Role of TGF-β1/Smads pathway in carotid artery remodeling in renovascular hypertensive rats and prevention by Enalapril and Amlodipine

Objective To investigate the role of transforming growth factor-β1 (TGF-β1), Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat (RHR) models with “two-kidney and one-clip” were established, including model group (n = 6), sham-operated group (n = 6), Enalapril group (10 mg/kg per day, n = 6), Amlodipine group (5 mg/kg per day, n = 6) and combination group (Amlodipine 2.5 mg/kg per day + Enalapril 5mg/kg per day, n = 6). The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness (MT), MT and lumen diameter ratio (MT/LD), and the expression levels of media α-smooth muscle actin (α-actin), proliferating cell nuclear antigen (PCNA), TGF-β1, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group (P P P P P Conclusions TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling in RHR; the role of Amlodipine and Enalapril in inversing carotid artery remodeling may be related to the change of TGF-β1/Smads pathway, the combination treatment of Amlodipine and Enalapril had better effects than single administration of Amlodipine.