Mechanism of the ropivacaine-induced increase in intracellular Ca2+ concentration in rat aortic smooth muscle
Mechanism of the ropivacaine-induced increase in intracellular Ca2+ concentration in rat aortic smooth muscle
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DOI：
10.1111/j.1399-6576.2007.01390.x
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发表时间：
2007-10-01
影响因子：
2.1
通讯作者：
Hatano, Y.
中科院分区：
文献类型：
--
作者：
Tokinaga, Y.;Ogawa, K.;Hatano, Y.
背景：罗哌卡因是一种长效局麻药，心脏毒性低，在体外和体内均可引起血管收缩。血管平滑肌张力受细胞内Ca 2+浓度（[Ca 2 +]（i））和肌丝Ca 2+敏感性的变化调节。因此，本研究的目的是研究罗哌卡因诱导的血管收缩中[Ca 2 +]（i）增加的潜在机制。方法：分别使用等长力传感器和荧光计检测罗哌卡因诱导的收缩反应和[Ca 2 +]（i）的变化。罗哌卡因诱导大鼠主动脉平滑肌[Ca 2 +]（i）和收缩反应的双相、浓度依赖性变化：[Ca 2 +]（i）在较低浓度（3 × 10（-5）至3 × 10（-4）M）时增加，在较高浓度（10（-3）至3 × 10（-3）M）时观察到减少。电压依赖性Ca ~（2+）通道拮抗剂、肌醇1，4，5-三磷酸受体拮抗剂和无Ca ~（2+）溶液均能显著抑制罗哌卡因引起的收缩和[Ca ~（2+）]（i）增加（P < 0.01，n= 6）。罗哌卡因诱导的大鼠主动脉平滑肌收缩，部分是，由来自细胞外间隙的Ca 2+内流和来自肌浆网的Ca 2+释放调节。
Background: Ropivacaine is a long-acting local anesthetic with low cardiac toxicity that induces vasoconstriction in vitro and in vivo. Vascular smooth muscle tone is regulated by changes in both intracellular Ca2+ concentration ([Ca2+](i)) and myofilament Ca2+ sensitivity. Therefore, the aim of this study was to examine the mechanism underlying the increase in [Ca2+](i) in ropivacaine-induced vascular contraction.Methods: Ropivacaine-induced contractile responses and changes in [Ca2+](i) were examined using an isometric force transducer and a fluorometer, respectively.Results: Ropivacaine induced a biphasic, concentration-dependent change in [Ca2+](i) and contractile response in rat aortic smooth muscles: an increase in [Ca2+](i) occurred at lower ropivacaine concentrations (3 x 10(-5) to 3 x 10(-4) M) and a decrease was observed at higher concentrations (10(-3) to 3 x 10(-3) M). Contraction and the [Ca2+](i) increase induced by ropivacaine were attenuated significantly by a voltage-dependent Ca2+ channel antagonist, an inositol 1,4,5-triphosphate receptor antagonist and Ca2+-free solution (P < 0.01, n= 6).Conclusion: Ropivacaine-induced contraction of rat aortic smooth muscle is, in part, regulated by Ca2+ influx from the extracellular space and Ca2+ release from the sarcoplasmic reticulum.