Chronic inhibition of cilazapril on pulmonary vascular and myocardial cell proliferation in hypoxic rats |
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Authors: | LI Zhi-bin LUO Zhu-quan WANG Xiao-chun ZOU Xia-ying OUYANG Yan |
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Affiliation: | 1.Department of Respiratory Medicine,2Department of Pathology,3Clinical Lab, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China |
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Abstract: | AIM: To explore the mechanism of cilazapril inhibiting proliferation of pulmonary vascular and myocardial cells in hypoxic rats. METHODS: 30 male Wistar rats were used and divided into three groups: normal control (group A), intermittent hypoxia for 4 weeks (group B) and intermittent hypoxia for 4 weeks plus cilazapril treatment (group C). The cell proliferation and structural remodeling in pulmonary vasculature and myocardium during hypoxia were studied by biochemical analysis, radioimmunoassay, immunohistochemistry, terminal deoxyuridine tripnosphate nick end labeling and correlated with hemodynamic. RESULTS: (1) The mean pulmonary artery pressure (mPAP) and the right ventricle to left ventricle plus ventricular septum ratio (R/L±S) were significantly higher in the hypoxic rat than that in control animals, while increased thickness of the pulmonary vascular wall and vascular lumen with decrease in the caliber as well as myocardial hypertrophy were observed in hypoxic rats. (2) The proliferative index (PI) of pulmonary arteria and myocardium was significantly higher in group B and C than that in group A. The distribution of ET-1 positive cells was seen in pulmonary arterial wall and cardiomyocytes. The ET-1 immunoreactivity was group B>group C>group A by turns. (3) The concentrations of plasma endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) were significantly higher in group B than that in group A. However, the ET-1 and ACE were significantly lower in group C than those in group B. (4) The ET-1 and ACE had a significant positive correlation with R/L+S, mPAP and PI, respectively. The multivariate linear regression analysis revealed that ET-1 and ACE were major factor affecting PI. CONCLUSION: The pulmonary vascular and myocardial structural remodeling are one of the pathogenesis accompanied with excessive cell proliferation in hypoxic pulmonary hypertension (PH). Cilazapril effectively prevents and treats the hypoxic PH by inhibiting cell proliferation and structural remodeling of pulmonary circulation, as induced by ET-1 and ACE. |
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