AIM: We investigated how AT1-R stimulated by mechanical stresses induces cardiac fibrosis. METHODS: We produced in vivo cardiac pressure overload model in angiotensinogen knockout( ATG- /-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG- /-mice both lack the participation of Ang II. RESULTS: Pressure overload for 4 weeks in ATG- /-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis,however,the TGF-β,a key regulatory factor of fibrosis,was not significantly increased in these ATG- /-mice. Meanwhile,the inhibitor for AT1-R significantly inhibited mechanical stress-induced cardiac fibrosis in these ATG- /-models whereas inhibition of TGF-β did not. CONCLUSION: The results showed that mechanical stress-induced fibrotic responses through AT1-R required the phosphorylation of Smad2 but not the involvement of TGF-β. AIM: We investigated how AT1-R stimulated by mechanical stresses induces cardiac fibrosis. METHODS: We produced in cardiac cardiac pressure overload model in angiotensinogen knockout (ATG- / -) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells ATG- / -mice both lack the participation of Ang II. RESULTS: Pressure overload for 4 weeks in ATG- / -mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis, however, the TGF-beta, a key regulatory factor of fibrosis, was not significantly increased in these ATG- / -mice. Meanwhile, the inhibitor for AT1-R significantly inhibited mechanical stress-induced cardiac fibrosis in these ATG- / -models while inhibition inhibition of TGF-β did not. CONCLUSION: The results showed that mechanical stress-induced fibrotic responses through AT1-R required the phosphorylation of Smad2 but not the involvement of TGF-β.