RT Journal Article SR Electronic T1 Bosentan inhibits cigarette smoke-induced ET receptor expression in pulmonary arteries JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP erj00214-2011 DO 10.1183/09031936.00021411 A1 J. Milara A1 E. Gabarda A1 G. Juan A1 J.L. Ortiz A1 R. Guijarro A1 M. Martorell A1 E.J. Morcillo A1 J. Cortijo YR 2011 UL http://erj.ersjournals.com/content/early/2011/08/04/09031936.00021411.abstract AB Endothelin system contributes to lung vascular tension and remodeling in smokers and chronic obstructive pulmonary disease (COPD) patients. This study examines the effect of cigarette smoke on endothelin receptor A (ETA) and B (ETB) expression, in human pulmonary artery smooth muscle cells (HPASMCs) and human small intrapulmonary arteries as well as their functional consequences.Cigarette smoke extract increased ETA and ETB expression in HPASMCs and small intrapulmonary arteries which were attenuated by bosentan, the ETA antagonist BQ123 the ETB antagonist BQ788 and by blocking ET-1 with a monoclonal antibody against ET-1, suggesting a feed-forward mechanism mediated by ET-1 release. Endothelin receptor antagonism attenuated the cigarette smoke extract-induced HPASMC proliferation. Furthermore, cigarette smoke extract exposure increased the acute ET-1-induced small intrapulmonary artery contraction which was attenuated by Bosentan, BQ123 and BQ788. Pulmonary arteries from smokers and COPD patients showed a higher expression of ETA and ETB than those of non-smoker patients. These results show a novel mechanism by which endothelin receptor blockade attenuates cigarette smoke-induced endothelin receptor over-expression and subsequently small intrapulmonary artery tension. These data may be of potential value to explain therapeutic effects of bosentan in some forms of disproportionate pulmonary hypertension in COPD patients.