title: Differential effects of short- and long-term bupivacaine treatment on α1-adrenoceptor-mediated contraction of isolated rat aorta rings and the reversal effect of lipid emulsion.
abstract: OBJECTIVE
  Arterial function is significantly influenced by bupivacaine at both clinically relevant concentrations and toxic concentrations, but the underlying mechanisms are not fully understood. In the present study we investigated the role of α1-adrenoceptors in bupivacaine effects on isolated rat aortas.
  
  
  METHODS
  Isolated aortic rings were prepared from rats and suspended in an organ bath. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (ACh)-induced vasodilation were recorded through an isometric force transducer connected to a data acquisition system.
  
  
  RESULTS
  Administration of bupivacaine (30-300 μmol/L) produced mild vasoconstriction, and this response declined with repeated administrations. Treatment of the aortic rings with bupivacaine (3-30 μmol/L) for 20 min enhanced Phe-induced vasoconstriction, while treatment for 40 min suppressed Phe-induced vasoconstriction. Both the short- and long-term bupivacaine treatment suppressed ACh-induced vasodilation. Incubation of the aortic rings with 0.2%-0.6% lipid emulsion (LE) for 100 min significantly increased the pD2 and Emax values of Phe-induced vasoconstriction, and incubation with 0.4% LE for 100 min reversed the inhibition of bupivacaine on vasoconstriction induced by Phe (30 μmol/L). In contrast, incubation with LE suppressed ACh-induced vasodilation, even at a lower concentration and with a 5-min incubation.
  
  
  CONCLUSIONS
  Bupivacaine exerts dual effects on α1-adrenoceptor-mediated vasoconstriction of isolated rat aortic rings: short-term treatment enhances the response, while long-term treatment inhibits it; the inhibition may be reversed via long-term incubation with LE.
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: He-fei
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Wen-qi
authors.initials: WQ
authors.lastname: Xu
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Lei-ming
authors.initials: LM
authors.lastname: Ren
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002045:Bupivacaine / Q000494:pharmacology*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D015016:Yohimbine; D011433:Propranolol; D000109:Acetylcholine; D002045:Bupivacaine