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The effect of peroxisome proliferator activated receptor ‐α activation and apocynin on superoxide dismutase and NADPH oxidase expression in the brains of mice during angiotensin II‐induced hypertension (1067.9)
Author(s) -
Bouchelion Michelle,
Mervin Addias,
Lee Dexter,
Allard Joanne
Publication year - 2014
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.28.1_supplement.1067.9
Subject(s) - apocynin , nadph oxidase , fenofibrate , superoxide dismutase , angiotensin ii , chemistry , endocrinology , reactive oxygen species , medicine , superoxide , nox1 , pharmacology , oxidative stress , peroxisome proliferator activated receptor , receptor , biochemistry , enzyme
Approximately 33% of American adults suffer from hypertension which significantly increasing their risk for heart attacks and strokes. Hypertension is also associated with elevated levels of reactive oxygen species (ROS), which can negatively affect cellular function. Studies suggest that NADPH oxidase enzymes (NOX) are major sources of ROS in both the central nervous systems and that NOX levels are increased with hypertension. Superoxide dismutase (SOD), a powerful antioxidant and anti‐inflammatory protein acts as a scavenger of ROS. Administration of compounds that increase SOD levels can provide protection from the harmful effects of hypertension. This study’s objective is to determine the effects of two anti‐oxidative drugs, fenofibrate, a peroxisome proliferator activated receptor‐α agonist, and apocynin, a NADPH oxidase inhibitor, on brain levels of NOX and SOD, in mice with Angiotensin II (Ang II) ‐induced hypertension. We hypothesize that Fenofibrate (145 mg/kg/day) and Apocynin (1 g/L) will attenuate the effects of Ang II by increasing SOD levels and decreasing the levels of NOX enzymes. Male Swiss‐Webster mice were divided into 4 groups. Control (C) mice were untreated. All other mice received Ang II (400 ng/kg/min) for 12 days. Apocynin and Fenofibrate groups received additional doses of either fenofibrate (145 mgkg/day) or Apocynin (1 g/L). Mean arterial pressure on day 12 of Ang II was 100 ± 3, 120 ± 1, 112 ± 5, 116 ± 1 mmHg for Control, Ang II, Ang II + Fenofibrate and Ang II + Apocynin, respectively. Mice were sacrificed, brains were dissected, and protein levels were evaluated using standard western blotting procedures. Results suggest that fenofibrate decreases SOD levels while increasing NOX levels in brain. These preliminary results do not support our initial hypothesis; therefore additional experiments will be conducted to elucidate the mechanisms of fenofibrate and apocynin in this mouse model of hypertension. Grant Funding Source : NHLBI 5K01HL092593‐05