Abstract | 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.
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Authors | Xiao-fang Fan, Ping Huang, Yong-sheng Gong, Xiao-mai Wu, Liang-gang Hu, Li-xian Tian, Chao-shu Tang, Yong-zheng Pang |
Journal | Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology
(Zhongguo Ying Yong Sheng Li Xue Za Zhi)
Vol. 23
Issue 4
Pg. 467-71
(Nov 2007)
ISSN: 1000-6834 [Print] China |
PMID | 21180135
(Publication Type: Journal Article)
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Chemical References |
- Adm2 protein, rat
- Neuropeptides
- Adrenomedullin
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Topics |
- Adrenomedullin
(metabolism)
- Animals
- Hypertension, Pulmonary
(etiology, metabolism)
- Hypoxia
(complications, metabolism)
- Lung
(metabolism)
- Male
- Neuropeptides
(metabolism)
- Rats
- Rats, Sprague-Dawley
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