PMID- 29694277 OWN - NLM STAT- MEDLINE DCOM- 20190729 LR - 20200930 IS - 1522-1598 (Electronic) IS - 0022-3077 (Print) IS - 0022-3077 (Linking) VI - 120 IP - 2 DP - 2018 Aug 1 TI - Inhibition of BDNF signaling in the paraventricular nucleus of the hypothalamus lowers acute stress-induced pressor responses. PG - 633-643 LID - 10.1152/jn.00459.2017 [doi] AB - Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during stress, and our recent studies indicate that BDNF induces sympathoexcitatory and hypertensive responses when injected acutely or overexpressed chronically in the PVN. However, it remained to be investigated whether BDNF is involved in the mediation of stress-induced cardiovascular responses. Here we tested the hypothesis that inhibition of the high-affinity BDNF receptor TrkB in the PVN diminishes acute stress-induced cardiovascular responses. Male Sprague-Dawley rats were equipped with radiotelemetric transmitters for blood pressure measurement. BDNF-TrkB signaling was selectively inhibited by viral vector-mediated bilateral PVN overexpression of a dominant-negative truncated TrkB receptor (TrkB.T1, n = 7), while control animals ( n = 7) received green fluorescent protein (GFP)-expressing vector injections. Rats were subjected to acute water and restraint stress 3-4 wk after vector injections. We found that body weight, food intake, baseline mean arterial pressure (MAP), and heart rate were unaffected by TrkB.T1 overexpression. However, peak MAP increases were significantly reduced in the TrkB.T1 group compared with GFP both during water stress (GFP: 39 +/- 2 mmHg, TrkB.T1: 27 +/- 4 mmHg; P < 0.05) and restraint stress (GFP: 41 +/- 3 mmHg, TrkB.T1: 34 +/- 2 mmHg; P < 0.05). Average MAP elevations during the poststress period were also significantly reduced after both water and restraint stress in the TrkB.T1 group compared with GFP. In contrast, heart rate elevations to both stressors remained unaffected by TrkB.T1 overexpression. Our results demonstrate that activation of BDNF high-affinity TrkB receptors within the PVN is a major contributor to acute stress-induced blood pressure elevations. NEW & NOTEWORTHY We have shown that inhibition of the high-affinity brain-derived neurotrophic factor receptor TrkB in the paraventricular nucleus of the hypothalamus significantly reduces blood pressure elevations to acute stress without having a significant impact on resting blood pressure, body weight, and food intake. FAU - Schaich, Chris L AU - Schaich CL AD - Department of Pharmacology, University of Vermont , Burlington, Vermont. FAU - Wellman, Theresa L AU - Wellman TL AD - Department of Pharmacology, University of Vermont , Burlington, Vermont. FAU - Einwag, Zachary AU - Einwag Z AD - Department of Pharmacology, University of Vermont , Burlington, Vermont. FAU - Dutko, Richard A AU - Dutko RA AD - Department of Pharmacology, University of Vermont , Burlington, Vermont. FAU - Erdos, Benedek AU - Erdos B AUID- ORCID: 0000-0002-9074-2491 AD - Department of Pharmacology, University of Vermont , Burlington, Vermont. LA - eng GR - F32 HL146075/HL/NHLBI NIH HHS/United States GR - R01 HL133211/HL/NHLBI NIH HHS/United States GR - T32 HL076132/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180425 PL - United States TA - J Neurophysiol JT - Journal of neurophysiology JID - 0375404 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) MH - Animals MH - *Arterial Pressure MH - Brain-Derived Neurotrophic Factor/*physiology MH - Eating MH - Heart Rate MH - Male MH - Paraventricular Hypothalamic Nucleus/*physiology MH - Rats, Sprague-Dawley MH - Rats, Transgenic MH - Receptor, trkB/*physiology MH - Signal Transduction MH - Stress, Psychological/*physiopathology PMC - PMC6139453 OTO - NOTNLM OT - TrkB OT - blood pressure OT - brain-derived neurotrophic factor OT - hypothalamus OT - stress EDAT- 2018/04/26 06:00 MHDA- 2019/07/30 06:00 PMCR- 2019/08/01 CRDT- 2018/04/26 06:00 PHST- 2018/04/26 06:00 [pubmed] PHST- 2019/07/30 06:00 [medline] PHST- 2018/04/26 06:00 [entrez] PHST- 2019/08/01 00:00 [pmc-release] AID - JN-00459-2017 [pii] AID - 10.1152/jn.00459.2017 [doi] PST - ppublish SO - J Neurophysiol. 2018 Aug 1;120(2):633-643. doi: 10.1152/jn.00459.2017. Epub 2018 Apr 25.