Urea Loading Research Articles

Osmotic diuresis before Homer W. Smith: A winding path to renal physiology

It was towards the end of the 18th century that a curiosity arose about what controlled the flow of urine. It was noted that though a patient's kidneys might be destroyed, the flow of urine continued until death. This puzzling phenomenon might have been understood had Ségalas's and Wöhler's observations been properly appreciated, that an extra load of urea, or any other substance that is excreted by the kidney, causes a diuresis. Nevertheless, these experiments were forgotten, and because of Bowman's and Ludwig's studies fluctuations in urine flow were ascribed to changes in blood pressure. It was not until 1870 to 1880 that Ustimowitsch, Falck and Richet stressed the role of urinary solutes on urine flow. Around 1900, Cushny also studied the diuretic effect of different solutes excreted in the urine and actually described what is now called an osmotic diuresis, though he did not use the term. These studies enabled him to deliver his "modern view" of the Secretion of the Urine. This was the first coherent concept which attempted to explain the formation of the urine and the regulation of its composition according to a pressure of a selective tubular reabsorption controlled by the needs of the "Milieu Intérieur." When glomerular and tubular functions became quantifiable, Homer W. Smith's disciples were able to define the exact nature of an osmotic diuresis and that explained the paradox of polyuria and renal failure.

Blood metabolite and regulatory hormone concentrations and response to metabolic challenges during the infusion of mimosine and 2,3-dihydroxypyridine in alpine goats.

Sixteen Alpine wethers (average BW 35 +/- 2 kg) were used to evaluate the effect of continuous 48-h intravenous infusions of saline (CON), mimosine (MIM; 200 mg.kg.75.d-1), 2-hydroxy-3(1H)-pyridine (2,3-DHP; 200 mg.kg.75.d-1, or MIM+2,3-DHP (100 mg of MIM plus 100 mg of 2,3-DHP-kg.75.d-1) on hepatic function and selected blood metabolite and circulating hormone concentrations. Neither MIM nor 2,3-DHP affected plasma ammonia N, glucose, cortisol, or insulin concentrations over time (P > .10). Jugular plasma total protein concentration was greater in the MIM group (P < .07). Plasma triiodothyronine (P < .01) and thyroxine (P < .08) concentrations were higher in the goats receiving the MIM, 2,3-DHP, and MIM+2,3-DHP infusions than in the goats receiving the CON infusion. Plasma urea N concentration was decreased by MIM (P < .10) and MIM+2,3-DHP (P < .03) compared with the CON infusion. A Propionate Load Test was conducted at 24 to 28 h into the infusion to assess the toxins' effects on the liver's ability to increase circulating glucose concentrations in the presence of elevated propionate levels. The results indicated that neither 2,3-DHP nor MIM reduced the liver's ability to respond to a bolus dose of propionate (P > .10). Following a Urea Load Test, circulating ammonia N and glucose concentrations in the MIM, 2,3-DHP, and MIM+2,3-DHP treatments had lower peak values than that in the CON treatment (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma metabolite and hormone concentrations in Friesian calves of low or high genetic merit: effects of sex and age

