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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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Název: Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta
Autoři: Ju-Tae Sohn, Youngju Lee, Seong-Ho Ok, Hyo-Jin Byon, Mun-Jeoung Choi, Yeran Hwang, Seong-Chun Kwon, Jungchul Park, Jiseok Baik
Přispěvatelé: 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
Zdroj: Int J Med Sci
Informace o vydavateli: Ivyspring International Publisher, 2015.
Rok vydání: 2015
Témata: 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
Popis: 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.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1449-1907
DOI: 10.7150/ijms.13299
Přístupová URL adresa: 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
Přístupové číslo: edsair.doi.dedup.....e8a94c8bedd3ab4c38ea6a2c6b4a42c2
Databáze: OpenAIRE
Popis
Abstrakt: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.
ISSN:14491907
DOI:10.7150/ijms.13299