The effect of endothelin receptor blockade on the development of the Sephadex-induced inflammation in the rat lung.
The non-peptide ET-receptor antagonist Bosentan was used to investigate the role of endogenous endothelin-1 (ET-1) in the development of the Sephadex-induced lung inflammation in the rat. Intratracheal instillation of Sephadex caused a 60-fold rise in endothelin-1-like-immunoreactivity (ET-1-LI) in bronchoalveolar lavage fluid (BALF) concomitant with development of lung oedema, an influx of inflammatory cells into the airways and a rise in the protein content in BALF. The ET-1-LI level in lung homogenate was not significantly affected. Pre-treatment with Bosentan reduced ET-1-LI content in the lung parenchyma but increased ET-1-LI levels in BALF, possibly indicating an effective displacement of ET-1 from its receptors. In Bosentan-treated animals there was an enhancement of the lung oedema formation following Sephadex instillation, but no significant change in the number of leucocytes or protein concentration in BALF. The present data thus do not support the hypothesis that endogenous ET-1 mediates oedema formation or leucocyte influx in this model. If anything, Bosentan enhanced the oedema formation in parallel with increased ET-1-LI in BALF.
Department of Physiology and Medical Biophysics, University of Uppsala, Sweden.
S E
SE
Andersson
A
A
Hemsén
J M
JM
Lundberg
D000818:Animals; D000077300:Bosentan; D003911:Dextrans / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D007249:Inflammation / Q000139:chemically induced; D008168:Lung / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*
D003911:Dextrans; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; C025614:sephadex; D000077300:Bosentan