Evaluation of the efficacy of oral rehydration solutions using human whole gut perfusion.

Whole gut perfusion in humans was used to compare the effect on intestinal water and electrolyte transport of the World Health Organisation oral rehydration solution (solution II, composition in mmol/l: glucose 111, sodium 90, bicarbonate 30, potassium 20; 308 mOsm/kg); a hypertonic commercial oral rehydration solution (solution III, glucose 188, sodium 50, bicarbonate 20, potassium 20 mmol/l; 335 mOsm/kg); and three experimental bicarbonate free, hypotonic oral rehydration solutions: solution IV (glucose 111, sodium 60, potassium 20 mmol/l; 260 mOsm/kg), solution V (glucose 80, sodium 60, potassium 20 mmol/l; 219 mOsm/kg), and solution VI (glucose 80, sodium 30, potassium 20 mmol/l; 177 mOsm/kg). Perfusion of the intestine with a standard cleansing solution (solution I, sodium 125, potassium 10, bicarbonate 20, sulphate 40, mannitol 80 mmol/l; 275 mOsm/kg) confirmed published data on minimal water and sodium absorption. Experimental solution VI produced maximum water absorption (mean (SE) +1660.0 (29.8) ml/h) significantly greater than solution II (+1195.3 (79.5) ml/h), III (+534.7 (140.3) ml/h), IV (+1498.0 (42.7) ml/h), and V (+1327.7 (24.4) ml/h; p less than 0.05). Sodium absorption was significantly greater with solution II (+97.4 (7.9) mmol/h) compared to VI (+43.3 (7.8) mmol/h; p less than 0.01) but not compared to IV (+67.2 (13.0) mmol/h). A hypotonic oral rehydration solution such as solution VI may provide optimal replacement treatment for patients with acute diarrhoea.     

Search for the ideal oral rehydration solution: studies in a model of secretory diarrhoea.

In situ perfusion of whole rat small intestine was used to compare the efficacy of five oral rehydration solutions in promoting water and sodium absorption in normal intestine and secreting intestine after exposure to cholera toxin. Solutions varied in their sodium (35-90 mmol/l) and glucose (111-200 mmol/l) concentrations, molar ratio of glucose:sodium (1.2-5.8), and osmolality (281-331 mOsmol/kg), and contained either bicarbonate (18-30 mmol/l) or citrate (10 mmol/l). In normal intestine all solutions promoted net water absorption. Cholera toxin induced reproducible water secretion but all solutions reversed this to absorption. Water absorption was greatest with solutions containing sodium 60 mmol/l and glucose 111 or 140 mmol/l, and with a glucose:sodium ratio approximately 2, in both normal and secreting intestine. All solutions promoted net glucose absorption in both normal and secreting intestine. Net sodium absorption occurred with solutions containing greater than or equal to 60 mmol/l sodium in normal intestine but sodium secretion occurred from all solutions in secreting intestine. Sodium movement was directly related to the sodium concentration of the solution and sodium secretion occurred despite net water and glucose absorption. We consider that these studies may guide future development of oral rehydration solutions.     

Sodium content of oral rehydration solutions: a reappraisal.

Proper choice of oral rehydration solution, with regard to sodium content, is a conflicting issue to general practitioners and pediatricians. World Health Organization (WHO) recommendations of oral rehydration solution containing 90mmol/1 sodium, have been effective throughout developing countries worldwide. In developed countries, however, such as England, this recommendation seems inappropriate; a recommendation of 50 - 60 mmol/1 sodium with 90 -111mmol/1 glucose is preferred. This combination will eliminate the need for free water recommended by the WHO maintenance therapy. Normonatraemia is maintained, and hyponatraemia and hypernatraemia can both be corrected. Sodium content is adequate in replacing stool loss resulting from viral and bacterial diarrheas. Iatrogenic hyponatraemia and hypernatraemia do not occur as they would with oral rehydration solutions with low (30-35) or high (90mmol/1) sodium concentration. Solutions containing 50-60 mmol/1 sodium is safer in neonates and young infants with immature renal functions, incapable of properly distributing increased sodium leads. Glucose concentration necessary to make oral rehydration with 50 - 60 mmol/1 isotonic, or hypotonic, resembles WHO - ORS, but is half that in 30-35 mmol/1 sodium solutions. In controlled clinical trials, oral rehydration solutions with 50-60 mmol/1 sodium have proven safe, and performance was compatible with WHO-ORS. For both rehydration and correction of acidosis, the solution proved effective. When oral rehydration solution sodium, concentrate is below 90 mmol/1, errors in reconstituting may be common, but offers less risk resulting in dangerous hypernatraemia. An "all purpose" physiological oral rehydration solution would make oral rehydration therapy, more economical, simpler, and safe in developed countries worldwide.     

