Aerosolized endothelin-1, but not its C-terminal hexapeptide, causes airway narrowing in the rat

We investigated the effects of aerosolized endothelin-1 (ET-1) and of its C-terminal hexapeptide, ET-(16-21), on the pulmonary mechanics of anaesthetized spontaneously-breathing rats. ET-1 inhalation caused a concentration-dependent increase in pulmonary resistance (RL) and decrease in dynamic lung compliance (Cdyn). In control conditions RL and Cdyn were 0.17 +/- 0.04 cmH2O.ml-1.s (mean +/- SE; n = 6) and 6.25 +/- 0.66 ml.cmH2O.1. respectively. After ET-1 4 x 10(-5) M RL and Cdyn averaged 1.45 +/- 0.28 cmH2O.ml-1.s (p less than 0.05) and 1.12 +/- 0.36 ml.cmH2O-1 (p less than 0.05), respectively. The pulmonary responses to ET-1 lasted up to 60 min. By contrast, ET-(16-21) inhaled up to a concentration of 10(-3) M did not affect pulmonary mechanics. These results indicate that the bronchoconstrictor activity of aerosolized endothelin-1 in the rat is not dependent on its C-terminal sequence, and suggests a role for endothelin-1 in the regulation of airway calibre.