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Maturation of the renal response to hypertonic sodium chloride loading in rats: micropuncture and clearance studies.

1. The ability of maturing rats to excrete a sodium load was studied by micropuncture and clearance procedures. 2. During control conditions, no change of glomerular filtration rate or sodium excretion was observed for the time period of the entire procedure (P greater than 0-20). During the infusion of hypertonic (4%) sodium chloride, fractional sodium excretion was 0-08 +/- 0-01 in rats 21-30 days old and 0-14 +/- 0-01 (P less than 0-01) in adults. However, the depression of proximal tubular water re-absorption was equal in both groups (P greater than 0-20). 3. Proximal glomerulotubular balance for water re-absorption was similar in all groups (P less than 0-20). Since end proximal tubular water excretion and depression of fractional water excretion were the same in all animals, differences of urinary sodium excretion during development are probably due to differences of function of segments beyond the proximal tubule during development. 4. Fractional potassium excretion was reduced in young rats (0-17 +/- 0-04) during hypertonic sodium chloride infusion, compared to adults (0-24 +/- 0-01, P less than 0-05). 5. Passage time of fast green through cortical segments in seconds is prolonged in young rats during control conditions. Similar decreases of passage time were seen in all groups during hypertonic sodium chloride infusion. No segmental differences of passage time were seen during developmental. 6. No difference in the relationship between fractional sodium and water excretion was seen during development of the renal response to hypertonic sodium chloride infusion. Thus, altered sensitivity to sodium chloride osmotic diuresis does not exist during maturation in rats.

Age Factors↗

Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet.

The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements. The impact of abundant dietary salt on skeletal health has yet to be established, but is potentially detrimental through increased urinary calcium losses. We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and, further, whether potassium citrate attenuates the effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225 mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum osteocalcin, and fasting serum PTH were measured at the end of the low- and high-salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12 mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N-telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake. Increased intake of dietary sources of potassium alkaline salts, namely fruit and vegetables, may be beneficial for postmenopausal women at risk for osteoporosis, particularly those consuming a diet generous in sodium chloride.

Aged↗

The specific requirement for sodium chloride for the active uptake of L-glutamate by Halobacterium salinarium.

1. Uptake of l-glutamate by Halobacterium salinarium is dependent on high concentrations of sodium chloride in the environment. When the sodium chloride is replaced by isomolar concentrations of potassium chloride, sodium acetate or potassium acetate, only negligible uptake occurs. 2. Most of the glutamate taken up can be shown to be in the cells in the free state and at a concentration of at least 50 times that in the medium. Sodium chloride is therefore required for an active transport of the glutamate into the cells. 3. The question whether sodium chloride is essential for the actual migration of glutamate across the cell envelope or for the mechanism supplying energy for this migration is discussed on the basis of experiments on endogenous respiration and with inhibitors.

Acetates↗

Importance of chloride for acute inhibition of renin by sodium chloride.

To evaluate the contribution of chloride to acute renin inhibition by sodium chloride, plasma renin activity (PRA) was measured before and after peripheral venous infusion of NaCl, NaHCO3, NaBr, NaNO3, lysine monohydrochloride, or lysine glutamate in NaCl-deprived rats. In contrast to controls and animals infused with other sodium salts, PRA decreased (P less than 0.01) after infusion with NaCl [from 28.3 +/- 2.8 to 13.3 +/- 1.8 ng/ml per h (SE)] and NaBr (from 40.6 +/- 6.2 to 21.8 +/- 3.9 ng/ml per h), and renal tubular halide reabsorption increased (P less than 0.05). Arterial pressure, plasma volume, inulin clearance, net sodium balance, serum Na+ and K+, and pH were not different among sodium-loaded groups. PRA was also suppressed (P less than 0.01) by infusion with lysine monohydrochloride (from 51.6 +/- 5.4 to 32.4 +/- 5.1 ng/ml per h) but not with lysine glutamate. These results suggest that inhibition of renin by sodium is dependent on an intrarenal effect of chloride. During infusion with sodium salts which suppressed renin, negative free water clearance (TcH2O) increased, whereas infusion with sodium salts that did not inhibit renin resulted in either no change or decreased TcH2O. The association of renin inhibition and increased TcH2O indirectly supports the hypothesis that renin suppression by chloride is related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle.

