Endoplasmic reticulum and oxidant stress mediate nuclear factor-[kappa]B activation in the subfornical organ during angiotensin II hypertension

• Published in: American Journal of Physiology: Cell Physiology 2015-05, Vol.308 (10), p.C803
• Main Authors: Young, Colin N, Li, Anfei, Dong, Frederick N, Horwath, Julie A, Clark, Catharine G, Davisson, Robin L
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Bioluminescence; Cells; Hypertension; Molecules; Signal transduction; T cell receptors
• ISSN: 0363-6143; 1522-1563

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 1α receptors (...), ER stress, and ROS induce activation of the transcription factor nuclear factor-kB (NF-kB) during ANG II-dependent hypertension. To spatiotemporally track NF-kB 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 NF-kB activity in the SFO at a time point prior to a significant rise in arterial blood pressure. SFO-targeted ablation of ..., inhibition of ER stress, or adenoviral scavenging of ROS in the SFO prevented the ANG II-induced increase in SFO NF-kB. 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 ...-, ER stress-, and ROS-dependent prehypertensive surge in NF-kB activity in the SFO. Furthermore, the increase in NF-kB activity before a rise in arterial blood pressure suggests a causal role for SFO NF-kB in the development of ANG II-dependent hypertension. (ProQuest: ... denotes formulae/symbols omitted.)