High dietary salt amplifies osmoresponsiveness in vasopressin-releasing neurons

High dietary salt increases arterial pressure partly through activation of magnocellular neurosecretory cells (MNC^VP) that secrete the antidiuretic and vasoconstrictor hormone vasopressin (VP) into the circulation. Here, we show that the intrinsic and synaptic excitation of MNC^VP 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 MNC^VP. 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 MNC^VP. These results reveal that dietary salt increases the excitability of MNC^VP through effects on the cell-autonomous and synaptic osmoresponsiveness of MNC^VP.