REGULATORY EFFECTS OF AEROSOLIZED BUDESONIDE AND ADRENALECTOMY ON THELUNG CONTENT OF ENDOTHELIN-1 IN THE RAT

This study was designed to investigate the effect of inflammation and glucocorticosteroids (GCS) on the content of endothelin-1-like immunor eactivity (ET-LI) in the rat lung. Following intratracheal instillatio n of Sephadex beads, which induces a long-lasting inflammation in the lung, there was an increase in the lung content of ET-LI measured by R IA. This increase was abolished by locally administered aerosolized bu desonide at doses that had only minor systemic effects (measured as a reduction in body weight). In a second series of experiments, rats wer e subjected to surgical adrenalectomy in order to reduce the levels of endogenous GCS. This procedure elevated the ET-LI levels in the lungs . In contrast, neither adrenalectomy nor high doses of budesonide admi nistered systemically affected the concentration of ET-LI in the kidne y. It is concluded that the lung ET levels are elevated in inflammator y conditions and that this increase is highly sensitive to locally adm inistered GCS. Endogenous GCS may, directly or indirectly, play a role in the regulation of lung ET content but there seems to be no general GCS effect on basal tissue levels of ET.