title: Gene expressions of nitric oxide synthase and matrix metalloproteinase-2 in monocrotaline-induced pulmonary hypertension in rats after bosentan treatment.
abstract: OBJECTIVE
  Nitric oxide (NO) is a major endothelium dependent vasomediator and growth inhibitor. NO synthesis is catalyzed by endothelial nitric oxide synthase (eNOS), and NO can also produce peroxynitrite, which activates matrix metalloproteinases (MMPs). The purpose of this study was to determine the gene expression of eNOS and MMP-2 in the lungs of a rat model of pulmonary hypertension after bosentan treatment.
  
  
  METHODS
  Six-week-old male Sprague-Dawley rats were treated as follows: control group, subcutaneous (sc) injection of saline; monocrotaline (MCT) group, sc injection of MCT (60 mg/kg); and bosentan group, sc injection of MCT (60 mg/kg) plus 20 mg/day bosentan orally. The rats were sacrificed after 1, 5, 7, 14 and 28 days.
  
  
  RESULTS
  The right ventricle/(left ventricle+septum) ratio significantly increased in the MCT group compared to the control group on day 14 and 28. The expression of eNOS messenger ribonucleic acid was significantly increased in the MCT group compared to the control group on day 28. MMP-2 gene expression was significantly increased in the MCT-treated rats compared to the control group on day 5 and 28. Following bosentan treatment to reduce pulmonary hypertension, the expression levels of MMP-2 gene were significantly decreased on day 7 and 28. eNOS and tissue inhibitor of MMPs genes were also significantly decreased on day 28 after bosentan treatment.
  
  
  CONCLUSIONS
  These results suggest that elevated eNOS expression may be responsible for MMP-2 activation. The causal relationship between eNOS and MMP-2 and their role in pulmonary hypertension require further investigations.
authors: Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul, Korea.
authors: Hee Sun
authors: HS
authors: Koo
authors: Kwan Chang
authors: KC
authors: Kim
authors: Young Mi
authors: YM
authors: Hong