Effects Of Valsatan On Expressions Of Angiotensin Converting Enzyme 2 In Myocardium In Rat Model Of Metabolic Syndrome

Objective:To determine the levels of expressions of angiotensin-converting enzyme 2(ACE2)and angiotensin-converting enzyme(ACE)within myocardium as well as angiotensinⅡin rat model of fructose-induced metabolic syndrome (MS)and to explore their changes with valsatan.Methods:Fifty adult male Wistar rats were grouped randomly as follows: control group(n=10),metabolic syndrome(MS)group(n=10),MS+medium dose valsartan group[10mg/(kg.d),n=10];MS+moderate dose valsartan group [20mg/(kg.d),n=10],MS+high dose valsartan group[30mg/(kg.d),n=10]for 6 weeks.The levels of mRNA expression of ACE2 and ACE were determined by reverse transcription-polymerase chain reaction(RT-PCR)and the distribution of ACE2 in myocardium by immunohistochemistry.Myocardium AngⅡand plasma AngⅡwere evaluated with radioimmunoassay(RIA).Systolic blood pressure (SBP)were measured by tail-cuff method. Results:1.SBP in MS group was higher than that of control group(144.47±3.26 vs 109.34±5.02,P=0.000).2.AngⅡin plasma and myocardium was higher in MS group than in control group(myocardium:59.69±7.06 vs 40.57±5.64, P=0.000;plasma:611.11±61.69 vs 412.25±58.33,P=0.000).3.ACE2 mRNA and protein in myocardium were found to be significantly decreased in MS rats compared with those of the control rats(mRNA:0.26±0.02 vs 0.85±0.03, P=0.000;protein:113.69±5.62 vs 168.20±3.46,P=0.000).ACE mRNA expression was significantly increased in MS rats(mRNA:0.81±0.04 vs 0.54±0.02,P=0.000).4.SBP of valsartan group rats was lower significantly than that of MS rats(132.75±4.15 vs 144.47±3.26,P=0.000;122.08±4.56 vs 144.47±3.26,P=0.000;110.48±4.42 vs 144.47±3.26,P=0.000).5.AngⅡin valsartan group was much higher than that of MS group(myocardium:76.99±10.64 vs 59.69±7.06,P=0.001;89.09±10.01 vs 59.69±7.06,P=0.000;124.75±9.59 vs 59.69±7.06,P=0.000;plasma:784.53±85.97 vs 611.11±61.69,P=0.000; 911.75±78.47 vs 611.11±61.69,P=0.000;1232.33±101.02 vs 611.11±61.69, P=0.000).6.Valsartan group showed a concentration dependent increasing expression of ACE2(mRNA:0.45±0.02 vs 0.26±0.03,P=0.000;0.65±0.03 vs 0.26±0.03,P=0.000;0.75±0.03 vs 0.26±0.03,P=0.000;protein:127.58±5.48 vs 113.69±5.62,P=0.000;140.66±4.18 vs 113.69±5.62,P=0.000; 157.63±3.49 vs 113.69±5.62,P=0.000)and decreasing expression of ACE (mRNA:0.72±0.02 vs 0.81±0.04,P=0.000;0.63±0.03 vs 0.81±0.04, P=0.000;0.46±0.03 vs 0.81±0.04,P=0.000).Conclusion:The myocardium ACE2 is down-regulated but ACE is up-regulated,along with SBP increasing and the level of AngⅡis increased in MS rats.Valsartan could reverse the regulation of ACE2 and ACE and benefit to lower the SBP partly due to increasing AngⅡ.