Mechanisms of inhibition by volatile anesthetics on beta-adrenoceptor-mediated relaxation in the vascular smooth muscle

挥发性麻醉药对β-肾上腺素受体介导的血管平滑肌松弛的抑制机制

• 批准号: 08671760
• 负责人: TSUCHIDA Hideaki
• 金额: $ 1.28万
• 依托单位: Sapporo Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671760/
• 关键词: Volatile anesthetics; Vascular smooth muscle; Beta adrenergic receptor; nitroglycerin; Cytosolic concentration of Calcium ion; βアドレナリン受容体作動薬; カルシウムイオン

This study was designed to determine whether the volatile anesthetics halothane and isoflurane inhibit beta-adrenoceptor-mediated responses, and which signal transduction steps are important for the inhibition if they do. We found that the volatile anesthetics used at clinically relevant concentrations can interfere with responses mediated by the beta-adrenoceptor agonist, isoproterenol. Halothane and isoflurane impaired isoproterenol-induced vasodilation and a decline of cytosolic concentrations of Ca^<2+> ([Ca^<2+>]i), whereas they only slightly affected vasodilation induced by the adenylyl cyclase activator, forskolin, and the membrane-permeable cyclic AMP, dbcAMP.This finding is consistent with the additional result that both anesthetics inhibited isoproterenol-induced, but not forskolin-induced, increases in cyclic AMP contents. Furthermore, both agents did not interfere with the ligand-binding property to the beta-adrenoceptor. These results indicate that halothane and isoflurane predominantly interfere with beta-adrenoceptor-mediated responses at the step between the beta-adrenoceptor and adenylyl cyclase ; the logical site would therefore include Gproteins.In addition to the vasorelaxation mediated by the beta-adrenoceptor-cyclic AMP system, we also investigated the effect of halothane on the vasorelaxation mediated by the nitric oxide (NO)-cyclic GMP system. We used nitroglycerin as a NO donor. We found that halothane interfered with nitroglycerin-induced vasorelaxation in a concentration-dependent fashion. Furthermore, halothane's inhibition was govemed by both [Ca^<2+>]i-dependent and [Ca^<2+>]i-independent mechanisms.

本研究旨在确定挥发性麻醉剂氟烷和异氟烷是否抑制β-肾上腺素受体介导的反应，以及如果它们抑制，哪些信号转导步骤对抑制很重要。我们发现，临床相关浓度的挥发性麻醉剂可以干扰β-肾上腺素受体激动剂异丙肾上腺素介导的反应。氟烷和异氟醚损害异丙肾上腺素诱导的血管舒张和胞浆Ca^<2+>浓度的下降（[Ca^<2+>]i），而它们仅轻微影响腺苷酸环化酶激活剂forskolin和膜渗透性环AMP dbcAMP诱导的血管舒张。这一发现与另外的结果一致，即两种麻醉剂均抑制异丙肾上腺素诱导的，但不抑制forskolin诱导的，cAMP含量增加。此外，这两种药物都不干扰β-肾上腺素受体的配体结合特性。这些结果表明，氟烷和异氟烷主要干扰β-肾上腺素受体介导的反应之间的步骤，β-肾上腺素受体和腺苷酸环化酶，逻辑网站，因此将包括Gproteins.除了由β-肾上腺素受体-环AMP系统介导的血管舒张，我们还研究了氟烷对一氧化氮（NO）-环GMP系统介导的血管舒张的影响。我们使用硝酸甘油作为NO供体。我们发现氟烷以浓度依赖性方式干扰硝酸甘油诱导的血管舒张。氟烷的抑制作用是通过[Ca^<2+>] i依赖性和[Ca^<2+>] i非依赖性两种机制共同作用的。

项目成果

Tanaka S, Tsuchida H.: "Effects of halothane and isoflurane on beta-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta" Anesthesiology. 89. 1209-17 (1998)

Tanaka S、Tsuchida H.：“氟烷和异氟烷对大鼠主动脉血管平滑肌 β-肾上腺素受体介导的反应的影响”麻醉学。

Namba H,Tsuchida H: "Effect of volatile anesthetics with and without verapamil on intracellular activity in vascular smooth muscle." Anesthesiology. 84. 1365-74 (1996)

Namba H，Tsuchida H：“含或不含维拉帕米的挥发性麻醉剂对血管平滑肌细胞内活动的影响。”

Tsuchida H, Tanaka S, et al.: "Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca^<2+> in the rat thoracic aorta" Anesth Analg. (in press).

Tsuchida H，Tanaka S，等人：“氟烷减弱硝酸甘油诱导的血管舒张和大鼠胸主动脉细胞内Ca 2+ 的减少”Anesth Analg。

Tsuchida H,Tanaka S,et al.: "Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca^<2+> in the rat thoracic aorta." Anesthesia & Analgesia. in press.

Tsuchida H、Tanaka S 等人：“氟烷可减弱硝酸甘油诱导的血管舒张和大鼠胸主动脉细胞内 Ca^2 的减少。”

Tanaka S,Tsuchida H: "Effects of halothane and isoflurane on β-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta" Anesthesiology. 89. 1209-17 (1998)

Tanaka S、Tsuchida H：“氟烷和异氟烷对大鼠主动脉血管平滑肌 β-肾上腺素受体介导的反应的影响”麻醉学 89. 1209-17 (1998)。