title: A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae.
abstract: The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH₂-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) γ-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC γ-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. mdoksh@naver.com.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. lishiuji@naver.com.
authors.forename: Soo Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Institute of Clinical and Translational Research, Catholic Kwandong University, College of Medicine, Gangneung 25601, Korea. skwon2028@cku.ac.kr.
authors.forename: Seong-Chun
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. choibak@nate.com.
authors.forename: Mun Hwan
authors.initials: MH
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. ilwooshin@hanmail.net.
authors.forename: Il-Woo
authors.initials: IW
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. jebiny@naver.com.
authors.forename: Sebin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea. ele93547@naver.com.
authors.forename: Miyeong
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Korea. ccarrot@hanmail.net.
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Hong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. jtsohn@nongae.gsnu.ac.kr.|Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea. jtsohn@nongae.gsnu.ac.kr.
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000779:Anesthetics, Local / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology*; D002045:Bupivacaine / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D004655:Emulsions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000779:Anesthetics, Local; D004655:Emulsions; D008055:Lipids; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D002118:Calcium; D002045:Bupivacaine
keywords: aorta; bupivacaine; lipid emulsion; myosin phosphatase target subunit; sodium orthovanadate; tyrosine kinase; vasodilation