Gene Expressions of Nitric Oxide Synthase and Matrix Metalloproteinase-2 in Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment.
- Author:
Hee Sun KOO
1
;
Kwan Chang KIM
;
Young Mi HONG
Author Information
- Publication Type:Original Article
- Keywords: Pulmonary hypertension; Monocrotaline; Gene expression; Nitric oxide synthase; Matrix metalloproteinases
- MeSH: Animals; Endothelium; Gene Expression; Humans; Hypertension, Pulmonary; Lung; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinases; Monocrotaline; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; RNA; Sulfonamides
- From:Korean Circulation Journal 2011;41(2):83-90
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: 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. MATERIALS AND 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. CONCLUSION: 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.
