Expression and distribution of 5-HT_(1B) receptors in lung tissue in rats with hypoxic pulmonary hypertension

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(P0.05),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(P0.05).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.