AIM: To examine and compare the effects of several ARBs that are widely used in clinics,on the ACE-Ang II-AT1 receptor and the ACE2-Ang(1-7)-Mas axis during the development of cardiac remodeling after pressure overload. METHODS: All of the mice used in the study underwent transverse aortic constriction( TAC) or sham operation for 2 or 4 weeks. A solution of either ARBs or saline was administered through a stomach tube 3 days before the operation. Meanwhile,to eliminate the influence of Ang II,a recombinant adenovirus expressing small interfering RNAs targeting angiotensinogen( Ad-ATG si RNA) was injected via the tail vein. The surgery was then performed and the drug was administered as mentioned above. Cardiac function and remodeling were evaluated by echocardiography,hemodynamic measurements and cardiac histology. Western blotting was used to determine the protein expression levels.Meanwhile,we performed similar experiments using ARBs with or without ATG si RNA in cardiomyocytes induced by mechanical stretch. RESULTS: Although all of the six ARBs,none of which repressed the elevation of left ventricular pressure after TAC,attenuated the development of cardiac hypertrophy and heart failure in the wild-type mice,the degree of attenuation by Olmesartan,Candesartan and Losartan tended to be larger than that of the other three drugs tested. Additionally,the degree of downregulation of the ACEAng II-AT1 axis and upregulation of the ACE2-Ang(1-7)-Mas axis was higher in response to Olmesartan,Candesartan and Losartan administration in vivo and in vitro. Additionally,Olmesartan had a larger influence when administered long term. However,the expression of ACE was not influenced by the administration of ARBs in vivo and in vitro. Moreover,in angiotensinogen-knockdown mice,TAC-induced cardiac hypertrophy and heart failure were inhibited by Olmesartan,Candesartan and Losartan but not by Telmisartan,Valsartan and Irbesartan administration. Furthermore,only Olmesartan and Candesartan could downregulate the ACE-Ang II-AT1 axis and upregulate the ACE2-Ang(1-7)-Mas axis in vitro. CONCLUSION: Olmesartan,Candesartan and Losartan could effectively inhibit pressure overload-induced cardiac remodeling even when with knockdown of Ang II,possibly through upregulation of the expression of the ACE2-Ang(1-7)-Mas axis and downregulation of the expression of the ACE-Ang II-AT1 axis. In contrast,Telmisartan,Valsartan and Irbesartan only played a role in the presence of Ang II,and Losartan had no effect in the presence of Ang II in vitro. AIM: To examine and compare the effects of several ARBs that are widely used in clinics, on the ACE-Ang II-AT1 receptor and the ACE2-Ang (1-7) -Mas axis during the development of cardiac remodeling after pressure overload. METHODS: All of the mice used in the study underwent transverse aortic constriction (TAC) or sham operation for 2 or 4 weeks. A solution of either ARBs or saline was administered through a stomach tube 3 days before the operation. Meanwhile, to eliminate the influence of Ang II, a recombinant adenovirus expressing small interfering RNAs targeting angiotensinogen (Ad-ATG si RNA) was injected via the tail vein. The surgery was then performed and the drug was administered as mentioned above. Cardiac function and remodeling were evaluated by echocardiography , hemodynamic measurements and cardiac histology. Western blotting was used to determine the protein expression levels. Meanwhile, we performed similar experiments using ARBs with or without ATG si RNA in cardiomyocytes induc ed by mechanical stretch. RESULTS: Although all of the six ARBs, none of which repressed the elevation of left ventricular pressure after TAC, attenuated the development of cardiac hypertrophy and heart failure in the wild-type mice, the degree of attenuation by Olmesartan, In addition, the degree of downregulation of the ACEAng II-AT1 axis and upregulation of the ACE2-Ang (1-7) -Mas axis was higher in response to Olmesartan , Candesartan and Losartan administration in vivo and in vitro., Olmesartan had a larger influence when administered long term. However, the expression of ACE was not influenced by the administration of ARBs in vivo and in vitro. Moreover, in angiotensinogen-knockdown mice , TAC-induced cardiac hypertrophy and heart failure were inhibited by Olmesartan, Candesartan and Losartan but not by Telmisartan, Valsartan and Irbesartan administration. Furthermore, only Olmesartan and CandesaCONCLUSION: Olmesartan, Candesartan and Losartan could effectively inhibit pressure overload-induced cardiac remodeling even when with knockdown of Ang (1-7) -Mas axis in vitro. II, possibly through upregulation of the expression of the ACE2-Ang (1-7) -Mas axis and downregulation of the expression of the ACE-Ang II-AT1 axis. In contrast, Telmisartan, Valsartan and Irbesartan only played a role in the presence of Ang II, and Losartan had no effect in the presence of Ang II in vitro.