title: Direct effect of ropivacaine involves lipoxygenase pathway activation in rat aortic smooth muscle.
abstract: OBJECTIVE
  Ropivacaine is a long-acting amino-amide local anesthetic that induces vasoconstriction in vitro and in vivo. The aim of this study was to investigate the pathways involved in arachidonic acid metabolism associated with S-ropivacaine-induced contraction of rat aortic smooth muscle in vitro.
  
  
  METHODS
  Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dose-response curves were generated with concentrations of 10(-5) to 10(-3) M ropivacaine enantiomer in the presence or absence of quinacrine dihydrochloride, nordihydroguaiaretic acid, quinacrine dihydrochloride plus nordihydroguaiaretic acid, indomethacin, fluconazole, AA-861, and verapamil. The maximal S-ropivacaine-induced contractile response achieved at 3x10(-4) M was also assessed in aortic rings pretreated with normal or calcium-free Krebs solution.
  
  
  RESULTS
  Ropivacaine enantiomers induced dose-dependent biphasic contractions in aortic rings. S-ropivacaine (10(-4), 3x10(-4) M) induced a stronger contraction than R-ropivacaine. Quinacrine dihydrochloride (2x10(-5), 4x10(-5) M) attenuated the S-ropivacaine-induced biphasic contraction in a dose-dependent manner. Indomethacin (3x10(-5), 6x10(-5) M), nordihydroguaiaretic acid (10(-5) M), and AA-861 (10(-5) M) also attenuated the S-ropivacaine-induced dose-dependent biphasic contraction, whereas fluconazole (3x10(-5)) had no effect. Combined pretreatment with quinacrine dihydrochloride and nordihydroguaiaretic acid almost completely abolished the S-ropivacaine-induced contraction. S-ropivacaine-induced contractile responses were attenuated by verapamil (10(-5) M) and calcium-free Krebs solution.
  
  
  CONCLUSIONS
  S-ropivacaine induces dose-dependent biphasic contractions in rat aortic smooth muscle through a mechanism requiring extracellular calcium that is mediated by activation of the lipoxygenase pathway and, to a lesser extent, the cyclooxygenase pathway.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, 660-702, Republic of Korea.
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Ji Seok
authors.initials: JS
authors.lastname: Baik
authors.forename: Koji
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007537:Isometric Contraction; D008084:Lipoxygenase / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D016718:Arachidonic Acid; D000077212:Ropivacaine; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium