It appears that the pharmacological activation of ACE2 promotes its beneficial effects due to an increased Ang-(1-7) production with concomitant degradation of Ang II. In fact, coadministration of A-779 abolished the protective effects of XNT on PH [117] . In addition, the antifibrotic effect of XNT observed in hearts of SHR was associated with increases in cardiac Ang-(1-7) expression [48] . However, it is also pertinent to point out that off-target effects of XNT on these beneficial outcomes cannot be ruled out at the present time.