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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

 Seong-Ho Ok  ;  Hyo-Jin Byon  ;  Seong-Chun Kwon  ;  Jungchul Park  ;  Youngju Lee  ;  Yeran Hwang  ;  Jiseok Baik  ;  Mun-Jeoung Choi  ;  Ju-Tae Sohn 
 International Journal of Medical Sciences, Vol.12(12) : 958-967, 2015 
Journal Title
 International Journal of Medical Sciences 
Issue Date
Amides/pharmacology ; Animals ; Aorta, Thoracic/drug effects* ; Aorta, Thoracic/physiology* ; Bupivacaine/administration & dosage ; Bupivacaine/antagonists & inhibitors* ; Bupivacaine/toxicity* ; Calcium/metabolism ; Cells, Cultured ; Emulsions ; In Vitro Techniques ; Lipids/administration & dosage* ; Male ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/physiology ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/pharmacology ; Protein Phosphatase 1/antagonists & inhibitors ; Protein Phosphatase 1/metabolism* ; Pyridines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sodium Fluoride/pharmacology ; Vasodilation/drug effects* ; Vasodilation/physiology ; rho-Associated Kinases/antagonists & inhibitors
aorta ; bupivacaine ; lipid emulsion ; myosin phosphatase target subunit 1 ; phenylephrine ; vasodilation
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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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
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변효진(Byon, Hyo Jin)
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