Objective To investigate the effects of single-drug or combination therapy of enalapril and irbesartan on aorta remodelling and its mechanisms.
Methods Renovascular hypertensive rats (RHD) induced by two-kidney one-clip method were treated with normal saline (model group, n=6), enalapril [10 mg/ (kg d), n=6], irbesartan [50 mg/ (kg·d), n=6] and enalapril+irbesartan [5 mg/ (kg d)+25 mg/ (kg d), n=6] for 6 weeks. Six sham-operated rats were used as controls. Aortic morphology and structural changes in the media were observed by HE staining, immunohistochemistry and Masson staining. The content of Angiotensin II (Ang II) was measured by radioimmunoassay. The activities and mRNA levels of Na+ pump and Ca2+ pump in aortic media were determined by enzyme assay and real-time PCR respectively.
Results The media area of aorta and the Ang II content were significantly increased in model group, while the activities and the mRNA levels of Na+ pump and Ca2+ pump in aortic media were obviously decreased, and Na+ pump and Ca2+ activities were increased in enalapril group and irbesartan group (p<0.01). The Ang II content was obviously decreased in enalapril group, while increased in irbesartan group (p<0.01). The mRNA levels of sodium pump a1-subunit and plasma membrane calcium pump isoform 1 (PMCA1) in aorta smooth muscle tissue were significantly increased in enalapril group (p<0.01). The amelioration of blood pressure, Na+ pump and Ca2+ pump activities, media area and thickness in combination group was significantly better than single-drug intervened group (p<0.01).
Conclusion The amelioration of aorta remodelling induced by enalapril and irbesartan may be associated with the increase of Na+ pump and Ca2+ pump activities. There may be some synergistic effects on ameliorating of Na+ pump and Ca2+ pump activities and aorta remodelling from combination of the two drugs. The effect of enalapril on Na+ pump and Ca2+ pump activities may be mediated by increasing their mRNA expression.