Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine.
10.3344/kjp.2014.27.3.229
- Author:
Seong Ho OK
1
;
Sung Il BAE
;
Seong Chun KWON
;
Jung Chul PARK
;
Woo Chan KIM
;
Kyeong Eon PARK
;
Il Woo SHIN
;
Heon Keun LEE
;
Young Kyun CHUNG
;
Mun Jeoung CHOI
;
Ju Tae SOHN
Author Information
1. Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Korea. jtsohn@nongae.gsnu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
aorta;
bupivacaine;
calcium sensitization;
phenylephrine;
vasodilation;
verapamil
- MeSH:
4-Aminopyridine;
Animals;
Aorta*;
Barium;
Bupivacaine;
Calcium Channels;
Calcium*;
Glyburide;
Nifedipine;
Phenylephrine*;
Potassium Channels;
Rats*;
Relaxation;
Vasodilation*;
Verapamil
- From:The Korean Journal of Pain
2014;27(3):229-238
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endotheliumdenuded rat aortas precontracted with phenylephrine. METHODS: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ([Ca2+]i) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. RESULTS: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100 mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced [Ca2+]i decrease in the aortas precontracted with phenylephrine. CONCLUSIONS: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine- induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.
