Uptake and Metabolism of Endothelin in the Isolated Perfused Rat Lung

The uptake and metabolism of endothelin was studied in the isolated perfused rat lung. 125I-Labeled endothelin (4 x 10(-12) M) was rapidly removed from the lung perfusate. More than 90% of the label was removed by 5 min, and only 4-5% remained in the perfusate after 30 min. In the presence of 10(-9) or 5 x 10(-9) M unlabeled endothelin added 6 min before 125I-labeled endothelin, the radiolabel was more slowly removed, so that after 30 min 19 or 73% of the label, respectively, remained in the perfusate. Although a high level of unlabeled endothelin in the perfusate reduced the uptake of 125I-labeled endothelin, it did not displace radiolabel previously taken up by the lung. Analysis of radiolabel composition showed that endothelin metabolism was less than 15% in both the lung and the perfusate after 30 min of lung perfusion. Autoradiography of the lung indicated that the radiolabel was located primarily within the alveolar wall. These results suggest that circulating endothelin is readily but finitely taken up in the pulmonary microvasculature where it is avidly bound but slowly metabolized.