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).