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ABSTRACT: 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.
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.
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.
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.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 02/2007; 23(1):75-9.
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ABSTRACT: The mechanism of pulmonary vascular structural remodeling and pulmonary hypertension induced by high pulmonary blood flow is still unclear. Nitric oxide (NO) and carbon monoxide (CO) are two gaseous molecules recently discovered; both can induce the relaxation of blood vessels and inhibit the proliferation of vascular smooth muscle cells. More recently, urotensin-II (U-II) has been considered as the most potent mammalian vasoconstrictor identified so far, which can promote the proliferation of vascular smooth muscle cells. The aim of this study was to investigate the alteration of micro- and ultrapathologic structure, gaseous molecules, and U-II in rats with pulmonary hypertension induced by increased pulmonary blood flow. Aortocaval shunting was produced in rats. After 11-weeks of shunting, pulmonary artery mean pressure (PAMP) was measured. Pulmonary vascular micro- and ultrastructure was examined. Meanwhile, the concentration of plasma NO and CO was measured by spectrophotometry. The expression of endothelial nitric oxide synthase (eNOS), heme oxygenase-1 (HO-1), and U-II by pulmonary arteries was detected by immunohistochemistry. The results showed that PAMP was significantly elevated after 11 weeks of aortocaval shunting (2.99 +/- 0.35 kPa vs 2.09 +/- 0.38 kPa, P < 0.01). Muscularization of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in shunt rats compared with controls. Ultrastructural changes were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased and eNOS expression by pulmonary artery endothelial cells was significantly augmented in rats of the shunting group, but there was no significant difference in plasma CO level and HO-1 expression by pulmonary artery smooth muscle cells between shunting and sham groups. Urotensin-II expression by pulmonary artery endothelial cells and smooth muscle cells was significantly strengthened in shunt rats compared with sham rats. The results suggest that pulmonary vascular structural remodeling is an important pathologic basis of pulmonary hypertension induced by a left-to-right shunt. Upregulation of U-II might play an important role in the development of high pulmonary blood flow-induced pulmonary hypertension. Nitric oxide, as a modifying factor, might be involved in the regulation of pulmonary vascular structural remodeling.
Heart and Vessels 04/2004; 19(2):81-8. · 2.05 Impact Factor
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ABSTRACT: To study human urotensin II (hUII) expression in intrapulmonary arteries of rats with pulmonary hypertension induced by high pulmonary blood flow and explore the role of hU II in the development of pulmonary hypertension induced by left to right shunt.
Aortocaval shunting was produced for 11 weeks in rats. Pulmonary artery mean pressure (PAMP) of each rat was evaluated using right cardiac catheterization. The pulmonary vascular structural changes, including the percentage of muscularized arteries of small pulmonary vessels and relative medial thickness of intra-acinar pulmonary arteries were examined. Meanwhile, the expression of hU II by pulmonary arteries was detected by immunohistochemistry.
After 11-week aortocaval shunting, PAMP was significantly increased. The percentage of muscularized arteries of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in shunting rats compared with controls (P < 0.01, respectively). Meanwhile, hU II expression by pulmonary artery endothelial cells and smooth muscle cells was significantly augmented in rats of shunt group, which was positively correlated with PAMP and the structural changes in pulmonary arteries.
The up-regulation of hU II in pulmonary arteries might be involved in the development of pulmonary vascular structural remodeling and pulmonary hypertension induced by high pulmonary blood flow.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 08/2003; 19(3):274-7.
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ABSTRACT: Pulmonary vascular structural remodeling induced by high pulmonary blood flow is an important pathologic basis of pulmonary hypertension with congenital heart disease of left-to-right shunt. However, the mechanism is still not clear. The present study aimed to examine the alteration of endogenous nitric oxide (NO) pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling, so as to explore the role of NO pathway in pulmonary hypertension induced by high pulmonary blood flow.
Sixteen male SD rats were randomly divided into control group (n = 8) and shunting group (n = 8). Aortocaval shunting was produced for 11 weeks in shunt rats. Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV + S)] was detected. Pulmonary vascular micro-and ultra-structure was examined by using a light microscope and a transmitted electronic microscope. Meanwhile, the concentration of plasma NO was measured by spectrophotometry. The expressions of endothelial NO synthase (eNOS) mRNA and protein by pulmonary arteries were detected by in situ hybridization and immunohistochemistry, respectively.
After 11-week aortocaval shunting, mPAP was significantly increased [(22.5 +/- 2.6) mmHg vs. (15.8 +/- 2.8) mmHg, 1 mmHg = 0.133 kPa, t = 4.97, P < 0.01], and RV/(LV + S) was also markedly increased (0.267 +/- 0.022 vs. 0.221 +/- 0.016, t = 4.85, P < 0.01). The percentage of muscularized arteries was obviously increased in shunt rats compared with controls [(23.2 +/- 2.4)% vs. (13.5 +/- 2.1)%, t = 7.82, P < 0.01], and relative medial thickness of pulmonary arteries was obviously increased in shunt rats [median pulmonary artery: (7.76 +/- 0.56)% vs. (4.82 +/- 1.03)%, t = 6.23, P < 0.01; small pulmonary artery: (11.94 +/- 0.66)% vs. (6.91 +/- 0.53)%, t = 14.96, P < 0.01]. Ultrastructural changes, such as hyperplasia and degeneration of endothelial cells, irregularity of internal elastic laminar and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased [(30.2 +/- 7.9) micromol/L vs (19.7 +/- 5.7) micromol/L, t = 3.05, P < 0.01) and eNOS mRNA and protein expressions by pulmonary arteries were significantly augmented in rats of shunting group.
The upregulation of eNOS/NO might be an adaptive response of pulmonary circulation to an increased blood flow in the development of pulmonary hypertension and pulmonary vascular structural remodeling.
Zhonghua er ke za zhi. Chinese journal of pediatrics 03/2003; 41(3):215-8.
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ABSTRACT: To explore the modulating effect of L-arginine on collagen metabolism of pulmonary artery in rats with high pulmonary blood flow-induced pulmonary hypertension and its molecular mechanism.
Eighteen rats were randomly divided into 3 groups of 6 rats: shunt group (pulmonary hypertension was established with an abdominal aorta and inferior vena cava shunting), shunt + L-Arg group (L-arginine, 1 g x kg(-1) x d(-1) was given into the stomachs of rats for weeks after shunting), and control group. After 11 weeks of experiment, the pulmonary hemodynamics were studied, the contents of collagen I and collagen III expressions were detected by immunohistochemical assay. The expressions of procollagen I mRNA, procollagen III mRNA, TIMP-1 mRNA and MMP-1 mRNA were detected by in situ hybridization.
After 11 weeks of experiment, the mean pulmonary artery pressure (MPAP) in shunt group was 23.0 mm Hg +/- 0.9 mm Hg, higher than that in shunt + L-Arg group (18.0 mm Hg +/- 1.8 mm Hg, P < 0.01) and that in control group (15.7 mm Hg +/- 1.1 mm Hg, P < 0.01). The expressing integral scores of collagen I and collagen III, the expression of procollagen I mRNA, Procollagen III mRNA, TIMP-1 mRNA, MMP-1 mRNA and the ratio of TIMP-1/MMP-1 were significantly higher in the shunt group than in the other 2 groups (P < 0.01 or P < 0.05).
L-arginine reduces the synthesis of extracellular matrix-collagen and increases its degradation. Thus L-arginine has important modulating effects on pulmonary hypertension and pulmonary vascular remodeling induced by high pulmonary blood flow.
Zhonghua yi xue za zhi 10/2002; 82(18):1273-5.
