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Online ISSN 1827-1596
Akhtar S. 1, Podgoreanu M. 2, Harrison B. A. 3, Brull S. J. 3
1 Department of Anesthesiology, Yale University School of Medicine,Yale-New Haven Hospital, New Haven, CT, USA;
2 Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA;
3 Department of Anesthesiology, Mayo Clinic College of Medicine, Jacksonville, FL, USA
Background. Endothelin-1 (ET-1) is a 21-amino acid peptide that induces airway smooth muscle (ASM) constriction by activating G-protein-coupled endothelin receptors A (ETA) and B (ETB), thereby increasing intracellular calcium ([Ca2+]i). Lidocaine can cause direct ASM relaxation by decreasing [Ca2+]i. This study investigated the direct relaxant effects of lidocaine on ET-1-induced contraction in rat tracheas.
Methods. Mid-tracheal rings (2-3 mm diameter) were excised and attached to a force transducer suspended in Krebs-Henseliet solution. Carbachol concentration-response curves (10 nM and 100 µM) were generated to determine maximal contractility (Cmax). ET-1 (3 nM to 200 nM) responses to lidocaine (100 nM, 10 µM, and 1 mM) were measured in the presence and absence of extracellular calcium. Contractile responses to ET-1 are presented as percentage of Cmax (% Cmax). Data were analyzed using analysis of variance and unpaired t-tests with Welsh correction.
Results. No significant effect on ET-1-induced constriction was noted in the presence of low concentrations of lidocaine (100 nM and 1 µM), with and without extracellular calcium. At a concentration of 1 mM, lidocaine decreased the response to 100 nM and 200 nM ET-1 by 26% in the presence of extracellular calcium and by 37 and 44%, respectively, in the absence of calcium.
Conclusion. The attenuating effect of lidocaine (1 mM) on ET-1-induced ASM contraction is not exclusively dependent on the blockade of intracellular calcium entry.