Water and solute absorption from hypotonic glucose-electrolyte solutions in human jejunum.

While oral rehydration therapy with glucose-electrolyte solutions is highly effective, the optimal formulation has not yet been defined. Recent clinical studies suggest that stool volume, and thus water losses, may be reduced if glucose is replaced by a polymeric substrate which reduces osmolality. It is possible that the efficacy of glucose monomer based oral rehydration solutions (ORS) will also improve if osmolality is decreased. Using jejunal triple lumen perfusion in healthy adult volunteers net water and solute absorption were studied from three hypotonic solutions with different sodium concentrations (46, 60, 75 mmol/l) but identical glucose concentrations (90 mmol/l), thus allowing osmolality to rise (210, 240, and 270 mOsm/kg, respectively). Results from these solutions (ORS 45:210, ORS 60:240, and ORS 75:270) were compared with the World Health Organisation oral rehydration solution (WHO-ORS). Greatest water absorption was seen with ORS 60:240 (p less than 0.01). Sodium absorption from ORS 60:240 and WHO-ORS was similar and greater than sodium absorption from ORS 45:210 (p less than 0.05). Potassium and glucose absorption were greater from ORS 60:240 than from any of the other hypotonic solutions (p less than 0.05) and were equal to absorption from WHO-ORS). These results in a short segment of healthy human jejunum suggest that hypotonic ORS containing monomeric glucose may increase water absorption.     

Absorption of water and solute from glucose-electrolyte solutions in the human jejunum: effect of citrate or betaine

The inclusion in oral rehydration solutions of solutes that are actively co-transported with sodium has been suggested as a means of increasing the effect of glucose on water absorption by the small intestine. Using a modified perfusion system we have examined water and solute absorption in the normal human intestine from two effervescent glucose-electrolyte solutions, containing either citrate or betaine hydrochloride, and compared the absorption rates with those from a commonly used bicarbonate-containing oral rehydration solution. Absorption of citrate (355 +/- 87 mumol/cm/h) and betaine (313 +/- 125 mumol/cm/h) occurred from the respective solutions. The inclusion of 46 mmol/l citrate or 36 mmol/l betaine in effervescent oral rehydration solutions had no effect on water or solute absorption.     

Acetate and citrate stimulate water and sodium absorption in the human jejunum

Using a standard perfusion technique, the organic anions acetate (50 mmol/l) and citrate (5 mmol/l) have been shown to stimulate absorption of water and sodium from the human jejunum. These observations may support further the rationale for including acetate or citrate in oral rehydration solutions for the treatment of acute diarrhoeal disease in humans.     

Absorption of a hypotonic oral rehydration solution in a human model of cholera.

