ABSTRACT
High dietary salt increases arterial pressure partly through activation of magnocellular neurosecretory cells (MNCVP) that secrete the antidiuretic and vasoconstrictor hormone vasopressin (VP) into the circulation. Here, we show that the intrinsic and synaptic excitation of MNCVP caused by hypertonicity are differentially potentiated in two models of salt-dependent hypertension in rats. One model combined salty chow with a chronic subpressor dose of angiotensin II (AngII-salt), the other involved replacing drinking water with 2% NaCl (salt loading, SL). In both models, we observed a significant increase in the quantal amplitude of EPSCs on MNCVP. However, model-specific changes were also observed. AngII-salt increased the probability of glutamate release by osmoreceptor afferents and increased overall excitatory network drive. In contrast, SL specifically increased membrane stiffness and the intrinsic osmosensitivity of MNCVP. These results reveal that dietary salt increases the excitability of MNCVP through effects on the cell-autonomous and synaptic osmoresponsiveness of MNCVP.
Subject(s)
Neurons/metabolism , Osmosis , Sodium Chloride, Dietary/adverse effects , Vasopressins/metabolism , Angiotensin II , Animals , Cell Membrane/drug effects , Cell Membrane/metabolism , Cytoskeleton/drug effects , Cytoskeleton/metabolism , Disease Models, Animal , Excitatory Postsynaptic Potentials/drug effects , Hypertension/pathology , Male , Mechanotransduction, Cellular/drug effects , Neurons/drug effects , Probability , Rats, Wistar , Synapses/drug effects , Synapses/metabolismABSTRACT
PURPOSE OF REVIEW: Dietary salt intake increases both plasma sodium and osmolality and therefore increases vasopressin (VP) release from the neurohypophysis. Although this effect could increase blood pressure by inducing fluid reabsorption and vasoconstriction, acute activation of arterial baroreceptors inhibits VP neurons via GABAA receptors to oppose high blood pressure. Here we review recent findings demonstrating that this protective mechanism fails during chronic high salt intake in rats. RECENT FINDINGS: Two recent studies showed that chronic high sodium intake causes an increase in intracellular chloride concentration in VP neurons. This effect causes GABAA receptors to become excitatory and leads to the emergence of VP-dependent hypertension. One study showed that the increase in intracellular chloride was provoked by a decrease in the expression of the chloride exporter KCC2 mediated by local secretion of brain-derived neurotrophic factor and activation of TrkB receptors. Prolonged high dietary salt intake can cause pathological plasticity in a central homeostatic circuit that controls VP secretion and thereby contribute to peripheral vasoconstriction and hypertension.
