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 investigat e the role of endogenous endothelin-l (ET-1) in the development of the Sephadex-induced lung inflammation in the rat. Intratracheal instilla tion of Sephadex caused a 60-fold rise in endothelin-1-like-immunoreac tivity (ET-1-LI) in bronchoalveolar ravage fluid (BALF) concomitant wi th development of lung oedema. an influx of inflammatory cells into th e 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 bur 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 instillati on, but no significant change in the number of leucocytes or protein c oncentration in BALF. The present data thus do not support the hypothe sis 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.