Abstract 210: Impaired Brain-Derived Neurotrophic Factor-TrkB Signaling in Nucleus Tractus Solitarius During Chronic Heart Failure Blunts Baroreflex Sensitivity
Blunted baroreflex function is a negatively prognostic marker of autonomic imbalance in chronic heart failure (CHF), yet the mechanisms underlying baroreflex blunting in CHF are not fully understood. The nucleus tractus solitarius (NTS) is the primary central target of baroreceptor afferents, and plays a critical role in regulating central baroreflex sensitivity. Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the NTS, but little is known about the role of BDNF signaling in the NTS. We hypothesized that in the NTS, BDNF enhances baroreflex sensitivity, and impaired BDNF-TrkB signaling contributes to the blunted baroreflex function in CHF. To test this hypothesis, 50 nl of BDNF or the selective TrkB antagonist ANA-12 were microinjected bilaterally into the dorso-medial NTS of sham-operated rats and myocardial infarct-induced CHF rats. BDNF evoked a greater decrease in blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in sham vs. CHF rats. Injection of ANA-12 increased MAP, HR, and RSNA to a greater extent in sham vs. CHF rats (Table). Following 125 μM ANA-12, baroreflex sensitivity was blunted in sham rats (3.7 ± 0.3 vs. 1.9 ± 0.1 bpm/mmHg max gain, p < .05 before vs. after, n = 4). CHF rats had blunted baroreflex sensitivity vs. sham (2.3 ± 0.1 bpm/mmHg, p < .05, n = 4), and ANA-12 had little effect on baroreflex sensitivity in CHF (2.0 ± 0.1 bpm/mmHg, n = 4). These data suggest that endogenous BDNF plays an important role in maintaining baroreflex sensitivity in the NTS, and that BDNF-TrkB signaling is impaired in CHF, which may contribute to blunted baroreflex sensitivity and autonomic imbalance.
Author Disclosures: B.K. Becker: None. H. Wang: None. I.H. Zucker: None.
- © 2014 by American Heart Association, Inc.