Effects Of High-salt Diet On Blood Pressure Variability And Kidneys In Wistar Rats And The Mechanism

Objective: To investigate the effects of high-salt diet on blood pressure variability and kidneys in Wistar rats and the mechanism.Methods: The 65 male Wistar rats were randomly divided into control group(containing 0.5% Na Cl,n=24)and 8% high-salt group(containing 8% Na Cl,n=41),both water and food were supplied ad libitum for 39 weeks.After 24 weeks of experiment,according to the results of systolic blood pressure and the intervention of the rats were divided into the following groups,Group 1: High-salt intervention group,the 8% high-salt group were divided into high-salt normal blood pressure group(HSN group,n=7)and high-salt hypertension group(HSH group,n=34).The HSH group were randomly divided into highsalt hypertension 2 group(HSH2 group,n=11)and high-salt hypertensive group 2(HSH group 2,n=23).The control group were randomly divided into control group 1(n=12)and control group 2(n=12).The control group 1,HSN group and HSH1 group were feeding for 24 weeks.Group 2: High-salt with telmisartan intervention group,the HSH group 2 were divided into high-salt hypertensive 2 group(HSH2 group,containing 8%Na Cl,n=13)and high-salt hypertensive 2 group + telmisartan(HSH2+T group,containing 8%Na Cl+telmisartan,n=10).The control group 2(containing 0.5% Na Cl,n=12),HSH2 group and HSH2+T group were continued to feeding for 15 weeks and drawed materials at 39 weeks.According to the experimental time,tail systolic blood pressure of rats in each group were monitored by tail-cuff artery pressure-measuring instrument,all groups of short-term BPV and long-term BPV were calculated after the end of the experiment.At the end of the experiment,the double renal hypertrophy index in each group of rats were calculated.HE staining and Masson trichrome staining were respectively used to observe the morphological structure and the degree of renal fibrosis in rats.The 24 h urine beta-Nacetyl glucosamine enzyme(NAG),24 h urine albumin,the last urine and serum creatinine were respectively detected by colorimetry,immune turbidimetry and picric.The Ang1-7 level in renal cortex homogenate was detected by ELISA.Immunohistochemistry and Western blotting were respectively used to distribution and expression of the Kim-1,ACE2 and Mas receptor protein in renal.Results: High-salt intervention for 24 weeks,compared with the control group 1,the systolic blood pressure,diastolic blood pressure,short-term systolic blood pressure variability(SBPV),short-term standard deviation of diastolic blood pressure(DSD),longterm SBPV and diastolic blood pressure variability(DBPV)were continuously increased in 8% high-salt group(P<0.05).The long-term SBPV was increased in HSN group(P<0.05).The systolic blood pressure,diastolic blood pressure,short-term SBPV,long-term SBPV,short-term DSD,long-term DBPV were increased in HSH group(P<0.05).Compared with HSN group,the systolic blood pressure,diastolic blood pressure,long-term SBPV and long-term DBPV were increased in HSH group(P<0.05).High-salt with telmisartan intervention for 15 weeks,compared with the control group 2,the systolic blood pressure,diastolic blood pressure,the short-term SBPV,short-term DBPV,long-term SBPV were increased in HSH2 group(P<0.05).After 15 weeks of treatment with telmisartan,compared with HSH2 group,there was no significant difference in the systolic blood pressure,diastolic blood pressure,short-term BPV,long-term BPV between HSH2+T group and HSH2 group.At the end of the experiment,the result of the HE and Masson staining shown that,compared with control group,there were different degrees of damage and fibrosis of kidney in HSN group,HSH1 group,HSH2 group.After 15 weeks of treatment with telmisartan,compared with HSH2 group,there was no significant improvement in renal hypertrophy index,however,the glomerular and renal interstitial fibrosis were increased in HSH2+T group(P<0.05).At 24 weeks of the experiment,compared with the control group 1,the 24 h urine NAG and albumin were increased significantly in HSN group and HSH group(P<0.05).The 24 h urine creatinine clearance rate,the level of Ang1-7 in renal cortex were decreased in HSN group and HSH1 group(P<0.05).The protein content of ACE2 protein in renal cortex of HSN group and HSH1 group were decreased(P<0.05),but the Mas R protein was no statistical significance.The protein content of Kim-1 protein were increased in HSH1 group(P<0.05).Compared with HSN group,the level of Ang1-7 in renal cortex of HSH1 group was decreased(P<0.05).At 39 weeks of the experiment,compared with the control group 2,the double renal hypertrophy index was increased(P<0.05),the 24 h urine creatinine clearance rate was decreased significantly(P<0.05),the level of Ang1-7 in renal cortex was decreased,the protein content of Kim-1 protein in renal cortex was increased,the protein content of ACE2 protein and Mas receptor protein in renal cortex were decreased in HSH2(P<0.05).Compared with HSH2 group,the protein content of Kim-1 protein in the renal cortex was increased in HSH2+T group(P<0.05).Compared with HSH2 group,there was no statistical significance between ACE2 protein and Mas receptor protein in HSH2+T group.Conclusion:(1)Long-term high-salt diet may induce increases the long-term SBPV,longterm DBPV,and earlier than the rise of blood pressure in high-salt hypertension group.(2)Long-term high-salt diet may induce increases the long-term SBPV in high-salt normal blood pressure group,and the increasing long-term SBPV can be one of the mechanisms independent of the renal damage.(3)The damage of ACE2/Ang1-7/Mas R axis may be involved in the pathogenesis of high-salt induced hypertension,abnormal BPV and renal damage.(4)Telmisartan does not play a role in lowering blood pressure and BPV,improving renal damage,which may be related to the impairment of the ACE2/Ang1-7/Mas receptor axis.