Plasma 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol concentrations are decreased in hind limb unloaded Dahl salt-sensitive female rats.

Plasma 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentration was shown to decrease during bed rest in several studies when baseline plasma 25-hydroxyvitamin D (25-OHD) concentration was sub-optimal. Dahl salt-sensitive female (S) rats, but not Dahl salt-resistant female (R) rats, demonstrated a 50% decrease in plasma 1,25-dihydroxycholecalciferol (1,25-(OH)(2)D(3)) concentration after 28 days of hind limb unloading (HU, disuse model) during low salt intake (0.3%). We tested the vitamin D endocrine system response of female S rats to hind limb unloading during high salt intake (2%, twice that of standard rat chow to mimic salt intake in the USA). Hind limb unloading resulted in lower plasma 25-OHD(3) concentrations in S-HU rats than in R-HU rats (P<0.05) and greater urinary loss of 25-OHD(3) by S-HU rats than by S rats (P<0.05). Plasma 1,25-(OH)(2)D(3) concentration of S-HU rats was half that of S rats, but was unchanged in R-HU rats. The association of low plasma 25-OHD concentration with decrease in plasma 1,25-(OH)(2)D concentration of hind limb unloaded rats and of bed rest participants (published studies) suggests that low vitamin D status might be a risk factor for decrease in plasma vitamin D hormone concentration during long-term immobilization or bed rest.

High dietary cholecalciferol increases plasma 25-hydroxycholecalciferol concentration, but does not attenuate the hypertension of Dahl salt-sensitive rats fed a high salt diet.

The Dahl salt-sensitive rat, a model for salt-induced hypertension, develops hypovitaminosis D during high salt intake, which is caused by loss of protein-bound vitamin D metabolites into urine. We tested the hypothesis that high dietary cholecalciferol (5- and 10-fold standard) would increase plasma 25-hydroxycholecalciferol (25-OHD(3)) concentration (indicator of vitamin D status) of salt-sensitive rats during high salt intake. Salt-sensitive rats were fed 0.3% salt (low salt, LS), 3% salt (HS), 3% salt and 7.5 microg cholecalciferol/d (HS-D5), or 3% salt and 15 microg cholecalciferol/d (HS-D10) and sacrificed at week 4. Plasma 25-OHD(3) concentrations of the two groups of HS-D rats were similar to that of LS rats and more than twice that of HS rats. Urinary cholecalciferol metabolite content of HS-D rats was more than seven times that of HS rats. Systolic blood pressures of the hypertensive HS and HS-D rats did not significantly differ, whereas LS rats were not hypertensive. We conclude that high dietary cholecalciferol increases plasma 25-OHD(3) concentration, but does not attenuate the hypertension of salt-sensitive rats during high salt intake. Low salt intake may be necessary to both maintain optimal vitamin D status and prevent hypertension in salt-sensitive individuals.

Black and white female adolescents lose vitamin D metabolites into urine.

BACKGROUND: The black American population has a higher prevalence of salt sensitivity compared with the white American population. Dahl salt-sensitive rats, models of salt-induced hypertension, excrete protein-bound vitamin D metabolites into urine, a process that is accelerated during high salt intake. We tested the hypothesis that urinary vitamin D metabolite content and 25-hydroxyvitamin D (25-OHD) binding activity of black female adolescents would be greater than that of white female adolescents. METHODS: Female adolescents (11-15 years old, 11 black and 10 white) were fed low (1.3 g, 56 mmol/24 hours sodium) and high salt (3.86 g, 168 mmol/24 hours sodium) diets for 3 weeks in a randomized order cross-over study design. RESULTS: White and black adolescents had similar mean urinary vitamin D metabolite content (low salt, black versus white: 50 +/- 10 versus 58 +/- 17 pmol/24 hours; high salt, black versus white: 47 +/- 7 versus 79 +/- 16 pmol/24 hours). Mean urinary 25-OHD binding activities of the black and white adolescents did not significantly differ. Urinary 25-OHD binding activity of 10/11 black adolescents and 7/10 white adolescents was greater at week 3 of high salt intake than at week 3 of low salt intake (r = 0.50, P = 0.002, n = 17). Plasma 24,25-dihydroxyvitamin D concentrations of the white female adolescents were significantly higher than that of the black female adolescents (P < 0.001). CONCLUSION: Urinary loss of vitamin D metabolites may be one cause of low vitamin D status, in addition to low dietary intake and reduced skin synthesis.

Dahl salt-sensitive rats develop hypovitaminosis D and hyperparathyroidism when fed a standard diet.

The Dahl salt-sensitive rat (S), a model for salt-sensitive hypertension, excretes protein-bound 25-hydroxyvitamin D (25-OHD) into urine when fed a low salt diet. Urinary 25-OHD increases during high salt intake. We tested the hypothesis that continuous loss of 25-OHD into urine would result in low plasma 25-OHD concentration in mature S rats raised on a standard diet. Dahl S and salt-resistant (R) male rats were raised to maturity (12-month-old) on a commercial rat diet (1% salt) and switched to 0.3% (low) or 2% (high) salt diets 3 weeks before euthanasia. Urine (24 h) was collected at the end of the dietary treatments. Urinary 25-OHD and urinary 25-OHD binding activity of S rats were three times that of R rats, resulting in lower plasma 25-OHD and 24,25-dihydroxyvitamin D concentrations in S rats than in R rats (P < 0.001). Plasma parathyroid hormone concentrations of S rats were twice that of R rats. S rats fed 2% salt had higher plasma 1,25-dihydroxyvitamin D concentrations than those fed 0.3% salt (P = 0.002). S rats excreted more calcium into urine than R rats (P < 0.001) and did not exhibit the expected calciuric response to salt. Proteinuria of the S rats was three times that of the R rats, suggesting kidney damage in the S rats. Low plasma 25-OHD and 24,25-dihydroxyvitamin D and high plasma 1,25-dihydroxyvitamin D and PTH concentrations seen in the mature S rats have also been reported for elderly patients with low-renin (salt-induced) hypertension. An implication of this study is that low vitamin D status may occur with age in salt-sensitive individuals, even when salt intake is normal.

The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model.

Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.