A proposed mechanism of bupivacaine-induced contraction of human umbilical artery smooth muscle cells

Rossner, Kenneth L.; Natke, E.; Liu-Barnett, M.; Freese, K. J.

doi:10.1016/s0959-289x(99)80148-4

Cited by 8 publications

(8 citation statements)

References 17 publications

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“…In agreement with results from a previous study (Rossner et al 1999), levobupivacaine (2 × 10 -5 and 5 × 10 -5 mol/L) increased intracellular calcium concentrations in a concentration-dependent manner. Together with results from previous studies (Norén et al 1991a(Norén et al , 1991bRossner et al 1999;Choi et al 2010), the present results indicate that levobupivacaine-induced contraction is primarily dependent on intracellular calcium levels that are largely regulated by calcium influx from the extracellular space via VOCCs. It is very difficult to elucidate the mechanism by which 3 × 10 -4 mol/L levobupivacaine gradually attenuates contraction induced by low-concentration levobupivacaine.…”

Section: Discussionsupporting

confidence: 92%

“…Local anesthetics modify the lipid environment of cell membranes, affecting the activities of receptors and ion channels via the conformational changes of such functional proteins embedded in these biomembranes (Tsuchiya and Mizogami 2008). Bupivacaine-induced contraction in isolated vessels is primarily dependent on calcium influx from the extracellular space and is attenuated by blockade of voltage-operated calcium channels (VOCCs) (Norén et al 1991a(Norén et al , 1991bRossner et al 1999). Levobupivacaine-induced contraction is mediated mainly by the activation of the lipoxygenase pathway, which seems to facilitate calcium influx via VOCCs (Choi et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 92%

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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“…In this vessel, there are some reports showing the effects of Ca 2+ channels antagonist on arterial contractility [12,13], and we have also reported that nifedipine induced a complete relaxation of HUA rings contraction induced by a depolarizing high K + solution [14]. However, there is no information regarding neither the electrophysiological characteristics nor the molecular structure of voltage-activated Ca 2+ channels expressed in this artery.…”

Section: Introductionmentioning

confidence: 82%

L, P-/Q- and T-type Ca<sup>2+</sup> Channels in Smooth Muscle Cells from Human Umbilical Artery

Salemme

Rebolledo

Speroni

et al. 2007

Cell Physiol Biochem

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The electrophysiological and pharmacological properties of Ca²⁺ current (I_Ca) were determined by the whole-cell configuration of the patch-clamp technique in smooth muscle cells from human umbilical artery. Using 5 mM extracellular Ca²⁺, depolarizing step pulses from -60 to 50 mV from a holding membrane potential of -80 mV evoked an I_Ca which activated at membrane potentials more positive than -50 mV and exhibited a maximum current density in a range of 10-20 mV. Steady-state inactivation protocols using a V_test of 10 mV gave a voltage at one-half inactivation and a slope factor of -35.6 mV and 9.5 mV, respectively. Nifedipine (1 µM), an L-type Ca²⁺ channels antagonist, completely inhibited I_Ca, while the L-type Ca²⁺ channels agonist Bay-K 8644 (1 µM) significantly increased I_Ca amplitude. Moreover, the selective blocker of P-/Q-type Ca²⁺ channels ω-agatoxin IVA partially blocked I_Ca (about 40 % inhibition at +20 mV by 20 nM). These pharmacological results suggest that L- and P-/Q-type Ca²⁺ channels, both nifedipine-sensitive, underlie the I_Ca registered using low extracellular Ca²⁺. The presence of the P-/Q-type Ca²⁺ channels was confirmed by immunoblot analysis. When I_Ca was recorded in a high concentration (30 mM) of extracellular Ca²⁺ or Ba²⁺ as current carrier, it was evident the presence of a nifedipine-insensitive component which completely inactivated during the course of the voltage-step (75 ms) at all potentials tested, and was blocked by the T-type Ca²⁺ channels blocker mibefradil (10 µM). Summarizing, this work shows for the first time the electrophysiological and pharmacological properties of voltage-activated Ca²⁺ currents in human umbilical artery smooth muscle cells.

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“…Lida et al reveal a differing influence of bupivacaine and ropivacaine on dog spinal pial vessel diameter, with ropivacaine causing vasoconstriction and bupivacaine vasodilatation [51]. Laser doppler imaging studies on human skin has revealed nitric oxide (NO) to be responsible for the vasodilatatory effect of local anaesthetics, however, NO does not appear to be involved when the blood vessel is uninnervated such as the in vitro umbilical artery [52, 53]. …”

Section: Local Anesthetic Systemic Toxicitymentioning

confidence: 99%

Lipid Emulsion for Local Anesthetic Systemic Toxicity

Ciechanowicz¹,

Patil²

2012

Anesthesiology Research and Practice

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The accidental overdose of local anesthetics may prove fatal. The commonly used amide local anesthetics have varying adverse effects on the myocardium, and beyond a certain dose all are capable of causing death. Local anesthetics are the most frequently used drugs amongst anesthetists and although uncommon, local anaesthetic systemic toxicity accounts for a high proportion of mortality, with local anaesthetic-induced cardiac arrest particularly resistant to standard resuscitation methods. Over the last decade, there has been convincing evidence of intravenous lipid emulsions as a rescue in local anesthetic-cardiotoxicity, and anesthetic organisations, over the globe have developed guidelines on the use of this drug. Despite this, awareness amongst practitioners appears to be lacking. All who use local anesthetics in their practice should have an appreciation of patients at high risk of toxicity, early symptoms and signs of toxicity, preventative measures when using local anesthetics, and the initial management of systemic toxicity with intravenous lipid emulsion. In this paper we intend to discuss the pharmacology and pathophysiology of local anesthetics and toxicity, and the rationale for lipid emulsion therapy.

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A proposed mechanism of bupivacaine-induced contraction of human umbilical artery smooth muscle cells

Cited by 8 publications

References 17 publications

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

L, P-/Q- and T-type Ca<sup>2+</sup> Channels in Smooth Muscle Cells from Human Umbilical Artery

Lipid Emulsion for Local Anesthetic Systemic Toxicity

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