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Long‐term high fat diet treatment activates NF kappa B signaling and increases endothelial dysfunction in angiotensin II hypertensive rats
Author(s) -
Elmarakby Ahmed A.,
Imig John D.
Publication year - 2007
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.21.6.a1196-c
Subject(s) - endocrinology , medicine , insulin resistance , endothelial dysfunction , angiotensin ii , leptin , renin–angiotensin system , kidney , insulin , blood pressure , obesity
Studies suggest that inflammatory cytokines play an important role in the progression of renal dysfunction in obesity and hypertension. Thus, we hypothesize that NFκB signaling activation contributes to insulin resistance and endothelial dysfunction in angiotensin II (ANG) infused rats fed a high fat diet. Two groups of male rats were fed either normal or high fat diet for 6 weeks and osmotic minipumps were implanted to deliver ANG for 4 more weeks. High fat diet treatment did not significantly enhance the increase in blood pressure in ANG infused rats (174±6 vs. 170±5 mmHg), however, body weight gain was higher in rats fed a high fat diet compared with those on a normal diet. Plasma insulin and leptin levels were significantly elevated in ANG/high fat rats compared to ANG/normal (6.8±0.9 vs. 4.3±.4 μg/l & 11.5±1 vs. 2.3±0.4 μg/l, respectively). Renal afferent arteriolar dilation to acetylcholine was impaired in ANG hypertension and further impaired in ANG rats fed a high fat diet. Renal cortical Cyp2c23 protein expression decreased in ANG/high fat rats compared to ANG/normal. Renal cortical NFκB activity and phospho‐IKKα/β protein expression also increased in ANG rat fed a high fat diet compared to those fed a normal diet. These data suggest that activation of NFκB signaling cascade and down‐regulation of Cyp2c23 may contribute to endothelial dysfunction and insulin resistance in ANG hypertensive rats fed a high fat diet.