Oral Water Intake Research Articles

Twelve years’ progress in surgery for perforated gastric and duodenal ulcers: a retrospective study of indications for laparoscopic surgery, post‐operative course and the influence of Candida infection

SummaryBackgroundTwelve years has passed since we introduced laparoscopic surgery for gastroduodenal perforation.AimTo list problems and to investigate the feasibility of our clinical protocol for treatment of gastroduodenal ulcer perforation.MethodsCase records of 62 patients and histology samples of 9 patients undergoing surgery for gastroduodenal perforation were retrospectively reviewed.ResultsLaparoscopic omental implantation is feasible for some cases of perforated peptic ulcer in patients who have either stenosis or massive perforations. In patients undergoing laparoscopic omental implantation, oral ingestion of water was started at 3.3 ± 0.5 post‐operative days. Helicobacter pylori was positive in 27 of 35 patients (77%). Of 22 cases in whom intraoperative ascitic culture was taken, Candida was positive in nine (41%), and in six of eight cases involving wound infection or intraperitoneal abscess. Histological examination of resected stomach revealed the fungi with hypha formation at the base of the ulcer in 44% of patients.ConclusionsLaparoscopic omental implantation was more feasible than in the past. The possibility of Candida infection and subsequent abscess formation must be considered in patients with gastroduodenal ulcer perforation.

Cine magnetic resonance imaging of the small bowel: comparison of different oral contrast media

To evaluate several substances regarding small bowel distension and contrast on balanced steady-state free precession (bSSFP) cine magnetic resonance (MR) images. Luminal contrast was evaluated in 24 volunteers after oral application of two different contrast agent groups leading to either bright lumen (pineapple, blueberry juice) or dark lumen (tap water, orange juice) on T1-weighted images. Bowel distension was evaluated in 30 patients ingesting either methylcellulose or mannitol solution for limiting intestinal absorption. Fifteen patients with duodeno-jejunal intubation served as the control. Quantitative evaluation included measurement of luminal signal intensities and diameters of four bowel segments, qualitative evaluation assessed luminal contrast and distension on a five-point scale. Quantitative and qualitative evaluation of the four contrast agents revealed no significant differences regarding luminal contrast on bSSFP images. Quantitative evaluation revealed significantly lower (P<0.05) small bowel distension for three out of four segments (qualitative evaluation: two out of four segments) for methylcellulose in comparison to the control. Mannitol was found to be equal to the control. Oral ingestion of tap water or orange juice in combination with mannitol is recommended for cine MR imaging of the small bowel regarding luminal contrast and small bowel distension on bSSFP sequences.

Time course of synergistic interaction between DOCA and salt on blood pressure: roles of vasopressin and hepatic osmoreceptors

In DOCA-salt rats, the time course of the synergistic interaction between osmolality and DOCA to produce hypertension is unknown. Therefore, in rats 2 wk after implantation of subcutaneous silicone pellets containing DOCA (65 mg) or no drug (sham), we determined blood pressure (BP) and heart rate (HR) responses, using telemetric pressure transducers, during 2 wk of excess salt ingestion (1% NaCl in drinking water). BP was unaltered in sham rats after increased salt, but in DOCA rats BP increased within 4 h. The initial hypertension of 30-35 mmHg stabilized within 2 days, followed approximately 5 days later by a further increment of approximately 30 mmHg. HR first decreased during the dark phase; the second phase was linked to an abrupt increase in HR and BP variability and decreased HR variability. Pressor responses to acute intravenous hypertonic saline infusion were doubled in DOCA-treated rats via vasopressin and nonvasopressin mechanisms. Only in DOCA-treated rats, portal vein hypertonic saline infusion increased BP, which was prevented by V(1) vasopressin blockade. After 2 wk of DOCA-salt, oral ingestion of water rapidly decreased BP. Intraportal infusion of water did not lower BP in DOCA-salt rats, suggesting that hepatic osmoreceptors were not involved. In summary, the hypertension of DOCA-treated rats consuming excess salt exhibits multiple phases and can be rapidly reversed. Hypertonicity-induced vasopressin and nonvasopressin pressor mechanisms that are augmented by DOCA, and hepatic osmoreceptors may contribute to the initial developmental phase. With time, combined DOCA-salt induces marked changes in the regulation of the autonomic nervous system, which may favor hypertension development.

