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Several different types of burial were identified during the excavation of the Roman military cemetery associated with the fort at Birdoswald, on Hadrian’s Wall (UK). Fragments of glass vessels and glass beads were recovered from many of the cremation deposits, as they were commonly used during cremation rituals, and many of these had been affected by heat. X-ray fluorescence spectroscopy and scanning electron microscopy were used to investigate the raw materials, colorants and opacifiers employed to produce the glass assemblage. Most of the large fragments are transparent with a blue-green colour, with a composition typical of recycled glass. The smaller fragments are from beads and are coloured and sometimes opaque. Colourants and opacifiers characteristic of Roman glass were added in this glass formulation, including cobalt-based compounds (blue glass), copper alloys (green glass), white calcium antimonate, and yellow lead antimonate. The multianalytical approach of this research has allowed for the distinguishing of the extreme depletion of sodium on the surface of the melted glass fragments due to the exposure to high temperatures during the cremation process, followed by surface weathering in a burial environment. Based on the chemical composition of the bulk of the samples, a model of high temperature viscosity of glass was applied in order to assess the cremation temperature in the pyre, providing relevant information about funerary rituals and cremation technology in Roman Britain.

Martínez-Navarro, I, Montoya-Vieco, A, Collado, E, Hernando, B, Panizo, N, and Hernando, C. Muscle Cramping in the marathon: Dehydration and electrolyte depletion vs. muscle damage. J Strength Cond Res 36(6): 1629–1635, 2022—Our aim was to compare dehydration variables, serum electrolytes, and muscle damage serum markers between runners who suffered exercise-associated muscle cramps (EAMC) and runners who did not suffer EAMC in a road marathon. We were also interested in analyzing race pacing and training background. Nighty-eight marathoners took part in the study. Subjects were subjected to a cardiopulmonary exercise test. Before and after the race, blood and urine samples were collected and body mass (BM) was measured. Immediately after the race EAMC were diagnosed. Eighty-eight runners finished the marathon, and 20 of them developed EAMC (24%) during or immediately after the race. Body mass change, post-race urine specific gravity, and serum sodium and potassium concentrations were not different between crampers and noncrampers. Conversely, runners who suffered EAMC exhibited significantly greater post-race creatine kinase (464.17 ± 220.47 vs. 383.04 ± 253.41 UI/L, p = 0.034) and lactate dehydrogenase (LDH) (362.27 ± 72.10 vs. 307.87 ± 52.42 UI/L, p = 0.002). Twenty-four hours post-race also values of both biomarkers were higher among crampers (CK: 2,438.59 ± 2,625.24 vs. 1,166.66 ± 910.71 UI/L, p = 0.014; LDH: 277.05 ± 89.74 vs. 227.07 ± 37.15 UI/L, p = 0.021). The difference in the percentage of runners who included strength conditioning in their race training approached statistical significance (EAMC: 25%, non-EAMC: 47.6%; p = 0.074). Eventually, relative speed between crampers and noncrampers only differed from the 25th km onward (p < 0.05). Therefore, runners who suffered EAMC did not exhibit a greater degree of dehydration and electrolyte depletion after the marathon but displayed significantly higher concentrations of muscle damage biomarkers. [ABSTRACT FROM AUTHOR]

• Patients with cystic fibrosis are prone to electrolyte disturbances. • Guidelines state to monitor sodium status. • Sodium/creatinine ratio is an excellent surrogate marker for fractional sodium excretion. • Cut-offs for sodium/creatinine ratio are age related. Electrolyte disturbances are common in patients with cystic fibrosis (CF). Current guidelines on monitoring sodium status are based on research in a small group of infants and require blood sampling. The aim of this study was to evaluate urinary salt parameters as a surrogate for sodium-status in different age-groups. Blood and urine samples for electrolytes were collected from 222 patients followed at the Ghent University Hospital CF-center. Fractional sodium excretion (FENa) and several urinary parameters were calculated. Clinical characteristics did not differ according to sodium status, defined as FENa <0.5%. ROC analysis demonstrated that sodium/creatinine ratio (UNa/Creat) predicted the sodium status most accurately with high sensitivity and specificity (97 and 91% respectively). The UNa/Creat cut-off predicting a FENa <0.5% differed significantly according to age. The UNa/Creat is an excellent marker for the sodium status defined as a FENa <0.5%. However, different cut-offs according to age category should be applied. [ABSTRACT FROM AUTHOR]

Several different types of burial were identified during the excavation of the Roman military cemetery associated with the fort at Birdoswald, on Hadrian's Wall (UK). Fragments of glass vessels and glass beads were recovered from many of the cremation deposits, as they were commonly used during cremation rituals, and many of these had been affected by heat. X-ray fluorescence spectroscopy and scanning electron microscopy were used to investigate the raw materials, colorants and opacifiers employed to produce the glass assemblage. Most of the large fragments are transparent with a blue-green colour, with a composition typical of recycled glass. The smaller fragments are from beads and are coloured and sometimes opaque. Colourants and opacifiers characteristic of Roman glass were added in this glass formulation, including cobalt-based compounds (blue glass), copper alloys (green glass), white calcium antimonate, and yellow lead antimonate. The multianalytical approach of this research has allowed for the distinguishing of the extreme depletion of sodium on the surface of the melted glass fragments due to the exposure to high temperatures during the cremation process, followed by surface weathering in a burial environment. Based on the chemical composition of the bulk of the samples, a model of high temperature viscosity of glass was applied in order to assess the cremation temperature in the pyre, providing relevant information about funerary rituals and cremation technology in Roman Britain. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Can Na+ depletion mobilize Na+ from the skin reservoir in ovariectomized rats? Does oestrogen replacement change the amount and the dynamics of skin Na+ storage? Is the reduced salt appetite after Na+ depletion in ovariectomized rats with oestrogen replacement related to changes in the skin Na+?What is the main finding and its importance?This work demonstrated that acute body Na+ depletion induced by frusemide mobilized the osmotically inactive skin Na+ reservoir to become osmotically active. Oestrogen treatment decreased the induced Na+ intake in ovariectomized rats but did not modulate the inactive Na+ reservoir in control conditions or its mobilization induced by Na+ depletion. Oestradiol, which is an important hormone for water and electrolyte balance, also has a role in the inhibition of induced Na+ appetite. Sodium can be stored in the skin in osmotically active or inactive forms, and this skin Na+ reservoir may be involved in the control of body Na+ levels during physiopathological challenges. In this study, we investigated whether the effect of sodium depletion by frusemide can mobilize Na+ from the skin reservoir and whether oestradiol replacement changes or mobilizes the Na+ reserves in the skin. Ovariectomized Wistar rats were treated with vehicle or oestradiol for 7 days to evaluate the effects of oestrogen on the hydroelectrolyte balance, intake responses and skin Na+ and water content in basal conditions. Furthermore, the effects of oestrogen were evaluated after 24 h frusemide‐induced whole‐body Na+ depletion. Oestradiol‐replaced rats exhibited reduced water intake without any significant changes in salt intake, Na+ excretion or water and Na+ skin content in basal conditions. After sodium depletion, both vehicle‐ and oestradiol‐treated rats exhibited an increase in the osmotically active skin Na+, which was associated with a decrease of the inactive skin Na+ reservoir. Oestrogen decreased the hypertonic saline intake induced by Na+ depletion, but it was not associated with any significant changes in the skin Na+ reservoir. Thus, sodium depletion is able to change the inactive–active skin Na+ reservoir balance. However, the oestrogenic modulation of sodium appetite after Na+ depletion is probably not related to the action of this hormone in the skin Na+ reservoir balance. [ABSTRACT FROM AUTHOR]

