Ok Seong-Ho, Kwon Seong-Chun, Kang Sebin, Choi Mun-Jeoung, Sohn Ju-Tae
Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea.
Department of Physiology, Catholic Kwandong University College of Medicine, Gangneung, Korea.
Korean J Anesthesiol. 2014 Dec;67(6):404-11. doi: 10.4097/kjae.2014.67.6.404. Epub 2014 Dec 29.
Mepivacaine induces contraction or decreased blood flow both in vivo and in vitro. Vasoconstriction is associated with an increase in the intracellular calcium concentration ([Ca(2+)]i). However, the mechanism responsible for the mepivacaine-evoked [Ca(2+)]i increase remains to be determined. Therefore, the objective of this in vitro study was to examine the mechanism responsible for the mepivacaine-evoked [Ca(2+)]i increment in isolated rat aorta.
Isometric tension was measured in isolated rat aorta without endothelium. In addition, fura-2 loaded aortic muscle strips were illuminated alternately (48 Hz) at two excitation wavelengths (340 and 380 nm). The ratio of F340 to F380 (F340/F380) was regarded as an amount of [Ca(2+)]i. We investigated the effects of nifedipine, 2-aminoethoxydiphenylborate (2-APB), gadolinium chloride hexahydrate (Gd(3+)), low calcium level and Krebs solution without calcium on the mepivacaine-evoked contraction in isolated rat aorta and on the mepivacaine-evoked [Ca(2+)]i increment in fura-2 loaded aortic strips. We assessed the effect of verapamil on the mepivacaine-evoked [Ca(2+)]i increment.
Mepivacaine produced vasoconstriction and increased [Ca(2+)]i. Nifedipine, 2-APB and low calcium attenuated vasoconstriction and the [Ca(2+)]i increase evoked by mepivacaine. Verapamil attenuated the mepivacaine-induced [Ca(2+)]i increment. Calcium-free solution almost abolished mepivacaine-induced contraction and strongly attenuated the mepivacaineinduced [Ca(2+)]i increase. Gd(3+) had no effect on either vasoconstriction or the [Ca(2+)]i increment evoked by mepivacaine.
The mepivacaine-evoked [Ca(2+)]i increment, which contributes to mepivacaine-evoked contraction, appears to be mediated mainly by calcium influx and partially by calcium released from the sarcoplasmic reticulum.
甲哌卡因在体内和体外均可引起收缩或血流量减少。血管收缩与细胞内钙浓度（[Ca(2+)]i）升高有关。然而，甲哌卡因诱发[Ca(2+)]i升高的机制尚待确定。因此，本体外研究的目的是探讨甲哌卡因诱发离体大鼠主动脉[Ca(2+)]i升高的机制。
在无内皮的离体大鼠主动脉中测量等长张力。此外，用fura-2负载的主动脉肌条在两个激发波长（340和380nm）下交替照射（48Hz）。F340与F380的比值（F340/F380）被视为[Ca(2+)]i的量。我们研究了硝苯地平、2-氨基乙氧基二苯硼酸（2-APB）、六水合氯化钆（Gd(3+)）、低钙水平和无钙的Krebs溶液对甲哌卡因诱发的离体大鼠主动脉收缩以及对fura-2负载的主动脉条中甲哌卡因诱发的[Ca(2+)]i升高的影响。我们评估了维拉帕米对甲哌卡因诱发的[Ca(2+)]i升高的影响。
甲哌卡因引起血管收缩并增加[Ca(2+)]i。硝苯地平、2-APB和低钙减弱了甲哌卡因诱发的血管收缩和[Ca(2+)]i升高。维拉帕米减弱了甲哌卡因诱导的[Ca(2+)]i升高。无钙溶液几乎消除了甲哌卡因诱导的收缩，并强烈减弱了甲哌卡因诱导的[Ca(2+)]i升高。Gd(3+)对甲哌卡因诱发的血管收缩或[Ca(2+)]i升高均无影响。
甲哌卡因诱发的[Ca(2+)]i升高导致甲哌卡因诱发的收缩，其似乎主要由钙内流介导，部分由肌浆网释放的钙介导。
