ENDOTHELIN-1-INDUCED EDEMA IN RAT AND GUINEA-PIG ISOLATED-PERFUSED LUNGS

Endothelin-1 caused an increase in perfusion pressure, bronchial resis tance, lung weight and tracheal effusion when infused through the pulm onary artery of rat and guinea-pig isolated lungs. In contrast to vaso constriction, the effects of endothelin-1 on bronchial resistance, lun g weight and tracheal effusion were not concentration-dependent. Recov ery from vasoconstriction occurred within 15-30 min when the lung was further perfused with Krebs buffer. Increases in lung weight, bronchia l resistance and tracheal effusion induced by endothelin-1 were irreve rsible when infused at concentrations above 10(-10) M. UK 38 485, a th romboxane A2 synthesis inhibitor, partly prevented the increase in lun g weight and tracheal effusion without altering the vasoconstriction i nduced by endothelin-1. Such an antagonism was not seen in guinea-pig lung at the concentration used. Iloprost, a stable analogue of prostac yclin, antagonized the effects of endothelin-1 on perfusion pressure a nd lung weight without reducing tracheal effusion in both rat and guin ea-pig lungs. Pretreatment with allopurinol did not alter the effects of endothelin-1. These results were taken as evidence for the potent l ung oedema-producing effect of the peptide which seems to be partially mediated by the secondary release of thromboxane A2.