The development of oral rehydration solutions (ORSs) has been one of the important therapeutic advances of this century. The optimal formulation, however, of ORSs for both cholera and other infective diarrhoeas is still debated. Part of the problem in developing ORSs has been the lack of adequate test systems for the assessment of new formulations before clinical trial. We have developed a jejunal perfusion, cholera toxin induced, secretory model in humans and have compared net water and solute absorption from a hypotonic ORS (HYPO-ORS: sodium 60 mmol/l, glucose 90 mmol/l, osmolality 240 mOsm/kg) and the British Pharmacopoeia recommended ORS (UK-ORS: sodium 35 mmol/l, glucose 200 mmol/l, osmolality 310 mOsm/kg) in six healthy volunteers. A plasma electrolyte solution (PES) was also perfused in all subjects to confirm a secretory state. Only HYPO-ORS reversed sodium secretion to absorption (p < 0.01). Both ORSs promoted net water absorption but this was greatest with HYPO-ORS (p < 0.01). Glucose and potassium absorption rates were similar for both ORSs whereas chloride absorption mirrored sodium absorption and was greatest from HYPO-ORS (p < 0.05). These results, in a biologically relevant model of secretory diarrhoea, suggest it may be possible to achieve improved rates of rehydration by the use of hypotonic ORS with mid range sodium concentrations.     

Effect of bicarbonate on efficacy of oral rehydration therapy: studies in an experimental model of secretory diarrhoea.

In situ perfusion of rat intestine was used to evaluate the effect of bicarbonate on the efficacy of a low sodium (35 mmol/l) glucose-electrolyte oral rehydration solution in normal and cholera toxin-treated rat small intestine. In normal intestine, absorption of water was greater (108 (8.1) microliters/min/g; p less than 0.01) and sodium secretion less (-4.3 (0.3) mumol/min/g; p less than 0.01) from the oral rehydration solution containing bicarbonate than from the solution in which bicarbonate was replaced by chloride ions (59.5 (7.2) microliters/min/g and -7.8 (0.8) mumol/min/g, respectively). Glucose absorption in normal intestine was similar with both solutions. In the secreting intestine, both oral rehydration solutions reversed net water secretion to absorption, but inclusion of bicarbonate resulted in significantly less net absorption of both water (2.18 (6.9) microliters/min/g; p less than 0.05) and glucose (18.7 (2.1) mumol/min/g; p less than 0.001) compared with bicarbonate free oral rehydration solution (19.4 (3.9) microliters/min/g and 35.8 (3.7) mumol/min/g, respectively). Net sodium secretion occurred in normal and secreting intestine but was significantly less with the bicarbonate containing oral rehydration solution. These findings suggest that the demonstrable advantage of bicarbonate in promoting water absorption from this oral rehydration solution in normal rat intestine does not apply to cholera toxin treated secreting intestine.     

Effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and metabolic parameters in elderly normotensive individuals: a randomized double-blind crossover trial

OBJECTIVE: To examine the effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and parameters of glucose and lipid metabolism in elderly normotensive individuals. METHODS: We examined 21 healthy men and women aged 60-72 years in a randomized, placebo-controlled, double-blind crossover trial. After reducing dietary salt intake to below 100 mmol/day, study participants were randomly assigned to drink 1.5 l daily of a sodium chloride-rich (sodium 84.5 mmol/l, chloride 63.7 mmol/l, bicarbonate 21.9 mmol/l), a sodium bicarbonate-rich (sodium 39.3 mmol/l, chloride 6.5 mmol/l, bicarbonate 48.8 mmol/l) and a low-sodium (placebo: sodium, chloride and bicarbonate < 0.02 mmol/l) mineral water for 4 weeks each in a three-phase crossover order. Each phase was separated by a 2-week washout period in which the study participants remained on a low-salt diet. Compliance was assessed by biweekly urinary electrolyte excretion and five study participants were excluded from analysis for failing to complete the trial or to fulfil the compliance criteria. RESULTS: Mean arterial blood pressure was significantly lower during the periods of consuming low-sodium -7.0 +/- 7.2 mmHg, P < 0.001) or sodium bicarbonate-rich (-5.7 +/- 6.4 mmHg, P < 0.05) water than at baseline. In contrast, blood pressure during the phase of drinking sodium chloride-rich water was identical to that at baseline. Ambulatory 24 h blood pressure, oral glucose tolerance and plasma lipids were not affected by the different regimens. Urinary calcium excretion was significantly reduced by drinking low-sodium or sodium bicarbonate-rich water but was unchanged under the sodium chloride-rich water. CONCLUSION: Consumption of sodium chloride-rich mineral water can abolish the blood pressure reduction induced by dietary salt restriction in elderly individuals. Sodium bicarbonate-rich mineral water in conjunction with a low-salt diet may have a beneficial effect on calcium homeostasis.     

