Mechanisms of angiotensin converting enzyme 2 activation in ameliorating pulmonary endothelial dysfunction in rats

Li Gang; Zhang Han; Zhao Xueting; Zhang Yaozhong; Yan Daole; Liu Yinglong

doi:10.3760/cma.j.issn.1673-4777.2017.07.010

Abstract：Objective To investigate possible mechanisms of angiotensin converting enzyme 2 (ACE2) activation in pulmonary endothelial protection to prevent pulmonary arterial hypertension (PAH) in rats.Methods Sixty healthy male SD rats (SPF) were completely randomly divided into blank control group,PAH group,ACE2 activation group[treated with ACE2 activator Resorcinolnaphthalein(Rec)],ACE2 inhibition group (treated with Rec + ACE2 inhibitor MLN-4760) and endothelial nitric oxide synthase (eNOS) block group(treated with Rec + NOS inhibitor L-NAME),with 12 rats in each group.PAH rate model was made by lung lobectomy and monocrotaline injection.Different interventions in each group lasted for 3 weeks and hemodynamic changes,endothelial function and pathological changes were analyzed;concentration of NO,expression of eNOS and phosphorylation of eNOS-Ser-1177 in lung tissue were tested.Results Compared to those in PAH group,the mean pulmonary arterial pressure(mPAP) in ACE2 activation group was significantly lower [(21 ± 3)mmHg vs (45 ± 5) mmHg] and the decrease range of mPAP induced by acetylcholine was significantly higher;NO concentration in ACE2 activation group was significantly higher [(4.20 ± 0.39) μmol/g protein vs (3.60 ± 0.24) μmol/g protein];eNOS expression in ACE2 activation group was significantly lower and eNOS-Ser-1177 phosphorylation was higher(all P ＜ 0.05).In eNOS block group,the decrease range of mPAP induced by acetylcholine was significantly lower than that in ACE2 activation group (P ＜ 0.05).Conclusion Activation of ACE2 can improve pulmonary endothelial function through enhancing phosphorylation of eNOS-Ser-1177 thus promoting NO release,which is an important mechanism of ACE2 in preventing PAH.