Increased sympathetic nerve activity and the activation of the central renin-angiotensin system are commonly associated with cardiovascular disease states such as hypertension and heart failure, yet the precise mechanisms contributing to the long-term maintenance of this sympatho-excitation are incompletely understood. Due to the established physiological role of neurotrophins contributing toward neuroplasticity and neuronal excitability along with recent evidence linking the renin-angiotensin system and brain-derived neurotrophic factor (BDNF) along with its receptor (TrkB), it is likely the two systems interact to promote sympatho-excitation during cardiovascular disease. However, this interaction has not yet been fully demonstrated, in vivo. Thus, we hypothesized that central angiotensin II (Ang II) treatment will evoke a sympatho-excitatory state mediated through the actions of BDNF/TrkB. We infused Ang II (20 ng/min) into the right lateral ventricle of male Sprague-Dawley rats for twelve days with or without the TrkB receptor antagonist, ANA-12 (50 ng/h). We found that ICV infusion of Ang II increased mean arterial pressure (+ 40.4 mm Hg), increased renal sympathetic nerve activity (+ 19.4% max activity), and induced baroreflex dysfunction relative to vehicle. Co-infusion of ANA-12 attenuated the increase in blood pressure (− 20.6 mm Hg) and prevented the increase in renal sympathetic nerve activity (− 22.2% max) and baroreflex dysfunction relative to Ang II alone. Ang II increased thirst and decreased food consumption, and Ang II + ANA-12 augmented the thirst response while attenuating the decrease in food consumption. We conclude that TrkB signaling is a mediator of the long-term blood pressure and sympathetic nerve activity responses to central Ang II activity. These findings demonstrate the involvement of neurotrophins such as BDNF in promoting Ang II-induced autonomic dysfunction and further implicate TrkB signaling in modulating presympathetic autonomic neurons during cardiovascular disease.
- (3–5): BDNF
- Blood pressure
ASJC Scopus subject areas
- Endocrine and Autonomic Systems
- Clinical Neurology
- Cellular and Molecular Neuroscience