ATTENUATION OF BRADYKININ-INDUCED MUCOSAL INFLAMMATION BY TOPICAL BUDESONIDE IN RAT TRACHEA

The extravasation of plasma proteins and formation of interendothelial gaps in submucosal microvessels by mucosally-applied bradykinin (BK), were studied in the rat trachea. The effects of topical and systemic (s.c.) glucocorticoid budesonide (BUD) were investigated in the presence or absence of inhibitors of BK-degradive enzymes (captopril and thiorphan 10-mu-M to inhibit angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), respectively). Inhibition of these enzymes markedly increased the inflammatory responses to BK. Topical BUD (3-mu-M, 10 min contact, 90 min before BK) significantly decreased the volume of plasma in the tracheal lumen, both in the absence and presence of the enzyme inhibitors. Thus, the main anti-transudation mechanism of topical BUD is not related to modulation of BK-breakdown. However, this may be the mechanism for systemic BUD. Neither topical nor systemic BUD prevented interendothelial gap formation.