Different Raas Inhibitors On Renal Hypertensive Rats Plasma At1r/at1r - Ab And Myocardial At1r/cs - 1 / Can The Influence Of The Signal Path

Objective To investigate the effects of Zofenopril, Olmesartan, Eplerenone, whichare different inhibitors of RAAS on peripheral AT1R and AT1R-Ab of2K1Crenovascular hypertension rats and the correlation of AT1R and AT1R-Ab withhypertension and myocardial hypertrophy.Methods120Male Sprague-Dawly rats were randomly divided into Sham group(Sham,n=24),2K1C group (2K1C,n=24),2K1C+Zofenopril group (Z,n=24),2K1C+Olmesartan group (O,n=24) and2K1C+Eplerenone group (E,n=24). The last fourgroup of2K1C hypertensive model was established in Sprague-Dawly rats by chronicpartial occlusion of left renal artery.4weeks after operation, rats in O, Z, E groupswere treated with the intragastric infusion of Olmesartan,3mg·kg-1, Zofenopril,10mg·kg-1,Eplerenone,100mg·kg-1,respectively,while rats in Sham and2K1C groupwere treated with equal-volume distilled water. Before operation and4,8,12also14weeks after operation,systolic blood pressure was measured by tail cuff plethysmo-graphy, the myocardial structure and function were detected by ultrasonography andthe plasma AT1R,AT1R-Ab were evaluated by ELISA(n=6).Results (1) After operation, systolic blood pressure and the thickness of left ventriclewall of rats in2K1C group were significantly higher than rats in Sham and controlgroups.But12and14weeks after operation,systolic blood pressure of rats in2K1Cgroup was significantly lower than8weeks.(2)12and14weeks after operation, thelevels of plasma AT1R of rats in2K1C group were significantly higher than Shamgroup.8weeks after operation, the levels of plasma AT1R in control groups werehigher than that of2K1C group.12and14weeks after operation, Z and E group werealso higher, while O group not.Conclusion Plasma levels of AT1R, AT1R-Ab, systolic blood pressure of rats in2K1C group was always changing with time. AT1R and AT1R-Ab are involved inthe pathogenesis of hypertension but not myocardial hypertrophy directly, maybe directly involved in cardiac contractility.Olmesartan, Zofenopril and Eplerenonedecreased blood pressure and the thickness of left ventricle，but up-regulated theplasma AT1R. Zofenopril and eplerenone not olmesartan reduced the levels ofAT1R-Ab. Mechanism of different inhibitors of RAAS in lowering BP andmyocardial hypertrophy may be partly with AT1R autoimmune response andOlmesartan may has immunosuppressive action,and Olmesartan may haveanti-autoimmune response. Objective To investigate the effects of Zofenopril, Olmesartan, Eplerenone, whichare different inhibitors of RAAS on myocardial AT1R, CaNAαand CS-1of2K1Crenovascular hypertensive rats.Methods120Male Sprague-Dawly rats were randomly divided into Sham group(Sham, n=24),2K1C group (2K1C, n=24),2K1C+Olmesartan group (O, n=24),2K1C+Zofenopril group (Z, n=24) and2K1C+Eplerenone group (E, n=24). The lastfour group of2K1C hypertensive model was established in Sprague-Dawly rats bychronic partial occlusion of left renal artery.4weeks after operation, rats in O, Z, Egroups were treated with the intragastric infusion o f Olmesartan,3mg·kg-1,Zofenopril,10mg·kg-1, Eplerenone,100mg·kg-1, respectively, while rats in Sham and2K1C group were treated with equal-volume distilled water. Before operation and4,8,12also14weeks after operation，systolic blood pressure was measured by tail cuffplethysmography, the myocardial structure and function were detected byultrasonography，and plasma CaN activity was evaluated by ELISA. MyocardialAT1R, CaNAαand CS-1of renovascular hypertension rats were evaluated byRT-PCR and Western blot.Results (1) After operation, the activity of CaN in2K1C were higher than in Shamand control groups.(2) After operation, AT1R and CaN expressed higher in2K1Crats and Olmesartan, Zofenopril, Eplerenone downregulated AT1R and CaN, whileCS-1upregulated.Conclusion Activity of CaN was upregulated in renovascular hypertention rasts andOlmesartan, Zofenopril and Eplerenone can decrease it. These findings suggest thatAT1R induces cardiac hypertrophy through calcineurin pathway and mechanisms ofdifferent inhibitors of RAAS that ameliorate myocardial hypertrophy may throughAT1R/CS-1/CaN pathyway.