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Aldosterone and Salt Induces Hypertension Associated with Increased Oxidative Stress in the Brain of Apolipoprotein E Knockout Mice
Author(s) -
Araki Shuichiro,
Hirooka Yoshitaka,
Kishi Takuya,
Ito Koji,
Koga Yasuaki,
Konno Satomi,
Yasukawa Keiji,
Utsumi Hideo,
Sunagawa Kenji
Publication year - 2009
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.23.1_supplement.1015.9
Subject(s) - oxidative stress , endocrinology , medicine , in vivo , chemistry , aldosterone , knockout mouse , kidney , biology , receptor , microbiology and biotechnology
Background Oxidative stress in brain plays a crucial role in the neural mechanism of hypertension. Apolipoprotein E‐knockout mice (apoEKO) reveal increased oxidative stress in the vasculature, heart, and kidney. Aldosterone (ALDO)‐salt load promotes hypertension and organ damage. We hypothesized that apoEKO was susceptible to ALDO‐salt thereby causing hypertension associated with the increased oxidative stress in the brain using an in vivo electron spin resonance (ESR) method. Methods and Results Eight‐week‐old apoEKO and their wild type (WT) were treated with either ALDO (6 microg/mouse/d, s.c. osmotic minipump) and 8% NaCl‐containing chow, or vehicle and standard chow (Veh). After 6‐week treatments, differences in SBP and the in vivo ESR/spin probe decay rates in brain, an index of oxidative stress in brain, between ALDO‐salt and Veh treatments were compared between apoEKO and WT. SBP was increased significantly in apoEKO (117.8±2.1 vs 105.2±1.8 mm Hg, n=6 each, P<0.05), but not in WT (111.8±2.1 vs 104.8±1.8 mm Hg, n=6 each, ns). In vivo ESR decay rate was increased significantly in apoEKO (0.297±0.009 vs 0.243±0.008 min −1 , P<0.01), but not in WT (0.248±0.011 vs 0.232±0.012, min −1 , ns). Oxidative stress evaluated by dihydroethidium staining in the rostral ventrolateral medulla was increased in ALDO‐salt‐treated apoEKO compared with Veh‐treated apoEKO. Conclusion These results suggest that ALDO‐salt induces hypertension associated with the increased oxidative stress in the brain in ApoEKO.