Background:We have shown previously that the calciuric response to salt does not differ in Dahl salt-sensitive (S) and salt-resistant (R) male rats. Clinical studies with women, however, suggest an effect of salt sensitivity on the calciuric response to salt. The objective of this study was to determine whether there is an effect of salt sensitivity on the calciuric response to salt of female S and R rats.Method:Dahl S and R female rats were fed high- (8%) or low- (0.3%) salt diets for 3 weeks. The rats were placed in metabolic cages for 24-hour urine collection at baseline and weekly (for sodium and calcium determination).Results:Blood pressure of female S rats was 177 ± 3.0 mm Hg at week 3 of high salt intake compared with 96 ± 1 mm Hg for female R rats. Female S rats excreted significantly more calcium than female R rats at baseline (P< 0.001), when fed a nonpurified diet, and during high salt intake (P= 0.004). Salt sensitivity significantly increased calcium excretion, water intake, and urine output when rats were fed a high-salt diet. Calcium excretion, water intake, and urine output of female S rats were time-dependent during high salt intake. Plasma 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations were markedly lower in female S rats fed a high-salt diet, but not in female R rats. Plasma parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not significantly differ between female S and R rats, but plasma concentrations of these two hormones at week 3 were significantly higher in S rats fed a high-salt diet compared with S rats fed a low-salt diet.Conclusions:Our data indicate that the calciuric response to salt is greater in female S compared with female R rats, thus supporting findings on the effect of salt sensitivity reported in several clinical studies with women. The greater calciuric response to salt of female S rats compared with female R rats, which was not seen in a previous study when male S rats were compared to male R rats, suggest a gender difference in the calciuric response to salt.