Glucagon-Like Peptide-1 Is Involved in Sodium and Water Homeostasis in Humans

In previous studies with glucagon-like peptide-1 (GLP-1) we have observed that this peptide modulates fluid intake and increases renal sodium excretion in healthy volunteers and in patients with diabetes mellitus type 2. The effect of GLP-1 on thirst, water intake and on osmoregulation has, however, not been examined in detail in humans. Methods: Seventeen healthy male subjects were enrolled in two double-blind, placebo-controlled studies. In study part A, 8 volunteers participated in a protocol with an intravenous salt load of 26.7 ± 0.9 g comparing the effect of an infusion of GLP-1 (1.5 pmol/kg × min) to isotonic saline (placebo). Sodium excretion and water intake were measured. In part B, 9 volunteers were challenged with an oral salt load of 27.7 ± 0.5 g; sodium excretion and water intake were determined comparing an infusion of GLP-1 (1.5 pmol/kg × min) to isotonic saline (placebo). In part C, intestinal biopsies along the gastrointestinal tract were obtained from 14 healthy subjects. Expression of human GLP-1 receptor mRNA was measured by real-time polymerase chain reaction. Results: In study part A, an increase in renal sodium excretion was demonstrated: FeNa rose from 1.6 ± 0.3 (placebo) to 2.7 ± 0.2% (GLP-1; p = 0.0005). There was no difference in water consumption between the two treatments: 1,291 ± 69 (saline) vs. 1,228 ± 74 ml (GLP-1; p = 0.49). In part B, an oral salt challenge of 27.7 ± 0.5 g led to an increased renal excretion of sodium during GLP-1: FeNa increased from 1.6 ± 0.2% (placebo) to 2.0 ± 0.2% (GLP-1; p = 0.012). In contrast to part A, oral water intake was reduced by 36% under GLP-1 treatment: 1,848 ± 331 ml (placebo) vs. 1,181 ± 177 ml (GLP-1; p = 0.0414). Three subjects in part B did not finish treatment with GLP-1 because of diarrhea. Human GLP-1 receptor mRNA expression was highest in the proximal human small intestine compared to terminal ileum and colon (p < 0.02). Conclusions: GLP-1 acts on renal tissue reducing sodium absorption, probably via similar sodium transporters, which also may be localized in the gastrointestinal tract. This hypothesis needs to be confirmed by further studies.

Twelve years’ progress in surgery for perforated gastric and duodenal ulcers: a retrospective study of indications for laparoscopic surgery, post‐operative course and the influence of Candida infection

SummaryBackgroundTwelve years has passed since we introduced laparoscopic surgery for gastroduodenal perforation.AimTo list problems and to investigate the feasibility of our clinical protocol for treatment of gastroduodenal ulcer perforation.MethodsCase records of 62 patients and histology samples of 9 patients undergoing surgery for gastroduodenal perforation were retrospectively reviewed.ResultsLaparoscopic omental implantation is feasible for some cases of perforated peptic ulcer in patients who have either stenosis or massive perforations. In patients undergoing laparoscopic omental implantation, oral ingestion of water was started at 3.3 ± 0.5 post‐operative days. Helicobacter pylori was positive in 27 of 35 patients (77%). Of 22 cases in whom intraoperative ascitic culture was taken, Candida was positive in nine (41%), and in six of eight cases involving wound infection or intraperitoneal abscess. Histological examination of resected stomach revealed the fungi with hypha formation at the base of the ulcer in 44% of patients.ConclusionsLaparoscopic omental implantation was more feasible than in the past. The possibility of Candida infection and subsequent abscess formation must be considered in patients with gastroduodenal ulcer perforation.

