Abstract MP04: In Vivo Bioluminescence Imaging Reveals a Pre-Hypertensive Surge of Nuclear-Factor-κ-B (NF-κB) Activity in the Subfornical Organ (SFO) During Obesity-Induced Hypertension

Abstract

The central nervous system has been implicated in obesity-induced sympathetic activation and hypertension, although the underlying mechanisms remain unclear. We tested the hypothesis that the transcription factor NF-κB is activated in the SFO, a key cardioregulatory brain center, during the development of obesity-induced hypertension. Male C57Bl/6 mice were instrumented with radiotelemeters for mean arterial pressure (MAP) recording, and underwent SFO-targeted microinjection of an adenovirus encoding firefly luciferase downstream of the NF-κB response elements. After recovery, mice were fed high fat diet (60% fat) or normal chow (5% fat), and SFO NF-κB activity was longitudinally monitored in vivo by bioluminescence imaging coupled with luciferin injections. In response to HFD, a slowly developing hypertension was observed, with an initial rise in MAP at 4 weeks (109 ± 1 vs 117 ± 1 mmHg; day 0 vs day 28; n=8; p<0.05) that was sustained for 8 weeks. NF-κB activity in the SFO increased gradually during HFD feeding, with a surge at 3 weeks, prior to a rise in MAP (day 21: 0.91 ± 0.08 vs 1.70 ± 0.25 photons/s fold baseline; normal chow vs HFD; n=4-7; p<0.05). SFO NF-κB activity transiently subsided and a second elevation was noted during the maintenance of obesity-induced hypertension at 6.5 weeks (day 42: 0.72 ± 0.14 vs 1.52 ± 0.07 photons/s fold baseline; normal chow vs HFD; n=4-7; p<0.05). These findings suggest that NF-κB is activated in the SFO during HFD feeding. The biphasic increase in NF-κB activity prior to and during a sustained increase in MAP suggests a casual role for SFO NF-κB in the development of obesity-induced hypertension. HL63887, HL84207, AHA13POST14410020, K99HL166776