Adrenomedullin relieves the pulmonary hypertension in hypoxic rats

Objective To investigate the effects and mechanisms of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) on hypoxia pulmonary hypertension (HPH) in rats.Methods Eighteen male Wistar rats were randomly divided into three groups:control group, hypoxic group and hypoxic plus ADM group.ADM was subcutaneously administered into rats with ADM. After 21 days, The mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index[RV/(LV+S)] were measured. Hypoxic pulmonary vascular remodeling(HPSR) was observed with morphometric analysis. The level of pulmonary arterial plasma ADM was measured by radioimmunoassay. The semiquantitate in situ hybridization was used to measure the expression of ADMR mRNA in pulmonary artery walls. Results (1) The level of mPAP, RV/(LV+S),the ratio of vascular wall thick ness to external diameter(MT%) and ratio of vascular wall area to total area (MA%) were significantly higher in hypoxia group than those in control group(2) The pulmonary artery plasma ADM level was significantly higher in hypoxic group and hypoxic plus ADM group than that in control group(P0.01), and the ADM level decreased in rat of hypoxicplus ADM group compared with hypoxic group(P0.05).(3) ADMR mRNA expressed more in pulmonary artery walls of hypoxia group and hypoxic plus ADM group(P0.01).Conclusion ADM may partly prevent the development of HPH and pulmonary vascular remodling. Exogenous ADM has no negative feedback effect on pulmonary arterial plasma ADM and ADMR mRNA.