Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

Ji Seok Baik, Ju Tae Sohn, Seong Ho Ok, Jae Gak Kim, Hui Jin Sung, Sang Seung Park, Jae Yong Park, Eun Mi Hwang, Young Kyun Chung

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26 Citations (Scopus)

Abstract

Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration-response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd3+, NW-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd3+ had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100 mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide - cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.

Original languageEnglish
Pages (from-to)467-476
Number of pages10
JournalCanadian Journal of Physiology and Pharmacology
Volume89
Issue number7
DOIs
Publication statusPublished - 2011 Jul
Externally publishedYes

Keywords

  • Aorta
  • Calcium
  • Contraction
  • Endothelium
  • Levobupivacaine
  • Nitric oxide
  • Verapamil

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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  • Cite this

    Baik, J. S., Sohn, J. T., Ok, S. H., Kim, J. G., Sung, H. J., Park, S. S., Park, J. Y., Hwang, E. M., & Chung, Y. K. (2011). Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent. Canadian Journal of Physiology and Pharmacology, 89(7), 467-476. https://doi.org/10.1139/Y11-046