Amino Acids↗

Base-substitution and frameshift mutagenesis by sodium chloride and potassium chloride in Saccharomyces cerevisiae.

Sodium chloride (NaCl) and potassium chloride (KCl) are both capable of inducing lethality and mutations when each is administered at a molarity of two for different lengths of time to logarithmic phase cells of the yeast Saccharomyces cerevisiae. Analysis of the revertants indicates that the reversions can be base substitutions, of both the transition and the transversion type, as well as frameshift mutations. At equal molarity, with the frequency of mutations as the criterion, KCl and NaCl are equally efficient in inducing all types of mutations.

Cell Survival↗

Effects of sodium bicarbonate and sodium chloride on the elimination of etorphine in equine urine.

The combination of large doses of sodium bicarbonate and the potent narcotic, etorphine, has reportedly been given to racehorses in attempts to improve their performance and also to "mask" the presence of etorphine in urine samples. The increased urinary output and pH associated with sodium bicarbonate (approximately 500 g) administration may reduce the urinary concentration of etorphine, making it more difficult to detect. Our experiment was designed to examine the effects of this combination. Six Thoroughbred horses were used in a latin-square design with three horse pairs and three treatments consisting of the following: etorphine (20 micrograms), etorphine (20 micrograms) plus sodium bicarbonate (1.0 g/kg), and etorphine (20 micrograms) plus sodium chloride (0.7 g/kg). Sodium chloride was used to distinguish between the urinary alkalinizing effects of sodium bicarbonate and the diuretic effects associated with the large electrolyte load. Venous blood and urine samples were collected prior to and for 24 h post-treatment. Sodium bicarbonate produced a significant metabolic alkalosis and an increase in urine pH. Both sodium bicarbonate and sodium chloride produced a profound diuresis. After sodium bicarbonate and sodium chloride treatments, the urinary concentration of etorphine, measured by radioimmunoassay (RIA), was reduced and in some cases could not be detected. Extraction of the urine samples, prior to RIA analysis, increased the sensitivity of the assay and in most cases gave a positive result. We conclude that the coadministration of etorphine and sodium bicarbonate or sodium chloride can make the detection of etorphine more difficult because of the dilutional effects associated with the administration of a large electrolyte load.

Animals↗

Sodium chloride and hypertension.

The hypothesis that sodium chloride deficiency, and not its overuse, is prime cause of hypertension and arteriosclerosis is presented. In the author's home town--a farflung part of northern China--hypertension is a rare disease and arteriosclerosis is a virtually unknown condition. The average intake of sodium chloride for these people is > 30 g/day compared with the typical sodium chloride intake of 10-12 g per day in the USA. When the 10-12 g salt ingested is mixed with the average daily water intake (2100 ml), 0.47% to 0.57% saline mixture is produced, which is hypotonic to extracellular fluid in salt content. Thus sodium conservation becomes necessary. All the hormones and ions involved in sodium conservation are inducers of hypertension; these include aldosterone, angiotensin 11, glucocorticoids, catecholamine, and vasopression. Plus, potassium waste, induced under the influence of aldosterone excess, participates in the development of hypertension.

Aldosterone↗

Sodium excretion in man, and adaptation to a low-sodium diet: effect of intravenous sodium chloride.

1. The aim of this study was to test whether a postulated gastrointestinal or portal monitor of sodium intake plays any part in adjusting renal sodium excretion when dietary sodium is reduced. 2. Normal male subjects were given 50 mmol of sodium chloride intravenously three times daily for 3 days to replace or to supplement a constant oral intake of sodium chloride. 3. When oral sodium chloride was replaced with intravenous sodium chloride, renal sodium excretion remained constant. 4. When oral sodium chloride was kept constant, sodium administered as intravenous sodium chloride was promptly excreted in three out of four subjects. There was a delay in the increase in sodium excretion in the fourth subject. 5. Infusions containing 50 mmol of sodium chloride in 50 ml given intravenously over 22 min produced a rise in plasma sodium concentration and a fall in concentration of total plasma solids. 6. These results provide no evidence for a gastrointestinal or portal monitor of sodium intake, but do not disprove the existence of such a monitor.

Adult↗

Acid tolerance and acid shock response of Escherichia coli O157:H7 and non-O157:H7 isolates provide cross protection to sodium lactate and sodium chloride.

