Levobupivacaine induces vasoconstriction via Ca<SUP>2＋</SUP>-dependent and -independent mechanisms in isolated rat thoracic aorta

DOI
  • Mukozawa Mai
    Department of Anesthesiology, Asahi University School of Dentistry
  • Takakura Ko
    Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, Fukui University
  • Obata Yurie
    Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, Fukui University
  • Shimo Koichi
    Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, Fukui University
  • Shigemi Kenji
    Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, Fukui University

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Purpose Levobupivacaine was developed as an alternative long-acting local anesthetic with a clinical profile similar to that of bupivacaine but with lower potential to induce systemic toxicity. Levobupivacaine has biphasic vasoactivities, namely, vasoconstriction at a low concentration and vasodilatation at a high concentration. The purpose of this study was to investigate the mechanisms underlying the vasoconstriction induced by levobupivacaine. Methods Functional examinations were performed in Krebs solution using isolated thoracic aortic rings from male Wistar rats. Changes in ring tension induced by levobupivacaine were measured on intact or endothelium-denuded rings. Changes in tension induced by levobupivacaine were also measured in the presence of EGTA in Ca2＋-free solution or in the presence of L-type Ca2＋-channel blocker(nifedipine). In addition, functional examinations were performed in the presence of various inhibitors: 2-APB(IP3 receptor inhibitor), ML-7(MLCK inhibitor), staurosporine(PKC inhibitor), H1152(ROK inhibitor), PD98059(ERK inhibitor) and phentolamine(α1-inhibitor). Results Levobupivacaine induced vasoconstriction in intact aortic rings as strongly as that in endothelium-denuded aortic rings. In Ca2＋-free Krebs solution with EGTA, levobupivacaine could not induce contraction at all. High-concentration levobupivacaine induced limited contraction in the presence of nifedipine. 2-APB and ML-7 inhibited levobupivacaine-induced vasoconstriction. Staurosporine, H1152 and PD98059 inhibited both phenylephrine- and levobupivacaine-induced vasoconstriction to the same degree. The inhibitory effect of phentolamine on levobupivacaine-induced vasoconstriction was limited. Conclusion Levobupivacaine-induced vasoconstriction was independent of the endothelium. Both Ca2＋-dependent pathway, that is, extracellular Ca2＋＋influx and sarcoplasmic reticulum Ca2＋ efflux including IP3 and MLCK pathway, and Ca2＋-independent pathway(PKC, ROK, and ERK pathway), which increases myofilament Ca2＋ sensitivity, participated in the contraction induced by levobupivacaine.

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  • 循環制御

    循環制御 34 (1-3), 71-77, 2013

    日本循環制御医学会

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