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Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta

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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
Authors: Ju-Tae Sohn, Youngju Lee, Seong-Ho Ok, Hyo-Jin Byon, Mun-Jeoung Choi, Yeran Hwang, Seong-Chun Kwon, Jungchul Park, Jiseok Baik
Contributors: College of Medicine, Dept. of Anesthesiology and Pain Medicine, Seong-Ho Ok, Hyo-Jin Byon, Seong-Chun Kwon, Jungchul Park, Youngju Lee, Yeran Hwang, Jiseok Baik, Mun-Jeoung Choi, Ju-Tae Sohn, Byon, Hyo Jin
Source: Int J Med Sci
Publisher Information: Ivyspring International Publisher, 2015.
Publication Year: 2015
Subject Terms: Male, Pyridines, Aorta, Thoracic, Bupivacaine/toxicity, myosin phosphatase target subunit 1, Sodium Fluoride/pharmacology, Rats, Sprague-Dawley, 0302 clinical medicine, Protein Phosphatase 1, Lipids/administration & dosage, Phosphorylation, vasodilation, Aorta, Cells, Cultured, Thoracic/physiology, Pyridines/pharmacology, rho-Associated Kinases, Cultured, Vasodilation/physiology, Protein Phosphatase 1/antagonists & inhibitors, Phosphorylation/drug effects, Bupivacaine/antagonists & inhibitors, rho-Associated Kinases/antagonists & inhibitors, Bupivacaine, Lipids, Vasodilation, Vasodilation/drug effects, Emulsions, Bupivacaine/administration & dosage, lipid emulsion, Research Paper, Calcium/metabolism, Cells, Myocytes, Smooth Muscle, Protein Phosphatase 1/metabolism, In Vitro Techniques, Smooth Muscle/physiology, 03 medical and health sciences, Animals, Thoracic/drug effects, Protein Kinase Inhibitors, Amides/pharmacology, Myocytes, bupivacaine, Smooth Muscle/drug effects, Amides, phenylephrine, Rats, Protein Kinase Inhibitors/pharmacology, Sodium Fluoride, Calcium, Sprague-Dawley
Description: 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.
Document Type: Article
Other literature type
Language: English
ISSN: 1449-1907
DOI: 10.7150/ijms.13299
Access URL: http://www.medsci.org/v12p0958.pdf
https://pubmed.ncbi.nlm.nih.gov/26664257
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26664257/
https://www.medsci.org/v12p0958.htm
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661294/
https://ir.ymlib.yonsei.ac.kr/handle/22282913/157073
https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/157073/1/T201505236.pdf
http://europepmc.org/articles/PMC4661294
Rights: CC BY NC
CC BY NC ND
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  Data: Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta
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  Label: Description
  Group: Ab
  Data: 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.
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        Value: 10.7150/ijms.13299
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 10
        StartPage: 958
    Subjects:
      – SubjectFull: Male
        Type: general
      – SubjectFull: Pyridines
        Type: general
      – SubjectFull: Aorta, Thoracic
        Type: general
      – SubjectFull: Bupivacaine/toxicity
        Type: general
      – SubjectFull: myosin phosphatase target subunit 1
        Type: general
      – SubjectFull: Sodium Fluoride/pharmacology
        Type: general
      – SubjectFull: Rats, Sprague-Dawley
        Type: general
      – SubjectFull: 0302 clinical medicine
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      – SubjectFull: Protein Phosphatase 1
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      – SubjectFull: Lipids/administration & dosage
        Type: general
      – SubjectFull: Phosphorylation
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      – SubjectFull: vasodilation
        Type: general
      – SubjectFull: Aorta
        Type: general
      – SubjectFull: Cells, Cultured
        Type: general
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      – SubjectFull: Vasodilation/physiology
        Type: general
      – SubjectFull: Protein Phosphatase 1/antagonists & inhibitors
        Type: general
      – SubjectFull: Phosphorylation/drug effects
        Type: general
      – SubjectFull: Bupivacaine/antagonists & inhibitors
        Type: general
      – SubjectFull: rho-Associated Kinases/antagonists & inhibitors
        Type: general
      – SubjectFull: Bupivacaine
        Type: general
      – SubjectFull: Lipids
        Type: general
      – SubjectFull: Vasodilation
        Type: general
      – SubjectFull: Vasodilation/drug effects
        Type: general
      – SubjectFull: Emulsions
        Type: general
      – SubjectFull: Bupivacaine/administration & dosage
        Type: general
      – SubjectFull: lipid emulsion
        Type: general
      – SubjectFull: Research Paper
        Type: general
      – SubjectFull: Calcium/metabolism
        Type: general
      – SubjectFull: Cells
        Type: general
      – SubjectFull: Myocytes, Smooth Muscle
        Type: general
      – SubjectFull: Protein Phosphatase 1/metabolism
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      – SubjectFull: Thoracic/drug effects
        Type: general
      – SubjectFull: Protein Kinase Inhibitors
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      – SubjectFull: Amides/pharmacology
        Type: general
      – SubjectFull: Myocytes
        Type: general
      – SubjectFull: bupivacaine
        Type: general
      – SubjectFull: Smooth Muscle/drug effects
        Type: general
      – SubjectFull: Amides
        Type: general
      – SubjectFull: phenylephrine
        Type: general
      – SubjectFull: Rats
        Type: general
      – SubjectFull: Protein Kinase Inhibitors/pharmacology
        Type: general
      – SubjectFull: Sodium Fluoride
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      – SubjectFull: Calcium
        Type: general
      – SubjectFull: Sprague-Dawley
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      – TitleFull: Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta
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      – PersonEntity:
          Name:
            NameFull: Dept. of Anesthesiology and Pain Medicine
      – PersonEntity:
          Name:
            NameFull: Seong-Ho Ok
      – PersonEntity:
          Name:
            NameFull: Hyo-Jin Byon
      – PersonEntity:
          Name:
            NameFull: Seong-Chun Kwon
      – PersonEntity:
          Name:
            NameFull: Jungchul Park
      – PersonEntity:
          Name:
            NameFull: Youngju Lee
      – PersonEntity:
          Name:
            NameFull: Yeran Hwang
      – PersonEntity:
          Name:
            NameFull: Jiseok Baik
      – PersonEntity:
          Name:
            NameFull: Mun-Jeoung Choi
      – PersonEntity:
          Name:
            NameFull: Ju-Tae Sohn
      – PersonEntity:
          Name:
            NameFull: Byon, Hyo Jin
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 01
              Type: published
              Y: 2015
          Identifiers:
            – Type: issn-print
              Value: 14491907
            – Type: issn-locals
              Value: edsair
            – Type: issn-locals
              Value: edsairFT
          Numbering:
            – Type: volume
              Value: 12
          Titles:
            – TitleFull: International Journal of Medical Sciences
              Type: main
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