The significant findings of this study are that human and rat atrial tissues express Piezo1 channels and that are activated by hypertension and that in atrial myocytes, HHP-induced activation of Piezo1 was coupled to the CaM/Src/Pitx2 pathway and participated the decrease of ICa,L contributing to APD shortening and an increase in susceptibility to AF. Here, PITX2 is linked to Hypertension.