Effect of lidocaine on endothelin-1-mediated airway smooth muscle contraction in the rat trachea.
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 ([Ca(2+)]i). Lidocaine can cause direct ASM relaxation by decreasing [Ca(2+)]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 microM) were generated to determine maximal contractility (C(max)). ET-1 (3 nM to 200 nM) responses to lidocaine (100 nM, 10 microM, 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 muM), 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.


CONCLUSIONS
The attenuating effect of lidocaine (1 mM) on ET-1-induced ASM contraction is not exclusively dependent on the blockade of intracellular calcium entry.
Akhtar
S
S
Department of Anesthesiology, Yale University School of Medicine,Yale-New Haven Hospital, New Haven, CT, USA.
Podgoreanu
M
M
Harrison
B A
BA
Brull
S J
SJ
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D019332:Endothelin-1 / Q000187:drug effects*; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D008012:Lidocaine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000502:physiology; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects*
D000779:Anesthetics, Local; D001993:Bronchodilator Agents; D015220:Calcium Channels; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D002217:Carbachol; D008012:Lidocaine; D002118:Calcium