The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

  • Ok, Seong Ho (Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Bae, Sung Il (Department of Anesthesiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine) ;
  • Kwon, Seong Chun (Department of Physiology, Kwandong University College of Medicine) ;
  • Park, Jung Chul (Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital) ;
  • Kim, Woo Chan (Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital) ;
  • Park, Kyeong Eon (Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital) ;
  • Shin, Il Woo (Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Lee, Heon Keun (Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Chung, Young Kyun (Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Choi, Mun Jeoung (Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital) ;
  • Sohn, Ju Tae (Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital)
  • Received : 2014.03.10
  • Accepted : 2014.03.17
  • Published : 2014.07.01
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Abstract

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

Keywords

References

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