Central neuregulin-1/ErbB signaling modulates cardiac function via sympathetic activity in pressure overload-induced heart failure

Ryuichi Matsukawa, Yoshitaka Hirooka, Koji Ito, Nobuhiro Honda, Kenji Sunagawa

研究成果: Contribution to journalArticle査読

10 被引用数 (Scopus)

抄録

OBJECTIVES:: Neuregulin-1 (NRG-1)/ErbB signaling in the heart is reported to have a crucial role in heart failure. We recently demonstrated that NRG-1 signaling has sympathoinhibitory effects in the brain cardiovascular control center. How this central signaling impacts sympathoexcitation in heart failure, however, is unknown. Here we examined the role of central NRG-1/ErbB signaling in modulating the sympathetic nervous system in pressure overload-induced heart failure. METHODS AND RESULTS:: Pressure overload-induced heart failure was induced in Wistar-Kyoto rats by banding the abdominal aorta. Rats were followed up for 15 weeks. Compared to sham-operated rats, aortic-banded rats showed left ventricle (LV) hypertrophy, LV dilation, and LV dysfunction [reducing fractional shortening (%fractional shortening), increased LV end-diastolic pressure, decreased positive and negative pressure differential (±dp/dtmax)], and increased urinary norepinephrine excretion. Aortic banding led to reduced expression of NRG-1 in the brainstem at 10 weeks after banding and reduced expression of ErbB2 at 5 weeks, but did not affect ErbB4. Central administration of recombinant NRG-1β at 5 weeks for 2 weeks attenuated LV hypertrophy, improved LV dilatation, prevented LV dysfunction (improvement of %fractional shortening and ±dp/dtmax, and reduction of LV end-diastolic pressure), and lowered urinary norepinephrine excretion at 10 weeks, and these effects were still observed at 15 weeks. CONCLUSION:: NRG-1/ErbB signaling in the brainstem is impaired during the progression of pressure overload-induced heart failure. Activation of central NRG-1 signaling improves cardiac function through sympathoinhibition. These findings provide a new treatment concept and support the benefit of NRG-1 treatment in heart failure.

本文言語英語
ページ(範囲)817-825
ページ数9
ジャーナルJournal of hypertension
32
4
DOI
出版ステータス出版済み - 4 2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内科学
  • 生理学
  • 循環器および心血管医学

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