Opacification of the Collecting System and Ureters on Excretory-Phase CT Using Oral Water as Contrast Medium

1All authors: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, 601 N. Caroline St./3235A, Baltimore, MD 21287. Address correspondence to S. Kawamoto (skawamo1@jhmi.edu). T is widely used as a primary imaging technique for evaluation of urinary tract abnormalities. Recently, there has been increasing interest in using CT for the evaluation of the renal collecting system and ureters because of technical advances including MDCT and 3D software development. Detailed evaluation of the renal collecting system and ureters is possible with increased spatial resolution and isotropic data sets that can now be created using MDCT. For evaluation of the renal collecting system and ureters, optimal opacification and distention is essential. Various techniques to optimize opacification and distention of the renal collecting system and ureters have been reported in the literature. To optimize opacification, abdominal compression [1–5], saline infusion [6, 7], multiple acquisitions [2], prone positioning [1, 6, 7], and furosemide administration [7] have been successfully used. Abdominal compression has also been used to improve distention of the renal collecting system [4]. As a part of a routine 3-phase CT examination in patients with suspected urinary tract abnormalities, we evaluated the degree of opacification of the renal collecting system and ureters on excretory-phase images obtained without abdominal compression, prone positioning, or IV administration of saline or furosemide. Instead, 750–1,000 mL of water was ingested as oral contrast and for diuresis. The purpose of this study is to evaluate the degree of opacification of the renal collecting system and ureters on excretory-phase contrast-enhanced CT using only oral ingestion of water without abdominal compression, saline infusion, or prone positioning.

NEUROLOGICAL FEATURES IN CHILDREN AND DIPHENYLARSINIC ACID PROBABLY DERIVED FROM CHEMICAL WARFARE AGENTS

Objectives: Diphenylarsinic acid (DPAA), an artificial organoarsinic compounds, is a material of diphenylcyanoarsine or diphenylchloroarsine, to use as emetic type chemical warfare agents. We found DPAA intoxication by oral ingestion of ground water in Kamisu, Japan. We reported that the characteristics of this intoxication for adults were homogeneous including cerebellar-brainstem symptoms such as ataxic gait and scanning speech, myoclonus, tremor, and sleep disorder, and cerebral symptoms such as visual impairment and memory impairment (Ishii K, et al., 2004). Here we report clinical features of children with oral ingestion of well water contained with DPAA.

Potential Role of Pancreatic and Enteric Hormones in Regulating Bone Turnover

Potential Role of Pancreatic and Enteric Hormones in Regulating Bone Turnover

Safety of endotoxin challenge in healthy volunteers: bradycardia

which is observed by an experienced physician present in the same room. This allowed detection of one case of brady-asystole in a young male volunteer who had had an uneventful medical history and who had passed medical and laboratory screening examinations. Prior to bradycardia, endotoxin elicited nausea and vomiting in this subject, which probably contributed to a pronounced vagal reflex, resulting in brady-asystole. Brady-asystole occurred 1–2 h after endotoxin infusion and lasted for one monitor length but did not cause unconsciousness in the young man. The subject recovered spontaneously without medical intervention or sequel. Based on van Eijk’s report [4] and our own data, we can estimate that the incidence of this adverse event is approximately seen in 1 out of 600 challenged individuals. Like van Eijk et al. [4], we recommend liberal oral water intake in fasting volunteers prior to endotoxin challenge, and in most clinical trials we additionally administer physiological saline solution (200 ml/h) to maintain adequate hydration. We have not observed any serious or severe adverse events following endotoxin infusion and thus concur with their conclusion that the model is a safe and a powerful tool for studying systemic inflammation, coagulation, and potential therapeutic interventions.