AbstractThis study investigated the potential use of blood metabolite and hormone concentrations as genetic markers for milk fat production and their possible interactions with sex and age. Two groups of calves, one from the Massey University high breeding index (HBI) line of dairy cattle (seven males, eight females) and the other from the low breeding index (LBI) line (four males, 11 females), were studied at 3·5 months and 7 months of age. The average breeding indices (BI) of the calves based on ancestry BI were 138 (s.d. 4·4) and 111 (s.d. 2·3) respectively. Serial blood sampling regimens were conducted in relation to feeding (chaffed lucerne hay at 1·3 times maintenance energy requirement), during an intravenous urea load (120 mg/kg live weight) and during fasting (63 h) and refeeding. Urea spaces and fractional decay constants at each age were estimated by a single compartment distribution model based on plasma urea concentrations following the intravenous urea load.Plasma concentrations of urea, creatinine and non-esterified fatty acids (NEFA) were not significantly different between the lines in any of the periods examined and at either age. In contrast, plasma concentrations of glucose and insulin were greater in the HBI calves than in the LBI calves although these differences were restricted mainly to the period immediately after feeding. Urea space at 7 months of age was also greater in the HBI animals than in the LBI animals. Plasma concentrations of all hormones and metabolites except insulin were significantly influenced by sex and/or age.The study does not confirm previous findings that genetic merit for dairying is expressed in terms of plasma levels of urea and NEFA, particularly those during a fast. However, the results of the present study are consistent with previous observations of differences in glucose and insulin metabolism between the tivo Massey University genetic merit lines. These traits may therefore have potential as genetic markers for milk fat production.

Dipsogenic effect of urea in rats.

Anephric rats injected subcutaneously with urea in isotonic saline drank much more than anephric control animals receiving isotonic saline alone. The pattern of water intake and urine output of normal rats, repeatedly injected with urea solution, was similar to that of rats injected with dipsogenic hypertonic NaCl and quite different from that of rats receiving furosemide. A well-evident dipsogenic effect (unrelated to the urine output) was observed in normal rats repeatedly injected with urea solution and having a rapid rise of serum urea concentrations. On the contrary, in rats receiving a single load of urea and showing first a very rapid increase, then followed by a slow decrease of serum urea concentrations, the dipsogenic effect was present only initially. These results demonstrate that urea exerts a direct dipsogenic action which may be interpreted as a consequence of an osmotic gradient between the extra- and the intracellular fluid. When this is positive, as in the case of a rapid rise of serum urea levels, cell dehydration ensues and thirst is stimulated. On the contrary, when serum urea levels are decreasing and, presumably, when the intra- and the extracellular concentrations of urea are in equilibrium, no cellular dehydration occurs and thirst does not appear.

The effects of intraruminal infusions of urea on the voluntary intake and milk production of cows receiving grass silage diets

Responses of dairy cows given silage diets to the intraruminal infusion of urea in progressively increasing doses were studied in four experiments, two with non-lactating cows and two with lactating cows. No clinical symptoms of NH3 toxicity were observed in any of the experiments. When urea was infused continuously, silage intake was depressed (P less than 0.05) when the total supply of N exceeded the equivalent of 250 g crude protein (CP)/kg DM in the total diet. However, when the urea load was administered twice daily, as opposed to continuously, intake depression (P less than 0.05) occurred at the equivalent of 170 g CP/kg DM. At the higher doses of urea, concentrations of NH3 in peripheral blood increased and were accompanied by increased concentrations of glucose and reduced levels of insulin in plasma. In general, responses of milk production followed those of silage intake but there was evidence of greater proportional reductions in the yield of lactose relative to that of fat and protein. It is concluded that the voluntary intake of high-protein silages may be depressed by factors associated with high rates of absorption of NH3 from the rumen.

Osmotic stability of red cells in renal circulation requires rapid urea transport.

Urea transport by the human erythrocyte occurs via an asymmetric-facilitated diffusion system with high Michaelis constants and high maximal velocities; the equivalent permeability in the limit of zero urea concentration is approximately 10(-3) cm/s (J. Gen. Physiol. 81: 221-237, 239-253, 1983). A physiological role for this system is revealed by numerical integration of the appropriate equations that show that rapid urea transport is essential for red cell stability in passing through the renal medulla. The calculation compares two cells. Cell A transports urea with permeability characteristics of normal red cells; cell B has urea permeability similar to lipid bilayers. On entering the hypertonic medulla, both cells shrink, but only B swells on leaving the medulla. The osmotic stress for cell B is greater than for A. Cell B is close to hypertonic hemolysis in the medulla and to hypotonic hemolysis in the cortex. Cell B remains swollen for some time after its exit; the resulting decreased deformability presents a hazard if B reenters the microcirculation. Furthermore, cell B removes a significant fraction of the filtered load of urea and compromises the osmotic gradients in the medulla.

