Circulating angiotensin II (Ang II) combined with high salt intake increases sympathetic nerve activity (SNA) in some forms of hypertension. Ang II-induced increases in SNA are modest, delayed, and specific to certain vascular beds. The brain targets for circulating Ang II are neurons in the area postrema (AP), subfornical organ (SFO), and possibly other circumventricular organs. Ang II signaling is integrated with sodium-sensitive neurons in the SFO and/or organum vasculosum of the lamina terminalis (OVLT) and drives sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) via the paraventricular nucleus (PVN). It is likely that, over time, new patterns of gene expression emerge within neurons of the SFO-PVN-RVLM pathway that transform their signaling properties. This transformation is critical in maintaining increased SNA. Identification of a novel gene supporting this process may provide new targets for treatment of neurogenic hypertension.