The effects of anesthetics on transmembrane potential, transmembrane currents and EDHF in resistance and capacitance blood vessels (microcirculation)

麻醉药对电阻和电容血管（微循环）中跨膜电位、跨膜电流和 EDHF 的影响

• 批准号: 11470319
• 负责人: YAMAZAKI Mitsuaki
• 金额: $ 7.36万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470319/
• 关键词: vascular smooth muscle; transmembrane potential; isoflurane; sevoflurane; propofol; potassium channel; EDHF; hypertension; cAMP; SQ22536; Rp-cAMPS; L-NAME; NO-cGMP系; K^+チャネル; EDHA; アセチルコリン; WKYラット; SHRラット

We indirectly assessed the in vivo effect of anesthetics on vascular smooth muscle (VSM) tone in SD rats by measurement of in situ responses of VSM transmembrane potential in small mesenteric arteries and veins. Measurements were made before, during, and after anesthetic or inhibitor infusions into vessels.1. Inhaled anesthetics attenuate both sympathetic neural and nonneural regulation of VSM transmembrane potentials and tone.2. In the neurogenic SH rat model of human hypertension, a primary mechanism underlying elevated isoflurane-induced VSM heperpolarization in both resistance- and capacitance-regulating blood vessels is a central neural inhibition of excitatory sympathetic input. Peripheral neural and nonneurally mediated hyperpolarization by isoflurane is similar in SH and WKY rat VSM.3. Measurements were taken in the presence and absence of selective inhibitors of eaeh of four types of potassium channels. Propofol-mediated hyperpolarization of VSM can be attributed in part to an opening of K_Ca and K_ATP but not K_V and K_IR.4. Ach hyperpolarized arterial, but not venous VSM. Ach-induced (EDHF) hyperpolarization was eliminated by propofol. These results suggest that propofol attenuates both sympathetic neural and nonneural regulation of VSM tone. They also suggest that propofol and Ach may act competitively in the second messenger cascade regulating VSMK^+ channel activity in mesenteric resistance arteries.5. Propofol-mediated hyperpolarization of VSM can be attributed in part to NO-cGMP pathway but not PGI_2-cAMP pathway.

我们通过测定肠系膜小动脉和静脉血管平滑肌跨膜电位的原位反应，间接评价了麻醉药对SD大鼠在体血管平滑肌张力的影响。在向血管内注入麻醉剂或抑制剂之前、期间和之后进行测量。吸入麻醉药可减弱交感神经和非神经对VSM跨膜电位和张力的调节。在神经源性高血压大鼠模型中，异氟醚引起的阻力和电容调节血管VSM超极化的一个主要机制是中枢神经抑制兴奋性交感神经传入。异氟醚对SH和WKY大鼠的外周神经和非神经介导的超极化作用相似。在存在和不存在四种类型钾通道的EAEH选择性抑制剂的情况下进行测量。异丙酚介导的VSM超极化可部分归因于K_Ca和K_ATP的开放，而不是K_V和K_IR的开放。ACh超极化的动脉，而不是静脉VSM。异丙酚可消除ACh诱发的(EDHF)超极化。这些结果表明，异丙酚同时减弱交感神经和非神经调节的VSM音调。他们还提示，异丙酚和乙酰胆碱可能在调节肠系膜阻力动脉VSMK^+通道活性的第二信使级联中起竞争作用。异丙酚介导的VSM超极化可能部分归因于NO-cGMP途径，而不是PGI2-cAMP途径。

项目成果

Mitsuaki Yamazaki et al.: "Effects of propofol on neural and endothelial control of in situ rat mesenteric vascular smooth muscle trans membrane potentials"Anesthesia & Analgesia. (in press).

Mitsuaki Yamazaki 等人：“异丙酚对原位大鼠肠系膜血管平滑肌跨膜电位的神经和内皮控制的影响”麻醉

Stekiel TA et al.: "Effect of isoflurane on in situ vascular smooth muscle transmembrane potential in spontaneous hypertension."Anesthesiology. 91. 207-214 (1999)

Stekiel TA 等人：“异氟醚对自发性高血压中原位血管平滑肌跨膜电位的影响。”麻醉学。

Yamazaki M et al.: "The effects of propofol on neural and endothelical control of in situ rat mesenteric vascular smooth muscle transmembrane potentials"Anesthesia & Analgesia. 94. 892-897 (2002)

Yamazaki M 等人：“异丙酚对原位大鼠肠系膜血管平滑肌跨膜电位的神经和内皮控制的影响”麻醉

Yamazaki M et. al: "The effects of propofol on neural and endothelial control of in situ rat mesenteric vascular smooth muscle transmembrane potentials."Anesthesia & Analgesia. 94. 892-897 (2002)

山崎 M 等。

Stekiel TA et al.: "Effect isoflurane on in situ vascular smooth muscle transmembrane potential in spontaneous hypertension"Anesthesiology. 91. 207-214 (1999)

Stekiel TA 等人：“异氟烷对自发性高血压中原位血管平滑肌跨膜电位的影响”麻醉学。