The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure

Background: Oral ingestion of water increases seated blood pressure in patients with chronic autonomic failure by mechanisms that remain unclear. As orthostatic hypotension is common in chronic autonomic failure, and...

Pressor effect of water instilled via a gastrostomy tube in pure autonomic failure

Background: The oral ingestion of water increases seated blood pressure in chronic autonomic failure although the mechanisms of this effect remain unclear. Recent studies in normal subjects suggest that oropharyngeal stimulation during swallowing may be of greater importance in causing a rise in blood pressure (BP) than the gastric effects of water. We therefore assessed the haemodynamic effects of water instilled directly into the stomach via a gastrostomy tube in pure autonomic failure (PAF). Methods: The subject had longstanding (>20 years) PAF. A gastrostomy tube had been previously placed because of dysphagia. Distilled water (480 ml) was instilled in the seated position with BP and heart rate (HR) measured over the following 40 min while the subject remained seated. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were recorded intermittently every 3 min with a Dinamap automated syphgmomanometer and continuously using a Portapres device. Subsequent model flow analysis of the Portapres data provided beat-to-beat estimates of cardiac output, stroke volume, and total peripheral resistance (TPR). Subjective orthostatic symptoms were recorded before and after water. Results: Seated SBP and DBP increased after water instillation with increases first noted between 5 and 8 min after the water had been instilled. The BP remained elevated until 35 min post water increase over baseline being +36.5 mm Hg SBP and +24.3 mm Hg DBP. HR, cardiac output, and stroke volume remained unchanged during the study. Total peripheral resistance (TPR) increased post water. These results are similar to those reported in a recent study involving oral ingestion of 480 ml of water in PAF subjects. Conclusions: Instilling water directly into the stomach in a patient with PAF resulted in similar haemodynamic responses to those seen when water is taken orally. Thus, oropharyngeal factors and swallowing do not appear to be essential in the generation of the water pressor effect in autonomic failure.

Different acute responses of serum type I collagen telopeptides, CTX, NTX and ICTP, after repeated ingestion of calcium

Background: N- and C-terminal fragments of type I collagen such as NTX, CTX and ICTP are released into circulation during bone resorption and can be quantified in serum. Their respective sensitivity as indices of osteoclastic activity was compared after a short-term inhibition of resorption induced by repeated drinking of calcium-fortified water. Methods: Serum NTX, CTX and ICTP were measured by specific immunoassays in one group of 15 subjects sampled at 08.00, 11.00, 14.00 and 17.00 (referred to as T0, T3h, T6h and T9h) and having ingested in two experimental periods 660 ml of either low-calcium mineral water or the same low-calcium mineral water fortified with calcium (300 mg/l) at three times (08.00, 11.00 and 14.00). Results: Oral intake of calcium-fortified water resulted in progressive decrease in serum CTX (by 38.7% at T3h, 61.0% at T6h and 60.4% at T9h) and NTX (by 19.0% at T3h, 24.1% at T6h and 25.2% at T9h) while serum ICTP concentrations were not significantly affected. Since ingestion of low-calcium water induced a modest but significant decrease in both CTX (−19.4%) and NTX (−10.6%) we compared the two sets of assays with repeated-measures two-factor analysis of variance with interaction. Ingestion of calcium-fortified water vs. low-calcium water resulted in a significant decrease in both serum CTX (time, P<0.0001; treatment, P<0.0001; time-by treatment, P<0.0001) and NTX (time, P<0.0001; treatment, P=0.0001; time-by treatment, P=0.0066). Conclusions: CTX is more sensitive than NTX while ICTP is not sensitive to calcium-induced acute changes in osteoclastic activity. The present results stress the importance of choosing appropriate biochemical bone markers to demonstrate the effects of calcium on bone resorption.

