The Effect Of Early LOS Treatment On Blood Pressure And Myocardial Fibrosis In Spontaneously Hypertensive Rats

Objective1.To observe the effects of early losartan(LOS) treatment on the blood pressure and the remodeling of myocardium and vessels in spontaneously hy pertensive rats(SHR).2.To observe the effects of losartan on Angll and AT1R.AT2R in SHR3.To study the effect s of losartan on myocardial mycofibrosis in SHRMethodsThirty-six four-week-old male SHR were randomized into three group.losartan treated four-week group(LOS group,20 mg.kg^-1.d^-1,n=12),losartan treated twelve-week group and distilled water control(SHR group,n=12).And Wistar-Kyoto rats(WKY group,n=16) were served as normal control.The former two groups were administered losartan for 4weeks,SHR and WKY control were given the same amount of distilled water.Systolic blood pressure was examined by the tail-cuff method.Wet weight of left ventricle to body weight ratio(LVM/BW) was assessed on sacrifice.Myocardial collagen fibers in the sections were observed under light microscope.The wall-to-lumen area ratios of thoracic aorta and mesenteric arteries(3th branch) were calculated.Plasma concentration of angiotensinâ…¡(Angâ…¡) was measured by radioimmunoassay(RIA).The expression ofATlR.AT2R was examined by immunohistochemistry and computer image analysis.Results1.After 4 weeks treatment with losartan,systolic blood pressure in 4 week group was markedly lower than that in SHR control group(P<0.01 vs SHR),SBP in 4 week LOS group also lower than 12 week group(P<0.01 vs 12weekSHR LOS). 2.Brief treatment whith Losatan reduced the LVM/BW ratio significantly in 4week and 12week group when was comparable in untreated SHR(P<0.05).The ratio was lower in 4week group than 12week group,but no significant difference was found between the two groups.(P>0.05)3.After 4 weeks treatment with losartan,plasma Angâ…¡concentration was lower in 4week group than that in SHR control group(P<0.05),and also lower than that in 12week group(P<0.05).4.Myocardial collagen volume fraction in the interstitial and endocardial area was significantly reduced by the treatment with LOS(P<0.01 vs SHR),whereas no significance was found between the two groups.5.In thoracic aorta,the wall area to lumen area ratio in SHR group was markedly higher than that in LOS group(P<0.01 vs SHR),but no significant difference was found between the two groups.6.In mesenteric arteries(3th branch),the wall-to-lumen area ratio was significantly reduced in LOS group than in SHR group(P<0.01 vs SHR),while no marked difference in 24 week was found.7.The expression of myocardium AT1R.AT2R in SHR was significantly higher(p less than 0.05) than in age-matched WKY rats.LOS treatment attenuated AT1R.Conclusions1.Early LOS treatment may prevent the development of arterial blood pressure in SHR.2.LOS may inhibit cardiac collagen fibers accumulating.3.LOS could attenuate the vessels hypertrophy in SHR4.Early LOS treatment could attenuate LVM/BW in SHR...