Treatment of severe diarrhoeal dehydration in hospital and home by oral fluids

This paper reports on 1330 infants, from birth to 24 months old, suffering from diarrhoea and moderate to severe dehydration who were hospitalized in Tehran University Hospital over a period of 11 months. Fifteen per cent of them had signs of shock and 36% had marasmus. All patients were treated orally in two phases: rehydration therapy and maintenance therapy. For rehydration, an isotonic fluid (sodium 80 mmol l-1, potassium 20 mmol l-1) was administered at a rate of 40 ml kg-1 h-1 until all signs of dehydration disappeared. Following complete hydration, the patients were discharged and maintenance therapy was performed at home, by mothers, administering Maintenance Solution (sodium 40 mmol l-1, potassium 30 mmol l-1) ad libitum. Intravenous fluids were not used, even in severe dehydration. The efficacy and safety of this regimen were confirmed by rapid and successful rehydration in 99.7% of the patients and correction of a wide variety of electrolyte abnormalities present on admission, though some relapsed. The study suggests that this protocol could be employed in varied types and severities of dehydration and electrolyte abnormalities, and could also be used in both well nourished infants and in those with severe marasmus. It also demonstrates that mothers can serve as effective health workers and can perform successful maintenance therapy. Nine per cent of treated children required readmission to hospital within 24 h of discharge and a further 8% were hospitalized elsewhere with recurrent symptoms.     

Effect of bicarbonate or base precursor on water and solute absorption from a glucose-electrolyte solution in the human jejunum

A modified perfusion technique was used to examine the effect on water and solute absorption in the healthy human jejunum of replacing bicarbonate (18 mmol/l) by equivalent amounts of different base precursors in a glucose-electrolyte solution. Acetate, citrate and lactate were absorbed from the perfusion solutions. Absorption of these base precursors appeared to have no effect on water uptake, but greater sodium (p less than 0.05) absorption occurred from solutions containing either acetate or lactate compared with the bicarbonate-containing solution. These data suggest that oral rehydration solutions with base precursors other than bicarbonate are as effective as bicarbonate-containing solutions in promoting absorption of water and electrolytes.     

Increased cell loss in the human jejunum induced by laxatives (ricinoleic acid, dioctyl sodium sulphosuccinate, magnesium sulphate, bile salts).

Two conjugated bile salts (10 mmol/l sodium glycocholate, 10 mmol/l sodium taurodeoxycholate) and three laxatives (30 mmol/l magnesium sulphate, 10 mmol/l ricinoleic acid, 2 mmol/l dioctyl sodium sulphosuccinate) were tested on seven subjects with no intestinal lesions in 14 experiments by intestinal perfusion of the jejunum. A 25 cm segment was studied. Each solution was perfused at the rate of 10 ml/min. Water and electrolyte fluxes, losses of deoxyribonucleic acid (DNA), and intestinal cell enzyme activity were measured in the fluids collected. All the laxatives and bile salts tested (except sodium glycocholate) induced water and electrolyte secretion, a rise in intraluminal DNA loss, and enzyme activity. It was possible to establish a significant correlation (p less than 0.001) between the amounts of water fluxes and DNA loss under the effect of dioctyl sodium sulphosuccinate and ricinoleic acid.     

