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 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-1-LI. The present model represents a very reactive system for analyzing the changes in ET-1 levels during inflammation.
Andersson
S E
SE
Department of Pharmacology, Astra-Draco, Lund, Sweden.
Hemsén
A
A
Zackrisson
C
C
Lundberg
J M
JM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019819:Budesonide; D002851:Chromatography, High Pressure Liquid; D003911:Dextrans; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism*; D011282:Pregnenediones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003911:Dextrans; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D009842:Oligopeptides; D011282:Pregnenediones; D019819:Budesonide; D006493:Heparin; C025614:sephadex; C002101:chymostatin; D006861:Hydrogen Peroxide; C008890:phosphoramidon