title: Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine.
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 endotheliumdenuded 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 100 mM 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: Department of Anesthesiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Bae
authors.affiliation: Department of Physiology, Kwandong University College of Medicine, Gangneung, Korea.
authors.forename: Seong Chun
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Jung Chul
authors.initials: JC
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Woo Chan
authors.initials: WC
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Kyeong Eon
authors.initials: KE
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Il Woo
authors.initials: IW
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Heon Keun
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Young Kyun
authors.initials: YK
authors.lastname: Chung
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Mun Jeoung
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Ju Tae
authors.initials: JT
authors.lastname: Sohn
keywords: aorta; bupivacaine; calcium sensitization; phenylephrine; vasodilation; verapamil