Circulating Ang II activates central angiotensinergic pathways, and an amplifying aldosterone (aldo)-MR-ENaC-AT 1 R neuromodulatory pathway which are critical for several forms of hypertension. We hypothesized that in addition Ang II increases BDNF expression in both the CNS and adrenal which plays a balancing role against Ang II excitatory actions. In the 1 st exp, Wistar rats were sc infused with Ang II at the high dose of 500 ng/kg/min for 7days. In the 2 nd exp, rats were treated with regular salt diet (0.4% NaCl), high salt diet (2% NaCl), sc Ang II at the low dose of 150 ng/kg/min, or sc Ang II with high salt diet for 14 days. In the 3 rd exp, MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT 1 R blocker (losartan) or vehicles (Veh) were icv infused combined with Ang II-salt. In the 4 th exp, rats were sc infused with aldo (1μg/hr) with saline as drinking fluid. mRNA levels of BDNF were measured by real-time qPCR. In the adrenals, Ang II dose-related increased BDNF mRNA, and Ang II-salt further enhanced BDNF mRNA. High dose Ang II increased BDNF mRNA in the RVLM but not in the PVN. Central blockades markedly decreased Ang II-salt induced BDNF expression in the adrenal cortex. In contrast, saline alone or aldo-saline decreased BDNF mRNA in the adrenal cortex with no effect in the PVN. Central blockades lower Ang II-salt induced BDNF expression in the adrenal, indicating that a central regulatory mechanism plays a role in adrenal BDNF expression. Activation of BDNF by Ang II -modulated by salt-, may provide an important balancing mechanism both centrally and peripherally for Ang II associated hypertension.