Calcium in mineral water can effectively suppress parathyroid function and bone resorption

The present study was designed to measure the effects, on parathyroid function and bone metabolism, of ingestion of high-calcium mineral water and of a calcium salt bringing the same dose (600 mg) of calcium as a reference. Fifteen healthy young men (mean ± SD age : 23.3 ± 1.2) ingested, during 3 different experimental periods chosen at random, a) high-calcium mineral water (596 mg/L), b) low-calcium mineral water as a control assay, c) one bag of tricalcium phosphate powder containing 600 mg of calcium. Serum concentrations of ionized calcium (iCa), intact parathyroid hormone (iPTH) and of a biochemical marker of bone resorption, type I collagen cross-linked C telopeptide (CTX), were measured before 08.00 and every hour from 09.00 to 17.00. Serum iCa concentrations were significantly ( P < 0.0001) higher and serum iPTH concentrations were significantly ( P < 0.01) lower after oral intake of both high-calcium water and tricalcium phosphate than in control period. Serum concentrations of CTX were significantly lower after either high-calcium water ( P < 0.0001) or tricalcium phosphate ( P = 0.011) than in the control period and a statistically significant difference ( P < 0.05) using Bonferroni t test between the effects of high-calcium mineral water and of tricalcium phosphate was observed from 14.00 to 17.00. The same total amount of calcium (# 600 mg) from one liter of high-calcium mineral water, divided into three intakes, at 3 hours intervals, resulted in a more prolonged suppression of serum CTX, than from the ingestion of a calcium salt.

Absence of painful neuropathy after chronic oral fluoride intake in Sprague–Dawley and Lou/C rats

The possibility that chronicle oral ingestion of fluoride-rich water could modify peripheral pain sensitivity was studied in two strains of adult rats, Sprague–Dawley and Lou/C rats. Sodium fluoride was given orally in water to male Sprague–Dawley (75 and 150 ppm) and Lou rats (150 ppm) for 15 and 27 weeks, respectively. Using classical behavioural evaluation methods of pain symptoms, only slight tendencies to a thermal hyperalgia and a mechanical allodynia were observed in Sprague–Dawley rats.

Effect of oral administration of electrolyte pastes on rehydration of horses

To determine whether the composition of electrolyte pastes formulated for oral administration influences voluntary water intake (WI) by horses recovering from furosemide-induced dehydration. 6 horses. Voluntary WI, body weight, and blood and urine constituents were measured before and after induction of dehydration by furosemide administration and overnight withholding of water; these same variables also were measured during a 36-hour rehydration period. Each horse was evaluated 4 times with random application of 4 treatments (electrolyte pastes) that provided 0.5 g of KCl/kg of body weight, 0.5 g of NaCl/kg, 0.25 g of NaCl and 0.25 g of KCl/kg, or no electrolytes (control treatment). Electrolyte pastes were administered 3 times (4, 8, and 12 hours after start of the rehydration period). Administration of all electrolyte pastes resulted in significantly greater voluntarily WI, compared with the control treatment, and was accompanied by significantly greater recovery of body weight when NaCl was a component of the paste. Administration of NaCl and NaCl-KCl pastes tended to produce a state of transient hyperhydration; however, electrolyte administration also resulted in significantly greater urine production and electrolyte excretion during the final 24 hours of the rehydration period. Adverse effects of oral administration of hypertonic electrolyte pastes were not observed. Oral administration of electrolyte pastes to dehydrated horses increases voluntary WI and improves rehydration during the rehydration period. Rehydration is more rapid and complete when NaCl is a component of the electrolyte paste.