The survival of Escherichia coli O157:H7 and non-O157:H7 due to an enhanced acid tolerance response (ATR), and enhanced acid shock response (ASR), or the stationary phase protective system when exposed to lactic acid and the resulting cross protection against increased concentration of sodium chloride and sodium lactate was studied. Escherichia coli O157:H7 isolates (1932 and 009) and a non-O157:H7 strain (ATCC 23716) were grown to stationary phase at 32 degrees C and O157:H7 to one of two treatments in an attempt to either acid shock or acid adapt the survivors. Acid shocked cells were exposed to lactic acid at pH 4.0. Acid-adapted cells were first exposed to a pH of 5.5 and then an acid challenge of pH 4.0. Sodium lactate (10%, 20%, or 30%) or sodium chloride (5%, 10%, or 15%) were added to a minimal glucose medium after the acidification treatment. When acid shocked and acid adapted isolate 932 and strain ATCC 23716 tolerated the elevated levels of sodium lactate, and the strain ATCC 23716 tolerated the elevated levels of sodium chloride. Acid adaption allowed isolate 932 to tolerate higher levels of sodium chloride; however, the acid shocking did not provide the same protection. Neither of the acid treatment provided increased tolerance to sodium chloride for isolate E009. Evidence of cross protection against acid and sodium chloride or acid and sodium lactate in E. coli O157:H7 could point to a need for further evaluation of whether these combinations of preservation means are sufficient to control this pathogen.

Escherichia coli O157↗

Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium.

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository system containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. The mixtures of P 407 (15%) and P 188 (15-20%) existed as a liquid at room temperature, but gelled at physiological temperature. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. Furthermore, the poloxamer gels with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum of rats for at least 6 h. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable and convenient rectal dosage form for diclofenac sodium.

Animals↗

Stability of foscarnet sodium in 0.9% sodium chloride injection.

The stability of foscarnet sodium in 0.9% sodium chloride injection was studied. Foscarnet sodium 24 mg/mL was added to polyvinyl chloride i.v. bags containing 0.9% sodium chloride injection to give a theoretical foscarnet sodium concentration of 12 mg/mL. Ten bags of solution were stored at 25 degrees C in normal laboratory light, 10 bags were stored at 25 degrees C in the dark, and 10 bags were stored at 5 degrees C in the dark. Samples were analyzed for foscarnet concentration by high-performance liquid chromatography on days 0, 3, 8, 10, 15, and 30. The solutions were visually inspected for particulates, and pH was measured. Foscarnet sodium was stable in all the solutions for up to 30 days under all the storage conditions; mean foscarnet concentrations did not decline below 99% of initial values. No particulates appeared, and there were no important changes in pH. Foscarnet sodium 12 mg/mL in 0.9% sodium chloride injection was stable for up to 30 days when stored at 25 degrees C and exposed to light, 25 degrees C and protected from light, or 5 degrees C and protected from light.

Chromatography, High Pressure Liquid↗

Collagen-silica hybrid materials: sodium silicate and sodium chloride effects on type I collagen fibrillogenesis.

Collagen-silica hybrid materials have been considered for potential biomedical applications. Understanding of the collagen-silica interactions is the key to control hybrids structure and properties. For this purpose, the effect of sodium silicate and sodium chloride addition at two concentrations, 0.83 and 10 mM, on the kinetic of the type I collagen fibrillogenesis at 20 degrees C, and pH 7.4 were studied. Absorbance profiles of fibrillogenesis experiments were collected together with measures of silicic acid concentration and transmission electron microscopy analysis. The specific effect of silica addition on the collagen fibrils self-assembly mechanisms was demonstrated by comparison with the sodium chloride. Sodium silicate at 10 mM inhibited the collagen fibrillogenesis. At the same concentration, the sodium chloride decreased the rate of the collagen fibril assembly. Collagen fibrillogenesis kinetic was not significantly disturbed by the presence of 0.83 mM of sodium chloride. However, the same concentration of sodium silicate modified the collagen fibrillogenesis kinetic. Transmission electron microscopy indicated for experiment with 0.83 mM of sodium silicate, the formation of longer and wider fibrils than for the equivalent collagen fibrillogenesis experiment with sodium chloride. The effect of sodium chloride is explained in terms of osmotic exclusion and influence on electrostatic interactions between collagen fibrils. The specific involvement of silicic acid in collagen helices hydrogen-bond interactions is suggested. Finally, the results of this study are discussed regarding the preparation of composites by co-gelation of type I collagen and sodium silicate, for potential application as bone repair device.

