The mechanism of action of endothelin in human lung

1 The peptides endothelin‐1 (ET‐1) and endothelin‐2 (ET‐2) elicited potent and sustained contractions of human isolated bronchus and pulmonary artery. 2 ET‐1 is one of the most potent contractile agonists investigated in these tissues with an EC50 value of 18.3 nm (95% confidence interval: 12.9, 25.9 nm; n = 26) in bronchus and 3.2 nm (95% confidence interval: 0.4, 23.9 nm; n = 5) in the arterial preparation. 3 ET‐1 is 2.5 times more potent than ET‐2 in both the airway and vascular tissues, and both forms of the peptide have geometric mean EC50 values 5 times greater in the isolated bronchial tissue than in the pulmonary artery. 4 Neither pretreatment with the voltage‐dependent calcium (VDC) channel antagonist verapamil (10 μm) nor with indomethacin (25 μm) significantly altered the response curve to ET‐1 in human isolated bronchus. Removal of calcium from the Krebs‐Henseleit solution did not affect ET‐1‐induced responses. 5 Specific binding on the smooth muscle of human airway and pulmonary arterial tissue to both ET‐1 and ET‐2 was detected in autoradiographic studies. There appeared to be no difference between the peptides in the location nor the density of binding sites. 6 We conclude that contraction of human bronchial tissue by ET‐1 is not dependent upon influence of extracellular calcium nor release of prostaglandins or thromboxane A2. It is likely that the action of ET‐1 in this tissue is due to binding of this peptide to specific receptors located on the smooth muscle.