The Direct Effect of Levobupivacaine in Isolated Rat Aorta Involves Lipoxygenase Pathway Activation and Endothelial Nitric Oxide Release

Choi, Yun Suk; Jeong, Young Seok; Ok, Seong-Ho; Shin, Il Woo; Lee, Seung Hwa; Park, Jae Yong; Hwang, Eun Mi; Hah, Young Sool; Sohn, Ju-Tae

doi:10.1213/ane.0b013e3181c76f52

Cited by 25 publications

(36 citation statements)

References 31 publications

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“…Levobupivacaine increases intracellular calcium concentration and intrinsically produces vasoconstriction in isolated vessels (Choi et al 2010). In addition, low doses of levobupivacaine produce vasoconstriction in human skin vessels in vivo because of its intrinsic vasoconstrictive properties (Newton et al 2000(Newton et al , 2005.…”

Section: Introductionmentioning

confidence: 99%

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

Baik

Sohn

et al. 2011

Can. J. Physiol. Pharmacol.

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Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration-response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd(3+), N(W)-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd(3+) had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100 mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide - cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.

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Section: Introductionmentioning

confidence: 99%

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

Baik

Sohn

et al. 2011

Can. J. Physiol. Pharmacol.

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“…However, it was shown that the effect of LEVO on rat aorta was dependent on nitric oxide released by the endothelium 8 . These findings reinforce that the vascular effects of LEVO may differ depending on some variables, such as the vascular bed used.…”

Section: Discussionmentioning

confidence: 98%

“…Studies showed that LEVO in 50% enantiomeric excess induced certain intrinsic vasoconstriction in vitro [8][9][10]12,16 and in vivo [17][18][19] . Therefore, this study aimed to assess the vasoactivity of LEVO in in vitro experiments using arterial rings prepared from isolated rat superior mesenteric artery, a resistant artery, which can reflect the possible effects on the vascular reactivity in smaller blood vessels such as those present in the area treated by local anesthetic in clinical dentistry.…”

Section: Discussionmentioning

confidence: 99%

“…Choi et al 8 , Baik et al 10 and Mukozawa et al 12 demonstrated that LEVO-induced vasoconstriction in the aorta is mediated mainly by the intracellular calcium and by Ca 2+ influx through Cavs 8,10,12 . However, our results suggest that LEVO acts via inhibition of Ca 2+ influx through these channels.…”

Section: Discussionmentioning

confidence: 99%

“…LEVO is considered as a new alternative to analgesia, which is associated with low toxicity when applied in the dental area and with minor vasoconstriction [8][9][10][11][12] . Thus, it is a satisfactory option for subjects in whom the use of vasoconstrictors is contraindicated 13 .…”

Section: Introductionmentioning

confidence: 99%

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Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery

Menezes

Souza

Santos

et al. 2016

Rev. odontol. UNESP

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ResumoIntrodução: Levobupivacaína pode ser uma nova alternativa para analgesia por apresentar baixa toxicidade e vasoconstrição, permitindo sua utilização em pacientes que apresentam contra-indicação no uso de vasoconstritores. Objetivo: Avaliar os efeitos da levobupivacaína utilizando a técnica de reatividade vascular em artéria mesentérica isolada de rato e comparar este efeito à lidocaína. Material e método: Anéis foram obtidos da artéria mesentérica de ratos machos Wistar e foram mantidos em cubas. Para o registro das contrações isométricas, cada anel foi suspenso por linhas de algodão fixadas a um transdutor de força acoplado a um sistema de aquisição. Resultado: Tanto a lidocaína como a levobupivacaína não apresentaram efeito vasocontritor sobre o tônus basal em anéis com endotélio functional. No entanto, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas induziram um vasorrelaxamento concentração-dependente. O efeito vasorrelaxante causado pela levobupivacaína não foi diferente após a remoção do endotélio, ou com o tetraetilamônio (1mM), um bloqueador não seletivo dos canais para. K + . Em anéis sem endotélio funcional e pré-contraídos com solução despolarizante de Tyrode (KCl 80mM), o vasorelaxamento induzido pela levobupivacaína não foi significativamente diferente daquele observado em anéis pré-contraídos com fenilefrina e não apresentou um efeito adicional significativo sobre o relaxamento máximo da nifedipina. Conclusão: Este estudo demonstrou que a levobupivacaína produz efeito vasorrelaxante em artéria mesentérica de rato, que é endotélio independente. Este efeito parece envolver os bloqueadores de canais para Ca 2+ em célula muscular vascular lisa.Descritores: Lidocaína; artéria mesentérica; vasodilatação. AbstractIntroduction: Levobupivacaine (LEVO) can replace analgesia because it exhibits low toxicity and causes minor vasoconstriction, enabling its use in patients in whom vasoconstrictors are contraindicated. Objective: We aimed to evaluate the effects of LEVO in isolated rat superior mesenteric artery by using the vascular reactivity technique and compare its effect to that of lidocaine. Material and method: Arterial rings were obtained from the mesenteric artery of male Wistar rats and kept in organ baths. For recording isometric contractions, each ring was suspended by cotton threads from a force transducer, which was connected to a data acquisition system. Result: Both lidocaine and LEVO did not show a vasoconstrictor effect on the basal tone of the arterial rings with functional endothelium. However, when the rings were pre-contracted with phenylephrine, both drugs were able to induce concentration-dependent vasodilatation. The vasodilator effect induced by LEVO did not change after removal of the endothelium, or with the addition of tetraethylammonium (1 mM), a non-selective K + channel blocker. In the rings without functional endothelium, which were pre-contracted with depolarizing Tyrode's solution (KCl 80 mM), LEVO-induced vasodilatation was not significantly differe...

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