Angiotensin type 1A receptors (AT 1a ) and reactive oxygen species (ROS) mediate nuclear factor‐κ‐B (NF‐κB) activation in the subfornical organ (SFO) during slow‐pressor Angiotensin‐II (Ang‐II) hypertension

We recently showed that NF‐κB is activated in the SFO of the brain during slow‐pressor Ang‐II hypertension (HTN). The molecular mechanisms contributing to NF‐κB activation, however, remain unclear. We tested the hypothesis that NF‐κB activation in the SFO during slow‐pressor Ang‐II HTN is mediated by AT 1a receptors and ROS. Male AT 1a flox mice underwent SFO‐targeted injections of an adenovirus encoding firefly luciferase downstream of NF‐κB response elements, in conjunction with adenoviral delivery of Cre‐recombinase (Cre) for selective deletion of AT 1a or control LacZ. After recovery, osmominipumps were implanted for slow‐pressor Ang‐II infusion (600ng/kg/min), and NF‐κB activity in the SFO was measured daily using in vivo bioluminescence imaging. A surge in SFO‐NF‐κB activity was seen at day 5 of slow‐pressor Ang‐II infusion and this was significantly reduced by deletion of AT 1a (LacZ 1.8 ± 0.7 vs Cre −0.2 ± 0.1 photons/s fold baseline, p<0.05, n=6). In a separate cohort of mice, scavenging of superoxide in the SFO via adenoviral overexpression of CuZnSOD also prevented the prehypertensive surge in NF‐κB activity (Day 5: LacZ 1.5 ± 0.7 vs CuZnSOD −0.5 ± 0.1 photons/s fold baseline, p<0.05, n=9–10). These findings suggest that AT 1a redox‐sensitive mechanisms are key steps mediating SFO‐NF‐κB activation during slow‐pressor Ang‐II HTN. HL864624