RESUMO
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.
RESUMO
Methylenetetrahydrofolate reductase (MTHFR) is associated with homocysteine level. In deficit of MTHFR, cardiovascular risk is increased with hyperhomocysteinemia and hypomethionemia. Mutation of the MTHFR gene is associated with the risk for premature cardiovascular diseases. However, the association between MTHFR mutation and cardiovascular risk is still controversial. The purposes of this study were to determine whether MTHFR genotype is associated with cardiovascular risks in hypertensive adolescents and to investigate the association between MTHFR genotype and carotid intima-media thickness (IMT). Forty-three hypertensive adolescents were included in this study. Serum lipid levels, insulin, vitamin B(12), folate, renin, aldosterone, angiotensin converting enzyme, and homocysteine levels were evaluated. The carotid IMT and diameter were estimated by ultrasound. Brachial-ankle pulse wave velocity was also measured. Polymerase chain reaction was conducted to amplify genomic DNA fragment containing C677T position of the MTHFR gene. The height, weight, body mass index, obesity index, arm circumference, fat mass, and fat distribution were significantly greater in patients with C677T mutation. The C677T mutation group showed significantly greater carotid IMT, higher homocysteine, and lower folic acid levels than the normal genotype group. Interpretation of MTHFR genotype might be useful in predicting the development of premature coronary artery disease in hypertensive adolescents.
