Korean J Pain.  2016 Oct;29(4):229-238. 10.3344/kjp.2016.29.4.229.

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

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea. jtsohn@nongae.gsnu.ac.kr
  • 2Department of Physiology, Institute for Clinical and Translational Research, Catholic Kwangdong University College of Medicine, Gangneung, Korea.
  • 3Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Korea.
  • 4Department of Anesthesiology and Pain Medicine, Pusan National University Hospital, Biomed Research Institute, Pusan National University School of Medicine, Busan, Korea.
  • 5Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.

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 ([Ca²âº]áµ¢) 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 [Ca²âº]áµ¢. 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.

Keyword

Bupivacaine; CPI-17; Lipid emulsion; PDBu; PKC; Vasodilation

MeSH Terms

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*
Anesthetics, Local
Bupivacaine
Calcium
Fura-2
Mepivacaine
Myosin-Light-Chain Phosphatase
Phorbol 12,13-Dibutyrate
Protein Kinase C
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