Release of Endothelin-1 into Rat Airways following Sephadex-Induced Inflammation; Modulation by Enzyme Inhibitors and Budesonide

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Abstract
The intratracheal (i.t.) instillation of Sephadex beads into the rat induced inflammation and a 30-fold increase in the endothelin-1-like immunoreactivity (ET-1-LI) of broncho-alveolar lavage fluid. The levels were highest 24 h after the instillation and had declined significantly after 48 h. At a dose of 1 mg kg-1 i.t., the glucocorticosteroid budesonide almost abolished this response. Phosphoramidon, which inhibits 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 to reduce the formation of ET-1, did not affect the increase in ET-l-LI. The present model represents a very reactive system for analyzing the changes in ET-1 levels during inflammation.

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