PMID- 29471140
OWN - NLM
STAT- MEDLINE
DCOM- 20181015
LR  - 20200930
IS  - 1879-3649 (Electronic)
IS  - 1537-1891 (Linking)
VI  - 106
DP  - 2018 Jul
TI  - Activation of endothelial TrkB receptors induces relaxation of resistance 
      arteries.
PG  - 46-53
LID - S1537-1891(17)30239-2 [pii]
LID - 10.1016/j.vph.2018.02.005 [doi]
AB  - While brain-derived neurotrophic factor (BDNF) was previously reported to induce 
      relaxation of conduit artery, whether the BDNF/TrkB (tropomyosin-related kinase) 
      pathway is involved in the tone control of resistance arteries is not known. This 
      study investigated TrkB receptors levels/localization and the vasomotor effect of 
      the TrkB receptor agonist LM22A-4 in isolated third-order mesenteric arteries 
      from rats. Immunostaining revealed the presence of both full-length and truncated 
      TrkB receptors, especially at the endothelial level. By using wire myography, 
      LM22A-4 induced vascular relaxation that was significantly decreased by 
      cyclotraxin B as a non-competitive TrkB antagonist and fully prevented by 
      endothelium removal. Inhibitors of NO, EDHF, PGI2 production and the PI3K/Akt 
      pathways separately reduced LM22A-4 induced-relaxation. By contrast, inhibition 
      of Raf/MEK, PLCgamma and CaM/CaMKII pathways did not change the relaxant effect of 
      LM22A-4. Interestingly, BDNF also induced an endothelium and TrkB-dependent 
      relaxation. These results indicate that endothelial TrkB activation results in 
      the relaxation of resistance vessels via PI3K/Akt-induced eNOS phosphorylation 
      and production of EDHF and PGI(2). These data are consistent with the 
      contribution of the endothelial BDNF/TrkB pathway to the regulation of peripheral 
      vascular tone. They also validate the use of LM22A-4 as a reliable 
      pharmacological agent for studying the vascular effect of BDNF.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Totoson, P
AU  - Totoson P
AD  - PEPITE EA4267, FHU INCREASE, Univ. Bourgogne Franche-Comte, F-25030 Besancon, 
      France.
FAU - Pedard, M
AU  - Pedard M
AD  - INSERM UMR 1093-CAPS, Univ. Bourgogne Franche-Comte, F-21000 Dijon, France.
FAU - Marie, C
AU  - Marie C
AD  - INSERM UMR 1093-CAPS, Univ. Bourgogne Franche-Comte, F-21000 Dijon, France. 
      Electronic address: chmarie@u-bourgogne.fr.
FAU - Demougeot, C
AU  - Demougeot C
AD  - PEPITE EA4267, FHU INCREASE, Univ. Bourgogne Franche-Comte, F-25030 Besancon, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180220
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (Benzamides)
RN  - 0 (Biological Factors)
RN  - 0 (N,N',N'-tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamide)
RN  - 0 (Vasodilator Agents)
RN  - 0 (endothelium-dependent hyperpolarization factor)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Benzamides/*pharmacology
MH  - Biological Factors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Epoprostenol/metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Mesenteric Arteries/*drug effects/metabolism
MH  - Myography
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Wistar
MH  - Receptor, trkB/*agonists/metabolism
MH  - Signal Transduction/drug effects
MH  - Vascular Resistance/*drug effects
MH  - Vasodilation/*drug effects
MH  - Vasodilator Agents/*pharmacology
OTO - NOTNLM
OT  - BDNF
OT  - Mesenteric artery
OT  - TrkB receptor
OT  - Vasodilation
EDAT- 2018/02/23 06:00
MHDA- 2018/10/16 06:00
CRDT- 2018/02/23 06:00
PHST- 2017/09/05 00:00 [received]
PHST- 2018/02/07 00:00 [revised]
PHST- 2018/02/17 00:00 [accepted]
PHST- 2018/02/23 06:00 [pubmed]
PHST- 2018/10/16 06:00 [medline]
PHST- 2018/02/23 06:00 [entrez]
AID - S1537-1891(17)30239-2 [pii]
AID - 10.1016/j.vph.2018.02.005 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2018 Jul;106:46-53. doi: 10.1016/j.vph.2018.02.005. Epub 2018 
      Feb 20.