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

Research output: Contribution to journalArticle

17 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 1 2011

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Sympathetic Nervous System
Heart Failure
Brain
Toll-Like Receptor 4
Angiotensin Type 1 Receptor
Intraventricular Infusions
Brain Stem
Mouse Tlr4 protein
Myocardial Infarction
Inflammation
Brain Infarction
Losartan
Second Messenger Systems
Angiotensin II
Coronary Vessels
Norepinephrine
Oxidative Stress

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor 4 in mice with heart failure. / Ogawa, Kiyohiro; Hirooka, Yoshitaka; Kishi, Takuya; Sunagawa, Kenji.

In: Journal of Cardiovascular Pharmacology, Vol. 58, No. 5, 01.11.2011, p. 543-549.

Research output: Contribution to journalArticle

Ogawa, Kiyohiro ; Hirooka, Yoshitaka ; Kishi, Takuya ; Sunagawa, Kenji. / Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor 4 in mice with heart failure. In: Journal of Cardiovascular Pharmacology. 2011 ; Vol. 58, No. 5. pp. 543-549.
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