Haemodynamics of the pressor effect of oral water in human sympathetic denervation due to autonomic failure

Oral water ingestion increases blood pressure in normal elderly subjects and in patients suffering from autonomic failure, but the time course of the haemodynamic changes is not known. We therefore studied 14 subjects with documented sympathetic denervation due to pure autonomic failure, with continuous haemodynamic recordings obtained before and after ingestion of 500 ml of distilled water at room temperature. The time course of changes in values of systolic and diastolic beat-by-beat finger blood pressure, heart rate, stroke volume, cardiac output, ejection fraction and total peripheral resistance were analysed. Systolic blood pressure rose from 115+/-8 mmHg (mean+/-S.E.M.) to 133+/-8 mmHg (P<0.001), and diastolic blood pressure from 64+/-4 to 73+/-4 mmHg (P<0.001), with the pressor response beginning a few minutes after water ingestion, plateauing between 10 and 35 min (peak at 14 min), and returning to baseline at 50 min. Heart rate fell from 71+/-2.5 to 67+/-2 beats/min (P<0.001), and total peripheral resistance increased from 1.31+/-0.19 to 1.61+/-0.24 m-units (P<0.001). There were no significant changes in ejection fraction, stroke volume or cardiac output. This study confirmed a pressor response to oral water in subjects with sympathetic denervation. The temporal profile of the response did not favour reflexly mediated sympathetic activation. As subjects with autonomic failure are prone to salt and water depletion, and since blood pressure is exquisitely sensitive to such changes, it may be that the observed response is due to repletion or restoration of intravascular and extravascular fluid volume.

Total-body-water measurement with 18O-labeled water in short-bowel patients with an ileostomy

The aim of this study was to evaluate the use of H 2 18O for total-body-water (TBW) determination in patients with short bowel because ileostomy losses of labeled water can falsify TBW. Thirteen adult short-bowel patients were studied after an overnight fast. Saliva, blood, urine and ileostomy output were collected before and 30, 60, 90, 120, 240, and 360 min after oral ingestion of 0.88 g/kg of 2.5% H 2 18O to measure 18O abundance by isotope-ratio mass spectrometry. TBW was calculated from the dilution of the isotopic water in saliva and plasma. The quantity of labeled water lost in the ileostomy was calculated from the isotopic enrichment of the ileostomy output from T0 to T360. The values obtained from saliva or plasma with (corrected) and without (uncorrected) considering H 2 18O lost in the ileostomy output were compared with a paired t test. Agreement was evaluated using the Bland-Altman method. From T0 to T360, the ileostomy output and the percentage of lost labeled water were 490 ± 314 mL and 6.38 ± 8.52%, respectively. TBW calculated from plasma or saliva isotopic enrichment was different, and a significant difference was also observed between corrected and uncorrected TBW values (saliva: uncorrected TBW = 32.35 ± 7.52 L, corrected TBW = 30.29 ± 6.09 L; plasma; uncorrected TBW = 30.80 ± 7.29 L, corrected TBW = 28.79 ± 5.79 L). The agreement between the values obtained from the two dilution spaces or between the two calculation methods was poor. Because of the large discrepancies between calculation methods, determination of TBW from oral ingestion of 18O-labeled water in patients with short bowel should be calculated only from plasma 18O space dilution and should consider ileostomy losses.

Mineral water as a source of dietary calcium: acute effects on parathyroid function and bone resorption in young men

Calcium is a major component of mineralized tissues and is required for normal growth and maintenance of bone. Epidemiologic studies showed that a large percentage of the population fails to meet the currently recommended guidelines for optimal calcium intake. The present study was designed to determine whether high-calcium mineral water is an efficient additional source of dietary calcium. Twelve healthy young men (mean +/- SD age: 21.1 +/- 1.2 y) ingested in a randomized order either 0.5 L of a mineral water containing 344 mg Ca/L or 0.5 L of a mineral water with a very low concentration of calcium (<10 mg/L) as a control. Blood samples were drawn before and 1, 2, 3, and 4 h after intake of the water. Urine was collected for 2 h before and every 2 h for 4 h after ingestion of the water. Serum concentrations of intact parathyroid hormone (iPTH) and serum concentrations and urinary excretion of a recently developed biochemical marker of bone resorption, type 1 collagen cross-linked C-telopeptide (CTx), were measured. Serum iPTH was significantly (P < 0.002) lower after ingestion of high-calcium water than after ingestion of the control. There was a significant (P = 0.01) progressive decrease in urinary CTx after ingestion of the high-calcium water, whereas after ingestion of low-calcium water the changes were modest and not significant. The fall in serum CTx concentrations was 34.7% 3 h after ingestion of high-calcium water, compared with 17.6% with the control. The decreases in serum CTx concentrations were significantly (P < 0.05) lower 1, 2, 3, and 4 h after ingestion of high-calcium water than after ingestion of the control. The present study showed that one oral intake of water containing a very moderate dose of calcium (172 mg) acutely inhibited iPTH secretion and bone resorption.

