Body weight was not measurably sensitive to high NaCl intake in either genotype (A). High NaCl intake increased fluid intake in both genotypes but to a significantly greater extent in NHE3loxloxCre compared to Con mice (B). NaCl intake increased ~3-fold initially in both genotypes. Whereas Con mice stayed at this level for the remainder of the experimental period, NHE3loxloxCre mice slightly decreased their NaCl intake over time. (C). Urinary Na+/creatinine increased 3-fold in response to high NaCl diet but was not significantly different during the remained of the experimental period between genotypes (D). In metabolic cage experiments, Na+ intake (E) was comparable and urinary Na+ excretion (F) was not different between genotypes. Comparable to low NaCl, urinary pH decreased in response to high NaCl in both genotypes; however, remained at a significantly higher level in NHE3loxloxCre compared to Con mice (G). n = 5–7/genotype. *P < 0.05 versus Con, #P < 0.05 versus baseline (day 0) same genotype.