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Brain‐Derived Neurotrophic Factor in Nucleus Tractus Solitarius is increased in Pressure Overload‐Induced Cardiac Hypertrophy via Heart‐to‐Brain Axis
Author(s) -
Takenaka Risa,
Ito Koji,
Kishi Takuya,
Hirooka Yoshitaka
Publication year - 2016
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.30.1_supplement.1233.1
Subject(s) - baroreflex , medicine , endocrinology , heart failure , baroreceptor , pressure overload , muscle hypertrophy , brain derived neurotrophic factor , neurotrophic factors , blood pressure , heart rate , receptor , cardiac hypertrophy
Cardiac hypertrophy is an independent risk factor for heart failure, and result in baroreflex dysfunction. Baroreflex dysfunction further deteriorates cardiac hypertrophy and, if prolonged, may progress into heart failure with a vicious cycle. However, it remains unclear how cardiac hypertrophy worsens baroreflex via the heart‐to‐brain axis. We focused cardiac afferent nerve as a component of the heart‐to‐brain axis. Nucleus tractus solitarius (NTS) is primary nucleus in central baroreceptor circuit and received cardiac afferent nerve. It is suggested that increased brain‐derived neurotrophic factor (BDNF) in NTS reduces the neuronal activity, which might disrupt baroreflex. The cardiac afferent nerve terminals express a transient receptor potential vanilloid type 1 (TRPV1), and TRPV1 increases in the hypertrophic heart from transgenic mice. We hypothesized that pressure overload‐induced cardiac hypertrophy increases BDNF in NTS via TRPV1 in cardiac afferent nerve. Methods We divided wild‐type (WT) and TRPV1 knockout mice (KO) with aortic banding (AB) or sham operation. At 8 weeks after the operation, we evaluated cardiac function by echocardiography and BDNF levels in the NTS by Western blot analysis. Result Echocardiographic left ventricular hypertrophy and heart weight were significantly greater in WT‐AB than in WT‐sham, and were attenuated in KO‐AB. Western blot analysis revealed a significant increase in BDNF in NTS of WT‐AB compared with WT‐sham (1.26±0.01 vs. 0.90±0.02 units, n=4, P<0.05). However, KO‐AB had significantly lower BDNF in NTS than WT‐AB (1.26±0.01 vs. 1.02±0.02 units, n=4, P<0.05). Conclusion Increased BDNF in NTS by pressure overload‐induced cardiac hypertrophy was inhibited by knockout of TRPV1. These findings support the novel concept that cardiac hypertrophy disrupts baroreflex via the “heart (TRPV1)‐to‐brain (BDNF in NTS) axis”. Support or Funding Information This study was supported by a Grant‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (24390198 to Dr. Hirooka and 25461112 to Dr. Ito).