Increased sodium concentrations in drinking water increase blood pressure in neonates

BACKGROUND : In a previous study, we found that increased sodium concentrations in the drinking water led to an increase in mean arterial pressure (MAP) and systolic blood pressure (SBP) in fourth- and fifth-grade school children. Milk powder formulae have a low content of sodium, almost identical to that of breast milk. However, the final sodium concentration in the milk formula depends upon the concentration of sodium in the diluting water, which varies remarkably. OBJECTIVE : To evaluate changes in blood pressure during the first 2 months of life in neonates receiving low-sodium mineral water (LSMW), high-sodium tap water (HSTW), or breast milk. DESIGN : A randomized, prospective study in a teaching hospital. METHODS : Fifty-eight Jewish term infants maintained on milk formula were randomly assigned to two groups. Group 1 consisted of 25 infants whose formula was diluted with LSMW (Eden Spring Mineral Water) having a sodium concentration of 32 mg/l (1.4 mmol/l). Group 2 contained 33 infants whose formula was diluted with HSTW having a sodium concentration of 196 mg/l (8.5 mmol/l). Fifteen breastfed babies served as the control group (group 3). Weekly weight, height, head circumference, heart rate, and systolic (SBP), diastolic (DBP) and mean (MAP) blood pressures were recorded for each infant for 8 consecutive weeks after birth. After 8 weeks, group 1 reverted to a diet similar to that of group 2. At 6 months of age (week 24), a follow-up blood pressure measurement was performed in 11, 20 and seven infants in groups 1, 2 and 3, respectively. Blood pressure was measured during sleep. Urinary sodium : creatinine ratio was determined monthly during the initial 2 months. RESULTS : Increases in weight and height were equal in all groups. Heart rate did not differ between groups during the entire study period. From the age of 6 weeks until week 8, MAP, SBP and DBP were found to be significantly greater in the group 2 (HSTW). In parallel, the urinary sodium : creatinine ratio was significantly greater in this group. At week 24, blood pressure values in group 1 increased towards those of group 2. CONCLUSIONS : Diluting milk formula with tap water containing a high concentration of sodium will result in the infant being fed a high-salt diet. To equilibrate with breast milk, formula should be diluted with low-salt water. Blood pressure in the neonate is increased by a high sodium intake via drinking water.     

Behavioural hypertension in sodium-loaded dogs is accompanied by sustained sodium retention

Instrumented dogs were presented with two daily avoidance conditioning sessions during 12 days of continuous saline infusion (1.3 l/day). Avoidance conditioning of sodium-loaded dogs resulted in progressive 24-h hypertension over the 12-day conditioning periods (systolic, 21 +/- 3 mmHg; diastolic, 15 +/- 1 mmHg) accompanied by a decreased 24-h heart rate (-14.8 +/- 4.0 beats/min). Under these conditions, renal excretion of sodium decreased relative to sodium intake (-88 +/- 19 mmol/12 days) while urine volume was increased relative to water intake (0.18 +/- 0.07 l/day). The sodium retention was accompanied by increased plasma sodium levels (1.8 +/- 0.7 mmol/l) and decreased plasma calcium levels (-1.2 +/- 0.2 mmol/l). Daily creatinine clearance decreased during the development of hypertension (-53 +/- 13% per day). Subsequently, each dog was exposed to 12 days of saline infusion in the absence of avoidance sessions. Under these conditions, arterial pressure and sodium balance remained stable. It was concluded that the rapidly developing and reversible hypertension occurring in sodium-loaded dogs exposed to recurrent behavioural stress is mediated by increased levels of total body sodium.     

A trial of the calcium antagonist nisoldipine in hypertensive non-insulin-dependent diabetic patients

