Yu J, Kakutani T, Mizumoto K, Hasegawa A, Hatano Y
Department of Anesthesiology, Wakayama Medical University, Wakayama City, Japan.
Acta Anaesthesiol Scand. 2006 Oct;50(9):1131-8. doi: 10.1111/j.1399-6576.2006.01119.x.
Propofol induces dose-dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)-mediated Ca2+ sensitization plays an important role in vascular smooth muscle contraction. This study is designed to examine the effects of propofol on the active phorbol ester (phorbol 12, 13-dibutyrate; PDBu)-induced, PKC-mediated contraction of rat aortic smooth muscle.
The PDBu-induced contraction of endothelium-denuded rat aortic rings was measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or propofol, using isometric force transducers. The PDBu-induced PKC phosphorylation of endothelium-denuded rat aortic strips was detected in the presence or absence of bisindolylmaleimide I or propofol, using Western blotting.
PDBu, but not the inactive phorbol ester, 4-alpha-phorbol 12-myristate-13-acetate, dose-dependently induced both a slowly developing sustained contraction and PKC phosphorylation of rat aortic smooth muscle, reaching the peak level at the concentration of 10(-6) M. The PDBu (10(-6) M)-induced contraction was dose-dependently inhibited by bisindolylmaleimide I with reductions of 6.8 +/- 1.8% (P > 0.05), 39.8 +/- 8.7% (P < 0.01) and 96.7 +/- 1.4% (P < 0.01) in response to concentrations of 5 x 10(-7) M, 10(-6)x M and 5 x 10(-6) M, respectively, and by propofol with decreases of 5.2 +/- 1. 6% (P > 0.05), 9.4 +/- 1.7% (P < 0.05), 65.3 +/- 9.2% (P < 0.01) and 96.2 +/- 1.6% (P < 0.01) in response to concentrations of 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M, respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu-induced increase in the density of the phosphorylated PKC bands in a dose-dependent manner, with decreases of 6.3 +/- 2.8% (P > 0.05), 42.9 +/- 3.2% (P < 0.01) and 96.6 +/- 3.4% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M or 5 x 10(-6) M bisindolylmaleimide I, respectively, and with decreases of 4.2 +/- 2.5% (P > 0.05), 13.5 +/- 1.7% (P < 0.05), 69.5 +/- 3.5% (P < 0.01) and 95.3 +/- 4.3% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M propofol, respectively.
Propofol dose-dependently inhibits PDBu-induced, PKC-mediated contraction of rat aortic smooth muscle.
在临床情况下，丙泊酚可引起剂量依赖性血管舒张和低血压，蛋白激酶C（PKC）介导的Ca2+致敏在血管平滑肌收缩中起重要作用。本研究旨在探讨丙泊酚对活性佛波酯（佛波醇12，13 - 二丁酸酯；PDBu）诱导的、PKC介导的大鼠主动脉平滑肌收缩的影响。
使用等长力传感器，在存在或不存在PKC抑制剂双吲哚马来酰亚胺I或丙泊酚的情况下，测量PDBu诱导的去内皮大鼠主动脉环的收缩。使用蛋白质印迹法，在存在或不存在双吲哚马来酰亚胺I或丙泊酚的情况下，检测PDBu诱导的去内皮大鼠主动脉条带的PKC磷酸化。
PDBu而非无活性的佛波酯4-α-佛波醇12-肉豆蔻酸酯-13-乙酸酯，剂量依赖性地诱导大鼠主动脉平滑肌缓慢发展的持续收缩和PKC磷酸化，在浓度为10(-6) M时达到峰值水平。双吲哚马来酰亚胺I剂量依赖性地抑制PDBu（10(-6) M）诱导的收缩，浓度为5×10(-7) M、10(-6) M和5×10(-6) M时，抑制率分别为6.8±1.8%（P>0.05）、39.8±8.7%（P<0.01）和96.7±1.4%（P<0.01）；丙泊酚也有类似作用，浓度为5×10(-7) M、10(-6) M、5×10(-6) M和10(-5) M时，抑制率分别为5.2±1.6%（P>0.05）、9.4±1.7%（P<0.05）、65.3±9.2%（P<0.01）和96.2±1.6%（P<0.01）。双吲哚马来酰亚胺I和丙泊酚均以剂量依赖性方式抑制PDBu诱导的磷酸化PKC条带密度增加，浓度为5×10(-7) M、10(-6) M或5×10(-6) M双吲哚马来酰亚胺I时，降低率分别为6.3±2.8%（P>0.05）、42.9±3.2%（P<0.01）和96.6±3.4%（P<0.01）；浓度为5×10(-7) M、10(-6) M、5×10(-6) M和10(-5) M丙泊酚时，降低率分别为4.2±2.5%（P>0.05）、13.5±1.7%（P<0.05）、69.5±3.5%（P<0.01）和95.3±4.3%（P<0.01）。
丙泊酚剂量依赖性地抑制PDBu诱导的、PKC介导的大鼠主动脉平滑肌收缩。
