Role Of AT1Blockade And ACE Inhibitor On Cardiac ACE,ACE2and Mas In Hypertensive Rats

ObjectiveThe aim of this study was to examine the changes of ACE,ACE2and Mas, to analyzethe influence of losartan and enalapril on these components, and to determine its role andmechanism in the hearts of hypertensive rats with abdominal aortic coarctation. The datawould provide a theoretic evidence of the mechanism and treatment of hypertension.MethodsFourty healthy adult SD rats were selected to perform suprarenal abdominal aorticbanding, then divided into four groups at random as followed(n=10each group):1.thesham-operated group;2.hypertensive group: aortic ligated alone;3.losartan group: aorticligated rats were fed with losartan at30mg/kg/d in drinking water;4.enalapril group:aorticligated rats were fed with enalapril at20mg/kg/d in drinking water. Blood pressure wasrecorded using a tail-cuff method. After four weeks of treatment, all rats were killed fordetection,including:detecting the mRNA expression levels of ACE、ACE2and Mas in theheart by RT-PCR respectively;detecting the protein levels of ACE and ACE2in the heartby Western blotting;detecting the levels of ACE2in the heart by immunohistochemistry.Results1. Blood pressure measurement:Compared with sham operated group(87.57±4.61mmHg),the blood pressure wassignificantly higher in other three groups(P<0.01), and the blood pressure of hypertensivegroup was stable(123.67±7.89mmHg). Compared with hypertensive group, bloodpressure was decreased in rats given losartan (107.73±8.31mmHg) or enalapril (105.83±6.74mmHg)(P<0.05).2. Immunohistochemisty detection of ACE2:In hypertensive group rats,ACE2level was decreased in the heart compared with thesham operated group(P<0.05).After the treatment of losartan or enalapril,ACE2level in the heart was increased(P<0.05).3.The expression of ACEmRNA、ACE2mRNA and Mas mRNA:3.1The mRNA expression of ACE: the expression of ACE in the heart ofhypertensive rats was significantly higher than that of sham operated rats(P<0.01).Compared with hypertensive group,after treatment of enalapril,the ACE mRNA level in theheart was decreased obviously(P<0.05), while there was no significant change betweenhypertensive group and losartan group(P>0.05).3.2The mRNA expression of ACE2:in the hypertensive group,ACE2mRNA levelwas decreased in the heart(P<0.01).After the treatment of losartan or enalapril, both of thecardiac ACE2expression were increased(P<0.05).3.3The level of MasmRNA expression:compared with sham operated group,MasmRNA of hypertensive group was lower in the heart(P<0.01). MasmRNA of losartangroup was significantly higher than that of hypertensive group(P<0.01), while there was noobvious change after enalapril treatment(P>0.05).4.The protein levels of cardiac ACE and ACE2:4.1The protein level of ACE in the heart:the level of ACE protein of hypertensive ratswas significantly higher than that of sham operated rats(P<0.01). After treatment ofenalapril,the cardiac ACE protein level was lower than the hypertensive group(P<0.05),while there was no significant change between hypertensive group and losartan group(P>0.05).4.2The protein level of cardiac ACE2:compared with sham operated group, ACE2protein level of the hypertensive group was decreased in the heart(P<0.01). After thetreatment of losartan or enalapril, both of the cardiac ACE2protein expression wereincreased(P<0.05).Conclusion1. In the heart of hypertensive rats with abdominal aortic coarctration, the balance ofACE and ACE2was disturbed obviously,but losartan and enalapril can improve thisunhealthy imbalance.2. The activity and function of ACE2-Ang(1-7)-Mas axis was obviously decreased inthe heart of hypertensive rats.3.This study proves for the first time that although treatment of losartan and enalaprilsignificantly decreases arterial blood pressure, losartan has an advantage in the influrenceof the effects of ACE2-Ang(1-7)-Mas axis in the heart of hypertensive rats.4.The function of antihypertension and the cardiac protective effect of ARB, losartan, may be due to the improvement of the function of ACE2-Ang(1-7)-Mas axis, while theantihypertensive action of ACEI, enalapril, mainly results from the upstream blocking ofthe ACE-AngⅡ-AT1axis which plays a crucial role in hypertension.