Adrenomedullin alleviates collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the effect of adrenomedullin (ADM) on the pulmonary vascular collagen metabolism in hypoxic rats in order to study the effect of ADM on chronic hypoxic pulmonary vascular structural remodeling and its possible mechanism.</p><p><b>METHODS</b>Nineteen male Wistar rats were randomly divided into three groups: normal control (n=6), hypoxia (n=7) and ADM-treated hypoxia (n=6). ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by mini-osmotic pump (300 ng/h) for two weeks. After two weeks of hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass[RV/ (LV+S)] was measured. The changes of pulmonary vascular microstructure were observed. Meanwhile, the expression levels of collagen I, collagen III and transforming growth factor (TGF)-β in pulmonary arteries were detected by immunohistochemical assay.</p><p><b>RESULTS</b>mPAP and RV/(LV+S) increased significantly in the hypoxia group compared with normal controls (P<0.01). The muscularization of small pulmonary vessels and the relative medial thickness of pulmonary arteries increased obviously in the hypoxia group compared with those in the normal control group (P<0.01). Meanwhile, the expression levels of collagen I, collagen III and TGF-β of pulmonary arteries in the hypoxia group increased markedly compared with those in the normal control group. However, mPAP and RV/(LV+S) were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group (P<0.01). ADM ameliorated pulmonary vascular structural remodeling of hypoxic rats, with a decrease in the expression of collagen I, collagen III and TGF-β of pulmonary arteries.</p><p><b>CONCLUSIONS</b>ADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling, through inhibiting the expression of TGF-β and alleviating the collagen accumulation of pulmonary arteries.</p>

Alterations of proadrenomedullin N-terminal 20-peptide in rats with pulmonary hypertension induced by high pulmonary blood flow / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The mechanism of high pulmonary blood flow-induced pulmonary hypertension remains unclear. The aim of this study was to explore the effect of proadrenomedullin N-terminal 20-peptide (PAMP) on pulmonary hypertension, through examining the alterations of pulmonary PAMP expression and plasma PAMP concentration in rats with pulmonary hypertension induced by high pulmonary blood flow.</p><p><b>METHODS</b>Sixteen male Sprague-Dawley rats were randomly divided into control (n=8) and shunt groups (n=8). Aortocaval shunting was produced in the shunt group. After 11 weeks of shunting, systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP) and mean pulmonary artery pressure (mPAP) were evaluated by using a right cardiac catheterization procedure. The ultrastructural changes in intra-acinar pulmonary arteries were observed. The concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP in pulmonary arteries was detected by immunohistochemical assay.</p><p><b>RESULTS</b>sPAP, dPAP and mPAP were significantly increased in shunt rats compared with controls (P < 0.01). Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, and hypertrophy and increased number of synthetic phenotype of smooth muscle cells, were found in intra-acinar pulmonary muscularized arteries in the shunt group. Plasma PAMP concentration (616 +/- 195 pg /mL vs 427 +/- 90 pg /mL) and PAMP expression in endothelial cells (0.62 +/- 0.09 vs 0.38 +/- 0.12) and in smooth muscle cells (0.24 +/- 0.07 vs 0.14 +/- 0.05) of pulmonary arteries increased significantly in the shut group compared with controls.</p><p><b>CONCLUSIONS</b>The up-regulation of pulmonary and plasm PAMP expression might be involved in the development of high pulmonary blood flow-induced pulmonary hypertension.</p>

Imbalance of endogenous homocysteine and hydrogen sulfide metabolic pathway in essential hypertensive children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H(2)S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension.</p><p><b>METHODS</b>Twenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H(2)S level was detected by a modified method with a sulfide electrode. Data were presented as mean +/- standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H(2)S as well as to the systolic pressure against the plasma H(2)S/Hcy ratio.</p><p><b>RESULTS</b>Plasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H(2)S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68 +/- 9.69) micromol/L vs (6.62 +/- 4.79) micromol/L (t = 2.996, P < 0.01); H(2)S: (51.93 +/- 6.01) micromol/L vs (65.70 +/- 5.50) micromol/L) (t = -8.670, P < 0.01)). The ratio of plasma H(2)S/Hcy in children with hypertension was 5.83 +/- 2.91, while that of the control group was 11.60 +/- 3.30, and the difference is significant with a t = -6.610 and P < 0.01. A negative correlation existed between plasma Hcy and H(2)S concentrations, r = -0.379, P < 0.05. And a negative correlation was found between systolic blood pressure and the plasma H(2)S/Hcy ratio, r = -0.687, P < 0.05.</p><p><b>CONCLUSION</b>There was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.</p>

