[Alterations of proadrenomedullin N-terminal 20-peptide in rats with pulmonary hypertension induced by high pulmonary blood flow].
OBJECTIVE
The mechanism of high pulmonary blood flow-induced pulmonary hypertension remains unclear. The aim of this study was to explore the effect of proadrenomedullin N-terminal 20-peptide (PAMP) on pulmonary hypertension, through examining the alterations of pulmonary PAMP expression and plasma PAMP concentration in rats with pulmonary hypertension induced by high pulmonary blood flow.


METHODS
Sixteen male Sprague-Dawley rats were randomly divided into control (n=8) and shunt groups (n=8). Aortocaval shunting was produced in the shunt group. After 11 weeks of shunting, systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP) and mean pulmonary artery pressure (mPAP) were evaluated by using a right cardiac catheterization procedure. The ultrastructural changes in intra-acinar pulmonary arteries were observed. The concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP in pulmonary arteries was detected by immunohistochemical assay.


RESULTS
sPAP, dPAP and mPAP were significantly increased in shunt rats compared with controls (P < 0.01). Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, and hypertrophy and increased number of synthetic phenotype of smooth muscle cells, were found in intra-acinar pulmonary muscularized arteries in the shunt group. Plasma PAMP concentration (616 +/- 195 pg /mL vs 427 +/- 90 pg /mL) and PAMP expression in endothelial cells (0.62 +/- 0.09 vs 0.38 +/- 0.12) and in smooth muscle cells (0.24 +/- 0.07 vs 0.14 +/- 0.05) of pulmonary arteries increased significantly in the shut group compared with controls.


CONCLUSIONS
The up-regulation of pulmonary and plasm PAMP expression might be involved in the development of high pulmonary blood flow-induced pulmonary hypertension.
Qi
Jian-Guang
JG
Department of Pediatrics, Peking University First Hospital, Beijing, China. qijianguang@sohu.com
Li
Xiao-Hui
XH
Ding
Ya-Guang
YG
Tang
Chao-Shu
CS
Du
Jun-Bao
JB
D053607:Adrenomedullin / Q000097:blood* / Q000235:genetics; D000818:Animals; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008297:Male; D011651:Pulmonary Artery / Q000648:ultrastructure; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D053607:Adrenomedullin