Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor 4 in mice with heart failure

Kiyohiro Ogawa, Yoshitaka Hirooka, Takuya Kishi, Kenji Sunagawa

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    18 Citations (Scopus)

    Abstract

    The activation of angiotensin II type 1 receptor (AT1R) in the brain plays a pivotal role in enhanced sympathetic drive in heart failure (HF). Activation of the AT1R in the brain produces oxidative stress and inflammation. Toll-like receptor 4 (TLR4) signaling in the brain induces the inflammatory cascade. We hypothesized that sympathoexcitation is mediated by the AT1R-activated TLR4 in the brainstem in HF. As a model of HF, the left coronary artery was ligated to induce a large myocardial infarction and subsequent chronic heart failure (CHF) in Institute of Cancer Research mice. On day 10 after the surgery, we started intracerebroventricular infusion of losartan (CHF-Los) or vehicle (CHF-Veh) via osmotic minipumps for 14 days. Expression level of the TLR4 in the brainstem was significantly higher in HF mice than in sham mice and significantly lower in CHF-Los mice than in CHF-Veh mice. Urinary norepinephrine excretion was significantly higher in HF mice than in sham mice and was significantly lower in CHF-Los than in CHF-Veh. Chronic intracerebroventricular infusion of angiotensin II increased the expression level of the second messenger of the TLR4. These results suggest that activation of the TLR4 via AT1R in the brainstem contributes to the sympathoexcitation probably due to the inflammation in the brain of the myocardial infarction-induced HF.

    Original languageEnglish
    Pages (from-to)543-549
    Number of pages7
    JournalJournal of Cardiovascular Pharmacology
    Volume58
    Issue number5
    DOIs
    Publication statusPublished - Nov 2011

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Cardiology and Cardiovascular Medicine

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