Ramipril Inhibits Pulmonary Vascular Remodeling by Regulating ERK 1/2 Activation in Rats with Pulmonary Arterial Hypertension

Objective To investigate whether or not that Ramipril by regulating [extracellular regulated protein kinases 1/2,(ERK 1/2)] activation inhibited pulmonary vascular remodeling in the model of pulmonary arterial hypertension induced by monocrotaline(MCT)in rats.Methods 30 Sprague-Dawley rats were randomly divided into three groups:normal control group,pulmonary arterial hypertension(PAH)group and PAH+Ramipril treatment group.The rats in two latter groups were injected 60mg/kg of MCT subcutaneously and then received normal drinking water or Ramipril in drinking water.The rats in normal control group were injected normal saline subcutaneously first and then received normal drinking water.After 4 weeks of treatment,right ventricular systolic pressure(RVSP)and right ventricular hypertrophy index(RVHI)were measured.Percentage of wall thickness(WT%)and percentage of wall area(WA %)of pulmonary arterioles were evaluated.AngiotensinⅡ(AngⅡ)concentration in lung was measured by radioimmunoassay.ERK 1/2 was analysed by Western blotting.Results After four weeks,those parameters of RVSP,RVHI,WT % and WA %,pulmonary AngⅡ concentration and the level of phosphorylation of ERK 1/2 in PAH group were significantly increased compared with control group.However,the above parameters were dramatically decreased in Ramipril treatment group.Conclusion Ramipril can prevent the development of pulmonary hypertension induced by monocrotaline and inhibit pulmonary vascular remodeling,which are associated with down-regulating the level of phosphorylation of ERK 1/2.