Dietary Na+ intake in healthy humans changes the urine extracellular vesicle prostasin abundance while vesicle excretion rate, NCC and ENaC are not altered
Zachar, Rikke, Boye L. Jensen, and Per Svenningsen. "Dietary Na+ intake in healthy humans changes the urine extracellular vesicle prostasin abundance while vesicle excretion rate, NCC and ENaC are not altered." American Journal of Physiology-Renal Physiology (2019).
Low Na+ intake activates aldosterone signaling which increases renal Na+ reabsorption through increased apical activity of NaCl co-transporter (NCC) and epithelial Na+ channel (ENaC). Na+ transporter proteins are excreted in urine as integral part of cell-derived extracellular vesicles (uEVs). It was hypothesized that Na+ transport protein levels in uEVs from healthy humans reflect their physiological regulation by aldosterone. Urine and plasma samples from ten healthy males (median age 22.8 years) were collected after five days on low (70 mmol/day) and five days on high (250 mmol/day) Na+ diet. Urine EVs were isolated by ultracentrifugation and analyzed by western blotting for EV markers (CD9, CD63 and ALIX), transport proteins Na+/K+ ATPase α1-subunit, NCC, α- and γ-ENaC subunits, aquaporin-2 and the ENaC cleaving protease prostasin. Plasma renin and aldosterone concentrations increased during low Na+ diet. Urine EV size and concentration was not different between diets by tunable resistive pulse sensing. EV markers ALIX and CD9 increased with low Na+ diet, while CD63 and AQP2 excretion were unchanged. Full-length ENaC γ-subunits were generally not detectable in uEVs, while αENaC, NCC and phosphorylated-NCC were consistently detected, but not changed by Na+ intake. Prostasin increased with low Na+ in uEVs. The uEV excretion of transporters was not correlated to blood pressure, urinary Na+ and K+ excretion, plasma renin or aldosterone. In conclusion, apical Na+ transporter proteins and proteases were excreted in uEVs, and while the excretion rate and size of uEVs were not affected, EV markers and prostasin increased in response to low Na+ diet.”View full article