Changes In NaCl Intake Research Articles

Regulation of the Na+-Cl− cotransporter by dietary NaCl: a role for WNKs, SPAK, OSR1, and aldosterone

This Commentary aims to integrate or interrelate the available data with the current study by Chiga and co-workers, which defines an important influence of aldosterone in the phosphorylation and thus activation of the Na(+)-Cl(-) cotransporter (NCC) in response to changes in NaCl intake and implicates the involvement of SPAK/OSR1 kinases and WNKs.

Gestational and early postnatal dietary NaCl levels affect NaCl intake, but not stimulated water intake, by adult rats.

We examined body fluid regulation by weanling (21-25 days) and adult (>60 days) male rats that were offspring of dams fed chow containing either 0.1, 1, or 3% NaCl throughout gestation and lactation. Weanling rats were maintained on the test diets until postnatal day 30 and on standard 1% NaCl chow thereafter. Ad libitum water intake by weanlings was highest in those fed 3% NaCl and lowest in those fed 0.1% NaCl. Adult rats maintained on standard NaCl chow consumed similar amounts of water after overnight water deprivation or intravenous hypertonic NaCl (HS) infusion regardless of early NaCl condition. Moreover, baseline and HS-stimulated plasma Na(+) concentrations also were similar for the three groups. Nonetheless, adult rats in the early 3% NaCl group consumed more of 0.5 M NaCl after 10 days of dietary Na(+) deprivation than did rats in either the 1% or 0.1% NaCl group. Interestingly, whether NaCl was consumed in a concentrated solution in short-term, two-bottle tests after dietary Na(+) deprivation or in chow during ad libitum feeding, adult rats in the 3% NaCl group drank less water for each unit of NaCl consumed, whereas rats in the 0.1% NaCl group drank more water for each unit of NaCl consumed. Thus gestational and early postnatal dietary NaCl levels do not affect stimulated water intake or long-term body fluid regulation. Together with our previous studies, these results suggest that persistent changes in NaCl intake and in water intake associated with NaCl ingestion reflect short-term behavioral effects that may be attributable to differences in NaCl taste processing.

Rat proximal NHE3 adapts to chronic acid-base disorders but not to chronic changes in dietary NaCl intake.

In the proximal tubule, the apical Na(+)/H(+) exchanger identified as NHE3 mediates most NaCl and NaHCO(3) absorption. The purpose of this study was to analyze the long-term regulation of NHE3 during alkalosis induced by dietary NaHCO(3) loading and changes in NaCl intake. Sprague-Dawley rats exposed to a low-NaCl, high-NaCl, or NaHCO(3) diet for 6 days were studied. Renal cortical apical membrane vesicles (AMV) were prepared from treated and normal rats. Na(+)/H(+) exchange was assayed as the initial rate of (22)Na(+) uptake in the presence of an outward H(+) gradient. (22)Na(+) uptake measured in the presence of high-dose 5-(N-ethyl-N-isopropyl) amiloride was not different among models. Changes in NaCl intake did not affect NHE3 activity, whereas NaHCO(3) loading inhibited (22)Na(+) uptake by 30%. AMV NHE3 protein abundance assessed by Western blot analysis was unaffected during changes in NaCl intake. During NaHCO(3) loading, NHE3 protein abundance was decreased by 65%. We conclude that proximal NHE3 adapts to chronic metabolic acid-base disorders but not to changes in dietary NaCl intake.

Water and NaCl consumption in Long-Evans rats and Egyptian spiny mice

Water and NaCl consumption in Long-Evans rats (Rattus norvegicus) and Egyptian spiny mice (Acomys cahirinus) was examined after periods of acute water deprivation (0–100 h) and NaCl deprivation (via 0–10 mg/kg furosemide i.p.). Rats’ intake of water was monotonically related to the length of the deprivation period, with only nominal changes in water intake observed for spiny mice. NaCl intake for rats was also monotonically related to furosemide dose, again with only nominal changes in NaCl intake observed for spiny mice. The patterns of water and NaCl consumption for rats were in agreement with those reported previously, whereas similar observations have not been described for spiny mice. Differences in adaptation to deprivation states were attributed to the desert heritage and physiological characteristics of the spiny mouse.

