PMID- 30909643 OWN - NLM STAT- MEDLINE DCOM- 20190717 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 6 DP - 2019 Mar 24 TI - Increased Brain-Derived Neurotrophic Factor in Lumbar Dorsal Root Ganglia Contributes to the Enhanced Exercise Pressor Reflex in Heart Failure. LID - 10.3390/ijms20061480 [doi] LID - 1480 AB - An exaggerated exercise pressor reflex (EPR) is associated with excessive sympatho-excitation and exercise intolerance in the chronic heart failure (CHF) state. We hypothesized that brain-derived neurotrophic factor (BDNF) causes the exaggerated EPR via sensitizing muscle mechanosensitive afferents in CHF. Increased BDNF expression was observed in lumbar dorsal root ganglia (DRGs) from CHF rats compared to sham rats. Immunofluorescence data showed a greater increase in the number of BDNF-positive neurons in medium and large-sized DRG subpopulations from CHF rats. Patch clamp data showed that incubation with BDNF for 4(-)6 h, significantly decreased the current threshold-inducing action potential (AP), threshold potential and the number of APs during current injection in Dil-labeled isolectin B4 (IB4)-negative medium-sized DRG neurons (mainly mechano-sensitive) from sham rats. Compared to sham rats, CHF rats exhibited an increased number of APs during current injection in the same DRG subpopulation, which was significantly attenuated by 4-h incubation with anti-BDNF. Finally, chronic epidural delivery of anti-BDNF attenuated the exaggerated pressor response to either static contraction or passive stretch in CHF rats whereas this intervention had no effect on the pressor response to hindlimb arterial injection of capsaicin. These data suggest that increased BDNF in lumbar DRGs contributes to the exaggerated EPR in CHF. FAU - Schiller, Alicia M AU - Schiller AM AD - Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA. alicia.schiller@unmc.edu. FAU - Hong, Juan AU - Hong J AD - Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA. juan.hong@unmc.edu. FAU - Xia, Zhiqiu AU - Xia Z AD - Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA. Zhiqiu.xia@unmc.edu. FAU - Wang, Han-Jun AU - Wang HJ AUID- ORCID: 0000-0001-5906-8980 AD - Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA. hanjunwang@unmc.edu. LA - eng GR - R01 HL121012/HL/NHLBI NIH HHS/United States GR - R01 HL126796/HL/NHLBI NIH HHS/United States GR - R01HL121012/NH/NIH HHS/United States PT - Journal Article DEP - 20190324 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antibodies, Monoclonal) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Body Weight MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/*metabolism MH - Disease Models, Animal MH - Ganglia, Spinal/*metabolism MH - Heart Failure/diagnosis/*etiology/*physiopathology MH - Hemodynamics MH - Immunohistochemistry MH - Lumbosacral Region MH - Male MH - Organ Size MH - *Physical Conditioning, Animal MH - Rats MH - *Reflex/drug effects MH - Sensory Receptor Cells/metabolism PMC - PMC6471760 OTO - NOTNLM OT - cardiovascular reflexes OT - exercise OT - mechanoreflex OT - neurotrophic factors COIS- The authors declare no conflicts of interest. EDAT- 2019/03/27 06:00 MHDA- 2019/07/18 06:00 PMCR- 2019/03/01 CRDT- 2019/03/27 06:00 PHST- 2019/01/19 00:00 [received] PHST- 2019/03/20 00:00 [revised] PHST- 2019/03/21 00:00 [accepted] PHST- 2019/03/27 06:00 [entrez] PHST- 2019/03/27 06:00 [pubmed] PHST- 2019/07/18 06:00 [medline] PHST- 2019/03/01 00:00 [pmc-release] AID - ijms20061480 [pii] AID - ijms-20-01480 [pii] AID - 10.3390/ijms20061480 [doi] PST - epublish SO - Int J Mol Sci. 2019 Mar 24;20(6):1480. doi: 10.3390/ijms20061480.