Summary: During sea urchins fertilization, the activating spermatozoon triggers a series of physiological changes that transforms the quiescent egg into a dynamic zygote. It has been suggested that several of these egg activation events, e.g. sperm-induced plasma membrane depolarization and the Ca2+-linked cortical reaction, play additional roles to prevent the entry of supernumerary spermatozoa. In particular, the abrupt shift in egg membrane potential at fertilization, which is sustained by a Na+ influx, has been considered as a fast mechanism to block polyspermy. To test the relevance of the Na+-mediated fast electrical block to polyspermy, we fertilized sea urchin eggs in artificial seawater with a low concentration of Na+; nearly all the eggs were still monospermic, as judged by the number of Hoechst 33422-stained sperm. When fertilized in normal seawater, eggs that were pre-incubated in the low Na+ medium exhibited impaired elevation of the fertilization envelope. Nevertheless, these eggs manifested entry of a single spermatozoon, suggesting that the fertilization envelope was not the primary determinant of the block to polyspermy. Furthermore, we showed that the abnormal cleavage patterns displayed by eggs pre-incubated in low Na+, which were often considered a hallmark of polyspermy, were due to the alterations in the cortical actin filaments dynamics following fertilization, and not to the formation of multipolar spindles associated with supernumerary sperm centrosomes. Hence, our results suggested that Paracentrotus lividus eggs do not utilize Na+ to rapidly prevent additional spermatozoa from entering the egg, at variance with the hypothesis of an electrical fast block to polyspermy. [ABSTRACT FROM AUTHOR]

Several studies of the quantitative relationship between sodium need and sodium intake in rats are reviewed. Using acute diuretic treatment 24 h beforehand, intake matches need fairly accurately when intake is spread out in time by using a hypotonic solution of NaCl. In contrast, using a hypertonic solution, intake is typically double the need. Using the same diuretic treatment, although the natriuresis occurs within ~1 h, the appetite appears only slowly over 24 h. Increased plasma levels of aldosterone parallel the increased intake; however, treatment with metyrapone blocks the rise in aldosterone but has no effect on appetite. Satiation of sodium appetite was studied in rats using sodium loss induced by chronic diuretic treatment and daily salt consumption sessions. When a simulated foraging cost was imposed on NaCl access in the form of a progressive ratio lever press task, rats showed satiation for NaCl (break point) after consuming an amount close to their estimated deficit. The chronic diuretic regimen produced hypovolemia and large increases in plasma aldosterone concentration and renin activity. These parameters were reversed to or toward non-depleted control values at the time of behavioral satiation in the progressive ratio protocol. Satiation mechanisms for sodium appetite thus do appear to exist. However, they do not operate quantitatively when concentrated salt is available at no effort, but instead allow overconsumption. There are reasons to believe that such a bias toward overconsumption may have been beneficial over evolutionary time, but such biasing for salt and other commodities is maladaptive in a resource-rich environment.

Our aim was to analyze the participation of inhibitory and stimulatory signals in the temporal dissociation between sodium depletion (SD) induced by peritoneal dialysis (PD) and the appearance of sodium appetite (SA), particularly 2 h after PD, when the rats are hypovolemic/natremic but SA is not evident. We investigated the effects of bilateral injections of the serotonin (5-HT) receptor antagonist, methysergide, into the lateral parabrachial nucleus (LPBN) on hypertonic NaCl and water intake 2 h vs. 24 h after PD. We also studied plasma renin activity (PRA) and aldosterone (ALDO) concentration 2 h vs. 24 h after PD. Additionally, we combined the analysis of brain Fos immunoreactivity (Fos-ir) with the detection of double immunoreactivity in 5HT and oxytocinergic (OT) cells 2 h after PD. Bilateral LPBN injections of methysergide (4 μg/200 nl at each site) increased NaCl intake when tested 2 h after PD compared to controls. We found a significant increase in PRA and ALDO concentration after PD but no differences between 2 and 24 h after PD. We also found for the first time a significant increase 2 h after PD in the number of Fos-ir neurons in the brainstem nuclei that have been shown to be involved in the inhibition of SA. In summary, the results show that 5HT-mechanisms in the LPBN modulate sodium intake during the delay of SA when the renin angiotensin aldosterone system (RAAS) is increased. In addition, the activation of brainstem areas previously associated with the satiety phase of SA is in part responsible for the temporal dissociation between SD and behavioral arousal. [ABSTRACT FROM AUTHOR]

An appetite for CaCl 2 and NaCl occurs in young rats after they are fed a diet lacking Ca or Na, respectively. Bilateral lesions of the parabrachial nuclei (PBN) disrupt normal taste aversion learning and essentially eliminate the expression of sodium appetite. Here we tested whether similar lesions of the PBN would disrupt the calcium-deprivation-induced appetite for CaCl 2 or NaCl. Controls and rats with PBN lesions failed to exhibit a calcium-deprivation-induced appetite for CaCl 2 . Nevertheless, both groups did exhibit a significant calcium-deprivation-induced appetite for 0.5 M NaCl. Thus, while damage to the second central gustatory relay in the PBN disrupts the appetite for 0.5 M NaCl induced by furosemide, deoxycorticosterone acetate, and polyethylene glycol, the sodium appetite induced by dietary CaCl 2 depletion remains intact. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated whether there was a relationship between cystic fibrosis and exercise associated hyponatremia. Researchers evaluated 798 runners in the 2010 and 2011 Western States Endurance Run ultramarathon. They found that no athletes with exercise associated hyponatremia tested positive for a cystic fibrosis genetic mutation.

