Yu Jingui, Tokinaga Yasuyuki, Ogawa Koji, Iwahashi Shizue, Hatano Yoshio
Department of Anesthesiology, Wakayama Medical University, Wakayama City, Japan.
Anesthesiology. 2004 Apr;100(4):879-84. doi: 10.1097/00000542-200404000-00018.
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.
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.
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.
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.
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。
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。
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）。
本研究表明 Ca2+ 和 cPKC-α 参与血管紧张素 II 诱导的血管收缩。七氟醚剂量依赖性地抑制血管紧张素 II 刺激的、cPKC 介导的大鼠主动脉平滑肌收缩，但不抑制 Ca2+ 引起的收缩。
