Ropivacaine-Induced Contraction Is Attenuated by Both Endothelial Nitric Oxide and Voltage-Dependent Potassium Channels in Isolated Rat Aortae

Seong-Ho Ok,Jeong Yeol Han,Mun-Jeoung Choi,Seong-Chun Kwon,Jungchul Park,Ju-Tae Sohn,Hui-Jin Sung,Seong Min Yang

doi:10.1155/2013/565271

Abstract

This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS) inhibitor N ω-nitro-L-arginine methyl ester (L-NAME), the neuronal NOS inhibitor N ω-propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC) inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP), the calcium-activated potassium channel inhibitor tetraethylammonium (TEA), the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, N ω-propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

Highlights

Ropivacaine is an aminoamide local anesthetic with a long duration that produces vasoconstriction both in vivo and in vitro, suggesting that intrinsic vasoconstriction induced by ropivacaine contributes to the drug’s long-lasting analgesic effect [1,2,3,4]
The cytochrome P450 epoxygenase inhibitor fluconazole had no effect on ropivacaine-induced contraction in endothelium-intact aortae (Figure 3(b)), but the cyclooxygenase inhibitor indomethacin (1 × 10−5 and 3 × 10−5 M) attenuated ropivacaineinduced contraction (P < 0.05 versus control at 1 × 10−4 to 1 × 10−3 M; Figure 3(c))
This study presents novel information suggesting that ropivacaine-induced contraction is attenuated primarily by endothelial nitric oxide (NO) and voltage-dependent potassium channels in endothelium-intact aortae

Summary

Introduction

Ropivacaine is an aminoamide local anesthetic with a long duration that produces vasoconstriction both in vivo and in vitro, suggesting that intrinsic vasoconstriction induced by ropivacaine contributes to the drug’s long-lasting analgesic effect [1,2,3,4]. Ropivacaine produces vasoconstriction at low concentrations, followed by vasodilation at 1 × 10−3 M [4]. The clinical profile of ropivacaine is similar to that of racemic bupivacaine, but its toxicity is relatively low compared with that of bupivacaine [5]. Ropivacaine is an aminoamide local anesthetic of the n-alkyl-substituted pipecolyl xylidine family, which includes levobupivacaine and mepivacaine [5]. Vasoconstriction induced by levobupivacaine and mepivacaine is attenuated by endothelial nitric oxide (NO) [6,7,8].

Methods

Results

Conclusion