title: Mepivacaine-induced contraction involves phosphorylation of extracellular signal-regulated kinase through activation of the lipoxygenase pathway in isolated rat aortic smooth muscle.
abstract: Mepivacaine is an aminoamide local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. This study investigated the arachidonic acid metabolic pathways involved in mepivacaine-induced contraction, and elucidated the associated cellular mechanism with a particular focus on extracellular signal-regulated kinase (ERK) in endothelium-denuded rat aorta. Isolated rat thoracic aortic rings were suspended for isometric tension recording. Cumulative mepivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, indomethacin, NS-398, SC-560, fluconazole, PD 98059, and verapamil. Mepivacaine-induced ERK phosphorylation, 5-lipoxygenase (5-LOX) expression, and cyclooxygenase (COX)-2 expression in rat aortic smooth muscle cells were detected by Western blot analysis in the presence or absence of inhibitors. Mepivacaine produced tonic contraction in isolated endothelium-denuded rat aorta. Quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, NS-398, PD 98059, and verapamil attenuated mepivacaine-induced contraction in a concentration-dependent manner. However, fluconazole had no effect on mepivacaine-induced contraction. PD 98059, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, and indomethacin attenuated mepivacaine-induced ERK phosphorylation. Mepivacaine upregulated 5-LOX and COX-2 expression. These results suggest that mepivacaine-induced contraction involves ERK activation, which is primarily mediated by the 5-LOX pathway and in part by the COX-2 pathway.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Lee
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.forename: So Young
authors.initials: SY
authors.lastname: Eun
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Sebin
authors.initials: S
authors.lastname: Kang
authors.forename: Il-Woo
authors.initials: IW
authors.lastname: Shin
authors.forename: Heon Keun
authors.initials: HK
authors.lastname: Lee
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Chung
authors.forename: Mun-Jeoung
authors.initials: MJ
authors.lastname: Choi
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Bae
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D008619:Mepivacaine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016718:Arachidonic Acid; D008619:Mepivacaine; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases