Effects Of High-salt Dieet On Blood Pressure And The Remodeling Of Carotid Arteries And The Intervention Of Telmisartan In Wistar Rats

Objective:To study the influence of high salt diet on blood pressure and carotid artery remodeling and the intervention of telmisartan in Wiatar rats.Methods:60 Wistar rats were fed a normal salt diet(NSD:0.5%NaCl), high salt diet(HSD:8% NaCl), or HSD+Telmisartan until 24 weeks, tail-cuff blood pressure were measured every two weeks. After the end of experiment, HSD group was divided into hypertension group (HHBp) and normal blood pressure group(HNBp) according of the tail-cuff blood pressure. Media thickness (MT), lumen diameter (LD), media thickness and lumen diameter ratio (MT/LD) and collagen fiber area percentage of carotid arteries were measured. The expression of a-smooth muscle actin(a-SMA), TGF-β1,smad2/3, smad7,AngⅡ,AT1,AT2 and PCNA in media of carotid arteries were measured by immunohistochemistry. Aldosterone in vessel and adrenal gland was mesured by radioimunoassay. The endogenous ouabain (EO) in adrenal gland,hypothalamus and the blood was mesured by radioimunoassay.Results:(1)At 7 week of experiments, tail-cuff blood pressure in HHBp group was much higher than that in other three groups (P<0.05), and continued to experiment ends. At 24 week, carotid artery pression in HHBp group was also much higher than in other three groups (P< 0.05).Tail-cuff blood pressure and carotid arteries pression were not statistically significant in the other three groups. (2) MT, MT/LD,PI,collagen fiber area percentage of carotid arteries in HHBp and HNBp groups were higher than those in the control group (P< 0.01), and MT, MT/LD,PI,collagen fiber area percentage in HSD+ telmisartan group were much lower (P< 0.01). (3) TGF-β1, smad2/3 of carotid arteries media in HHBp and HNBp groups were higher than in the control group (P< 0.01), and in telmisartan group were much lower (P< 0.01). smad7 of carotid arteries media in control group was much higher than in other three groups (P< 0.01), in telmisartan group were much higher than in HHBp and HNBp groups (P< 0.01).(4) AngⅡof carotid artery was no difference in each group. AT1 expression of carotid arteries media in HHBp and HNBp groups were higher than in the control group (P< 0.01). and were much lower in telmisartan group (P< 0.01). The expression of AT2 in carotid arteries media in HHBp were higher than in other three groups (P< 0.01).AT2 of carotid arteries media in HHBp and telmisartan group were higher than in the control group (P< 0.01). But aldosterone level in carotid arteries media were higher in HNBp groups than the control group (P< 0.05), much higher than in telmisartan group (P< 0.01). Aldosterone level in adrenal gland were higher than in other three groups (P< 0.01).EO level in adrenal gland,hypothalamus and the blood were no differences among all groups.Conclusion:(1)Long-term high-salt diet can cause the carotid artery remodeling directly or through high blood pressure, the structure is characterized by medial thickening, vascular smooth muscle cell proliferation and collagen deposition.(2) High salt-induced carotid artery remodeling may be related to positive and negative regulation of signal transduction in TGF-(31/smads and the upregulation of RAAS components (ATI, AT2) in local tissues, increased aldosterone and TGF-β1 upregulation may be the main mechanism in high salt-induced hypertension and carotid artery remodeling.(3) Telmisartan can inhibit proliferation of vascular smooth muscle cells and collagen accumulation, and prevent high salt-induced hypertension and remodeling of carotid artery, its pharmacological mechanism may be inhibiting the local RAAS and regulating TGF-β1/smads signaling pathways.