EFFECTS OF ENALAPRIL AND IRBESARTAN ON CAROTID ARTERY REMODELLING AND TGF-β1/SMADS PATHWAY IN RENOVASCULAR HYPERTENSIVE RATS

Objectives To investigate the effects of single-drug or combination therapy of enalapril and irbesartan on carotid artery remodelling and TGF-β1/Smads signal pathway. Methods Renovascular hypertensive rats (RHR) developed by ‘two-kidney and one-clip’ method were treated respectively with distilled water (model group, n=6), enalapril (10 mg/(kg d), n=6), irbesartan (50 mg/(kg/d), n=6) and enalapril plus irbesartan (5 mg/kg/d+25 mg/(kg d), n=6) for 6 weeks. Six sham-operated rats were used as controls. Carotid artery morphology and structural changes were observed through HE staining, immunohistochemical staining and Masson staining. Media thickness (MT), lumen diameter (LD), media thickness and lumen diameter ratio (MT/LD) and collagen fibre area percentage of carotid arteries were measured. Moreover, the immunohistochemical staining was applied to detect the expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), TGF-β1, p-Smad2/3 and Smad7. Results In the model group, the media thickness was significantly increased, and the volume of vascular smooth muscle cell (VSMC) increased and disarranged. MT, LD, MT/LD, α-SMA, PCNA and collagen fibre area percentage of carotid arteries in the model group were higher than those in the sham-operated group (p Conclusions The TGFβ1/Smads signalling pathway may be involved in carotid remodelling of RHR. Enalapril or irbesartan can attenuate carotid remodelling of RHR through regulating TGF-β1/Smads pathway and both combination treatment seems to have interaction.