Gene Expressions of Nitric Oxide Synthase and Matrix Metalloproteinase-2 in Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment

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.

Gene Expressions of Nitric Oxide Synthase and Matrix Metalloproteinase-2 in Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment

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.

Pulse wave velocity and ankle brachial index in obese adolescents / 소아과

PURPOSE: The prevalence of childhood obesity has doubled over the last 30 years. Obesity-associated sequelae in the vasculature begins in the early stages of life. The purpose of this study was to investigate how pulse wave velocity (PWV) and ankle brachial index (ABI) change with height, weight and body mass index (BMI) in obese adolescents. METHODS: Seventy-nine obese adolescents (group 1: 85thBMI<95th percentile, n=40; group 2 (BMI95th percentile, n=39) were included. The control group(group 3) included 99 healthy adolescents. Brachial-ankle (ba) PWV and ABI were estimated with blood pressure from four extremities. Heart rate (HR), and pre-ejection period/ejection time (PEP/ET) were also estimated. BMI was calculated from individual height and weight. Linear regression analysis was performed to evaluate the correlations between BMI and PWV. RESULTS: Blood pressure and baPWV were significantly higher in group 2, compared to either group 1 or group 3. However, there was no significant difference in ABI, HR and PEP/ET between the groups. PWV showed linear correlation with both BMI and body weight. CONCLUSION: Obesity was associated with higher arterial stiffness in adolescents, which was demonstrated by an increase in PWV. There was no significant correlation between obesity and ABI.

Pulse wave velocity and ankle brachial index in obese adolescents / 소아과

PURPOSE: The prevalence of childhood obesity has doubled over the last 30 years. Obesity-associated sequelae in the vasculature begins in the early stages of life. The purpose of this study was to investigate how pulse wave velocity (PWV) and ankle brachial index (ABI) change with height, weight and body mass index (BMI) in obese adolescents. METHODS: Seventy-nine obese adolescents (group 1: 85thBMI<95th percentile, n=40; group 2 (BMI95th percentile, n=39) were included. The control group(group 3) included 99 healthy adolescents. Brachial-ankle (ba) PWV and ABI were estimated with blood pressure from four extremities. Heart rate (HR), and pre-ejection period/ejection time (PEP/ET) were also estimated. BMI was calculated from individual height and weight. Linear regression analysis was performed to evaluate the correlations between BMI and PWV. RESULTS: Blood pressure and baPWV were significantly higher in group 2, compared to either group 1 or group 3. However, there was no significant difference in ABI, HR and PEP/ET between the groups. PWV showed linear correlation with both BMI and body weight. CONCLUSION: Obesity was associated with higher arterial stiffness in adolescents, which was demonstrated by an increase in PWV. There was no significant correlation between obesity and ABI.

Serum Cytokine Levels in Hypertensive Children: Tumor Necrosis Factor-alpha, Interleukin-6

BACKGROUND AND OBJECTIVES: Acute systemic inflammation is associated with an increased risk of acute cardiovascular events. Recently published data have suggested that chronic inflammation could be an independent risk factor for hypertension. Association between interleukin (IL)-6 or tumor necrosis factor (TNF)-alpha and hypertension is controversial. The purpose of this study is to investigate the association between blood pressure and cytokines such as TNF-alpha, IL-6 and adiponectin in hypertensive children. SUBJECTS AND METHODS: Eighty hypertensive children were included in this study. The obesity index, body mass index (BMI) and skin fold thickness of the subjects were measured, and the fat mass and distributions analyzed. Blood pressure was also measured, as were the serum aldosterone, renin, angiotensin converting enzyme (ACE), insulin and homocysteine levels. The serum TNF-alpha, IL-6 and adiponectin levels were also estimated. RESULTS: The serum renin, insulin, homocysteine and IL-6 levels were significantly increased in hypertensive compared to normal children. The serum TNF-alpha level had positive correlation with the insulin and negative correlations with adiponectin levels, respectively. The level of insulin had a significant negative correlation with that of adiponectin. CONCLUSION: The serum IL-6 level was significantly increased in hypertensive children. Further long-term follow-up studies will be required to reveal the role of cytokines in hypertensive children.

Effects of Smoking on the Pulse Wave Velocity and Ankle Brachial Index in Adolescents

BACKGROUND AND OBJECTIVES: Smoking is known to increase arterial stiffness in adults. The pulse wave velocity (PWV) is known as an established index of arterial stiffness. The effects of smoking on the PWV in adolescents have not yet been established. We measured the PWV and ankle-brachial index (ABI) in adolescents to determine the effects of smoking on adolescents. SUBJECTS AND METHODS: Four hundred twenty-seven adolescents between 14 to 16 years of age were enrolled from three high schools in Seoul, Korea. The study group was comprised of 48 smokers (38 males and 10 females) and 379 nonsmokers (254 males and 125 females). Measurements of the height, weight and body mass index (BMI) were performed. The blood pressures of the extremities, and the PWV, the ABI, the ejection time and the pre-ejection period were measured using an automatic device (VP-1000). Among the smoking group, we investigated the association between the duration of smoking, the age at which smoking started and the total number of cigarettes smoked with the PWV and ABI. RESULTS: The brachial-ankle PWV (baPWV) in the smoking group was higher than that of the non-smoking group, but the difference was not statistically significant. There was no significant difference between the ABI of the two groups. Among the smokers, the heart-brachial PWV (hbPWV) was significantly associated with the duration of smoking and the total number of cigarettes smoked. CONCLUSION: Our study showed no significant difference in the PWV between the two groups. A longitudinal, long-term investigation is needed to more accurately determine the effects of smoking on adolescents.