The antihypertensive and metabolic effects of a new calcium antagonist nisoldipine (10 to 20 mg at night) were investigated in 14 mild to moderately hypertensive non-insulin-dependent diabetic patients (median age 62, range 50-70 years). In a 12-week placebo controlled single blind study, sitting and standing blood pressure were significantly lowered (p less than 0.001). Heart rate was unchanged as were blood urea, creatinine, bilirubin, mmol/l (mean +/- SEM) and uric acid concentrations. Plasma sodium levels fell during active therapy (142 +/- 0.5 mmol/l (mean +/- SEM) versus 139 +/- 0.5 (p less than 0.001) and remained lower during the washout period. Plasma calcium concentrations increased during nisoldipine therapy (2.41 +/- 0.02 versus 2.51 +/- 0.03 mmol/l, p less than 0.001) and returned towards baseline during the washout period. Plasma ionized calcium concentrations showed similar changes but plasma sodium and calcium remained within the normal laboratory ranges in all patients at all times. Serum triglyceride concentrations fell (placebo 1.9 +/- 0.02 mmol/l vs nisoldipine 1.6 +/- 0.2, p less than 0.05), but fasting cholesterol was unchanged. Fasting blood glucose, and the blood glucose response to oral glucose challenge (75 g) showed no differences though HbA1 concentrations fell (10.6 +/- 0.7 versus 9.2 +/- 0.05%, p less than 0.05) and tended to rise when the drug was withdrawn. Haemoglobin concentrations also fell during active therapy (14.7 +/- 0.4 vs 14 +/- 0.32 g/dl p less than 0.001) and also remained lower after the washout period (13.9 +/- 0.03 g/dl).(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of renal and adrenocortical function by the renin-angiotensin system in two euryhaline teleost fishes

Plasma ions and cortisol levels were measured sequentially during the adaptation of European eels (Anguilla anguilla) from fresh water (FW) to sea water (SW). The importance of the renin-angiotensin system in the regulation of this adaptation was assessed using captopril (SQ14225, an inhibitor of angiotensin I-converting enzyme). The effects of captopril on renal function in FW- and SW-adapted trout were also examined. During the first 5 hr in sea water, plasma levels of cortisol in eels increased threefold, plasma sodium rose steadily from 137 to 156 mmol/l and plasma potassium fell from 2.1 to 1.6 mmol/l. In contrast, captopril-treated eels when adapted to sea water had plasma cortisol levels twice those of controls. Captopril treatment did not affect the electrolyte responses to seawater adaptation. Captopril injected into eels which were fully adapted to and wholly maintained in sea water had no effect on plasma levels of cortisol, sodium, and potassium. Plasma cortisol was 30% lower in freshwater eels 2 hr after an injection of captopril but plasma sodium and potassium levels were unchanged. In both FW- and SW-adapted trout, captopril infusions doubled the glomerular filtration and urine production rates and the tubular transport maxima for glucose without changes in plasma composition.     

Salt sensitivity and cell permeability.

We have recently shown that changes in blood sodium concentration within the limited range of +/- 15 mmol/l induce changes in blood pressure which are directly related to intracellular sodium concentration and inversely related to the transmembrane sodium gradient. It followed from this that the blood pressure response to an incremental change in blood sodium concentration induced by an intraperitoneal salt load should be a function of the rate of accumulation of cell sodium. This was tested in rats treated with deoxycorticosterone acetate (DOCA)-saline for 3 days since at this time cell permeability to sodium is known to be increased. The rise of cell sodium when blood sodium concentration, measured 30 min after loading, ranged from 140-160 mmol/l, was significantly increased in treated animals (0.14 versus 0.21 mmol/kg dry weight for each 1 mmol/l rise in extracellular sodium concentration) and the rise in blood pressure was correspondingly greater (0.81 versus 1.43 mmHg for a 1 mmol/l rise in extracellular sodium concentration). The increased accumulation of cell sodium was not accompanied by a similar increase in water, so that the rise in intracellular sodium concentration was also exaggerated. Prior uninephrectomy slowed the excretion of the salt load sufficiently to exaggerate the rise of blood sodium concentration in response to a given load. The osmotic effects of intraperitoneal high sodium or high sucrose were both equally reduced, indicating that the increased permeability induced by DOCA is not specific for sodium but affects non-electrolytes as well; thus, it probably involves the phospholipid matrix.     