Most ingested sodium is contained in food. The aim was to investigate whether sodium depletion, dehydration, or DOCA alters intakes of salted and unsalted foods by rats given choices of two foods: salted (0.2-0.5% Na) and unsalted food containing either similar or different other dietary components. Diuretic-induced (furosemide or acetazolamide, two treatments on successive days) sodium depletion always caused pronounced falls in intake of unsalted food within 24 h, continuing at least another 2 days (e.g., 20.9 ± 1.6 pretreatment to 14.8 ± 1.2, 10.6 ± 1.5, and 14.3 ± 1.3 g/day for 3 days of depletion). Intake and preference for salted food increased after 24-72 h (e.g., 6.5 ± 1.2 pretreatment to 7.1 ± 1.1, 16.4 ± 2.3, and 17.0 ± 1.5 g/day at 1, 2, and 3 days of depletion). Valsartan (10 mg/day) blocked the increased intake of salted food but not the reduced intake of unsalted food. DOCA (2 mg/day) caused equivalent increase and decrease in intakes of salted and unsalted food, respectively. Water-deprived rats reduced intake (e.g., 14.2 ± 3.1 to 3.2 ± 2.0 g/day) of and preference for salted food (e.g., 56 ± 13% to 21 ± 11%) after 2 days of dehydration but did not consistently reduce intake of unsalted food. Total food ingested/day fell in both sodium-depleted and dehydrated rats. Rats regulate intakes of different foods to balance sodium needs, osmoregulatory homeostasis, and energy requirements. Reduced appetite for unsalted food may be a homeostatic response to sodium depletion, which together with subsequent generation of appetite for salted food, drives animals to ingest sodium-containing food, thereby restoring sodium balance. [ABSTRACT FROM AUTHOR]

Aldosterone acting on the brain stimulates sodium appetite and sympathetic activity by mechanisms that are still not completely clear. In the present study, we investigated the effects of chronic infusion of aldosterone and acute injection of the mineralocorticoid receptor (MR) antagonist RU 28318 into the fourth ventricle (4th V) on sodium appetite. Male Wistar rats (280-350 g) with a stainless-steel cannula in either the 4th V or lateral ventricle (LV) were used. Daily intake of 0.3 M NaCl increased to 46 ± 15 and 130 ± 6 ml/24 h after 6 days of infusion of 10 and 100 ng/h of aldosterone into the 4th V (intake with vehicle infusion: 2 ± 1 ml/24 h). Water intake fell slightly and not consistently, and food intake was not affected by aldosterone. Sodium appetite induced by diuretic (furosemide) combined with 24 h of a low-sodium diet fell from 12 ± 1.7 ml/2 h to 5.6 ± 0.8 ml/2 h after injection of the MR antagonist RU 28318 (100 ng/2 ±l) into the 4th V. RU 28318 also reduced the intake of 0.3 M NaCl induced by 9 days of a low-sodium diet from 9.5 ± 2.6 ml/2 h to 1.2 ± 0.6 ml/2 h. Infusion of 100 or 500 ng/h of aldosterone into the LV did not affect daily intake of 0.3 M NaCl. The results are functional evidence that aldosterone acting on MR in the hindbrain activates a powerful mechanism involved in the control of sodium appetite. [ABSTRACT FROM AUTHOR]

Abstract: Many investigations have been devoted to determining the role of angiotensin II (ANG II) and aldosterone (ALD) in sodium-depletion-induced sodium appetite, but few were focused on the mechanisms mediating the salty taste changes accompanied with sodium depletion. To further elucidate the mechanism of renin-angiotensin-aldosterone system (RAAS) action in mediating sodium intake behavior and accompanied salty taste changes, the present study examined the salty taste function changes accompanied with sodium depletion induced by furosemide (Furo) combined with different doses of angiotensin converting enzyme (ACE) inhibitor, captopril (Cap). Both the peripheral and central RAAS activity and the nuclei Fos immunoreactivity (Fos-ir) expression in the forebrain area were investigated. Results showed that sodium depletion induced by Furo+low-Cap increased taste preference for hypertonic NaCl solution with amplified brain action of ANG II but without peripheral action, while Furosemide combined with a high dose of captopril can partially inhibit the formation of brain ANG II, with parallel decreased effects on salty taste changes. And the resulting elevating forebrain ANG II may activate a variety of brain areas including SFO, PVN, SON and OVLT in sodium depleted rats injected with Furo+low-Cap, which underlines salty taste function and sodium intake behavioral changes. Neurons in SFO and OVLT may be activated mainly by brain ANG II, while PVN and SON activation may not be completely ANG II dependent. These findings suggested that forebrain derived ANG II may play a critical role in the salty taste function changes accompanied with acute sodium depletion. [Copyright &y& Elsevier]

Abstract: The role of the central opioid system in the control of water and salt intake is complex, with both stimulatory and inhibitory effects having been observed. The aim of the present study was to investigate the participation of the central κ-opioid receptors in the control of salt appetite. Male Wistar rats were submitted to two different experimental protocols: sodium deficit produced by the diuretic, furosemide, and brain angiotensinergic stimulation in rats under normal sodium balance. Lateral ventricle (LV) injections of Nor-binaltorphimine (Nor-BNI) at different doses (5, 10 and 20nmol) inhibited hypertonic saline solution (1.5%) intake in sodium-depleted rats. The salt appetite induced by an LV injection of angiotensin II (AngII) (10ng) was also blocked by Nor-BNI injections into the LV, while no significant change was observed in water intake. Furthermore, the decrease in salt intake seems not to have been due to a general inhibition of locomotor activity or to any change in palatability, since central administration of Nor-BNI failed to modify the intake of a 0.1% saccharin solution when the animals were submitted to a “dessert test” or to induce any significant locomotor deficit in the open-field test. Also the central administration of Nor-BNI was unable to modify blood pressure in sodium-depleted animals. The present results suggest that activation of endogenous κ-opioid receptors modulates salt appetite induced by sodium depletion and by central angiotensinergic stimulation in rats. [Copyright &y& Elsevier]