Animals↗

Developmental sensitivity to high dietary sodium chloride in borderline hypertensive rats.

The present study compared the postweaning blood pressures and body weights of borderline hypertensive rats exposed to a high (8%) sodium chloride maternal diet either from conception to weaning or only during the weaning period with borderline hypertensive rats consistently exposed to a normal (1%) sodium chloride maternal diet. Because the effects of early sodium chloride exposure may be most evident during a subsequent challenge, rats from each group were assigned to receive either an 8% sodium chloride or a 1% sodium chloride diet from 8 to 17 weeks of age. Exposure to an 8% sodium chloride diet from conception through weaning increased the adult blood pressure of borderline hypertensive rats compared with that of controls exposed to a 1% sodium chloride diet; exposure to an 8% sodium chloride diet only during weaning did not increase blood pressure. An 8% sodium chloride diet beginning at 8 weeks of age increased systolic blood pressure. The effects of perinatal and adult exposure to high dietary sodium chloride were additive. Behavioral observations and urinary electrolyte measures confirmed that pups exposed to an 8% sodium chloride diet during weaning ingested the high-sodium chloride diet. The blood pressure and heart rate response to autonomic nervous system ganglionic blockade were assessed at 17 weeks of age. Borderline hypertensive rats exposed to an 8% sodium chloride diet from conception through weaning showed an increased bradycardic response, but no difference in depressor response, to ganglionic blockade. These data suggest that the window of developmental sensitivity for modulation of blood pressure regulation by high dietary sodium chloride occurs during prenatal and early postnatal development.

Animals↗

Lactating dairy cow responses to dietary sodium, chloride, and bicarbonate during hot weather.

Twelve Holstein and eight Jersey cows in the first half of lactation were assigned to one of four concentrate formulations to provide supplemental sodium salts in the total diet dry matter of 1) .5% sodium chloride, 2) .5% sodium chloride plus .72% sodium bicarbonate, 3) .5% sodium chloride plus .72% sodium bicarbonate, and 4) 1.44% sodium bicarbonate to measure effects on body temperature and respiration rate, milk yield and composition, and blood components that reflect acid-base balance. After data were adjusted for body weight, age, and a covariate based on differences within individuals in the standardization period, they were analyzed with a model that included breed, treatment, week, temperature-humidity index, and interactions. Cow fed sodium bicarbonate and no supplemental sodium chloride had lower body temperatures than the other groups. High sodium and chloride in basal diet and drinking water prevented the large change in dietary amount and ratio of these two electrolytes that treatments were designed to impose. More stringent control of dietary amounts and greater heat stress will be necessary to show effects of these elements on acid-base balance.

Animals↗

Sodium and potassium intakes and excretions of normal men consuming sodium chloride or a 1:1 mixture of sodium and potassium chlorides.

Two groups of 10 healthy young men were matched on the basis of their free-choice consumptions of regular table salt. For 28 days they were then fed carefully controlled low-sodium foods. One group was permitted free-choice seasoning of these foods with regular table salt, the other with a 1:1 mixture of sodium and potassium chlorides. Intakes and urinary and fecal excretions of sodium and potassium were determined by analysis. The results were: 1) the subjects salted their food with essentially the same amounts of regular table salt as of the 1:1 mixture; 2) the sodium intake associated with seasoning at the table was reduced with the 1:1 mixture to 44 percent of the amount consumed with regular table salt; and 3) over a 28-day period there was no tendency for subjects to increase their use of a 1:1 mixture, when used in place of regular table salt, to compensate for their reduced sodium intakes. Under the conditions of this study, the use of the 1:1 mixture as a seasoning agent for foods that contained no added salt resulted in an average total intake of sodium (food plus seasoning) which was 55 percent that of the subjects using regular table salt.

Adult↗

Preparation of 99Tcm-MAG3: no confirmation that sodium chloride injections from plastic containers affect radiochemical purity.

