Effects of adrenomedullin on hemodynamics and cytokine expression in rats with hypoxic pulmonary hypertension

Objective To investigate the effect of adrenomedullin(ADM) on hemodynamic indexes,pulmonary vascular structural remodeling and cytokines in rats with hypoxic pulmonary hypertension(PH),and to study the effect of ADM on chronic hypoxic PH and its possible mechanism. Methods Thirty rats were randomly divided into three groups: normal control( n = 10),hypoxia( n = 10) and ADM-treated hypoxia( n = 10). ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by a mini-osmotic pump(300 ng / h) for two weeks. After two weeks of hypoxic challenge,indexes of hemodynamics were calculated. Aldosterone and human ADM levels in rat serum were measured by radioimmunoassay before the rats were sacrificed and the ratio of the RV weight to LV plus septum weight [RV /( LV + S)]was calculated for assessment of right ventricular hypertrophy. Histological sections of the lungs were stained with hematoxylineosin(HE) and pulmonary arterioles were studied using a computerized image analyzer. The ratio of vessel wall thickness to pulmonary artery diameter( MT%) and the ratio of vessel wall area to total area( MA%) were calculated. Meanwhile,the expression of transforming growth factor( TGF)-β1,endothelin-1(ET-1) and tumor necrosis factor(TNF-α) in pulmonary arteries were detected by Western blotting. Results The pulmonary artery systolic pressure( PASP),pulmonary artery diastolic pressure( PADP),mean pulmonary artery pressure( mPAP),RV /( LV + S),MT% and MA% increased obviously in the hypoxia group compared with normal controls. The levels of serum aldosterone and the protein expression levels of TGF-β1,ET-1 and TNF-α of pulmonary arteries in the hypoxia group were increased more significantly than in the control group. PASP,PADP,mPAP and RV /( LV + S) were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group. ADM markedly reduced MT% and MA% of hypoxic rats,with a decrease in the levels of serum aldosterone and expression of TGF-β1,ET-1 and TNF-α. Conclusion ADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling by decreasing the levels of serum aldosterone and inhibiting the expression of TGF-β1,ET-1 and TNF-α.