Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model

ABSTRACT

Introduction

Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS.

Methods and Results

Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice.

Conclusion

TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.

KEYWORDS:

• Autonomic nervous system
• cardiac hypertrophy
• transient receptor potential vanilloid 1
• brain-derived neurotrophic factor
• brain

Acknowledgments

This work was supported by JSPS Grants-in-Aid for Scientific Research (JP17K16012, JP19K17604, and 21K08032, K.S.; JP17K09508 and 20K08431, Y.H.) and grants from SENSHIN Medical Research Foundation (K.S.) and Salt Science Research Foundation (No. 1644, H.Y.).

Disclosure statement

K.S. reports grants from Daiichi Sankyo and Nippon Boehringer Ingelheim. H.T. reports grants and/or personal fees from Daiichi Sankyo, Novartis Pharma, Otsuka pharmaceutical, Pfizer Japan, Mitsubishi Tanabe Pharma, Teijin Pharma, Nippon Boehringer Ingelheim, Bayer Yakuhin, Bristol-Myers Squibb, AstraZeneca, Ono Pharmaceutical, Kowa, Japan Tobacco, IQVIA Service Japan, Omron Healthcare, MEDINET, Medical Innovation Kyushu, Abbott Medical Japan, Teijin Home Healthcare, and Boston Scientific Japan. The other authors report no conflicts..

Additional information

Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS);SENSHIN Medical Research Foundation;Salt Science Research Foundation;