TY - JOUR T1 - Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats JF - European Respiratory Journal JO - Eur Respir J SP - 904 LP - 912 DO - 10.1183/09031936.00003909 VL - 35 IS - 4 AU - Y. Chen AU - M. Hanaoka AU - Y. Droma AU - P. Chen AU - N. F. Voelkel AU - K. Kubo Y1 - 2010/04/01 UR - http://erj.ersjournals.com/content/35/4/904.abstract N2 - We hypothesised that endothelin (ET)-1 plays an important role in the pathogenesis of emphysema. We attempted to apply ET-1 receptor antagonists to demonstrate and further elucidate the molecular pathogenesis pathways through which ET-1 may cause emphysematous changes. Sprague-Dawley rats were divided into four groups: control, cigarette smoke extract (CSE), CSE+BQ-123 (a selective endothelin receptor type A (ETA) antagonist) and CSE+bosentan (a mixed ETA/ETB receptor antagonist). The CSE was injected intraperitoneally once a week for 3 weeks, and BQ-123 or bosentan was administered daily for the same duration. The expression of ETA receptor, apoptosis index, caspase-3 activity, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and tumour necrosis factor (TNF)-α and interleukin (IL)-1β concentrations were measured in the lung tissue. The ET-1 levels and antioxidant activity were measured in the serum. Both BQ-123 and bosentan prevented the development of CSE-induced emphysema, blocked the expression of ETA receptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-α and IL-1β, and improved the biological antioxidant activity in the serum. Emphysema development is suppressed by ET-1 receptor antagonists. ET-1 may cause emphysematous changes through molecular pathogenesis pathways involving apoptosis, proteinase and antiproteinase imbalance, inflammation and oxidative stress. ER -