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-degradtive enzymes (captopril and thiorphan 10 microM 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 microM, 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.
Brattsand
R
R
AB Draco, Lund, Sweden.
O'Donnell
S R
SR
Miller-Larsson
A
A
Rauchle
K L
KL
D000287:Administration, Topical; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019819:Budesonide; D002196:Capillaries / Q000378:metabolism; D005938:Glucocorticoids; D007279:Injections, Subcutaneous; D009092:Mucous Membrane / Q000187:drug effects; D011282:Pregnenediones / Q000008:administration & dosage / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D014136:Tracheitis / Q000139:chemically induced / Q000517:prevention & control*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D005938:Glucocorticoids; D011282:Pregnenediones; D011480:Protease Inhibitors; D019819:Budesonide; D001920:Bradykinin