Effect of high-salt diet on urine volume (A), urine sodium excretion (B), and urinary cGMP levels (C) in wild-type and GC-A null mice. Data are presented as means ± SE; n = 5 for each genotype. On days 1–4, mice were fed standard chow (0.7% NaCl) and then the diet was changed to 8% NaCl on day 5. Urine volume and sodium excretion increased in both genotypes in response to the high-salt diet (P < 0.0001, two-way ANOVA). Urine volume was significantly higher in wild-type mice compared with null (P < 0.05, two-way ANOVA), but there was no significant difference between the genotypes with respect to urine sodium excretion (P = 0.39, two-way ANOVA). Only wild-type mice showed significant elevations of urinary cyclic GMP in response to the high-salt diet (P < 0.05, repeated-measures ANOVA), and urinary cGMP levels were significantly higher in wild-type mice compared with null mice (P < 0.0005, unpaired t test).