasks an endothelium-dependent relaxation to the converting enzyme inhibitor trandolaprilat in isolated canine coronary arteries." Journal of Pharmacology and Experimental Therapeutics.272. 885-891 (1995

Desta,B.,et al.：“先前接触缓激肽揭示了离体犬冠状动脉中转换酶抑制剂群多普利拉的内皮依赖性松弛。”

中島幹夫 他: "Endothelinによる血管平滑筋の内皮依存性過分極反応" Pharmacoanesthesiology. 7. 75-76 (1994)

Mikio Nakajima 等人：“内皮素诱导的血管平滑肌的内皮依赖性超极化反应”，Pharmacoanesthesiology 7. 75-76 (1994)。

Mombouli, JV.: "Endothelium-dependent relaxation and hyperpolarization evoked by bradykinin in canine coronary arteries." enhancement by exercise-training British Journal of Pharmacology. 117. 413-418 (1996)

Mombouli, JV.：“犬冠状动脉中缓激肽引起的内皮依赖性松弛和超极化。”

Nakashima M et al: "Isoproterenol causes hyperpolarization through opening of ATP-sensitive potassium channels in vascular smooth muscle of the canine saphenous vein." Journal of Pharmacology and Experimental Therapeutics. 272. 379-384 (1995)

Nakashima M 等人：“异丙肾上腺素通过打开犬隐静脉血管平滑肌中 ATP 敏感的钾通道引起超极化。”