Mechanism of impaired urinary concentration in chronic primary glomerulonephritis

AbstractMechanism of impaired urinary concentration in chronic primary glomerulonephritis. To define the role of medullary damage and the influence of solute load and blood pressure (BP) in impairing urinary concentration, patients with chronic glomerulonephritis were investigated by histological and functional studies. In 59 biopsy specimens, the degree of medullary fibrosis was correlated inversely with urinary specific gravity and was significantly greater in hypertensive than in normotensive subjects. The following clearance studies were carried out in patients with a GFR of 15 to 40ml/min in maximal antidiuresis: (1) Eight patients were studied while receiving a high sodium and protein diet and then after 1 week of low sodium, low protein diet; (2) ten patients were loaded with hypertonic saline (3%) to increase urine volume up to 25 to 30% of GFR; (3) the concentrating ability was compared in 15 normotensives and 15 hypertensives with comparable GFR; (4) the concentrating ability was studied in nine hypertensive patients before and after drug-induced normalization of BP. In (1) no change occurred in maximal urine osmolality (UOsm) even if fractional sodium excretion and filtered load of urea were reduced. In (2), values of UOsm fell below those of plasma osmolality. In (3), UOsm and negative free-water generation were lower in hypertensive than in normotensive subjects. In (4), normalization of BP was not associated with any change in UOsm These results indicate that osmotic diuresis does not play a critical role in reducing urinary concentration. This defect is better accounted for by an intrinsic medullary damage, enhanced in hypertensive patients, which may impair the permeability of collecting ducts to water.Mécanisme de l'altération de la concentration urinaire au cours des glomérulonéphrites chroniques primitives. Afin de définir le rôle des altérations médullaires et de l'influence de la charge en solutés et de la pression sanguine (BP) dans le défaut de concentration urinaire, des malades atteints de glomérulonéphrite chronique ont été explorés par des études histologiques et fonctionnelles. Dans 59 biopsies, le degré de fibrose médullaire était inversement corrélé à la densité spécifique urinaire, et était significativement plus important chez les hypertendus que chez les normaux tendus. Les études de clearance suivantes ont été entreprises chez des malades dont GFR était de 15–40ml/min en antidiurèse maximale: (1) huit malades ont été étudiés alors qu'ils recevaient un régime riche en sodium et en protides, puis après une semaine de régime pauvre en sodium et pauvre en protides; (2) dix malades ont reçu une surcharge de soluté salé hypertonique; (3) la capacité de concentration a été comparée chez 15 normotendus et 15 hypertendus à GFR comparable; (4) la capacité de concentration a été étudiée chez 9 hypertendus avant et après normalisation médicamenteuse de la BP. Chez (1), aucune modification de l'osmolalité urinaire maximale (Uosm) ne s'est produite, même si l'excrétion fractionnelle du sodium et la charge uréique filtrée étaient réduites. Chez (2), les valeurs de Uosm ont chuté en dessous de celles de l'osmolalité plasmatique. Chez (3), Uosm et la génération d'eau libre négative étaient moindres chez les hypertendus que chez les normotendus. Chez (4), la normalisation de BP n'était associée à aucune modification de Uosm. Ces résultats indiquent qu'une diurèse osmotique ne joue pas de rôle critique dans la réduction de la concentration urinaire. Ce défaut est mieux expliqué par une perturbation médullaire intrinsèque, accrue chez les hypertendus, qui pourrait altérer la perméabilité des canaux collecteurs à l'eau.

Urea reabsorption in the medullary collecting duct of protein-depleted young rats before and after urea infusion.

