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 short-term treatment (1-2 days) with high sodium salt had no effect on the morphology of human vascular smooth muscle cells (hVSMCs). However, chronic (long-term treatment, 6-16 days) high sodium salt (CHSS) induced hypertrophy and decreased the relative density of the glycocalyx in hVSMCs. Whether this CHSS effect is reversible at both the morphological and the intracellular calcium and sodium levels is unknown. In the present study, we tested the hypothesis that the effect of CHSS on the morphological and functional levels of hVSMCs is reversible. However, it induced an irreversible increase in the sensitivity of the cells following short-term treatment with high extracellular Na. We tested the effects of the removal of CHSS treatment on the morphology and intracellular sodium and calcium of hVSMCs. Our results showed that restoring average sodium concentration (145 mM) modeled back the relative density of the glycocalyx, the intracellular resting calcium and sodium levels, and the whole cell and nuclear volumes of hVSMCs. In addition, it induced a permanent remodeling of hVSMCs' response to a short-term increase in the extracellular level of sodium salt by developing spontaneous cytosolic and nuclear calcium waves. Our results showed that CHSS is reversible at both the morphological and basal intracellular ionic levels. However, it maintained a high sensitivity to short-term elevation of extracellular sodium. These results suggest that even if chronic high salt is corrected, it induces a high sodium salt-like sensitive memory.