Abstract:

Objective  To investigate the roles of adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide(PAMP) in pulmonary hypertension due to high pulmonary blood flow in rat lungs. Methods  21 male Wistar rats were randomly divided into 2 groups. The left common carotid artery to external jugular vein shunt operations were performed on experimental rats to establish left to right shunt animal models. The common carotid artery and external carotid artery of the control group rats were  isolated without connection. 12 weeks later, the mean pulmonary artery pressure (mPAP), the right ventricle to left ventricle plus septum ratio  (weight, RV/(LV+SP)), and the percentage of media wall  thickness (MT%) were calculated. The changes and relative protein contents of ADM and PAMP in the lungs were measured by imunohistochemical staining and Western blot analysis. The relative gene expression of ADM, p46-p54 stress-actived protein kinase (SAPK) and p44 extracellular signal-regulated protein kinase 1 (ERK1) were investigated by RT-PCR. Results  The muscular and the tunica intimae layer of the pulmonary artery were thicker in the experimental group than in the control group, and the mPAP increased significantly in the shunt group compared with the control group(P＜0.001). The ratios of RV/(LV+SP) and MT% increased statistically in the experimental group in contrast to the control group(P＜0.001 and P＜0.01). Western blot and integrated optical density showed that the content of ADM and PAMP increased in the shunt group rats (P＜0.01 and P＜0.001).  mRNA expression of ADM, SAPK and ERK1 was up-regulated in the experimental group compared to the control group (P＜0.01 and P＜0.001 respectively). Conclusions  The phenomenon of intramolecular regulation of ADM and PAMP, which both derived from proadrenomedullin, existed in the development of pulmonary hypertension due to the left to right shunt. The mitogen-activated protein kinases (MAPKs) signal pathway has been activated in the formation of left to right shunt pulmonary hypertension.

Key words: Adrenomedullin; Proadrenomedullin-N-terminal 20 peptide; High pulmonary blood flow; Pulmonary hypertension; Mitogen-activated protein kinase