Effect of lidocaine on endothelin-1-mediated airway smooth muscle contraction in the rat trachea

Minerva Anestesiol. 2008 Nov;74(11):643-50.

Abstract

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / pharmacology*
  • Animals
  • Bronchodilator Agents / pharmacology
  • Calcium / pharmacology
  • Calcium Channels / metabolism
  • Calcium Signaling / drug effects
  • Carbachol / pharmacology
  • Endothelin-1 / drug effects*
  • Extracellular Fluid / metabolism
  • Female
  • Lidocaine / pharmacology*
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A / drug effects
  • Receptor, Endothelin A / physiology
  • Receptor, Endothelin B / drug effects
  • Receptor, Endothelin B / physiology
  • Trachea / drug effects*

Substances

  • Anesthetics, Local
  • Bronchodilator Agents
  • Calcium Channels
  • Endothelin-1
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Carbachol
  • Lidocaine
  • Calcium