Salt intake of rats fed diets deficient in calcium, iron, magnesium, phosphorus, potassium, or all minerals

Groups of nine to ten male rats fed diets deficient in calcium, iron, magnesium, phosphorus, potassium, or all minerals (i.e. no mineral mix) were given 0.3 m NaCl and water to drink. Over the first 30 days of dietary treatment, 0.3 m NaCl intake was progressively increased by deprivation of calcium or iron, unaltered by deprivation of phosphorus, and increased and then decreased by deprivation of magnesium, potassium, or all minerals. The changes in NaCl intake of rats deprived of potassium or all minerals were matched by corresponding changes in water intake. Water intakes of the other groups were unaltered. Thus, NaCl preference was increased by deprivation of calcium or iron, unaltered by deprivation of phosphorus, potassium, or all minerals, and decreased by deprivation of magnesium. To determine whether these changes were specific to the salty modality, animals maintained for 32 days on the diets deficient in calcium, iron, magnesium, and phosphorus received 24-h two-bottle tests with water vs. 2.5 m m saccharin, 2.5 m m citric acid, 0.368 m m sucrose octa-acetate, or 0.3 m NaCl. Relative to controls, rats deprived of calcium drank less 2.5 m m saccharin, those deprived of magnesium drank less 0.3 m NaCl, and those deprived of calcium or iron drank more 0.3 m NaCl. These results show that different mineral deficiencies have different effects on NaCl intake. They argue against the hypothesis that animals deprived of any mineral develop a chronic appetite for salt.

Nephrogenous cyclic GMP production during NaCl loading and ANP infusion.

To further study the mechanisms of the renal effects of ANP, we examined the effects of NaCl loading and ANP infusion on nephrogenous cGMP production. Six normotensives (NTs) and 7 essential hypertensives (HTs) were placed on 7-day low (3 g/day) and then 7-day high NaCl diets (20 g/day). On the last day of each period, the natriuretic and nephrogenous cGMP responses to ANP infusion at 25 ng/kg/min for 40 min were determined. ANP infusion markedly increased the plasma concentrations of ANP and cGMP and the urinary excretions of Na and cGMP. These changes were accompanied by a rise in nephrogenous cGMP. Increases in nephrogenous cGMP during ANP infusion were not different between HTs and NTs despite a greater natriuretic response in HTs. NaCl loading significantly increased the natriuretic response to ANP infusion in both groups. However, nephrogenous cGMP production induced by ANP infusion was not affected by changes in NaCl intake. Thus, although ANP-induced natriuresis is associated with an increase in nephrogenous cGMP, the natriuretic effect of ANP seems to be modified to a greater extent by indirect mechanisms such as renal perfusion pressure and body fluid volume status.

Hemodynamic and endocrine changes associated with potassium supplementation in sodium-loaded hypertensives.

To clarify the mechanism by which potassium (KCl) protects against the blood pressure rising action of sodium (NaCl), we studied the effects of KCl loading in patients with idiopathic hypertension who, after a period of NaCl restriction, partook of a high NaCl diet. Eleven patients who had taken the KCl supplement (96 mEq/day) during the high NaCl period showed lesser mean blood pressure (MAP) rise with changes in NaCl intake from 25 to 250 mEq/day than 12 patients who had not taken the KCl supplement (p less than 0.001). With a high NaCl diet, the KCl-supplemented patients retained less NaCl, gained less weight, and showed a lesser increase in plasma volume and cardiac output than the non-KCl-supplemented ones. Overall, the increase in blood pressure levels during the high Na diet correlated directly either with changes in plasma volume (p less than 0.05) or with changes in cardiac output (p less than 0.01). The results suggest that KCl may prevent a rise in blood pressure with NaCl loads in hypertensive patients by attenuating the increase in cardiac output, mainly as a result of the natriuresis. Furthermore, plasma norepinephrine was measured to estimate the sympathetic activity, since the sympathetic nervous system is known to control urinary NaCl excretion. From the low NaCl diet to Day 3 of the high NaCl diet, plasma norepinephrine was significantly (p less than 0.01) decreased in the KCl-supplemented patients, whereas it remained unchanged in the non-KCl-supplemented ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a Zinc Deficient Diet upon Fluid Intake in the Rat

