The Journal of Steroid Biochemistry and Molecular Biology
Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake
Introduction
Dahl salt-sensitive (S) and salt-resistant (R) rats are widely studied genetic models of salt-sensitivity and salt-resistance [1], [2]. The Dahl salt-sensitive rat, but not the salt-resistant rat, develops hypertension, hyperlipidemia, and progressive renal disease when fed a high salt diet. The kidneys have been shown to play a role in the blood pressure increase [3], [4].
There are several studies which suggest a role of the Vitamin D endocrine system in the modulation of vascular structure and function [5], [6], [7], [8], [9], [10], [11], [12], [13]. Clinical studies have also shown an association between the Vitamin D endocrine system and salt-induced hypertension [14], [15], [16], [17], [18]. 25-Hydroxyvitamin D (25-OHD), which is synthesized in the liver, serves as precursor to 1,25-dihydroxyvitamin D (1,25-(OH)2D), the hormonal form of Vitamin D, and 24,25-dihydroxyvitamin D (24,25-(OH)2D). The kidneys are the major sites of synthesis of these two compounds. The 25-OHD 1-hydroxylase is under stringent control. 1,25-(OH)2D is synthesized when Vitamin D, phosphate, and calcium concentrations are low and parathyroid hormone concentrations are high. 24,25-(OH)2D is synthesized under opposite conditions.
We have reported [19] an inverse association between plasma 25-OHD concentration and blood pressure of S rats during high salt intake. Plasma 25-OHD concentrations decreased with time on the diet, as blood pressure increased. There was no effect of exogenous 25-OHD on blood pressure, due to a higher rate of metabolism and/or clearance of 25-OHD, when salt-sensitive rats were fed a high salt diet [20]. Plasma 24,25-(OH)2D concentrations of S rats fed a high salt diet were also significantly lower than those of S rats fed a low salt diet [19]. We report here on the temporal relationship between high salt intake and plasma 24,25-(OH)2D concentration of Dahl salt-sensitive and salt-resistant rats.
Section snippets
Materials
25-Hydroxycholecalciferol (25-OHD3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) were purchased from BIOMOL (Plymouth Meeting, PA) and ICN (Costa Mesa, CA). Concentrations of these compounds dissolved in ethanol were determined by ultraviolet spectroscopy at 265 nm using a Lambda 3B spectrophotometer (Perkin-Elmer, Norvalk, CT) and a molar absorption coefficient of 18,200 M−1 cm−1. Organic solvents were analytical or HPLC grade.
Animals and diets
All protocols involving animals were previously approved by the
Results
Plasma 24,25-(OH)2D concentrations of salt-sensitive rats were reduced to 50% within two days of high salt intake, before there was a significant decrease in plasma 25-OHD concentrations or an increase in blood pressure (Fig. 1). Plasma 24,25-(OH)2D concentration remained at that level from day 2 to day 7, but there was further decrease in plasma 24,25-(OH)2D concentration between day 7 and 14, perhaps caused by markedly decreased plasma concentrations of its precursor, 25-OHD. S rats fed a
Discussion
We have previously examined the effect of a high salt diet on plasma 25-OHD concentration of Dahl salt-sensitive rats. Dahl S rats, but not Dahl R rats, responded to a high salt diet with significant decreases in plasma 25-OHD and 24,25-(OH)2D concentrations and increases in blood pressure. Blood pressure was directly correlated (r=0.97) and plasma 25-OHD concentration indirectly correlated (r=−0.98) with the number of days that S rats were fed a high salt diet [19]. An inverse correlation (r
Acknowledgements
This work was supported by NASA NCC 9-112, NIH/NIGMS S06 GM08248, and support services of NIH/RCMI RR03034. The authors thank Detrice Sherman for aid in preparation of the manuscript.
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