Abstract: Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on the measures of licking microstructure in rats, we suggested that the level of activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and is updated, or “reboosted”, on the basis of a dopamine D2-like receptor-mediated reward evaluation. To further test this hypothesis, we examined the effects of the dopamine D2-like receptor antagonist raclopride (0, 25, 125, 250μg/kg) and of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40μg/kg) on the microstructure of licking for two different NaCl solutions (0.9% and 2.7%) in rats in sodium-replete status and in the sodium-depleted status induced by the diuretic drug furosemide. Rats were exposed to each solution for 180 seconds after the first lick. Both in sodium-replete and in sodium-depleted status, SCH 23390 produced a decrease of burst number, a measure of behavioural activation, without affecting their size, a measure of reward evaluation. Raclopride reduced burst number but appeared also to exert some effects on burst size. Sodium depletion resulted in an increased intake for both NaCl solutions due to an increase in burst number and size, and in a reduced sensitivity to the effect of raclopride on lick number. These results are not in contrast with the proposed hypothesis and are consistent with previous evidence suggesting a role for dopamine D2-like receptors in the increased NaCl appetite induced by sodium depletion. [Copyright &y& Elsevier]

The article discusses a study which examines the physiological regulation of the receptor (Pro)renin receptor (PRR) as expressed in renal vasculature and tubules in kidney diseases. It hypothesized that the depletion of sodium increases PRR expression through cGMP-protein kinase G (PKG) signaling pathway. The hypothesis was proven after discovering that the signaling pathway enhances the binding of cAMP response element binding protein 1, nuclear factor-kB p65 and c-Jun to PRR promoter.

During ingestion of water, chocolate, sucrose, and saccharin, pain-related behaviors are suppressed. This ingestion analgesic effect is reversed when the hedonic valence of a food is switched from "good" to "bad" as occurs during conditioned taste aversion. Here, we tested the converse hedonic shift to determine if ingestion analgesia occurs when 0.3 M NaC1 is made palatable by inducing a sodium appetite. In Experiment 1, shamand sodium-depleted rats were tested for paw withdrawal and lick latencies to brief noxious heat during quiet wake and intraoral NaCl ingestion. Only sodium-depleted rats showed a suppression of heat-evoked reactions during NaCI ingestion. In Experiment 2, we tested whether this analgesic effect is mediated by the brainstem nucleus raphe magnus (NRM). Inactivation of NRM with muscimol blocked ingestion analgesia during NaCI ingestion by sodium-depleted rats. This attenuation was not due to a hyperalgesic effect of NRM inactivation. Muscimol microinjections into a nearby region, the nucleus raphe obscurus (NRO), were ineffective. The present findings demonstrate that the internal milieu of an animal can modify ingestion analgesia, and that the analgesia during NaCI ingestion by sodium hungry rats is mediated by NRM. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the effects of electrolytic damage to the central nucleus of the amygdala on brain c-fos expression and 0.3 M NaCl intake of adult male rats (n =6–12/group) submitted to a cycle of 36 h of water deprivation (WD) followed by 2 h water intake until satiety or partial rehydration (PR). The groups were divided into sham lesion (CEAs), bilateral lesion of the CEA (CEAX) and misplaced lesion with intact CEA (CEAm). The WD–PR produced a marked increase in c-fos expression in the medial parabrachial nucleus (MPBN) and some increase in the parvocelullar portion of the hypothalamic paraventricular nucleus (PVNp), compared to respective hydrated control (no water deprivation) state in CEAX, but not in CEAs or CEAm. The WD–PR induced similar c-fos expression in the lamina terminalis, supraoptic nucleus, magnocellular PVN and lateral parabrachial nucleus in both CEAX and CEAs. The CEAX showed the typical reduced daily need-free 0.3 M NaCl intake compared to CEAs. However, the 0.3 M NaCl intake of CEAX, unexpectedly, was not significantly different from CEAs or intact rats in the sodium appetite test that followed a cycle of WD–PR. The results do not allow associating the alterations in c-fos expression to the typical inhibition of sodium appetite well known in the literature to be produced by damage to the CEA. Nevertheless, the enhanced cell activation in the MPBN and PVNp suggests an inhibitory role for the CEA on the activity of these nuclei when water-deprived rats have quenched their thirst. [Copyright &y& Elsevier]

The effects of enalapril and sodium depletion on renin synthesis and secretion were studied in mice with a left hydronephrotic kidney caused by unilateral ureteral ligation (UUL). In the control animals, there was no difference in plasma renin concentration between the right and left renal veins. In mice with left ureteral ligation, the renin concentration in the vein draining the hydronephrotic kidney was similar to or lower than that in the aorta under control conditions and after either stimulation with enalapril or depletion of sodium. Enalapril and sodium restriction increased plasma renin concentration, and this increase was due to secretion from the nonhydronephrotic kidney. The renin concentration per gram of kidney tissue and the mRNA for renin per gram of kidney tissue were similar in both the control and hydronephrotic kidney, and the values rose 3-4-fold in both kidneys after enalapril or sodium depletion. Immunostaining for renin confirmed these findings and indicated that renin per glomerulus was higher in the hydronephrotic kidney. Thus, removal or reduction of angiotensin II activity or depletion of sodium stimulated synthetic activity to a similar extent in the normal and hydronephrotic kidneys; however, secretion from the kidney without a macula densa (hydronephrotic) was not increased. Thus, the signals that control synthesis and secretion are different, and for these stimuli, secretion appears to require an intact macula densa. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies, which have mostly focused on concentrated NaCl solution intake, have suggested sodium depletion may be accompanied with salt taste sensory changes. To further investigate whether the function of the salt taste system changes in different patterns for highly concentrated and diluted NaCl taste stimuli, the effects of sodium depletion on NaCl taste detection threshold in rats were examined. After a conditioned taste aversion (CTA) to a suprathreshold concentration of NaCl (0.1 M) was established, rats were given a series of two-bottle choice tests between distilled water and different concentrations of NaCl. Conditioned rats will generalize the aversion to diluted solutions when they are detected. The taste detection threshold for NaCl is defined as the lowest concentration at which there is a reliable difference in the preference scores between conditioned and control subjects. The results showed that detection threshold for NaCl lay between 0.003 M and 0.005 M in sodium-replete rats, whereas in sodium-depleted rats that have an amplified action of angiotensin II in the brain, the threshold significantly decreased to be between 0.0001 M and 0.0003 M. However, in rats with a blocked action of angiotensin II in the brain the decreased NaCl detection threshold was between 0.001 M and 0.003 M. These findings suggest that sodium-depleted rats could decrease the NaCl taste detection threshold to increase the ability to find sodium ions. And the regulation of the salt taste sensitivity may be related to the action of angiotensin II in brain. [Copyright &y& Elsevier]

