Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine.
10.3344/kjp.2016.29.4.229
- Author:
Hyunhoo CHO
1
;
Seong Ho OK
;
Seong Chun KWON
;
Soo Hee LEE
;
Jiseok BAIK
;
Sebin KANG
;
Jiah OH
;
Ju Tae SOHN
Author Information
1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea. jtsohn@nongae.gsnu.ac.kr
- Publication Type:Original Article
- Keywords:
Bupivacaine;
CPI-17;
Lipid emulsion;
PDBu;
PKC;
Vasodilation
- MeSH:
Anesthetics, Local;
Animals;
Aorta;
Blotting, Western;
Bupivacaine*;
Calcium;
Fura-2;
In Vitro Techniques;
Mepivacaine*;
Muscle, Smooth, Vascular;
Myosin-Light-Chain Phosphatase;
Phorbol 12,13-Dibutyrate;
Phosphorylation;
Protein Kinase C;
Rats;
Solubility;
Vasodilation*
- From:The Korean Journal of Pain
2016;29(4):229-238
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. METHODS: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca²⁺]ᵢ) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. RESULTS: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca²⁺]ᵢ. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. CONCLUSIONS: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.
