RESUMO
Extracellular adenosine production by the GPI-anchored Ecto-5'-Nucleotidase (Ecto-5'-Nu) plays an important role in the cardiovascular system, notably in defense against hypoxia. It has been previously suggested that HMG-CoA reductase inhibitors (HRIs) could potentiate the hypoxic stimulation of Ecto-5'Nu in myocardial ischemia. In order to elucidate the mechanism of Ecto-5'-Nu stimulation by HRIs, Ecto-5'-Nu activity and expression were determined in an aortic endothelial cell line (SVAREC) incubated with lovastatin. Lovastatin enhanced Ecto-5'-Nu activity in a dose-dependent manner. This increase was not supported by de novo synthesis of the enzyme because neither the mRNA content nor the total amount of the protein were modified by lovastatin. By contrast, lovastatin enhanced cell surface expression of Ecto-5'-Nu and decreased endocytosis of Ecto-5'-Nu, as evidenced by immunostaining. This effect appeared unrelated to modifications of cholesterol content or Ecto-5'-Nu association with detergent-resistant membranes. The effect of lovastatin was reversed by mevalonate, the substrate of HMG-CoA reductase, by its isoprenoid derivative, geranyl-geranyl pyrophosphate, and by cytotoxic necrotizing factor, an activator of Rho-GTPases. Stimulation of Ecto-5'-Nu by lovastatin enhanced the inhibition of platelet aggregation induced by endothelial cells. In conclusion, lovastatin enhances Ecto-5'-Nu activity and membrane expression in endothelial cells. This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5'-Nu endocytosis through a decrease of Rho-GTPases isoprenylation.
Assuntos
5'-Nucleotidase/metabolismo , Membrana Celular/metabolismo , Endotélio Vascular/metabolismo , Lovastatina/farmacologia , beta-Ciclodextrinas , Proteínas rho de Ligação ao GTP/metabolismo , 5'-Nucleotidase/genética , Animais , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Colesterol/metabolismo , Ciclodextrinas/farmacologia , Relação Dose-Resposta a Droga , Endocitose/efeitos dos fármacos , Endotélio Vascular/citologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Ácido Mevalônico/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Fosfatos de Poli-Isoprenil/farmacologia , Prenilação de Proteína/efeitos dos fármacos , RNA Mensageiro/biossíntese , RatosRESUMO
Using a serum raised in rabbits against a calcium binding protein extracted from rat skin, the cutaneous localization of this protein was studied by indirect immunofluorescence. The skin calcium binding immunoreactivity was found in the epidermis but not in the dermis; it was localized in the cytoplasm of the basal cell layer of both skin and malpighian mucosa. There was not species specificity; this allowed the tracing of the protein in human epidermis as well where it was also expressed only in the basal cells. This is the first demonstration of the unique localization of a specific protein within the cytoplasm of the basal cell layer of the epidermis. This localization may help to elucidate the physiological role of this protein.
Assuntos
Proteínas de Ligação ao Cálcio/análise , Epiderme/análise , Animais , Proteínas de Ligação ao Cálcio/imunologia , Citoplasma/análise , Imunofluorescência , Cobaias , Coelhos , Ratos , Vitamina D/biossínteseRESUMO
25-Hydroxyvitamin D3 1 alpha- and 24-hydroxylase, NADPH-cytochrome c reductase, heme oxygenase, and ATPase activities were studied in viable kidney cells isolated from rats submitted to unilateral kidney damage (cortical electrocoagulation) and during the development of acute renal failure subsequent to excision of the contralateral undamaged kidney. Measurements of blood pH, plasma total and ionized calcium, phosphorus, creatinine, kidney histology, and phosphorus nuclear magnetic resonance spectroscopy determinations of phosphorus-containing compounds in kidney tissue were also performed. Seventy-two hours after unilateral kidney damage, no significant changes were observed in blood pH or in the plasma parameters studied. During this period, a significant increase in the activity of the 25-hydroxyvitamin D3 hydroxylases could be demonstrated in the cells of the contralateral undamaged kidney. A similar pattern of compensatory rise in the activity of the other enzymes studied was not detected. However, in the damaged kidney viable cells, the hydroxylase activities remained unchanged relative to those in sham-operated controls, despite a 5-fold increase in the inorganic phosphate content and a marked decrease in the organophosphorus and ATP content of this tissue. During the development of acute renal failure, a significant decrease in the activity of the hydroxylases occurred only when the rise in plasma creatinine concentration suggested severe renal insufficiency.
Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Injúria Renal Aguda/enzimologia , Sistema Enzimático do Citocromo P-450 , Rim/enzimologia , Esteroide Hidroxilases/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Lateralidade Funcional , Heme Oxigenase (Desciclizante)/metabolismo , Rim/patologia , Espectroscopia de Ressonância Magnética , Masculino , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Ratos , Ratos Endogâmicos , Vitamina D3 24-HidroxilaseRESUMO
Dietary ketoanalogues (KAs) were shown to replace their essential amino acids with a 50% efficiency for valine and leucine. We determined the optimal concentration of the racemic KA of isoleucine (KMVA) in uremic and control rats: nutrition responses were compared between a diet containing optimal isoleucine concentration and diets containing various KMVA concentrations. Isomolar replacement of isoleucine produced anorexia, stunting, and poor nitrogen balance. Doubling KMVA partially improved these indices. Tripling KMVA lessened urea production and improved growth up to that obtained with the isoleucine diet in uremic but not in control rats (20% lower). A further KMVA increase produced no further benefit. Among plasma branched-chain amino acids, only alloisoleucine was affected; it increased with increasing KMVA concentration, being maximum after tripling KMVA. Racemic KMVA could replace isoleucine with a 35% efficiency but supported no growth acceleration in uremic rats and no maximal growth in control rats. Plasma alloisoleucine rose without adverse nutrition effects.
Assuntos
Isoleucina/análogos & derivados , Cetoácidos/farmacologia , Uremia/dietoterapia , Aminoácidos Essenciais/metabolismo , Aminoácidos Essenciais/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Nitrogênio/metabolismo , Necessidades Nutricionais , Ratos , Ratos Endogâmicos , Ureia/metabolismo , Uremia/metabolismo , Valina/farmacologiaRESUMO
Insufficient protein diets supplemented with ketoanalogue/essential amino acid (KA/EAA) mixtures are proposed to maintain nutrition and to retard renal deterioration. We compared in growing and in adult uremic rats diets containing limited or usual amounts of protein (12%, 20% for growing rats, and 10% and 16% for adult rats) with diets containing 50% or 60% less casein plus a KA/EAA mixture providing KA at an equimolar amount of removed EAA or at higher amounts. The latter supplement caused stunting, the former caused no anorexia, a slight growth deficit when added to the lowest basal casein diets, and almost normal growth when added to higher casein diets. Growth was normal with EAA supplements. The plasma EAA changes were unrelated to intake and to growth. Thus, KA utilization is maximal, provided that basal protein is sufficient and KA are not in excess.
Assuntos
Aminoácidos Essenciais/uso terapêutico , Fenômenos Fisiológicos da Nutrição Animal , Dieta , Cetoácidos/uso terapêutico , Uremia/dietoterapia , Aminoácidos de Cadeia Ramificada/sangue , Aminoácidos Essenciais/administração & dosagem , Aminoácidos Essenciais/sangue , Animais , Proteínas Alimentares/administração & dosagem , Ingestão de Alimentos , Cetoácidos/administração & dosagem , Masculino , Nitrogênio/metabolismo , Ratos , Ratos Sprague-Dawley , Ureia/sangue , Aumento de PesoRESUMO
Effects of various intakes of the ketoanalogues of leucine (KICA) and valine (KIVA) on growth, nitrogen, and urea excretion were examined and compared to those of an optimal intake (A) of the corresponding amino acids. Diet KICA and KIVA contents varied from 1 to 4 times A. In controls, growth was significantly reduced with equimolar substitution, corrected with twice A, and unchanged at higher levels. Doubling KICA corrected growth except with substantial anorexia. In uremic rats fed KIVA, growth was corrected at twice A. Low-KICA diets reduced plasma-leucine level; higher KICA diets normalized plasma leucine and revealed branched-chain amino acid (BCAA) antagonism. Changes in 2-ketoacids were unrelated to those of BCAA. In uremia, KICA decreased plasma and urinary urea without changing nitrogen retention. Ketoacid substitution for amino acids was 50% efficient in normal rats and not altered by uremia. BCKAs, specifically KICA, could modify urea metabolism.
