Epithelial Modulation of Airway Smooth Muscle Response to Endothelin-1

We investigated the role of epithelial modulation of contraction caused by endothelin-1 in airway smooth muscle in guinea pigs in situ. Airway responses were assessed isometrically as tracheal force and simultaneously as change in lung resistance. Intravenous administration of 10−8 mol/kg endothelin-1 caused a biphasic response in tracheal active tension: initial relaxation (−0.82 ± 0.22 g/cm after 30 s, p < 0.05 versus baseline) followed by contraction (1.65 ± 0.28 g/cm after 7 min, p < 0.05 versus baseline). Endothelin-1 also elicited immediate bronchoconstriction; lung resistance increased from 0.148 ± 0.030 to 0.992 ± 0.274 cm H2O/L/s (p < 0.005) after 10−8 mol/kg endothelin-1 given intravenously. Active tension elicited by 10−8 mol/kg endothelin-1 after removal of the epithelium from the tracheal segment (0.59 ± 0.16 g/cm) was less than in segments with an intact epithelium (1.65 ± 0.28 g/cm, p < 0.01). Both tracheal contraction and bronchoconstriction were attenuated by pretreatment with indomethaci...