In the central nervous system, it has been shown that NO reduces, whereas oxidative stress increases, sympathetic activity [45] [46] [47] . Overexpressing ACE2 in the PVN normalized the decreased neuronal nitric oxide synthase (NOS) protein levels in this region in CHF rats and was accompanied with improved sympathetic nerve activity, suggesting the inhibitory effects of ACE2 on sympathoexcitation involve an NO mechanism [42] . Similarly, Gao et al. [43] showed that overexpression of ACE2 in the brain prevented the downregulation of NOS expression in the CHF mice, contributing to the improvement of baroreflex sensitivity and the reduction of sympathoexcitation. This is confirmed by our observation showing that overexpression of ACE2 in the brain upregulated NOS expression and increased NO levels in the cerebrospinal fluid [33••]. In addition, ACE2 overexpression in the brain prevented the Ang II-mediated decrease in NOS expression in regions modulating blood pressure regulation [33••]. Furthermore, we observed that ACE2 gene deletion leads to increased superoxide levels in various brain nuclei of aged mice [48] , supporting the antioxidant capacity of ACE2 in the brain. These data indicate that the protective effects of ACE2 could be linked to an increased NO availability and decreased oxidative stress in the brain.