Effect of isoflurane on endothelin-1 mediated airway smooth muscle contraction

Endothelin-1 (ET-1) is an endogenously produced 21 amino acid peptide that can cause significant airway smooth muscle (ASM) constriction. Volatile anesthetics e.g. isoflurane, can attenuate ASM constriction. This investigation was undertaken to study the direct effects of isoflurane, at a clinically relevant dose, on endothelin-induced constriction in rat trachea. Five Sprague-Dawley female rats (weight 325-350 g) were euthanized. Four 2-3 mm rings were excised from the mid portion of the trachea, attached to a force transducer for isometric measurement, and were then suspended in jacketed baths containing 37 degreesC KH solution, bubbled with 95% O2 and 5% CO2. Carbachol dose-response curves (10(-8)-10(-4)M) were obtained to establish the maximal contractility (Cmax) for each tracheal ring. Carbachol was then washed out of the bath solution until the tissue tension returned to the baseline. Subsequently, ET-1 dose response curves (3-200 nM) were generated in the absence (ET-1, control) and in the presence of 2% isoflurane. Our data suggests that isoflurane at 2% concentration, attenuated ET-1 induced tracheal contraction at 100 and 200 nM concentrations by 20%. This is the first demonstration indicating that, at a clinically relevant dose, isoflurane depresses ET-1 induced ASM constriction.