CALL FOR PAPERS Endoplasmic Reticulum Stress Endoplasmic reticulum and oxidant stress mediate nuclear factor- B activation in the subfornical organ during angiotensin II hypertension

Young CN, Li A, Dong FN, Horwath JA, Clark CG, Davisson RL. Endoplasmic reticulum and oxidant stress mediate nuclear factorB activation in the subfornical organ during angiotensin II hypertension. Am J Physiol Cell Physiol 308: C803–C812, 2015. First published March 11, 2015; doi:10.1152/ajpcell.00223.2014.—Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the brain circumventricular subfornical organ (SFO) mediate the central hypertensive actions of Angiotensin II (ANG II). However, the downstream signaling events remain unclear. Here we tested the hypothesis that angiotensin type 1a receptors (AT1aR), ER stress, and ROS induce activation of the transcription factor nuclear factorB (NFB) during ANG II-dependent hypertension. To spatiotemporally track NFB activity in the SFO throughout the development of ANG II-dependent hypertension, we used SFO-targeted adenoviral delivery and longitudinal bioluminescence imaging in mice. During low-dose infusion of ANG II, bioluminescence imaging revealed a prehypertensive surge in NFB activity in the SFO at a time point prior to a significant rise in arterial blood pressure. SFO-targeted ablation of AT1aR, inhibition of ER stress, or adenoviral scavenging of ROS in the SFO prevented the ANG II-induced increase in SFO NFB. These findings highlight the utility of bioluminescence imaging to longitudinally track transcription factor activation during the development of ANG II-dependent hypertension and reveal an AT1aR-, ER stress-, and ROS-dependent prehypertensive surge in NFB activity in the SFO. Furthermore, the increase in NFB activity before a rise in arterial blood pressure suggests a causal role for SFO NFB in the development of ANG II-dependent hypertension.