79924

ADM2

AM2|dJ579N16.4;adrenomedullin 2;ADM2;adrenomedullin 2

intermedin

22q13.33

protein-coding

Count: Adm2; 399475

AIM: To investigate the changes and probable roles of adrenomedullin2/intermedin (AIDM2/IMD), a novel micromolecular bioactive peptide, in the lungs of rats with chronic hypoxic pulmonary hypertension. METHODS: Twenty male SD rats were randomly divided into normal control group (NC) and normobaric hypoxia group (4H). The protein levels of ADM and ADM2/IMD) in the plasma and lung were measured by radioimmunoassay and immunohistochemistry. The mRNA expressions of ADM, ADM2/IMD and their receptors C (RLR, RAMP1, RAMP2 and RAMP3 in the lung tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) The rat model of chronic pulmonary hypertension was confirmed by the increased mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] in 4H group compared to NC group. (2) The concentrations of ADM in the plasma and lung homogenate of 4H group were 2.3 and 3.2 folds of NC group, respectively (all P < 0.01). The levels of ADM2/IMD were higher 89.6% and 45.0% in the plasma and lung homogenate of 4H group than those of NC group (respectively, P < 0.01, P < 0.05). (3) The mRNA expressions of ADM2/IMD and ADM in the lung of 4H group were up-regulated (respectively, P < 0.01, P < 0.05 vs. NC group). The expressions of CRLR and RAMP1 mRNAs were down-regulated (all P < 0.01 vs. NC group), while the levels of RAMP2 and RAMP3 mRNAs were no significant difference between the two groups. (4) The strong ADM2/IMD immunostaining was detected in the endothelial and adventitial cells of the rat pulmonary arteriole. CONCLUSION: ADM2/IMD, like its paralog ADM, might be closely related to the chronic hypoxic pulmonary hypertension in rats. The disorders of the gene expression and/or the synthesis and metabolism of ADM2/IMD and its receptor CRLR/RAMP1 possibly take part in the pathogenesis of chronic hypoxic pulmonary hypertension in rats.

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 rat model of pulmonary hypertension was successfully 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, IMD/ADM2 contents in blood 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 mRNA expressions of CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the results show that the level of IMD/ADM2 increases in the rats with chronic hypoxia-induced pulmonary hypertension.

AIM: To study the effect and significances of two-week hypoxia on the expression of intermedin/adrenomedullin2 (IMD/ADM2) in plasma and the tissues of heart and lung in rats. METHODS: Twenty male SD rats were randomly divided into normal control group and hypoxia group. The concentrations of IMD/ADM2 and adrenomedullin (ADM) in plasma, right ventricle and lung tissue were measured by radioimmunoassay. RT-PCR was used to detect the mRNA levels of IMD/ADM2 and ADM in right ventricle and lung tissue. RESULTS: (1) The mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) of hypoxia group were significantly higher than those of normal control group (P < 0.01). (2) The concentrations of IMD/ADM2 and ADM in plasma were significantly higher in hypoxia group, compared with normal control group (P < 0.01). (3) The concentration of ADM in right ventricle and lung tissue in hypoxia group was significantly higher than that in normal control group (P < 0.01), while there was no significant difference in IMD/ADM2 between the two groups. (4) The mRNA levels of IMD/ADM2 and ADM in right ventricle and lung tissues were significantly up-regulated in hypoxia group (P < 0.05). CONCLUSION: The expressions of IMD/ADM2 peptides and gene in plasma, right ventricular and pulmonary tissues are different in the early-middle pathological proceeding of pulmonary hypertension induced by two-week hypoxia in rats.