Abstract: The aim of this work was to test mineral preference in hydrated rats that received a pulse intracerebroventricular (icv p ) injection of ANG II at a dipsogenic dose (50ng). The icv p ANG II induced a four-fold higher ingestion of 0.15M NaHCO3 than of other mineral solutions at palatable concentrations (0.15M NaCl, 0.05mM CaCl2 and 0.01M KCl) in a five-bottle test with water available in a fifth bottle; water intake was not consistently high in this test. Contrary to what is predicted by the mineralocorticoid/angiotensin II synergy hypothesis, the 0.15M NaCl intake in the five-bottle test was not enhanced by icv p ANG II preceded by deoxycorticosterone (DOCA) treatment (2.5mg/day for 3 days); neither was the NaHCO3 intake. This result contrasted with the vigorous ingestion of both isotonic sodium solutions, but mostly of NaCl, rather than of other fluids, by sodium-depleted (furosemide 10mg sc+24h removal ambient sodium) rats in a sodium appetite test. The results suggest that mineralocorticoid combined to icv p ANG II does not simulate the sodium preference shown during sodium appetite. The results also show that a dipsogenic dose of central ANG II induces a reliable ingestion of isotonic sodium bicarbonate in the rat. [Copyright &y& Elsevier]

Objective: To evaluate and compare vitrification and choline-supplemented sodium-depleted slow freezing of mouse oocytes. Design: Animal study. Setting: University-affiliated hospital. Animal(s): CD-1 mice. Intervention(s): Oocyte cryopreservation by vitrification or choline-supplemented sodium-depleted slow freezing. Main Outcome Measure(s): Survival rate, fertilization and embryonic development in vitro, meiotic spindle and chromosome configuration, and aneuploidy screening after parthenogenetic activation. Result(s): A total of 564 oocytes were vitrified, and 791 oocytes were cryopreserved using the slow freezing. The survival rates were 91.8% (518/564) and 73.3% (579/791), respectively. After IVF, the cleavage and blastocyst formation rates of vitrified oocytes were significantly higher than those of slow-frozen oocytes (63.6% vs. 39.9% and 30.50% vs. 20.2%, respectively). Vitrified oocytes were more likely than slow-frozen oocytes to maintain normal meiotic spindles and chromosome alignment (86.9% vs. 70.1%). However, the incidence of aneuploidy was similar in vitrified oocytes and slow-frozen oocytes (9.30% vs. 8.7%). Conclusion(s): Vitrification is superior to choline-supplemented sodium-depleted slow freezing, leading to improved survival, fertilization, and embryonic development in vitro. Analysis of meiotic spindle integrity and chromosome alignment indicates that less damage was detected in vitrified oocytes. However, the incidence of aneuploidy is similar in both vitrified and slow-frozen oocytes. [Copyright &y& Elsevier]

Abstract: GABAergic activation in the lateral parabrachial nucleus (LPBN) induces sodium and water intake in satiated and normovolemic rats. In the present study we investigated the effects of GABAA receptor activation in the LPBN on 0.3M NaCl, water, 2% sucrose and food intake in rats submitted to sodium depletion (treatment with the diuretic furosemide subcutaneously+sodium deficient food for 24h), 24h food deprivation or 24h water deprivation. Male Holtzman rats with bilateral stainless steel cannulas implanted into the LPBN were used. In sodium depleted rats, muscimol (GABAA receptor agonist, 0.5nmol/0.2μl), bilaterally injected into the LPBN, produced an inconsistent increase of water intake and two opposite effects on 0.3M NaCl intake: an early inhibition (4.3±2.7 versus saline: 14.4±1.0ml/15min) and a late facilitation (37.6±2.7 versus saline: 21.1±0.9ml/180min). The pretreatment of the LPBN with bicuculline (GABAA receptor antagonist, 1.6nmol) abolished these effects of muscimol. Muscimol into the LPBN also reduced food deprivation-induced food intake in the first 30min of test (1.7±0.6g versus saline: 4.1±0.6g), without changing water deprivation-induced water intake or 2% sucrose intake in sodium depleted rats. Therefore, although GABAA receptors in the LPBN are not tonically involved in the control of sodium depletion-induced sodium intake, GABAA receptor activation in the LPBN produces an early inhibition and a late facilitation of sodium depletion-induced sodium intake. GABAA activation in the LPBN also inhibits food intake, while it consistently increases only sodium intake and not water, food or sucrose intake. [Copyright &y& Elsevier]

Abstract: The Zucker obese rat is an important model for the metabolic syndrome, which includes renal disease and salt-sensitive hypertension, suggesting abnormalities of body fluid regulation. Here, in Zucker rats, lean and obese, and of both sexes, we compared 48 h of sodium intake and fluid regulation responses with repeated depletions with furosemide to repeated control saline injections. Increased urine volume excretion was observed after each furosemide administration for the 4 groups and obese rats excreted more than the leans on the control days. Male obese rats did not excrete sodium nor increase intake of 2% NaCl following the first furosemide administration, whereas the other 3 groups did. Subsequent depletions increased 2% NaCl consumption and urinary sodium excretion in all groups. Males excreted more sodium in their urine than the females on the control days. Females showed an increase in 2% NaCl intake on control days. Water intake increased in the female leans after each depletion, increased in the males after the 2nd and 3rd depletion and increased in the obese females only after the 2nd depletion. These findings show clearly that there are gender- and weight-related differences in the response of Zucker rats to furosemide-induced depletion. However, the main differences occurred with the first depletion. With repeated depletions the rats adjusted sodium and fluid intake and excretion so that differences due to gender and body weight tended to disappear. Our findings caution against drawing conclusions about differences due to gender and body weight based on single treatments. [Copyright &y& Elsevier]

