High Salt Intake Increases Blood Pressure via BDNF-Mediated Downregulation of KCC2 and Impaired Baroreflex Inhibition of Vasopressin Neurons

Katrina Y. Choe, Su Y. Han, Perrine Gaub, Brent Shell, Daniel L. Voisin, Blayne A. Knapp, Philip A. Barker, Colin H. Brown, J. Thomas Cunningham, Charles W. Bourque

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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 invivo 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.

Original languageEnglish
Pages (from-to)549-560
Number of pages12
JournalNeuron
Volume85
Issue number3
DOIs
StatePublished - 4 Feb 2015

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    Choe, K. Y., Han, S. Y., Gaub, P., Shell, B., Voisin, D. L., Knapp, B. A., Barker, P. A., Brown, C. H., Cunningham, J. T., & Bourque, C. W. (2015). High Salt Intake Increases Blood Pressure via BDNF-Mediated Downregulation of KCC2 and Impaired Baroreflex Inhibition of Vasopressin Neurons. Neuron, 85(3), 549-560. https://doi.org/10.1016/j.neuron.2014.12.048