title: Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta.
abstract: Lipid emulsions are widely used for the treatment of systemic toxicity that arises from local anesthetics. The goal of this in vitro study was to examine the cellular mechanism associated with the lipid emulsion-mediated attenuation of vasodilation induced by a toxic dose of bupivacaine in isolated endothelium-denuded rat aorta. The effects of lipid emulsion on vasodilation induced by bupivacaine, mepivacaine, and verapamil were assessed in isolated aorta precontracted with phenylephrine, the Rho kinase stimulant NaF, and the protein kinase C activator phorbol 12,13-dibutyrate (PDBu). The effects of Rho kinase inhibitor Y-27632 on contraction induced by phenylephrine or NaF were assessed. The effects of bupivacaine on intracellular calcium concentrations ([Ca(2+)]i) and tension induced by NaF were simultaneously measured. The effects of bupivacaine alone and lipid emulsion plus bupivacaine on myosin phosphatase target subunit 1 (MYPT1) phosphorylation induced by NaF were examined in rat aortic vascular smooth muscle cells. In precontracted aorta, the lipid emulsion attenuated bupivacaine-induced vasodilation but had no effect on mepivacaine-induced vasodilation. Y-27632 attenuated contraction induced by either phenylephrine or NaF. The lipid emulsion attenuated verapamil-induced vasodilation. Compared with phenylephrine-induced precontracted aorta, bupivacaine-induced vasodilation was slightly attenuated in NaF-induced precontracted aorta. The magnitude of the bupivacaine-induced vasodilation was higher than that of a bupivacaine-induced decrease in [Ca(2+)]i. Bupivacaine attenuated NaF-induced MYPT1 phosphorylation, whereas lipid emulsion pretreatment attenuated the bupivacaine-induced inhibition of MYPT1 phosphorylation induced by NaF. Taken together, these results suggest that lipid emulsions attenuate bupivacaine-induced vasodilation via the attenuation of inhibition of MYPT1 phosphorylation evoked by NaF.
authors.affiliation: 1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: 2. Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea; ; 8. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Jinju-si, 52727, Republic of Korea.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Byon
authors.affiliation: 3. Department of Physiology, Institute for Clinical and Translational Research, Catholic Kwandong University College of Medicine, Gangneung, 25601, Korea;
authors.forename: Seong-Chun
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: 4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, 660-702, Republic of Korea;
authors.forename: Jungchul
authors.initials: J
authors.lastname: Park
authors.affiliation: 4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, 660-702, Republic of Korea;
authors.forename: Youngju
authors.initials: Y
authors.lastname: Lee
authors.affiliation: 4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, 660-702, Republic of Korea;
authors.forename: Yeran
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: 5. Department of Anesthesiology and Pain Medicine, Pusan National University Hospital, Biomed Research Institute, Pusan National University School of Medicine, Busan, Republic of Korea;
authors.forename: Jiseok
authors.initials: J
authors.lastname: Baik
authors.affiliation: 6. Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju, 660-702, Republic of Korea;
authors.forename: Mun-Jeoung
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: 1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea; ; 7. Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea;
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology*; D002045:Bupivacaine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004655:Emulsions; D066298:In Vitro Techniques; D008055:Lipids / Q000008:administration & dosage*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012969:Sodium Fluoride / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000577:Amides; D004655:Emulsions; D008055:Lipids; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D012969:Sodium Fluoride; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D002118:Calcium; D002045:Bupivacaine
keywords: aorta; bupivacaine; lipid emulsion; myosin phosphatase target subunit 1; phenylephrine; vasodilation