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In vivo bioluminescence imaging reveals a pre‐hypertensive surge of nuclear‐factor‐ κ B (NF‐ κ B) activity in the subfornical organ (SFO) during slow‐pressor angiotensin‐II (Ang‐II) hypertension
Author(s) -
Young Colin N.,
Butler Scott D.,
Sharma Ram V.,
Davisson Robin L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.661.1
Subject(s) - subfornical organ , angiotensin ii , in vivo , luciferase , endocrinology , blood pressure , medicine , nf κb , mean arterial pressure , chemistry , saline , renin–angiotensin system , biology , heart rate , biochemistry , gene , transfection , microbiology and biotechnology , inflammation
We have shown that redox signaling in the SFO of the brain mediates slow‐pressor Ang‐II hypertension (HTN), a model that recapitulates features of human essential HTN. However the molecular mechanisms remain unclear. We tested the hypothesis that the redox‐regulated transcription factor NF‐κB is activated in SFO during the development of slow‐pressor Ang‐II HTN. Male C57Bl/6 mice were instrumented with telemeters for mean arterial pressure (MAP) recording, and an SFO‐targeted injection of an adenovirus encoding firefly luciferase downstream of NF‐κB response elements was performed. After recovery, osmominipumps were implanted for infusion of AngII (600 ng/kg/min s.c.) or saline and NF‐κB activity was longitudinally monitored in vivo by bioluminescence imaging (Xenogen). Ang‐II caused slowly developing HTN, with an initial rise in MAP at days 7–9 and a peak increase in MAP during the second week of infusion (day 11: 139 ± 9 vs. day 0: 96 ± 2; n=3, p<0.05). NF‐κB activity in the SFO increased gradually during the Ang‐II infusion, with a robust surge at day 5, prior to a rise in blood pressure (Ang II 177,732 ± 93425 vs. saline 42,728 ± 5039 photons/s; n=4–5, p<0.05). NF‐κB returned to baseline levels by day 7, still prior to peak rise in MAP. This suggests that NF‐κB is transiently activated in the SFO during slow‐pressor Ang‐II HTN. The increase in NF‐κB activity prior to a rise in MAP also suggests a casual role for SFO NF‐κB in the development of HTN. HL864624