High salt-induced morphological and glycocalyx remodeling of human vascular smooth muscle cells is reversible but induces a high sodium salt-like sensitive memory.

Our recent work showed that chronic high sodium salt (CHSS) induced hypertrophy and decreased glycocalyx in human vascular smooth muscle cells (hVSMCs). However, whether this CHSS effect is reversible at both the morphological and calcium homeostasis levels is unknown. In the present study, we tested the hypothesis that the effect of CHSS is reversible only at the morphological and intracellular levels of ionic homeostasis but permanently remodel the sensitivity of hVSMCs to a short-term increase of Na+. We tested the effects of removal of chronic (6-16 days) high sodium salt treatments of hVSMCs. Our results showed that restoring average sodium concentration (145 mM) modeled back the relative density of membrane glycocalyx, the intracellular resting calcium level, and the whole cell and nuclear volumes of hVSMCs. In addition, it induced a permanent remodeling of hVSMCs' response to an increase in the extracellular level of sodium salt by developing spontaneous cytosolic and nuclear calcium waves. Our results showed that chronic high salt is reversible at both the morphological and basal and ionic levels, however, it induced high sensitivity to increase of extracellular sodium. These results suggest that even if chronic high salt is corrected, it induces a high sodium salt-like sensitive memory.