Expression and distribution of 5-HT1B receptors in lung tissue in rats with hypoxic pulmonary hypertension |
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Authors: | WANG Jia-xing TANG Fa-kuan XIAO Jun HUA Ning BU Lun WANG De-shui WANG Hong-ye ZHANG Yu-shun |
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Institution: | 1. Department of Cardiology, 309 Hospital of PLA, Beijing 100091, China;2. Second Department of Cardiology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, China. E-mail: zys2889@sina.com |
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Abstract: | AIM: To investigate the changes of 5-hydroxytryptamine(5-HT)levels and to observe the expression and distribution of 5-HT1B receptors in the lung tissues of hypoxic pulmonary hypertension(HPH) rats for exploring the mechanisms of hypoxic pulmonary hypertension.METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups: normoxia control(control group), 3 weeks hypoxia group, 4 weeks hypoxia group and 5 weeks hypoxia group. The rats in normoxia control group stayed in normal environment. The rats in 3 weeks hypoxia group, 4 weeks hypoxia group and 5 weeks hypoxia group were kept respectively in hypoxia chamber for 3 weeks, 4 weeks and 5 weeks respectively to establish the HPH animal model. After HPH was established, the mean pulmonary pressure(mPAP) and the right ventricular systolic pressure(RVSP) were recorded by a micro-catheter. RV/(LV+S) ratio was calculated to assess the right ventricular hypertrophy. 5-HT levels in plasma and lung tissues of HPH rats were measured by ELISA. The expression and distribution of 5-HT1B receptors in the lung tissues were measured by the methods of immunohistochemistry and Western blotting. RESULTS: Compared to the normoxia controls, mPAP, RVSP and RV/(LV+S)% in 3 weeks hypoxic rats increased significantly(P<0.05), and continued to increase following prolonged hypoxia. The results of ELISA showed that 5-HT levels in plasma and lung tissues of HPH rats continued to increase following prolonged hypoxic exposure(P<0.05). The 5-HT1B receptors were localized mainly in the intima of the pulmonary arteries in normal rats. Exposed to hypoxia, the immuno-reactivity for 5-HT1B receptors increased in the media of pulmonary arteries in 3 weeks hypoxic rats, particularly those bordering the adventitia. The increase in the expression of 5-HT1B receptor was observed following prolonged hypoxic exposure. The results of Western blotting showed the same changes of 5-HT1B receptor expression in the lung tissues as that of 5-HT1B immuno-reactivity in pulmonary arteries.CONCLUSION: Hypoxia induces the high 5-HT levels and the over-expression of 5-HT1B receptors in the pulmonary arteries of HPH rats, indicating the underlying mechanism of 5-HT in the development of HPH. |
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