Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats.
Eur Respir J
; 35(4): 904-12, 2010 Apr.
Article
in En
| MEDLINE
| ID: mdl-19897563
ABSTRACT
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 (ET(A)) antagonist) and CSE+bosentan (a mixed ET(A)/ET(B) 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 ET(A) receptor, apoptosis index, caspase-3 activity, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta 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 ET(A) receptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-alpha and IL-1beta, 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.
Full text:
1
Database:
MEDLINE
Main subject:
Peptides, Cyclic
/
Pulmonary Emphysema
/
Sulfonamides
/
Endothelin A Receptor Antagonists
Limits:
Animals
Language:
En
Journal:
Eur Respir J
Year:
2010
Type:
Article
Affiliation country:
Japan