RELEASE OF ENDOTHELIN-1 INTO RAT AIRWAYS FOLLOWING SEPHADEX-INDUCED INFLAMMATION - MODULATION BY ENZYME-INHIBITORS AND BUDESONIDE

The intratracheal (i.t.) instillation of Sephadex beads into the rat i nduced inflammation and a 30-fold increase in the endothelin-1-like im munoreactivity (ET-I-LI) of broncho-alveolar lavage fluid. The levels were highest 24 h after the instillation and had declined significantl y after 48 h. At a dose of 1 mg kg(-1) i.t., the glucocorticosteroid b udesonide almost abolished this response. Phosphoramidon, which inhibi ts neutral endopeptidase, an enzyme reported to degrade ET-1 and also to inhibit the endothelin-converting enzyme, potentiated the Sephadex- induced rise in ET-1-LI. Chymostatin and heparin, which are reported t o reduce the formation of ET-1, did not affect the increase in ET-1-LI . The present model represents a very reactive system for analyzing th e changes in ET-1 levels during inflammation.