The dynamic changes in endogenous hydrogen sulfide pathway at the early stage of pulmonary hypertension induced by high pulmonary flow in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the time-dependent changes of endogenous hydrogen sulfide system at the early stage of pulmonary hypertension induced by high pulmonary flow in rats.</p><p><b>METHODS</b>Eighty male SD rats, whose weight ranged 140 - 160 g, were randomly divided into control group (n = 40) and shunt group (n = 40). Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. After 1 d, 3 d, 1 week, 4 week and 8 weeks of experiment, systolic pulmonary artery pressure (SPAP) of each rat, the H2S of rat lung tissue and CSEmRNA of rat lung tissue were evaluated, respectively.</p><p><b>RESULTS</b>SPAP increased significantly as compared with those in control group in 1 week and 8 weeks of experiment. In contrast to control group, the H2S of rat lung tissue increased significantly on 3 d and in 4 weeks, respectively. Meanwhile, in contrast to control group, relative amount of CSE mRNA of lung tissues elevated significantly on 3 d and in 4 weeks, respectively. Moreover, SPAP and the H2S of rat lung tissue, the CSE mRNA of rat lung tissue correlated negatively in 1 week, 4 weeks and 8 weeks of experiment.</p><p><b>CONCLUSION</b>Animal model of rats with high pulmonary blood flow exhibited pulmonary hypertension. Lung tissue H2S and CSE mRNA of rats exhibited double peaks within 8 weeks. These results revealed that endogenous H2S system might be relevant with the development of pulmonary hypertension induced by high pulmonary blood flow, and probably, it played a protective role in the regulation of pulmonary hypertension, especially, at its early stage.</p>

Range of plasma hydrogen sulfide in children / 中国医学科学院学报

<p><b>OBJECTIVE</b>To measure the range of plasma hydrogen sulfide (H2S) in children.</p><p><b>METHODS</b>Totally 200 healthy children were classified into 4 groups based on age and sex: 7-14 years old group (n = 75, 43 boys and 32 girls), 15-19 years old group (n = 125, 64 boys and 61 girls). Plasma H2S level was detected by a modified sulfide electrode-based method.</p><p><b>RESULTS</b>Plasma H2 S levels were (52.2181 +/- 17.9400) micromol/L in 7-14 years old boys, (51.9441 +/- 16.5448) micromol/L in 7-14 years old girls, (52.8771 +/- 14.1444) micromol/L in 15-19 years old boys, and (53.6551 +/- 14.5563) micromol/L in 15-19 years old girls (P > 0.05). In summary, the range of plasma H2S in children was about (52.8234 +/- 15.4339) micromol/L.</p><p><b>CONCLUSION</b>The range of plasma H2S in children is about (52.8234 +/- 15.4339) micromol/L.</p>

Observation of Dynamic Changes in Ultra-Micro-Structure of Pulmonary Arteries and Endogenous Hydrogen Sulfide in Rats with Left-Right Shunt / 实用儿科临床杂志

Objective To explore the relationship between dynamic changes in ultra-micro-structural of pulmonary arteries and endogenous hydrogen sulfide in rats with left-right shunt.Methods Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of pulmonary artery structural remodeling. After 1 day, 3 days, 1 week, 4 weeks and 8 weeks of experiment, the ultra-micro-morphologic changes of pulmonary arteries of rats were observed under electronic microscope and H_2S concentration in serum was evaluated by modified sulfide electrode method.Results The changes of ultra-micro-structure of pulmonary arteries were progressively exacerbated, endothelial cells became swollen and large in size on 3 days, smooth muscular cells increased in size as well as the change of endothelial cells in 1 week, and they changed from contractile phenotype to synthetic phenotype in 4 weeks.Conclusions Shunt exhibited changes of ultra-micro-structure of pulmonary arteries are accompanied by the changes of endogenous H_2S. It is suggested that endogenous H_2S might play a protective role in changes of ultra-micro-structure of pulmonary artery.

Effect of Adrenomedullin Subcutaneously Administered by Mini-Osmotic Pump on Hypoxic Pulmonary Hypertension in Rats / 实用儿科临床杂志

Objective To study the modulation effect of adrenomedullin (ADM) on hypoxia pulmonary hypertension in rats.Methods Twenty-four male Wistar rats were randomly divided into control group ( n =8), hypoxic group ( n =8), hypoxic with ADM group ( n =8). ADM was subcutaneously administered into rats of hypoxic with ADM group by mini-osmotic pump (300 ng/h). After two weeks hypoxic challenge, systolic pulmonary arterial pressure (sPAP) and mean pulmonary arterial pressure (mPAP) were evaluated by a right cardiac catheterization procedure. Mean systemic artery pressure (mSAP) was measured. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+S)] was detected.Results sPAP, mPAP and RV/(LV+S) significantly increased in hypoxic rats compared with controls ( P

Changes Hydrogen Sulfide in Plasma of Children with Congenital Heart Disease / 实用儿科临床杂志

Objective To investigate the changes of hydrogen sulfide (H_2S) level in plasma in order to explore the role of H_2S in the development of pulmonary hypertension (PH) secondary to congenital heart disease (CHD).Methods There were 9 CHD patients and 9 normal children in this study. The plasma concentration of H_2S and pulmonary artery pressure (PAP) of each child were measured. Meanwhile, the relationship between H_2S level and PAP was analyzed.Results The plasma level of H_2S in the group of CHD significantly decreased compared with control group (32.13?2.25) ?mol/L vs [(43.69?2.05)?mol/L, P