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

Abstract

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 saltsensitive rats during high salt intake. Salt-sensitive rats were fed 0.3% salt (low salt, LS), 3% salt (high salt, HS), 3% salt and 7.5 μg cholecalciferol/d (HS-D5), or 3% salt and 15 μg 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.

Vitamin D and the Cardiovascular System

“…A smaller increase was observed when these rats were fed a high-salt diet, supporting the hypothesis that the high-salt diet affects vitamin D clearance or metabolism [66]. Other studies tested the effect of cholecalciferol [63] or paricalcitol [75] on blood pressure reduction in DSS rats. Both reported negative results.…”

“…In one study, high salt intake did not change urinary 25(OH)D 3 or 25(OH)D 3 binding activity in either salt-sensitive or salt-resistant rats compared to low-salt diet [62]. However, a subsequent study from the same group reported that high-salt diet increased urinary 25 (OH)D 3 binding activity by threefold and vitamin D 3 metabolite content by approximately twofold in DSS rats compared to their low-salt-fed counterparts [63]. An inverse relationship was found between plasma 25 (OH)D 3 concentration and the length of time that saltsensitive rats were fed a high-salt diet [64].…”

“…The hyperparathyroidism and hypercalciuria could result from a dysfunctional vitamin D system in these rats. Finally, plasma 25(OH) D 3 levels were inversely correlated with blood pressure (r ¼ À0.76, P ¼ 0.047, n ¼ 7) in low-salt-and highsalt-fed DSS rats [63]. In similar fashion, an inverse relationship was found between plasma 25(OH)D 3 concentrations and blood pressure across three group of DSS rats, including those on a low-salt diet, those on a high-salt diet, or those on a high-salt diet with exogenous 25(OH)D 3 (r ¼ e0.99, P < 0.01) [66].…”

“…In that study plasma 25(OH)D 3 levels were not changed significantly by low-salt (0.3% NaCl) vs. high-salt diet (2% NaCl) for 3 weeks in either group. However, in another study, feeding a high-salt (3% NaCl) diet to DSS rats for 28 days lowered plasma 25(OH)D 3 levels by 36%, compared to the low-salt diet (0.3% NaCl) [63]. Compared to DSR rats, urinary 25(OH)D 3 binding activity and urinary 25(OH)D 3 levels were at least three times higher in DSS rats [62].…”

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

“…The procedure has been previously described by us [9, 41]. The limits of detection in the urine samples were 0.078 pmol/ml for 25-OHD 3 and 0.030 pmol/ml for 24,25-(OH) 2 D 3 .…”