Effects of ramipril on nitric oxide concentration and endothelial nitric oxide synthase activation in lung of rats with pulmonary arterial hypertension induced by monocrotaline

Objective To investigate the effects of ramipril on nitric oxide(NO) concentration and endothelial nitric oxide synthase(eNOS) activation in lung of rats with pulmonary arterial hypertension induced by monocrotaline(MCT).Methods Sixty Sprague-Dawley rats were randomly divided into three groups: normal control group,MCT group and ramipril group.Rats in MCT group and ramipril group were subcutaneously injected with 60mg/kg of MCT.Then the rats in ramipril group received ramipril gavage and rats in MCT group received normal saline gavage for 4 weeks,respectively.Rats in control group were subcutaneously injected with normal saline first and then received normal saline gavage for 4 weeks.Right ventricular systolic pressure(RVSP) and right ventricle hypertrophy index(RVHI) were measured.The ratio of arteriol wall thickness/vascular external diameter(WT%) and wall area percentage(WA%) were evaluated.NO concentration in lung was determined.eNOS,P-Ser1177-eNOS and Akt phosphorylation were analyzed by Western blotting.Results The RVSP,RVHI,WT%,WA% were significantly increased,and NO concentration,the level of eNOS,P-Ser1177-eNOS,the state of Akt phosphorylation were significantly decreased in MCT group compared with that in control group(P0.05) after 4 weeks.However,the RVSP,RVHI,WT% and WA% were significantly decreased,and NO concentration,the level of eNOS,P-Ser1177-eNOS and the state of Akt phosphorylation were significantly increased in ramipril group compared with that in MCT group(P0.05).Conclusions Ramipril might prevent the development of pulmonary hypertension induced by MCT and inhibit pulmonary vascular remodeling.The mechanism seems to be associated with up-regulation of eNOS activation,resulting in an increase of NO concentration.