Chronic Heart Failure (CHF) is a disease characterized by overactivation of the renin-angiotensin system, increased sympathetic outflow, and high oxidative stress. In conditions of high oxidant stress, Nuclear factor erythroid 2 related factor 2 (Nrf2) is dissociated from Kelch-like ECH associated protein 1 (Keap1) to activate antioxidant response element (ARE) genes such as heme oxygenase 1 (HO1) and NQO1 as a compensatory mechanism. p65 nuclear factor kappa B (NF-kB) is one of the primary transcription factors that contributes to the etiology of CHF, recruiting creb binding protein (CBP) to both increase transcription of pro-inflammatory proteins and inhibit transcription of AREs. Exercise training (ExT) has been shown to decrease sympathetic outflow and oxidative stress and improve quality of life in patients with cardiovascular disease, however the mechanism(s) by which ExT is protective remain unclear. The purpose of this study was to investigate the convergence of the Nrf2/Keap1 and NF-kB pathways on CBP in the rostral ventrolateral medulla (RVLM) of the rat brain following CHF and ExT. Animals were anesthetized with isoflourane (0.5-2% in oxygen), intubated and mechanically ventilated. Animals were then infarcted using coronary artery ligation. Following confirmation of CHF by a decrease in ejection fraction using echocardiography, some animals were exercised four weeks post-surgery on a treadmill at a final speed of 25 m/min for 60 minutes, 5 days a week for 6 weeks. Western blot analysis of RVLM micropunches demonstrated that in CHF, there was a significant upregulation in NF-kB and Keap1 proteins compared to sham and a decrease in Nrf2 (n=4-5 per group, p=0.003 for Nrf2 and Keap1, p=0.0016 for NF-kB by unpaired t-test). ExT significantly increased Nrf2 and Keap1 expression compared to both sham and CHF groups but normalized NF-kB expression in CHF animals (n=4-5 per group). Co-immunoprecipitation experiments were then performed to examine the interaction of NF-kB and Nrf2 with CBP. In CHF, there was an increase in NF-kB/CBP interaction and a decrease in Nrf2/CBP association compared to sham (p=0.01 for NF-kB/CBP and Nrf2/CBP by unpaired t-test, n=2). However, during ExT in both sham and CHF groups, there was an increase in Nrf2/CBP interaction and a compensatory decrease in NF-kB/CBP interaction (n=2). Taken together, these data suggest that central Nrf2 is downregulated in CHF and that NF-kB and Nrf2 compete for CBP during CHF and following ExT.