七氟醚抑制血管紧张素 II 诱导的、蛋白激酶 C 介导的，但不抑制 Ca2+ 引起的大鼠主动脉平滑肌收缩。

Sevoflurane inhibits angiotensin II-induced, protein kinase c-mediated but not Ca2+-elicited contraction of rat aortic smooth muscle.

作者信息

Yu Jingui, Tokinaga Yasuyuki, Ogawa Koji, Iwahashi Shizue, Hatano Yoshio

机构信息

Department of Anesthesiology, Wakayama Medical University, Wakayama City, Japan.

出版信息

Anesthesiology. 2004 Apr;100(4):879-84. doi: 10.1097/00000542-200404000-00018.

DOI:10.1097/00000542-200404000-00018

PMID:15087623

Abstract

BACKGROUND

Whether volatile anesthetics attenuate angiotensin II-mediated vascular tone has not been determined. The current study was designed to investigate the effects of sevoflurane on the angiotensin II-stimulated, Ca2+- and protein kinase C (PKC)-mediated contraction of rat aortic smooth muscle.

METHODS

The dose-dependent effects of sevoflurane on angiotensin II (10 m)-induced contraction, the increase in intracellular Ca2+ concentration, and PKC phosphorylation of rat aortic smooth muscle were measured using an isometric force transducer, a fluorometer, and Western blotting, respectively.

RESULTS

Angiotensin II induced a transient increase in intracellular Ca2+ concentration, phosphorylation of Ca2+-dependent PKC (cPKC)-alpha, and consequently, a transient contraction of rat aortic smooth muscle. Phosphorylation of the Ca2+-independent PKC-epsilon was not detected. The angiotensin II-induced contraction was almost completely abolished by removing extracellular Ca2+ and was significantly inhibited by the selective cPKC inhibitor Gö 6976 (10 M) but was not inhibited by the nonselective PKC inhibitor Ro 31-8425 (10 M). Sevoflurane dose-dependently inhibited the angiotensin II-induced contraction, with reductions of 14.2 +/- 5.2% (P > 0.05), 26.7 +/- 8.9% (P < 0.05), and 38.5 +/- 12.8% (P < 0.01) (n = 10) in response to 1.7, 3.4, and 5.1% sevoflurane, respectively. The angiotensin II-elicited increase in intracellular Ca2+ concentration was not significantly influenced by 3.4, 5.1, or 8.5% sevoflurane. However, cPKC-alpha phosphorylation induced by angiotensin II was inhibited dose dependently by 1.7, 3.4, and 5.1% sevoflurane, with depressions of 20.5 +/- 14.2% (P > 0.05), 37.0 +/- 17.8% (P < 0.05), and 62.5 +/- 12.2% (P < 0.01) (n = 4), respectively.

CONCLUSION

The current study indicates that Ca2+ and cPKC-alpha are involved in angiotensin II-induced vascular contraction. Sevoflurane dose-dependently inhibited the angiotensin II-stimulated, cPKC-mediated but not Ca2+-elicited contraction of rat aortic smooth muscle.

摘要

背景

挥发性麻醉剂是否能减弱血管紧张素 II 介导的血管张力尚未确定。本研究旨在探讨七氟醚对血管紧张素 II 刺激的、Ca2+ 和蛋白激酶 C（PKC）介导的大鼠主动脉平滑肌收缩的影响。

方法

分别使用等长力传感器、荧光计和蛋白质印迹法，测量七氟醚对血管紧张素 II（10 μM）诱导的大鼠主动脉平滑肌收缩、细胞内 Ca2+ 浓度升高和 PKC 磷酸化的剂量依赖性影响。

结果

血管紧张素 II 引起细胞内 Ca2+ 浓度短暂升高、Ca2+ 依赖性 PKC（cPKC）-α 磷酸化，进而导致大鼠主动脉平滑肌短暂收缩。未检测到非 Ca2+ 依赖性 PKC-ε 的磷酸化。去除细胞外 Ca2+ 后，血管紧张素 II 诱导的收缩几乎完全消除，选择性 cPKC 抑制剂 Gö 6976（10 μM）可显著抑制该收缩，但非选择性 PKC 抑制剂 Ro 31-8425（10 μM）无抑制作用。七氟醚剂量依赖性地抑制血管紧张素 II 诱导的收缩，分别给予 1.7%、3.4% 和 5.1% 七氟醚时，收缩抑制率分别为 14.2±5.2%（P>0.05）、26.7±8.9%（P<0.05）和 38.5±12.8%（P<0.01）（n = 10）。3.4%、5.1% 或 8.5% 七氟醚对血管紧张素 II 引起的细胞内 Ca2+ 浓度升高无显著影响。然而，1.7%、3.4% 和 5.1% 七氟醚剂量依赖性地抑制血管紧张素 II 诱导的 cPKC-α 磷酸化，抑制率分别为 20.5±14.2%（P>0.05）、37.0±17.8%（P<0.05）和 62.5±12.2%（P<0.01）（n = 4）。