Atrial natriuretic peptide in children with pneumonia

Atrial natriuretic peptide (ANP) has known natriuretic, diuretic, and vasodilatatory effects. It is synthesized and stored in the atrial cells. Stretching of the atrial muscle fibers during an increase in venous return sets a response of ANP release into the blood stream. High levels of ANP were measured in a number of lung diseases. Pneumonia in children is frequently accompanied by the hyponatremia of the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH). High levels of ANP were found among patients with SIADH. Our objective was to determine if ANP plasma levels are altered in children with pneumonia, and to evaluate a possible correlation between severity of pneumonia and ANP levels. Blood samples from 28 children diagnosed with pneumonia were collected. Plasma ANP levels were determined by radioimmunoassay and compared to levels in 25 children without pneumonia. ANP levels in the pneumonia group (mean +/- SD, 16.02 +/- 11.69 pg/ml) increased significantly (P < 0.01) compared to levels in the control group (mean +/- SD, 7.44 +/- 9.29 pg/ml). Children in the pneumonia group also exhibited low levels of plasma sodium (mean +/- SD, 134.88 +/- 2.5 mmol/l) compared to levels in children without pneumonia (mean +/- SD, 139.77 +/- 4.15 mmol/l) (P < 0.01). There was no correlation between ANP plasma levels and severity of pneumonia. In conclusion, ANP levels in children with pneumonia, as in other lung diseases, are increased. High ANP levels may play a role in maintaining water and electrolyte equilibrium during a state of inappropriate ADH secretion accompanying pneumonia.     

Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration solutions in two models of diarrhea

BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its effectiveness for water and electrolyte absorption in normal rats. The present study extends these observations on GA in ORS to two rat models of diarrheal disease. METHODS: Juvenile rats were either treated for 1 week with magnesium citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5 or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium, and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with GA-supplemented ORS showed an expansion of the basolateral intercellular spaces between villus absorptive epithelial cells and the lamina propria, reflecting enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0 g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS: These experimental studies in models of diarrhea suggest that GA may be a useful additive to ORS for the potentiation of water and electrolyte absorption. (Gastroenterology 1997 Jun;112(6):1979-85)     

The renin-aldosterone axis in patients with diabetes insipidus

OBJECTIVE The objective of the present study was to investigate the renin-aldosterone axis in neurogenic diabetes insipidus in man, in view of the fact that profound abnormalities of this axis have been described in experimental animals with congenital neurogenic diabetes insipidus. DESIGN AND PATIENTS Nine patients with neurogenic diabetes insipidus and 11 healthy subjects (controls) were examined under basal conditions, following the standard 8-hour water deprivation test and 1 hour after a subsequent oral rehydration. MEASUREMENTS Plasma and urine osmolalities were determined by freezing point depression, plasma sodium and potassium by a method using an ion-selective electrode, plasma AVP, Cortisol, aldosterone and plasma renin activity by radioimmunoassay. RESULTS Plasma renin activities under basal conditions were significantly higher in patients with diabetes insipidus than in controls (mean ± SEM 23.4 ± 6.6 vs 7.8 ± 1.2 ng/ I min). In the diabetes insipidus group, water deprivation caused a twofold Increase in plasma renin activities (48 ± 13.8 ng/l min), while in the control group plasma renin activity levels were not significantly altered (10.2 ± 1.2 ng/l min). Rehydration did not alter plasma renin activity levels in either group (patients 50.4 ± 13.2, controls 9.0 ± 2.4 ng/l min). Plasma aldosterone concentrations under basal conditions did not differ between the two groups (patients 302.4 ± 37, controls 326.4 ± 36.5 pmol/l) and did not change in patients with diabetes insipidus after water deprivation or rehydration (307.5 ± 67.2 and 385.5 ± 91 pmol/l, respectively). Conversely, controls showed a significant decrease in plasma aldosterone levels after dehydration (201 ± 27.9 pmol/l), which was attributed to the circardian variation in aldosterone secretion, as shown by a parallel decrease in plasma Cortisol levels. CONCLUSIONS Patients with diabetes insipidus are hyper-reninaemic, probably because of chronic volume contraction. There is a dissociation between renin and aldosterone in patients with diabetes insipidus under basal conditions, which is exaggerated during water deprivation.