Effects Of Angiotensionll,kaluretic Peptide,MMP-2,MMP-3,TIMP-1 On Renal Lesion,and The Protective Effects Of Angiotensionll Receptor Antagonist Losartan And Calcium Channel Blockade Amlodipine On Kidney Function Of Spontaneously Hypertensive Rats

The major renal pathological change in essential hypertension is glomerular sclerosis which is due to the proliferation of mesangial cell and accumulation of ertracellular matrix(ECM).AII,ET,TGF- ~ ,TNF- a are the key mediums for regulating the cell proliferation and ECM producing.Imbalance of MMPs and/or TIMPs is the direct reason for ECM synthesis increased and/or decomposition decreased and inducing the accumulation of ECM.The objective of the present study is to investigate the possible mechanism of the hypertensive renal injury of SHR and to investigate the renal protective effect against progress of sclerotic injury of Losartan and Amlodipine in the rat model by means of treatment SHR with CCB or AURA ,and through observing the changes of blood pressure(BP) and excretion of proteinuria and observing the level of AII,ET,ANP,KP,A1d in the SHR s blood and observing the expression of CoIV,LM,MMP-2,MMP-3,TIMP-l in the SHR s renal tissues. So as to seek after the new method which can reverse the process of hypertensive nepbrosclerosis and solve the problem thoroughly.Materials and Methods:30 of 16-month-old SHR were randomly divided into 3 groups: the Losartan-treatment group(n=10),the Amlodipine-treatment group(n=lO) and the control group(n=1O) which is not treated. Meanwhile, 10 of 16-month-old WKY rats were used as healthy control group(n=l0).Therapeutic time was 3 months. The tail cuff method was used to measure the blood pressure of rats at 0 week. 6 week and 12 week respectively. Blood and urine were8 remained at 0 week and 12 week in order to detect Bun,Scr,Ccr and 24h proteinuria excretion. After the experiment, the levels of AII,ET,ANP,KP,A1d in the blood were determined by means of RIA. Renal tissues were obtained,embedded in paraffin,cut 4 i~ m thick, stained with HE,PAS reagent. They were examined under a light microscope. The expression of CoIV. LM,MMP-2 ,MMP-3,TIMP-l in the renal tissues were respectively observed through the immunohistochemical method.Results:1 .Compare with the results from WKY rats,SHR s BP increased(PO.05) ;Ccr decreased (P0.05) .SHR s renal tissues showed marked pathological changes: remarkable glomerular atrophy and compensatory hypertrophy; tubule-interstitial changes were noted. Intrarenal arteriolosclerosis with thickening of wall accompanied by luniinal narrowing and complete mural hyalinosis with luminal encroachment formed. Mesangial proliferation, matrix expansion, segmental to global sclerosis and hyalinosis. The expression of Collagen IV, Laminin in the renal tissues increased (P0.05) in the renal tissues.2.After treatment, compared with SHR control group, Losartan and Amlodipine group BP decreased by 25.75 %,24.3% respectively (P<0.05 ) ;24h proteinuria decreased by 42.5%,14.2% respectively (P<0.0 1, P<0.05) ;Bun,Scr,Ccr decreased slightly (P>O.05) .Plasma All increased by 154.3%,109.2% respectively (P<0.Ol) ;ET decreased by 7.98%,8.63% respectively (P>O.05) ;KP increased by 22.2%,4.66% respectively (P>O.05) ;ANP increased by 4.03%, 18.73% respectively (P>O.05) ;Ald decreased by 23.9%,60.7% respectively (P>O.05,9 9PO.05)Concultion:1. Compared with WKY rats, SHR renal tissues pathological changes were markedly deteriorated. Renal function impaired evidently. After treatment, SHR s pathological changes lessened generally and impaired renal function improved. The results indicate that Losartan and Amlodipine have renal protective effect and they can be prevented and delayed...