Abstract: Sodium depletion is a strong natural motivator that creates a pronounced sodium appetite and has been shown to activate neural regions associated with fluid and sodium balance. However, it is not known whether sodium appetite affects the mesolimbic circuitry associated with reward motivation. The present studies examined expression of the immediate early gene Fos in the nucleus accumbens (NAc) as a marker of neuronal activation following the induction and expression of furosemide-induced sodium appetite. During sodium appetite expression, sham-drinking and normal drinking were used to dissociate effects of NaCl taste stimulation from the repletion that follows absorption of sodium. These studies revealed that the combination of NaCl taste stimulation and persistent sodium depletion experienced by sham-drinking animals dramatically activates the NAc, while neither induction nor expression of sodium appetite alone is sufficient to increase Fos expression in this region. Results are discussed in terms of current theories of reward motivation. [Copyright &y& Elsevier]

Salt appetite was investigated in 14 patients with congenital adrenal hyperplasia of the salt-wasting form (SW group), 12 patients with the simple virilized form who are not salt losing, and 18 healthy siblings. Salt appetite was evaluated by questionnaire, preference tests, and dietary analyses. The findings showed that SW who were not therapeutically normalized showed increased salt appetite but no change in sweet preference. Their salt appetite correlated with symptoms of salt wasting, namely, plasma renin activity, plasma K+ and urine Na+ and (inversely) with blood pressure. Sensitivity to the taste of NaCl was not altered. Factor analyses of a larger group confirmed the distinction between salt appetite and sweet preference, but intake of dietary Na+ and sweet carbohydrates and intake of salty and sweet snacks did not reflect distinct salt or sweet preferences. We confirm that putative perinatal dehydration, due to maternal nausea and vomiting during pregnancy, childhood vomiting, and diarrhea with occasional saline infusion, was related to increased salt appetite in adolescence. The findings suggest that salt appetite in humans is determined by interdependent, innate, physiological, and acquired attributes. Salt appetite in SW patients is an adaptive response mediated by the renin-angiotensin system, an innate predisposition to acquire salt preference (in anticipation of both sodium loss and its consequence), and imprinting by perinatal hyponatremic occurrences. Our findings contribute to understanding human salt intake, provide insight into the motivation for salt in patients with congenital adrenal hyperplasia 21-OH deficiency, and may point the way to improvements in therapeutic compliance in these patients. [ABSTRACT FROM AUTHOR]

It is known that mice injected peripherally with ANG II do not show a drinking response but that cFos immunoreactivity (ir) is induced in brain regions similar to those in rats. We now show in Crl:CD 1(ICR) mice that peripheral injection of the ANG II type 1 receptor antagonist losartan was sufficient to prevent this induction of Fos-ir in the subfornical organ (SF0). Injection of ANG II into the lateral cerebral ventricle produced a robust water intake in mice and induced Fos-ir in SF0, as well as in median preoptic (MnPO) and paraventricular (PVN) nuclei. Peripheral injection of losartan blocked this drinking response and prevented the induction of Fos-ir in each of these brain regions. Hypovolemia produced by polyethylene glycol (PEG) produced a robust water intake but no evidence of sodium appetite, and it induced Fos-ir in SF0, MnPO, and PVN. Peripheral injection of losartan did not affect this drinking response. Fos-ir induced by PEG in SF0 and MnPO was reduced by treatment with losartan, while that induced in the PVN was further increased by losartan. Sodium depletion with furosemide and low-sodium diet produced a strong sodium appetite and induced Fos-ir in SF0 and MnPO. Treatment with losartan completely blocked the sodium appetite, as well as the induction of Fos-ir in these brain regions. These data indicate that endogenous production of ANG II and action at forebrain receptors is critically involved in depletion-related sodium appetite in mice. The absence of an effect of losartan on PEG-induced drinking suggests the critical involvement of other factor(s) such as arterial or venous baroreceptor input, and we discuss how this factor could also explain why peripheral ANG II is not dipsogenic in mice. [ABSTRACT FROM AUTHOR]

We chart the postnatal ontogeny of urine preference in the suckling rat. Twelve-day-old sucklings, when offered urine, NH4Cl, or NaCl, ingest more urine and NH4Cl than NaCl. When rendered sodium hungry by ivc renin or by sodium depletion, these sucklings prefer urine and NH4Cl to NaCl, dilute urine, or an NaCl and KCl mineral mix equimolar to urine; however, by 18 days of age, urine and NH4Cl are no longer preferred to NaCl. Hence, urine preference in the suckling may be specific and preparatory for the variety of purposes urine preference serves in the adult rat, and it might guide the pup to urinary sodium in the nest. Since preference for urine and NH4Cl covary during postnatal development, the high preference for NH4Cl in midterm sucklings might be because its ammonium flavor is similar to urine. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 46: 111–117, 2005. [ABSTRACT FROM AUTHOR]

Repeated sodium depletion enhances spontaneous sodium intake in animals and humans, and may be a significant determinant of lifelong sodium intake. In rats, even a single sodium depletion is reported to enhance both need-induced and spontaneous sodium intakes enduringly. Both types of increases are reported to plateau after two to three depletions, and to be greater in females. Here, in two strains of rats, Wistar (W) and Sprague–Dawley (SD), and in two laboratories using different W substrains, in Israel and France, we studied the influence of repeated sodium depletions on need-induced and spontaneous sodium intake. Need-induced intake in W increased incrementally, but in SD, need-induced intake occurred fully at the first depletion. In both cases, the response was not related to changes in the diuretic efficacy of furosemide. In all strains, depletions enhanced spontaneous sodium intake, but the enhancement dissipated within days following each depletion, and only attained significance over the whole 7-week experiment in male SD. Enhancement was not greater in females, despite their greater spontaneous sodium intakes. Finally, in rats given a choice of NaCl and CaCl2, depletions enhanced only NaCl intake, both need-induced and spontaneous, attesting to the specificity of the appetite in both its forms. Our findings show that enhancement of need-induced and spontaneous sodium intake resulting from repeated sodium depletions depends upon the gender and strain of rats, and it does not result from an altered diuretic response. Persistent enhancement of spontaneous sodium intake is not a ubiquitous phenomenon. [Copyright &y& Elsevier]

