AIM： To examine the alteration of proadrenomedullin N -terminal 20 -peptide （PAMP） in rats with chronic hypoxic pulmonary hypertension and pulmonary vascular structural remodeling. METHODS： Eighteen male Wistar rats were randomly divided into control group （ n = 9） and hypoxic group （ n = 9 ）. After two - week hypoxic challenge, mean pulmonary arterial pressure （mPAP） of each rat was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass [ RV/（ LV ＋ S） ] was detected. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra - acinar pulmonary arteries were observed. Mean- while, the concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP by pulmonary arteries was detected by immunohistochemical assay, and the expression of adrenomedullin （ADM） mRNA in pulmonary arteries was detected by in situ hybridization. RESULTS： mPAP and RV/（ LV ＋ S） were significantly increased in rats exposed to two - week hypoxia （ P 〈 0.01, respectively ）. Muscularization of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in hypoxic rats compared with controls. Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intra - acinar pulmonary muscularized arteries of hypoxic rats. Meanwhile, plasma PAMP concentration was increased. The PAMP protein and ADM mRNA expressions in pulmonary arteries were significantly augmented in rats of hypoxic group as compared with control group. CONCLUSION ： The up - regulation of PAMP due to hypoxia is probably involved in the development of chronic hypoxic pulmonary hypertension and pulmonary vascular structural remodeling.
Chinese Journal of Pathophysiology