title: High salt intake increases blood pressure via BDNF-mediated downregulation of KCC2 and impaired baroreflex inhibition of vasopressin neurons.
abstract: The mechanisms by which dietary salt promotes hypertension are unknown. Previous work established that plasma [Na(+)] and osmolality rise in proportion with salt intake and thus promote release of vasopressin (VP) from the neurohypophysis. Although high levels of circulating VP can increase blood pressure, this effect is normally prevented by a potent GABAergic inhibition of VP neurons by aortic baroreceptors. Here we show that chronic high salt intake impairs baroreceptor inhibition of rat VP neurons through a brain-derived neurotrophic factor (BDNF)-dependent activation of TrkB receptors and downregulation of KCC2 expression, which prevents inhibitory GABAergic signaling. We show that high salt intake increases the spontaneous firing rate of VP neurons in vivo and that circulating VP contributes significantly to the elevation of arterial pressure under these conditions. These results provide the first demonstration that dietary salt can affect blood pressure through neurotrophin-induced plasticity in a central homeostatic circuit.
authors.affiliation: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada.
authors.forename: Katrina Y
authors.initials: KY
authors.lastname: Choe
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Su Y
authors.initials: SY
authors.lastname: Han
authors.affiliation: Montreal Neurological Institute, 3801 University Street, Montreal, QC H3A2B4, Canada.
authors.forename: Perrine
authors.initials: P
authors.lastname: Gaub
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Sciences Centre, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Shell
authors.affiliation: Neurocentre Magendie, INSERM U862, 146, rue Léo Saignat, 33077 Bordeaux, France.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Voisin
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Sciences Centre, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Blayne A
authors.initials: BA
authors.lastname: Knapp
authors.affiliation: Montreal Neurological Institute, 3801 University Street, Montreal, QC H3A2B4, Canada.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barker
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Colin H
authors.initials: CH
authors.lastname: Brown
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Sciences Centre, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Cunningham
authors.affiliation: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada. Electronic address: charles.bourque@mcgill.ca.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D020318:Rats, Long-Evans; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D027981:Symporters / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017673:Sodium Chloride, Dietary; D027981:Symporters; D014667:Vasopressins; D000096922:K Cl- Cotransporters