Abstract 5076: Differential Response of Renal Tubule Sodium Transporters in Salt Sensitive and Salt Resistant Mouse Strains to Salt Load
We have reported that C57BL6 and SJL mice from Jackson laboratory have different responses to a chronic salt load: blood pressure increases in C57BL6 but not in SJL mice. We have suggested that the increase in blood pressure with NaCl loading in C57BL6 mice is due to a dysfunction of renal dopamine receptors caused by increased expression and activity of G protein-coupled receptor kinase 4. In order to determine if the salt sensitivity in C57BL6 mice can be related to increased expression of renal sodium transporters, we studied the effects of chronic NaCl loading on renal sodium transporters in these two mouse strains. C57BL6 and SJL mice (10 weeks old, male) were fed high NaCl (6%) or normal NaCl (0.8%NaCl) (n =5/group) diet. The blood pressures (measured by telemetry) were similar at baseline but increased in C57BL6 not in SJL mice after 1 and 3 weeks of salt loading. The urinary sodium excretions were also similar at baseline (2.34±0.27 vs 2.3±0.18,mEq/mg Cr, respectively) and increased to a lesser extent in C57BL6 than in SJL mice (1 wk: 4.39±0.9 vs 7.96±0.59, P<0.05; 3 wks: 3.5±0.4 vs 5.0±0.9, P =0.16, respectively). On normal NaCl diet, the renal protein expression (immunoblotting) of sodium hydrogen exchanger 3 (NHE3, 287±33, % of SJL) sodium chloride cotransporter (NCC, 167±24, %) and β-epithelial sodium channel (ENaC,169±9, % ) was greater in C57BL6 than in SJL mice. Urinary aldosterone excretion and renal α-ENaC expression (an aldosterone-induced protein) were decreased by the salt load to a similar extent in the two mouse strains. In contrast, one and three weeks of salt loading decreased renal NCC, another aldosterone-induced protein, in SJL but not in C57BL6 mice. There was a difference in the molecular size of the NCC upper band (SJL = 160 kDa; C57BL6 = 175 kDa) while the 110 kDa band was similar in the two strains. The upper band is glycosylated NCC (proved by N-glycosidase F studies) which may be the active transporter; it remains to be determined if glycosylation affects NCC activity in mice. We conclude that the increased renal NCC expression, which is independent of aldosterone levels, may be responsible for the decreased sodium excretion in C57B6 mice. Our studies provide a renal molecular mechanism to the salt sensitivity in C57BL6 mice.