Ischemic renal injury can be classified into the initiation and extension phase followed by the recovery phase. The recovery phase is characterized by increased dedifferentiated and mitotic cells in the damaged tubules. Suppression subtractive hybridization was performed by using RNA from normal and ischemic kidneys to identify the genes involved in the physiological response to ischemia-reperfusion injury (IRI). The expression of stathmin mRNA increased by fourfold at 24 h of reperfusion. The stathmin mRNA did not increase in sodium-depleted animals or in animals with active, persistent injury secondary to cis-platinum. Immunofluorescent labeling demonstrated that the expression of stathmin increased dramatically at 48 h of reperfusion. Labeling with antibodies to stathmin and proliferating cell nuclear antigen (PCNA) indicates that the expression of stathmin was induced before the upregulation of PCNA and that all PCNA-positive cells expressed stathmin. Double immunofluorescent labeling demonstrated the colocalization of stathmin with vimentin, a marker of dedifferentiated cells. Stathmin expression was also significantly enhanced in acute tubular necrosis in humans. On the basis of its induction profile in IRI, the data indicating its enhanced expression in proliferating cells and regenerating organs, we propose that stathmin is a marker of dedifferentiated, mitotically active epithelial cells that may contribute to tubular regeneration and could prove useful in distinguishing the injury phase from recovery phase in IRI. [ABSTRACT FROM AUTHOR]

Central injections of the α2 adrenergic/imidazoline receptor agonist moxonidine inhibit water and NaCl intake in rats. In the present study, we investigated the possible involvement of central α2 adrenergic receptors on the inhibitory effect of moxonidine in 0.3 M NaCl intake induced by 24 h sodium depletion. Male Holtzman rats with stainless-steel cannulas implanted into the lateral ventricle (LV) were used. Sodium depletion was produced by the treatment with the diuretic furosemide (20 mg/kg of body weight) injected subcutaneously +24 h of sodium-deficient diet. Intracerebroventricular (icv) injections of moxonidine (20 nmol/1 μl) reduced sodium depletion-induced 0.3 M NaCl intake (6.6±1.9 ml/120 min vs. vehicle: 12.7±1.7 ml/120 min). Pre-treatment with the α2 adrenoreceptor antagonists RX 821002 (80 nmol/1 μl), SK&F 86466 (640 nmol/1 μl) and yohimbine (320 nmol/3 μl) injected icv abolished the inhibitory effect of icv moxonidine on sodium depletion-induced 0.3 M NaCl intake (13.3±1.4, 15.7±1.7 and 11.8±2.2 ml/120 min, respectively). The results show that the activation of α2 adrenoreceptors is essential for the inhibitory effect of central moxonidine on sodium depletion-induced NaCl intake. [Copyright &y& Elsevier]

In the present study, we investigated the participation of central 5-HT2B/2C and 5-HT3 receptors in the salt intake induced by sodium depletion in Wistar male rats. Sodium depletion was produced by the administration of furosemide associated with a low salt diet. Third ventricle injections of mCPP, a 5-HT2B/2C agonist, at doses of 80, 160 and 240 nmol, promoted a dose-dependent reduction in salt intake in sodium-depleted rats. The inhibitory effect produced by central administration of mCPP was abolished by the central pretreatment with SDZ SER 082, a 5-HT2B/2C antagonist. Similar results were obtained with third ventricle injections of m-CPBG (80, 160 and 240 nmol), a selective 5-HT3 agonist that also induced a dose-related decrease in salt intake in sodium-depleted rats. The central pretreatment with LY-278,584, a selective 5-HT3 receptor antagonist, was able to impair the salt intake inhibition elicited by third ventricle injections of m-CPBG. Central administration of each one of the antagonists alone or a combination of both antagonists together did not significantly change salt intake after sodium depletion. On the other hand, the central administration of both mCPP and m-CPBG, in the highest dose used to test their effect on salt intake (240 nmol), was unable to modify blood pressure in sodium-depleted rats. It is concluded that: (1) pharmacological activation of central 5-HT2B/2C and 5-HT3 receptors diminishes salt intake during sodium depletion, (2) an inhibitory endogenous drive exerted by central 5-HT2B/2C and 5-HT3 receptors does not seem to exist and (3) the reduction in salt intake generated by the pharmacological activation of these central receptors is not produced by an acute hypertensive response. [Copyright &y& Elsevier]

The present study investigated malnutrition in rats fed a diet deficient in proteins, lipids, vitamins and minerals, including sodium chloride. The renal function of malnourished 3-month old Wistar rats, assigned from weaning to the multideficient diet, supplemented or not supplemented with sodium chloride was evaluated. Compared with standard diet fed rats the groups maintained on the multideficient diet, regardless of the sodium content, showed body weight reduced by at least 58% and higher urinary sodium excretion. The rats on the multideficient diet not supplemented with sodium chloride exhibited low renal vascular resistance and high renal blood flow. In contrast, the rats on the multideficient diet supplemented with sodium chloride failed to show alterations in either the renal vascular resistance or in the renal blood flow. Although severe, the malnutrition was characterized by a negative balance of sodium that might have contributed with the renal vasodilatation seen when the content of sodium was low in diet. [Copyright &y& Elsevier]

Two circumventricular organs, the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), may mediate salt appetite in response to acute intravenous infusions of angiotensin (ANG) II. Fluid intakes and mean arterial pressures were measured in rats with sham lesions or electrolytic lesions of the SFO or OVLT during an intravenous infusion of 30 ng/min ANG II. Beginning 21 h before the 90-min infusion, the rats were depleted of sodium with furosemide and given a total of 300 mg/kg captopril in 75 ml/kg water in three spaced gavages to block the usual salt appetite and to hydrate the rats. No other food or fluids were available for ingestion. Sham-lesioned rats drank 9.3±1.2 ml if 0.3 M NaCl alone was available and drank 8.9±1.6 ml of saline and 3.7±1.6 ml of water if both were available. Either SFO or OVLT lesions reduced the intakes of saline to <5 ml in both conditions and of water to <1 ml. Mean arterial pressure did not differ among the groups and was maintained above 100 mmHg after the depletion and captopril treatments because of the large doses of water. Thus, a full expression of salt appetite in response to an acute intravenous infusion of ANG II requires the integrity of both the SFO and OVLT. [Copyright &y& Elsevier]

Calcium channels mediate the actions of many drugs. The present work investigated whether diltiazem, an L-type calcium channel blocker, alters the inhibition of sodium appetite induced by noradrenaline and the α2-adrenoceptor agonist clonidine. Adult male Holtzman rats (N=4–8) with cannula implanted into the third cerebral ventricle were submitted to sodium depletion (furosemide sc+24-h removal of ambiente sodium). Sodium depleted control animals that received 0.9% NaCl as vehicle injected intracerebroventricularly (i.c.v.) ingested 13.0±1.5 ml/120 min of 1.8% NaCl. Intracerebroventricular injection of either noradrenaline (80 nmol) or clonidine (20 nmol) inhibited 1.8% NaCl intake from 70 to 90%. Prior i.c.v. injection of diltiazem (6–48 nmol) inhibited from 50 to 100% the effect of noradrenaline and clonidine in a dose–response manner. Diltiazem alone at 100 nmol inhibited, but at 50 nmol had no effect on, sodium appetite. The results suggest: (1) common ionic mechanisms involving calcium channels for the inhibition that noradrenaline and clonidine exert on sodium appetite and (2) a dual role for the benzothiazepine site of L-type calcium channels in the control of sodium appetite. [Copyright &y& Elsevier]

