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Toll‐like receptor expression is increased via activation of AT1 receptor in the brain associated with sympathoexcitation in mice with heart failure
Author(s) -
Ogawa Kiyohiro,
Hirooka Yoshitaka,
Kishi Takuya,
Sunagawa Kenji
Publication year - 2010
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.24.1_supplement.809.15
Subject(s) - heart failure , medicine , angiotensin ii receptor type 1 , losartan , endocrinology , tlr4 , receptor , angiotensin ii , myocardial infarction , cardiology
Background Previous studies suggest that heart failure (HF) is associated with sympathoexcitation due to oxidative stress in the brain induced by AT1 receptor (AT1R) and NAD (P) H oxidase. They are also known as an upstream of inflammatory signaling pathway mediated by Toll‐like receptor 4 (TLR4) in the brain. The aim of the present study was to determine whether AT1R‐induced sympatho‐excitation is mediated by TLR4 in the brain of heart failure model or not. Methods and Results As a HF model, ligation of the left coronary artery was performed to make large myocardial infarction (MI) and subsequent HF in ICR mice. On day 10 after left coronary artery ligation, mice received either intracerebroventricular (icv) losartan (10μg/h, CHF‐Los) or vehicle (CHF‐Veh) by osmotic minipumps for 14 days. Urinary norepinephrine excretion as a parameter of sympathetic nervous system activity was significantly higher in HF than in sham mice and was significantly lower in CHF‐Los than in CHF‐Veh(0.34±0.04 vs 0.62±0.06, n=3, P<0.05). The expression of TLR4 in the whole brain determined by Western blot analysis was significantly higher in HF than in sham mice, and was significantly lower in CHF‐Los than in CHF‐Veh. Conclusion Toll‐like receptor expression is increased via activation of AT1 receptor in the brain associated with sympathoexcitation in mice with heart failure.