The Relationship Between Left Ventricular Remodeling And The Expression Of Cardiac AT2-R And ACE2 In Spontaneously Hypertensive Rat

Objective: To investigate the effect of Valsantan on left ventricularremodeling and the expression of the components of cardiacrenin-angiotensin system(RAS) of spontaneously hypertensive rat(SHR),and to explore the relationship between left ventricular remodeling inhypertension and AT2 receptor and ACE2.Methods:24 male SHRs of 12-week-old were randomized to three groups:SHR-C (placebo),SHR-L (valsartan 10mg/kg/d), and SHR-H(valsartan30mg/kg/d),each group consisting of 8 rats. 8 male normotensive WKY ratswith mathed age and weight were served as normal control group(WKY-C).Systolic blood pressure (SBP) was messured by RPB-I instrument. All ratswere killed after 12 weeks of treatment. Left ventricular mass(LVM) wasmeasured,which was used to calculate the left ventricular mass index(LVMI).Plasma and myocardial concentrations of AngII were determined byradioimmunoassay(RIA). The sections of the rat heart were stained bypicric acid-Sirius red,and the degrees of myocardial interstitialfibrosis were assessed by means of image analysis. The expression levelsof AT1-RmRNA,AT2-RmRNA,ACEmRNA and ACE2mRNA in heart were detectedby RT-PCR. The expression levels of ACE2 protein were determined withWestern Blot.Results:(1)The level of SBP in SHR-C was remarkably higher than thatin WKY-C(P<0.05). Valsartan decreased SBP and LVMI in SHRs(P<0.05),especially in SHR-H.(2)Plasma concentration of AngII in SHR-C wasslightly higher than that in WKY-C(P>0.05),and the level of myocardialAngII in SHR-C was remarkably higher than that in WKY-C(P<0.05).Valsartan increased the level of plasma AngII,but decreased that ofmyocardial AngII (P<0.05),especially in SHR-H.(3)The content of collagenwithin myocardial interstitium in SHR-C was higher than that in WKY-C(P<0.05).Administration of Valsartan prevented the development ofmyocardial interstitial collagen deposition(P<0.05),especially inSHR-H.(4)Compared with WKY-C,the expression levels of AT1-RmRNA,ACE2mRNAand ACE2 protein were reduced in heart of SHR-C(P<0.05),and the expressionlevel of ACEmRNA was higher than that in SHR-C (P<0.05). However,the levelof AT2-RmRNA was just slightly higher than that in SHR-C(P>0.05).The expression levels of AT1-RmRNA,AT2-RmRNA,ACE2mRNA and ACE2protein were increased by valsartan (P<0.05),without exerting any impacton the expression levels of ACEmRNA(P<0.05).Conclusions(1) Compared with WKY,the expression levels of ACE2mRNA,ACE2 protein and AT1-RmRNA were markedly reduced in heart of SHR (P<0.05),and the expression level of ACEmRNA was increased. However,the level of AT2-RmRNA was just slightly increased. The level of myocardialAngII in SHR was remarkably increased. Plasma concentration of AngII inSHR was not distinctly changed.(2)Valsartan significantly decreased SBP,reversed the leftventricular hypertrophy and alleviate myocardial fibosis. These actionshave the dosage dependence.(3) The expression levels of cardiac ACE2mRNA,ACE2 protein,AT2-RmRNAand AT1-RmRNA were increased during the process of valsartan treatment,but not ACEmRNA. At the same time,the increase of plasma concentrationof AngII and the decrease of level of myocardial AngII were displayed.(4)An increase of the expression levels of AT2 receptor and ACE2 may be involved in the process of valsartan inhibiting left ventricular remodeling.