Body fluid expansion is not essential for salt-induced hypertension in SS/Jr rats.

To evaluate the importance of volume in the development of hypertension in inbred Dahl salt-sensitive rats (SS/Jr), we measured the changes in blood pressure (BP) that occurred with oral intake of food (salt) and water in rats whose body weight was permitted to increase versus those in which body weight was maintained constant with a servo-control system. We hypothesized that if volume expansion is essential in the development of hypertension, then BP would not increase if body weight was held constant. We found that oral presentation of chow containing 4% salt to SS/Jr rats caused BP to increase 32.2 +/- 2.9 mmHg over 4 days when body weight was controlled at its initial value. Plasma sodium increased from 142.0 to 145.2 meq/l during 4 days of high salt. Neither plasma volume, hematocrit, nor central venous pressure changed significantly on the high-salt diet. In contrast, the inbred Dahl salt-resistant rats (SR/Jr) did not increase their BP during body weight control when given 4% salt. This demonstrates that volume expansion is not an obligatory step in the pressure response to increased salt in SS/Jr rats. Our results obtained with oral presentation of salt, in contrast to intravenous, represent a physiological evaluation of the significance of volume changes in response to dietary salt because no potential regulatory reflexes have been bypassed.

Rescue of the mineralocorticoid receptor knock-out mouse.

The mineralocorticoid receptor knock-out mouse (MR-/-), resembling inborn pseudohypoaldosteronism, dies 8-12 days after birth in circulatory failure with all the signs of terminal volume contraction. The present study aimed to examine the functional defects in the kidney and colon in detail and to attempt to rescue these mice. In neonatal (nn) MR-/- the amiloride-sensitive short-circuit current in the colon was reduced to approximately one-third compared to controls (MR+/+ and MR+/-). In isolated in vitro perfused collecting ducts the amiloride-induced hyperpolarization of the basolateral membrane (Vbl) of nn MR-/- was similar to that of controls, but urinary Na+ excretion was markedly increased to 4.3 micromol/day.g (BW). Based on this measured urinary Na+ loss we tried to rescue nn MR-/- mice by injecting NaCl twice daily (3.85 micromol/g BW), corresponding to 22 microliter of isotonic saline/g BW subcutaneously. This regimen was continued until the animals had reached a body mass of 8.5 g. Thereafter, in addition to normal chow and tap water, NaCl drinking water (333 mmol/l) and pellets soaked in 333 mmol/l NaCl were offered. Unlike the untreated nn MR-/- most of these mice survived. The adult animals were examined between days 27 and 41, some were used for breeding. When compared to age-matched controls the growth of MR-/- was delayed until day 20. Then their growth curve increased in slope and reached that of controls. MR-/- retained their Na+-losing defect. Amiloride's effect on urinary Na+ excretion was not significant in MR-/- mice and the effect on Vbl in isolated cortical collecting ducts was attenuated. The renin-producing cells were hypertrophic and hyperplastic. Plasma renin and aldosterone concentrations were significantly elevated in MR-/- mice. These data indicate that MR-/- can be rescued by timely and matched NaCl substitutions. This enables the animals to develop through a critical phase of life, after which they adapt their oral salt and water intake to match the elevated excretion rate; however, the renal salt-losing defect persists.