Zinc deficient rats demonstrate an increased intake of sodium chloride (NaCl) containing solutions as compared to normal rats, presumably related to decreased taste acuity. The purpose of this study was to determine if zinc deficient rats would show altered intake of other solutions since changes in NaCl intake may be reflective of serious pathophysiologic processes not related to taste. Eight littermate pairs of inbred Fisher CDF rats, 29 days of age, were divided into two groups and individually housed in stainless steel cages. One group was pair-fed a zinc deficient diet supplemented with ZnSO4, 100 ppm, while the second group was fed the zinc deficient diet, ad libitum. Using a two-bottle preference test, the rats fed the zinc deficient diet showed significantly increased preferences for 5 X 10(-2), 1.5 X 10(-1) and 3 X 10(-1) M NaCl as compared to controls, supporting previous observations. In addition, they showed significantly increased mean preferences for 3.0 X 10(-2) M sucrose, 1.3 X 10(-6) M quinine sulfate and 2.5 X 10(-3) M hydrochloric acid. Analysis of the individual water and fluid intakes showed that the altered preferences were generally the result of increased fluid intake with variable differences observed in water intake. The results demonstrate that zinc deficient rats exhibit altered intake of several different chemical compounds, and support the hypothesis that zinc deficient animals may have alterations in taste acuity.

Further evidence of the toxicity of NaCl. Increased blood pressure and mortality in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) of Okamoto and Aoki (4) develops significant hypertension without added dietary salt. Many patients with hypertension have little or no alteration in blood pressure from increments or decrements of salt intake. Such observations have led to a widespread belief that dietary NaCl is important in hypertensives only if blood pressure changes are observed after changes in NaCl intake. Such a simplistic view of hypertension fails to take into account the possibility that morbidity and mortality might be lowered by restricting dietary NaCl, without a concomitant lowering of blood pressure. The effect of a high NaCl intake for periods up to 1 yr has been studied in the SHR with the following conclusions: (a) NaCl accelerated the rate at which hypertension developed in both sexes. (b) The ultimate levels of blood pressure reached by males on either high or low salt diets were similar, however. (c) In females, (1) on high NaCl the average blood pressure ultimately became indistinguishable from males whereas (2) on low NaCl pressure remained significantly lower than that of males. (d) The addition of NaCl to the regimen had a devastating effect on mortality of both sexes and was not directly correlated with the level of blood pressure. Earlier reports were reviewed bearing on the possibility that NaCl is inimical to blood vessels without a necessary relationship to its hypertensinogenic effect. It was concluded that restriction of dietary NaCl would reduce morbidity and mortality in hypertension, whether or not blood pressure was reduced by such measures.

Effect of variation in dietary NaCl intake on the intrarenal distribution of plasma flow in the rat.

The effect of dietary variation in sodium chloride intake on the intrarenal distribution of plasma flow was investigated in rats using the antiglomerular basement membrane antibody technique. Rats were placed on a liquid diet containing either 9.86 (n = 9) or 0 (n = 9) mEq NaCl/daily portion for 2 wk. Labeled antibody was injected and the diets were reversed. After an additional 2 wk period, antibody labeled with a different radionuclide was injected and the animals were sacrificed. Fractional plasma flow distribution was then calculated for each dietary period. No change in flow to any cortical region could be detected. In six additional awake rats on identical dietary regimen, total plasma flow was estimated by the clearance of hippuran-(131)I. No change in this parameter occurred with changes in NaCl intake. We conclude, therefore, that no change in either total renal plasma flow or intracortical distribution of plasma flow occurs with wide variations in dietary sodium chloride intake in the rat. The implications of this constancy of regional plasma flow are discussed with reference to presumed concomitant alterations in the intrarenal distribution of nephron filtration rate.