Alteration of ACE2 expression or activity in the brain has been found in pathologic conditions related to cardiovascular diseases. Kawajiri et al. [35] reported decreased ACE2 and increased ACE concentration in cerebrospinal fluid from patients with multiple sclerosis compared to those with non-neurologic diseases. Similarly, downregulated ACE2 and upregulated ACE protein and mRNA expression were observed in various brain nuclei (including PVN, NTS, and RVLM ) from pacing-induced chronic heart failure (CHF) rabbits with increased sympathetic nerve activity [34] . These data suggest that the alteration of ACE/ACE2 in the brain is involved in the development of cardiovascular diseases. Moreover, we recently showed decreased ACE2 activity in the brain of a chronically hypertensive mouse model with increased Ang II level [31••]. These observations support the critical role of ACE2 in the central nervous system in the maintenance of normal cardiovascular function.