The aims of the present study were to examine urea handling along the length of the medullary collecting duct (MCD) in protein-depleted young rats and to determine the effect of urea infusion on MCD function and urine concentrating ability. In 10 young rats on a low protein diet, urea reabsorption equivalent to 18.3% of the filtered load was observed along the MCD (4.5 mm) using the microcatheterization technique. Collecting duct urea reabsorption occurred almost entirely (16.6%) in the distal portion of the MCD (mid-zone to papillary tip, 2.8 mm). These results are in contrast to the lack of net urea reabsorption along the MCD in protein-replete adult rats [21]. After urea infusion which raised plasma urea level from 3.5 to 10.5 mmol/l in protein-depleted rats, urine non-urea solute concentration increased in the non-exposed right kidney from 827 to 1,199 mosm kg−1 (P<0.001) but the increase was not significant in the experimental left kidney (590 to 619 mosm kg−1). Thus exposure of the papilla interfered with urea-induced enhancement of urine concentrating ability. After urea infusion, fractional urea reabsorption in the distal portion of the MCD was similar to that before infusion (21.1%) of filtered load) but the absolute load of urea delivered to the MCD and reabsorbed along the duct was markedly increased (2.7-fold). In 6 rats with an increase in urine non-urea solute concentration in the experimental kidney after urea infusion, fluid reabsorption along the duct was significantly increased. The results indicate that in protein-depleted young rats (1) there is significant urea reabsorption in the distal portion of the medullary collecting duct, (2) urea infusion contributes to enhanced urine concentrating ability, in part, by increasing absolute urea reabsorption and also water reabsorption in the collecting duct.

Method for the microassay of endogenous creatinine in blood and urine of small murid rodents.

The estimation of endogenous creatinine clearance yields information useful to the renal physiologist without the need to introduce a marker compound. The method has been limited in its application to mammalian species of bodyweight 200 g and above due to the blood sample size required. A modification is described whereby this procedure may be applied to animals of bodyweight as low as 25 g. Use of this microassay is illustrated in an investigation of the effect of salt and urea loading on renal function in an Australian desert mouse, Notomys alexis.

Urea handling by the distal tubule and collecting duct of the rat during urea--saline, isotonic saline, or urea diuresis.

The aims of the present study were to examine the effects of urea and isotonic saline loads separately and together on urea handling in the medullary collecting duct and surface distal tubules of the rat kidney. Microcatheterization of the medullary collecting duct during isotonic saline diuresis (saline at 5% of body weight per hour, plasma urea 4.3 mM/L), showed an increase in the remaining fraction of filtered urea from 56.2% at the beginning (corticomedullary junction) to 68.5% at the end (papillary tip) of the medullary collecting duct (n = 17 paired samples in six rats, p less than 0.05). There was no change in the fraction of filtered urea along the medullary collecting duct during urea diuresis (plasma urea 87 mM/L, n = 15 paired samples in six rats) or during urea--saline diuresis (plasma urea 103 mM/L, n =32 paired samples in nine rats). Micropuncture of surface distal tubules in the same animals showed an increase in the fraction of filtered urea between end-distal samples and the beginning of the medullary collecting duct from 28.9 to 56.2% during isotonic saline diuresis (p less than 0.001), and from 53.6 to 75.3% during urea--saline diuresis (p less than 0.01), but no change during urea diuresis (63.6 to 60.0%, p = NS). Our conclusions are as follows. (1) Urea entry into the medullary collecting duct during steady-state diuresis occurs at low intratubular urea contractions (isotonic saline diuresis) but not at high concentrations (urea--saline diuresis and urea diuresis). (2) Urea entry between the surface distal tubule and the beginning of the medullary collecting duct occurs during saline diuresis (isotonic saline diuresis and urea--saline diuresis) but not urea diuresis. The latter finding suggests that isotonic saline loads affect urea transport differently in juxtamedullary nephrons compared to superficial nephrons.

