Activation of endothelial TrkB receptors induces relaxation of resistance arteries

Abstract : 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 inducedrelaxation. By contrast, inhibition of Raf/MEK, PLC gamma 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.
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01857505
Contributeur : Caps - Université de Bourgogne <>
Soumis le : jeudi 16 août 2018 - 14:46:24
Dernière modification le : mercredi 5 septembre 2018 - 17:04:04

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P. Totoson, Martin Pedard, Christine Marie, C. Demougeot. Activation of endothelial TrkB receptors induces relaxation of resistance arteries. Vascular Pharmacology, Elsevier, 2018, 106, pp.46 - 53. ⟨https://www.sciencedirect.com/science/article/pii/S1537189117302392?via%3Dihub⟩. ⟨10.1016/j.vph.2018.02.005⟩. ⟨hal-01857505⟩

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