The salt‐sensitivity in C57Bl/6J mice is linked to increased renal protein expressions of SLC4A4 and SLC4A5

Abstract

BackgroundRenal regulation of sodium reabsorption largely depends on the function and protein expression of exchanger /transporters /channels for sodium and other ions along the nephron. Decreased protein expression of NCC mediated aldosterone‐escape, a reflection of pressure natriuresis phenomenon. However, the role of renal ion transporters in salt‐sensitive mice is not well understood. Therefore, we studied the effect of varying amounts of sodium intake on the blood pressure (BP) and renal expression of exchanger /transporters/channels for sodium and other ions in salt‐sensitive C57Bl/6J mice and salt‐resistant BALB/c mice.MethodsMale C57BL6 and Balb/c mice were 3 months old, fed normal salt (0.6% NaCl, NS), low salt (<0.02% NaCl, LS) and high salt (4% NaCl, HS) diet, respectively, for 1 week. The mice were placed in metabolic cages for 24 hr urine collection. BP was measured under anesthesia before sacrificing the mice. The kidneys were removed for immunoblotting and immunostaining. Data were analyzed with one‐way ANOVA, Holm‐Sidak test (P<0.05 is significant).Results4% NaCl diet increased the BP (ΔBP=+20 mm Hg) of C57Bl/6J (n=5) but not of sex‐and agematched BALB/c mice (n=5). Additional studies show that C57Bl/6J mice on high NaCl intake (1.6%, 4%, 6%) had higher BP (ΔBP=+20 mm Hg) relative to when they were on low or normal NaCl intake (<0.09%, 0.6%, 0.8%). The dietary salt‐induced increase in BP was observed in anesthetized and conscious, un‐anesthetized mice, measured by telemetry. There were no differences in water/food intake, urinary excretion, and serum concentrations of Na+, K+, and Cl− between the two mouse strains. High salt intake increased the renal protein expressions of SLC4A5 (NBCe2) (162±8% vs. 100±5%) compared to normal salt diet in C57Bl/6J mice, which was not observed in BALB/c mice. High salt intake increased the renal protein expressions of SLC4A4 (NBC1) (163±12%) compared to normal salt diet in C57Bl/6J mice. By contrast, the 4% NaCl diet increased renal SLC26A6 (Pendrin L1) in both C57Bl/6J (190±1%) and BALB/c (161±8%) mice. Increased NaCl intake did not affect the renal protein expression of NHE3 in either mouse strain. Renal protein expressions of NCC and αENaC, but not of NKCC2 and γENaC, were decreased by high salt diet in BALB/c mice (normal response to HS intake), but not in C57Bl/6J mice. SLC4A5 was located in proximal tubules and distal convoluted tubules, colocalized with NHE3 and NCC respectively in the mouse renal cortex. We conclude that the salt‐sensitivity of BP of C57Bl/6J mice is associated with increased renal protein expressions of SLC4A4 and SLC4A5 and impaired salt‐mediated down‐regulation of NCC and αENaC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.