Abstract:AimTo observe the effects of amlodipine only or with the enalapril on aorta remodeling and the activities of Na+ pump and Ca2+ pump, and the mRNA expressions of α1 subunit of Na+ pump and plasma membrane calcium pump isoform 1(PMCA1), and investigate the possible mechanisms of aorta remodeling attenuation by amlodipine and enalapril.MethodsRenovascular hypertensive rat model was induced by two-kidney-one-clip method, and rats were consecutively treated with normal saline(model group), amlodipine [5 mg/(kg·d)], enalapril [10 mg/(kg·d)] and amlodipine +enalapril [2.5 mg/(kg·d)+ 5 mg/(kg·d)] for 6 weeks(n=6).Sham -operated rats were treated with normal saline as controls(n=6).Aortic morphology and structural changes in the aortic media,the ratio of media thick-ness/ luminal diameter (MT/ LD), and media area/ luminal area (MA/LA) were observed by HE staining, immunohistochemical staining and Masson staining.The content of angtension Ⅱ(AngⅡ) was measured by radioimmunoassay, the activity of Na+ pump and Ca2+ pump in aortic media were determined by enzyme colorimetry, and the mRNA expressions of α1 subunit of Na+ pump and PMCA1 were detected by Real-time PCR, respectively.ResultsIn the model group, the ratio MT/ LD and MA/ LA of aorta and the AngⅡ content were significantly increased while the activities and the mRNA levels of Na+ pump and Ca2+ pump were obviously decreased(p<0.05~p<0.01).In the amlodipine group and the enalapril group, the blood pressure ,the ratio MT/ LD and MA/ LA and the AngⅡ content were obviously decreased while the Na+ pump and Ca2+ pump activities were obviously increased(all p<0.01).In the amlodipine group, the mRNA level of PMCA1 was significantly increased.But in the enalapril group, the mRNA levels of both sodium pump a1-subunit and PMCA1 were obviously increased(all p<0.01).In combination group, the amelioration of the ratio MT/ LD and MA/ LA,ion pump activity and mRNA levels of PMCA1 were significantly greater than in single-drug intervened group (all p<0.01), and the AngⅡcontent also was decreased more greater than in single-drug intervened group (all p<0.01), and there were synergistic effects.ConclusionsThe combination of amlodipine and enalapril is better than single-drug therapy in the attenuation of aorta remodeling, and there may be some synergistic effects in inhibiting tissue RAS and increasing the activities of ion pumps.Ca2+ pump activity stimulated by amlodipine may be partially mediated through up-regulating PMCA1 mRNA.