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Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension

Gong Yongsheng, Fan Xiaofang, Wu Xiaomai, Hu Lianggang, Tang Chaoshu, Pang Yongzheng, Qi Yongfen

Institute of Cor Pulmonale and Teaching Centre of Functional Experiment,Wenzhou Medical College.Wenzhou 325035,Zhejiang；China

Abstract

The purpose of the present study was to explore the expression changes of intermedin/adrenomedullin 2 (IMD/ADM2), a novel small molecular bioactive peptide, and its receptors, calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2, RAMP3) in the right ventricle of rats with chronic hypoxia-induced pulmonary hypertension. Twenty male Sprague-Dawley rats were randomly divided into 4-week hypoxia group and normal control group (each n=10). The rats in hypoxia group were placed in an isobaric hypoxic chamber, in which O_(2) content was maintained at 9%--11% by delivering N_(2), and CO_(2) content was maintained at <3% for 4 weeks (8 h/d, 6 d/week). The rats in the control group were housed in room air. The protein levels of IMD/ADM2 and adrenomedullin (ADM) in blood plasma and right ventricular tissue were measured by radioimmunoassay. The mRNA expressions of IMD/ADM2, ADM and their receptors CRLR, RAMP1, RAMP2, RAMP3 in right ventricular tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the ratio of right ventricle weight to left ventricle plus septum weight［RV/(LV+S)］ and mean pulmonary arterial pressure (mPAP) were higher in hypoxia group than those in the control group (all P<0.01), suggesting that the successful rat model of pulmonary hypertension was established. However, the mean carotid arterial pressure (mCAP) between the two groups had no significant difference. Compared with that in the control group, ADM contents in plasma and right ventricular tissue in hypoxia group increased by 1.26 and 1.68 folds (all P<0.01), respectively. Likewise, the IMD/ADM2 contents in plasma and right ventricular tissue in hypoxia group increased by 0.90 and 1.19 folds (P<0.01), respectively, compared with that in the control group. The data of RT-PCR showed that mRNA levels of ADM, IMD/ADM2 and RAMP2 in hypoxia group increased by 155.1%(P<0.01), 80.9% (P<0.01) and 52.9% (P<0.05), respectively. compared with those in the control group. There were no significant differences in the mRNA expressions of CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the results show that the levels of IMD/ADM2 increase in the rats with chronic hypoxic-induced pulmonary hypertension.

Key words: Adrenomedullin;intermedin;Receptor;Hypoxia;Hypertension;pulmonary

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Citing This Article：

Gong Yongsheng, Fan Xiaofang, Wu Xiaomai, Hu Lianggang, Tang Chaoshu, Pang Yongzheng, Qi Yongfen. Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension. Acta Physiol Sin 2007; 59 (2): 210-214 (in Chinese with English abstract).