Reports have suggested that when sodium chloride injections from a plastic ampoule are used during the preparation of 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3), the radiochemical purity of the final product might be reduced. A study was therefore undertaken to examine the effect of sodium chloride injections from five manufacturers on the radiochemical purity and stability of 99Tcm-MAG3. One sodium chloride injection was supplied in a glass vial, three in plastic ampoules and one in a plastic infusion bag. Three batches of sodium chloride injections from each manufacturer were tested. The radiopharmaceutical was prepared at a radioactive concentration of 1.1 GBq in 10 ml according to the instructions of the manufacturer of TechneScan MAG3. Analysis of radiochemical purity was performed by high-performance liquid chromatography immediately after preparation and 6 h later. Using 95% as the minimum acceptable radiochemical purity, all the products were satisfactory over the 6 h test period. No manufacturer's sodium chloride injection was found to have a statistically significant effect on the radiochemical purity. Based on the 15 batches of sodium chloride injection tested, this study cannot confirm that sodium chloride injections from a plastic container affect the radiochemical purity of 99Tcm-MAG3. However, in view of the known sensitivity of some 99Tcm radiopharmaceuticals to external influences, it is probably good practice to test radiochemical purity when new batches of ancillary materials, such as sodium chloride injections, are introduced.

Chromatography, High Pressure Liquid↗

Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram.

Cocaine abuse is associated with a number of cardiovascular complications that include arrhythmias and sudden cardiac death. Although the mechanism(s) remain unclear, cocaine-induced block of sodium channels resulting in slowed cardiac conduction is thought to play an important role. Several reports suggest that the effects of cocaine effects on cardiac sodium channels can be reversed by administration of sodium bicarbonate. Whether the beneficial effects of sodium bicarbonate are due to sodium ions or an increase in blood pH is unknown. Therefore the purpose of this study was to compare the effects of sodium loading alone (by using sodium chloride) versus sodium loading with an associated increase in arterial pH (by using sodium bicarbonate) on reversing cocaine-induced effects on the electrocardiogram (ECG) in a canine model. Seventeen anesthetized dogs received three i.v. injections of cocaine, 5 mg/kg, with each dose separated by 15 min. Two minutes after the third cocaine dose, each dog was randomly assigned to receive 2 mEq/kg i.v. sodium bicarbonate (1 mEq/ml) or 2 mEq/kg i.v. sodium chloride (1 mEq/ml). ECG, electrophysiologic, and hemodynamic data were recorded at baseline, after each cocaine injection, and after administration of sodium bicarbonate or sodium chloride. In both groups of animals, the first cocaine injection significantly (p < 0.05) prolonged the PR, QTc, AH, and HV intervals, and QRS duration compared with baseline. All intervals continued to lengthen in a dose-dependent manner after the second and third cocaine doses. Sodium bicarbonate significantly (p < 0.05) reduced cocaine-induced prolongation of PR [(147 +/- 5-130 +/- 5 ms), AH (81 +/- 6 - 72 +/- 6 ms), and HV intervals (55 +/- 2 - 39 +/- 1 ms). and QRS duration (96 +/- 6 - 66 +/- 4 ms), peak effect after third cocaine dose versus after sodium bicarbonate, respectively]. Sodium chloride had no effect on reversing cocaine-induced effects on the ECG. Cocaine produces dose-dependent slowing of cardiac conduction that is effectively reversed by sodium bicarbonate. The lack of efficacy of sodium chloride suggests that the increase in arterial pH associated with sodium bicarbonate is responsible for reversal of the effects of cocaine on the ECG. Therefore sodium bicarbonate may be clinically useful in the treatment of cocaine-induced cardiac arrhythmias, primarily as a result of its effects on arterial pH.

Animals↗

Sodium detection threshold and preference for sodium chloride in humans on high and low sodium diets.

Sodium detection threshold and preference for sodium chloride was examined in human volunteers on 2 week periods of high and low salt diets. There was no significant difference in salivary electrolytes or sodium detection threshold between the high and low salt diet periods. Sodium preference, defined as the final sodium concentration of unsalted tomato juice following the ad libitum addition of NaCl, was significantly less on the low salt diet when compared to the high salt period. These results suggest that short periods of dietary salt modification can result in marked shifts in preference for NaCl in the absence of changes in the physiological parameters measured.

Adult↗