The possible role of a reduction in plasma volume (PV) by surgery as well as the importance of dietary Na supply in denervation natriuresis have been investigated on Inactinanesthetized male rats subjected to acute unilateral renal sympathectomy. Four groups were studied: I. Normal Na diet ( n=14); II. Low Na diet (boiled rice for 2 weeks)-isotonic glucose infusion ( n=10); III. Low Na diet-isotonic saline infusion ( n=5); IV. Normal and low Na diet rats served as conscious control ( n=10). Surgery caused a 9-11% increase in hematocrit and a 15-18% decrease in PV in groups I-III. Plasma volume repletion (PVR) reverted these changes. In group I sodium excretion from both kidneys was only a fraction of that in conscious animals kept on the same diet (group IV) and marked denervation natriuresis was observed. After PVR sodium output of innervated (I) kidneys was not different from that of conscious rats but denervated (D) kidneys excreted twice that amount. In group II Na excretion was increased compared to conscious Na depleted controls, and PVR augmented further this difference. Surprisingly, the difference in urinary sodium excretion (UV) between I and D kidneys was absent after surgery and was minimal after PVR in this group. In group III physiological saline infusion reverted the effect of Na depletion and denervation natriuresis was present both before and after PVR. It is concluded that PV reduction does not play a major role in denervation phenomenon. In Na depleted anesthetized rats denervation natriuresis is absent or minimal. [ABSTRACT FROM AUTHOR]

During a 4–year period, acute renal failure was observed in 27 patients (mean age 65 years) treated by various angiotensin-converting-enzyme (ACE) inhibitors for hypertension, heart failure, or a combination of both. None had significant renal artery stenosis on angiography. Overt volume depletion was present in 21 and hypotension in 12 cases. All patients received diuretic therapy and/or a lowsalt diet. Other facilitating factors included cardiac failure, pre-existing chronic renal insufficiency, combined therapy with non-steroidal anti-inflammatory drugs, and diabetes mellitus. Twenty-two patients had two or more of these factors at presentation. A renal biopsy performed in 10 cases showed severe arteriosclerosis of small renal arteries in eight and acute tubular necrosis in five instances. Therapy comprised volume expansion, and withdrawal of diuretics and, except in two patients, of ACE inhibitors. Twenty-one patients recovered normal renal function, two died, and permanent renal damage remained in four. These results suggest that sodium depletion has a critical role in inducing acute renal failure, whose outcome is not always benign. A combination of diuretics and ACE inhibitors should be prescribed with caution, especially in older patients with small as well as with large renal vessel disease. [ABSTRACT FROM PUBLISHER]

The pressor effect of three doses of angiotensin II (AT) and of single doses of norepinephrine (N) and tyramine (T) was measured in sodium replete and deplete rats before and after ganglionic blockade. In sodium deplete rats, plasma renin concentration (PRC) and hematocrit were significantly higher and plasma sodium was significantly lower than in sodium replete rats. The pressor effect of AT, but not that of N and of T was blunted in sodium deplete rats before and after ganglionic blockade. The relationship between the pressor effect of AT and PRC was significantly negative in the combined material of all groups before ganglionic blockade. The correlation was more pronounced after ganglionic blockade, and it became significant also in the sodium deplete group alone. The pressor effect of AT was not significantly related to plasma sodium concentration and hematocrit, while both exhibited a significant correlation with PRC. Results suggest that the influence of sodium depletion on the pressor action of angiotensin may be mediated by preexisting renin or angiotensin levels and that this relationship is influenced by the autonomous nervous system. [ABSTRACT FROM AUTHOR]

In 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment, the effect of 2 weeks of additional therapy with the converting enzyme inhibitor (CEI) enalapril on blood pressure and body fluid volumes has been evaluated. The objective was to examine the influence of a diuretic-stimulated renin-angiotensin-aldosterone system (RAAS) on haemodynamics and body fluid volume. Mean arterial pressure (MAP −21%), total peripheral resistance index (TPRI −22%) and plasma aldosterone concentration (PAC −39%) were decreased, and plasma renin activity (PRA 660%) was increased. The average heart rate (HR), cardiac index (CI), plasma volume (PV), blood volume (BV), extracellular fluid volume (ECFV) and body weight (BW) remained unchanged. A negative correlation was found between the per cent changes in ECFV and PAC. Thus, body fluid volumes during chronic diuretic treatment are well preserved even when the RAAS with its sodium retaining properties is suppressed by CEI. Possible mechanisms are a volume (not angiotensin II) - dependent stimulation of aldosterone and a fall in blood pressure. [ABSTRACT FROM AUTHOR]

To evaluate the influence of different types of natriuresis on the renal clearance of digoxin (Cl) and the Cl/Cl ratio, studies were performed in which sodium-depleted patients were placed on a moderately high sodium diet for 6 days. In another group natriuresis was evoked by furosemide. In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Cl, which was accompanied by an increase in Cl from 57.5±32, and 60.7±27.3 (duplicate measurements) to 103.9±55.4 ( p<0.01) and 103.8±46.5 ml min ( p<0.01). Cl/Cl rose from 0.60±0.24 and 0.61±0.16 to 0.91±0.31 and 0.91±0.21, respectively (both p<0.005). Serum digoxin concentration declined from 1.24±0.35 and 1.19±0.40 to 1.02±0.35 and 0.97±0.32 µg/l (both p<0.01) during the high sodium diet. In the furosemide - induced natriuresis (6 patients), changes in Na excretion and V were a multiple of those caused by Na loading, but the Cl/Cl ratio was not increased. The results are in accordance with the concept of digoxin backdiffusion in the proximal tubules, which is dependent on proximal Na reabsorption. In the more distal segments of the nephron, where the action of furosemide occurs, there does not appear to be any transtubular movement of digoxin. [ABSTRACT FROM AUTHOR]