The regulation of the sympathetic nervous system in chronic heart failure (CHF) is mediated by both abnormal peripheral reflexes and alterations in the sensitivity of neurons in the medulla and hypothalamus. Angiotensin II (Ang II) plays an important role in modulating the discharge sensitivity of central sympathetic neurons. There is clear evidence that the expression of the Ang II type 1 (AT1) receptor in these areas of the brain is up regulated in the CHF state. Blockade of central AT1R's by losartan reduces renal sympathetic nerve activity (RSNA) and improves baroreflex sensitivity in CHF. The mechanism by which AT1R expression is up regulated involves the activation of several transcription factors including activator protein 1 (AP1) and nuclear factor kappa B (NF-kB). Both of these transcription factors are active in animals with CHF and in animals infused with central Ang II. The activation of these transcription factors depends on a positive feedback mechanism via AT1R activation. Furthermore, the transcriptional regulation of AT1R expression is sensitive to the production of reactive oxidant species (ROS) in the central nervous system in animals with CHF and in cultured neurons treated with Ang II. Central blockade of ROS using the SOD mimetic tempol reduces binding of AP1 to DNA and decreases AT1R expression in animals with CHF.