Food intake and behavioral caloric compensation after protein repletion in the rat

The food intake response of rats to intragastrically infused or orally consumed protein was characterized and compared to the response to similarly administered carbohydrate. In Experiment 1, protein hydrolysate loads administered at the beginning of the dark phase via chronic intragastric cannulae led to rapid (complete within 3–4 hr), dose-related suppressions of food intake in comparison to sham loads or to urea loads controlling for volume, concentration and pH. The suppression remained evident in cumulative intake records through 24 hr and represented a greater than caloric compensation for the amount of metabolizeable energy delivered (1.38 and 1.12 kcal/kcal in Experiments 1a and 1b, respectively). In Experiment 2, protein hydrolysate loaded by gavage suppressed food intake significantly more than isocaloric glucose loads (1.32 vs 0.81 kcal/kcal after 24 hr). Water intake in both experiments was elevated by protein loads, although this occurred after the food intake suppression. Differential satiety responses to protein and carbohydrate repletion were shown in Experiment 3 to extend to orally consumed, naturally occurring macronutrients—casein vs starch and disaccharide diets. These data suggest that satiety in the rat is not solely graded with respect to the energy delivered by the preceding meal but rather that repletion with different macronutrients leads to quantitatively (or perhaps qualitatively) different satieties.

Cross-circulation study of natriuretic factors in rats with reduced nephron mass.

The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2-3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.

Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.

Urea and the concentrating defect of chronic renal failure in man.

Renal concentrating defect was studied in 15 patients with chronic pyelonephritis of different degrees of impairment in renal function. Maximal urine osmolality showed a significant correlation to glomerular filtration rate (GFR), fractional sodium and urea excretion (FENa, Furea) increased with decreasing GFR. Maximal urine urea concentration was estimated by infusion of hypertonic urea over 6 hrs; a significant correlation to GFR be demonstrated. Urinary electrolyte concentration was unaltered at GFR levels from 10–80 ml/min, below 10 ml/min urine electrolyte concentration showed an impairment, too. The studies demonstrate that urinary concentrating defect in human pyelonephritis is caused mainly by an impaired ability of the diseased kidney to concentrate urea. An increase in plasma urea concentration to 4–5 fold the control values did not influence FENa. In all patients FENa remained constant despite marked elevations of osmotic load per nephron. This demonstrates that an increased urea load does not influence FENa in chronic pyelonephritis.

The effect of formaldehyde treatment of a casein supplement on urea excretion and on digesta composition in sheep

The urinary excretion of urea, the fate of an intravenous dose of urea, overall nitrogen metabolism and the composition of rurnen and abomasal samples were studied in crossbred sheep given a basal roughage diet to which supplements of starch, casein or formaldehyde-treated casein were added. Urea excretion was closely related to plasma urea level (r = 0.935) and to the filtered load of urea (r = 0.957). The amount of urea reabsorbed by the kidney increased as'the amount filtered increased; the relationship was improved when values obtained at urine flow rates less than 1 rnl/rnin were omitted. When sheep were given the starch and treated casein diets, the rate at which they cleared a small dose of urea from their plasma was greater than the renal clearance rate; only 75% of a large dose was recovered in the urine. The capacity to dispose of exogenous urea by extra-renal pathways was apparent only when rumen ammonia nitrogen levels were less than about 200 mg/l. Formaldehyde treatment reduced nitrogen digestibility but reduced urine nitrogen excretion to a greater extent so that nitrogen retention increased. Treatment was associated with reduced plasma urea levels, reduced rumen and abomasal ammonia levels, reduced total VFA levels, increased proportions of acetic acid and decreased proportions of isobutyric, isovaleric and n-valeric acids, and more protein in abomasal contents.

