Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake

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Abstract

Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)2D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)2D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2—when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)2D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), administered at a level that increased plasma 24,25-(OH)2D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)2D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)2D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.

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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