Changes in β-adrenergic receptor-mediated vascular response in the septic rat thoracic aorta

脓毒症大鼠胸主动脉β-肾上腺素能受体介导的血管反应的变化

• 批准号: 11671515
• 负责人: TSUCHIDA Hideaki
• 金额: $ 2.24万
• 依托单位: Kanazawa 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671515/
• 关键词: rat; aorta; sepsis; endothelium-dependent vasorelaxation; β-adrenergic receptor; muscarinic receptor; Ca concentration; halothane; 内皮依存性拡張; 細胞内カルシウム濃度; 内皮依存性血管拡張; 細胞内Ca濃度

The mechanism (s) underlying the inhibitory effect of anesthetics or sepsis on endothelium-dependent vasorelaxation is still controversial. This study intended to clarify how anesthetics or sepsis interfered with endothelium-mediated vasorelaxation.The volatile anesthetic halothane inhibited carbachol-induced increase in cytosolic Ca^<2+> concentration and resultant decrease in muscle tension in aconcentration-dependent manner. In addition,halothane concentration dependently inhibited nitroglycerin-induced vasorelaxation partly in a Ca^<2+>-dependent fashion. These findings strongly indicated that halothane interfered with endothelium-mediated vasorelaxation both at the NO synthetic process and at the NO-mediated vasorelaxing process. Dobutamine, a β1 adrenergic agonist, and salbutamol, a β2 adrenergic agonist, induced vasorelaxation in endothelium-intact vascular strip. In contrast, dobutamine's effect was almost abolished in endothelium-denuded strip, suggesting that dobutamine's effect was mediated by endothelium. Not only α-adrenergic receptor-mediated vasoconstriction, but β-adrenergic receptor-mediated vasorelaxation was inhibited in the septic rat aorta. Therefore, sepsis induces multifactorial inhibition on vascular relaxation.

麻醉药或脓毒症对内皮依赖性血管舒张的抑制作用的机制仍有争议。本研究旨在阐明麻醉剂或脓毒症如何干扰内皮介导的血管舒张，挥发性麻醉剂氟烷以浓度依赖性方式抑制卡巴胆碱诱导的细胞内Ca^<2+>浓度升高和由此引起的肌张力降低。另外，氟烷浓度依赖性地抑制硝酸甘油诱导的血管舒张，部分是以Ca^<2+>依赖的方式。这些结果强烈表明，氟烷干扰内皮介导的血管舒张在NO合成过程和NO介导的血管舒张过程。β1肾上腺素能激动剂多巴酚丁胺和β2肾上腺素能激动剂沙丁胺醇可引起内皮完整血管条的血管舒张。而多巴酚丁胺的作用在内皮剥脱后几乎消失，提示多巴酚丁胺的作用是由内皮介导的。在脓毒症大鼠主动脉中，不仅α-肾上腺素能受体介导的血管收缩，而且β-肾上腺素能受体介导的血管舒张也受到抑制。因此，脓毒症诱导多因素抑制血管舒张。

项目成果

Nakayama,M., Tsuchida,H., Kanaya,N., Namiki,A.: "Effects of epidural anesthesia on the cardiovascular response to a rapid increase in isoflurane concentration"J Clin Anesth. 12. 14-18 (2000)

Nakayama,M.、Tsuchida,H.、Kanaya,N.、Namiki,A.：“硬膜外麻醉对异氟醚浓度快速增加的心血管反应的影响”J Clin Anesth。

Seki,S., Ichimiya,T., Tsuchida,H., Namiki,A.: "A case of normalization of Wolff-Parkinson-White syndrome conduction during propofol anesthesia"Anesthesiology. 90. 1779-1782 (1999)

Seki,S.、Ichimiya,T.、Tsuchida,H.、Namiki,A.：“异丙酚麻醉期间沃尔夫-帕金森-怀特综合征传导正常化的一个案例”麻醉学。

Kanaya N, Kimura H, Nakayama M, Tsuchida H, et al.: "The direct effect of halothane on myocardial contraction in rat myocytes with poorly developed gapjunctionalintercellular communication"Acta Anaesthesiol Scand. 43. 91-96 (1999)

Kanaya N、Kimura H、Nakayama M、Tsuchida H 等人：“氟烷对间隙连接细胞间通讯发育不良的大鼠心肌细胞心肌收缩的直接影响”Acta Anaesthesiol Scand。

Tsuchida H, Tanaka S, Seki S, et al.: "Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca^<2+> in the rat thoracic aorta"Anesth Anaig. 88. 49-54 (1999)

Tsuchida H、Tanaka S、Seki 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 Anaig。

Nakayama,M., Kanaya,N., Tsuchida,H., Namiki,A.: "The effect of propofol and thiamylal on hypertensive responses to a rapid increase in isoflurane concentration"J Clin Anesth. 11. 8-10 (1999)

Nakayama,M.、Kanaya,N.、Tsuchida,H.、Namiki,A.：“异氟烷浓度快速增加时异丙酚和硫淀粉醛对高血压反应的影响”J Clin Anesth。