Corrigendum - The effect of formaldehyde treatment of a casein supplement on urea excretion and on digesta composition in sheep

The urinary excretion of urea, the fate of an intravenous dose of urea, overall nitrogen metabolism and the composition of rurnen and abomasal samples were studied in crossbred sheep given a basal roughage diet to which supplements of starch, casein or formaldehyde-treated casein were added. Urea excretion was closely related to plasma urea level (r = 0.935) and to the filtered load of urea (r = 0.957). The amount of urea reabsorbed by the kidney increased as'the amount filtered increased; the relationship was improved when values obtained at urine flow rates less than 1 rnl/rnin were omitted. When sheep were given the starch and treated casein diets, the rate at which they cleared a small dose of urea from their plasma was greater than the renal clearance rate; only 75% of a large dose was recovered in the urine. The capacity to dispose of exogenous urea by extra-renal pathways was apparent only when rumen ammonia nitrogen levels were less than about 200 mg/l. Formaldehyde treatment reduced nitrogen digestibility but reduced urine nitrogen excretion to a greater extent so that nitrogen retention increased. Treatment was associated with reduced plasma urea levels, reduced rumen and abomasal ammonia levels, reduced total VFA levels, increased proportions of acetic acid and decreased proportions of isobutyric, isovaleric and n-valeric acids, and more protein in abomasal contents.

Analysis of cortical urea sequestration in rat renal tissue slices.

In antidiuretic rats plasma urea concentration (P u )was elevated up to 35 mM by intravenous urea loading. In renal cortical tissue (T) water content and unlabeled (u) and 14-C-urea (u *) were determined. Water content of total renal cortex and of superficial and juxtamedullary layers were not significantly different and were not changed by the elevation ofP u . In the control group (P u <10 mM), bothT/P u (3.06±0.71;n=29) and plasma specific activity were significantly higher than values forT/P u * (2.20±0.57;n=12) and tissue specific activity, respectively.T/P u andT/P u * were decreased significantly to the same level (1.68±0.35;n=20 and 1.51±0.21;n=7, respectively) atP u >20 mM and plasma and tissue specific activity became equal. Deproteination of tissue homogenates did not depress 14-C-activity. JuxtamedullaryT/P u was significantly higher than superficialT/P u .The difference was independent ofP u . The data suggest, that renal cortical tissue urea concentration is determined (i) by distal tubular fluid urea concentration, which is inversely correlated withP u and (ii) by a constant amount of urea in an extraluminal compartment not readily exchanging. The mechanism by which urea concentration in this extraluminal compartment is maintained independent ofP u might be urea neogenesis or urea binding to cellular structures or proteins.

Effects of urea loading in patients with far-advanced renal failure : W. Johnson, W. Hagge, R. Wagoner, R. Dinapoli, and J. Rosevear ( 47: 21, 1972)

Effects of urea loading in patients with far-advanced renal failure : W. Johnson, W. Hagge, R. Wagoner, R. Dinapoli, and J. Rosevear ( 47: 21, 1972)

Effects of urea loading in patients with far advanced renal failure : William Johnson, Wolfgang Hagge, Richard Wagoner, Robert Dinapoli, John Rosevear ( 47: 21, 1972)

Effects of urea loading in patients with far advanced renal failure : William Johnson, Wolfgang Hagge, Richard Wagoner, Robert Dinapoli, John Rosevear ( 47: 21, 1972)

Postabsorptively induced suppression of appetite and the energostatic control of feeding

The inhibition of feeding that follows intragastric administration of glucose had previously been shown to result in an ultimate net decrement in food intake which was equivalent in available energy to the amount of glucose loaded. Stomach loads of acetate, alanine, citrate, ethanol, glucose, glutamate, glycerol, lactate, oleate or valine (10 mmoles of each) were given in the present experiments. Food was withheld for 1 or 2 hr after gavage and then continuous access was restored. Relative to sodium chloride or urea loads, the metabolizable loads all inhibited feeding at some time in the subsequent few hr—in some cases at a time which followed complete absorption of the load. The net food intake decrement over 24 or 48 hr following gavage reliably correlated with the expected energy yield of the load. It is suggested that the primary metabolic control of food intake is an adjustment of the meal pattern which brings the current energy balance towards the null point.