Assuntos
Dieta , Crescimento/efeitos dos fármacos , Cetoácidos/administração & dosagem , Uremia/metabolismo , Animais , Hemiterpenos , Leucina/administração & dosagem , Masculino , Nitrogênio/urina , Valor Nutritivo , Ratos , Ratos Endogâmicos , Ureia/metabolismo , Valina/administração & dosagemRESUMO
Changes in intestinal calcium-binding protein and calcium binding activity were studied at resection and 3 months after 90% small bowel resection in piglets and one adult pig. A calcium-binding protein (MW congruent to 11.000) with calcium-dependent eletrophoretic mobility was partially purified from mucosal extract of proximal jejunum, mid-gut, and ileum. The concentration of calcium-binding protein and the calcium-binding activity of the intact animals were found highest in the proximal jejunal segment, lowest in the ileal segment. After resection in the four surviving animals out of nine, a significant increase in calcium-binding activity was observed in the proximal jejunum and in the distal ileal segment. The change in calcium-binding activity was much more marked in the ileum than the jejunum. These data demonstrate that pig intestinal mucosa possesses an adaptive capacity to increase the synthesis of calcium-binding protein after massive small bowel resection.
Assuntos
Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Intestino Delgado/fisiologia , Suínos/metabolismo , Adaptação Fisiológica , Animais , Íleo/fisiologia , Mucosa Intestinal/fisiologia , Intestino Delgado/cirurgia , Jejuno/fisiologia , Masculino , Ligação ProteicaRESUMO
The metabolism of 25-hydroxycholecalciferol (25-(OH)D3), plasma concentration of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) and the amount of calcium-binding protein (CaBP) in duodenal mucosa were determined in ovariectomized rats and were compared with data observed in normal age-matched cyclic rats. Sephadex LH-20 and high-pressure liquid chromatography were used for the study of the metabolism of 25-(OH)D3. The concentration of 1,25-(OH)2D3 in plasma and prolactin in serum were measured by radioimmunoassay. Calcium-binding protein in duodenal mucosa was determined immunologically using electroimmunodiffusion. The results showed that the lack of ovarian hormones and low prolactin levels observed in ovariectomized rats did not promote a significant change in the metabolism of 25-(OH)D3, in the levels of 1,25-(OH)2D3 in the circulation or in the amount of CaBP in duodenal mucosa. It is possible that the regulation of 25-(OH)D3 by sex hormones is restricted to the state of calcium stress such as during egg-laying in birds or pregnancy and lactation in mammals.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Castração , Duodeno/metabolismo , Mucosa Intestinal/metabolismo , Vitamina D/metabolismo , Animais , Peso Corporal , Dieta , Di-Hidroxicolecalciferóis/sangue , Feminino , Hidroxicolecalciferóis/metabolismo , Prolactina/sangue , RatosRESUMO
A high-sucrose (S) diet accentuates anorexia and stunts growth in uremic (U) rats, and an oral S load induces a greater hyperfructosemia in U rats than in control (C) rats. Four studies were performed to determine the roles of S feeding and an acute S load on liver carbohydrate (CHO) metabolism in U and C rats (eight to 10 rats per group). We also examined the plasma responses to either water or a S load. Levels of the main metabolites of glycolysis, gluconeogenesis, and glycogenesis were measured under basal conditions (7 hours' postmeal) in U and C rats fed either a cornstarch diet (study I) or S diet (study II) and at 30 and 60 minutes after an intragastric S load (studies III and IV) in s-fed U and C rats. The weight gain, food intake, and plasma creatinine and urea levels of the rats in the four studies were comparable. Weight gain and liver weight (g/100 g body weight) were lower in U than in C rats. In the plasma, baseline levels of lactate were decreased by uremia and S feeding and those of glucose (G) were increased by S feeding. The increases in plasma G and fructose (F) levels after a S load were greater in U rats than in C rats, whereas those of plasma lactate were comparable. In the liver under basal conditions, uremia markedly decreased levels of glycogen, F-1,6-diphosphate (F-1,6-diP), F-2,6-diP, 3-glycero-phosphate (3-glycero-P), dihydroxyacetone phosphate (DHAP), pyruvate, lactate, and adenosine triphosphate (ATP), and the phosphorylation state (ATP/adenosine diphosphate [ADP] x inorganic phosphorus [PI]), increased phosphoenolpyruvate (PEP), ADP, and Pi levels, but did not affect the cytosolic redox state (pyruvate/lactate). In addition to uremia, S feeding further decreased levels of glycogen, F-2,6-diP, 3-glycero-P, and ATP. After S loading, liver F levels increased more in U than in C rats, but glycogen and 3-glycero-P levels increased less in U than in C rats. Liver lactate and pyruvate levels increased more in U than in C rats, and the pyruvate/lactate and DHAP/3-glycero-P ratios were higher in U than in C rats after a S load. The ATP level and the phosphorylation state in U rats increased 30 minutes later in U than in C rats. Our findings indicate that uremia causes a depletion in liver glycogen, which is enhanced by S feeding and could be partially attributed to decreased glycogen synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Metabolismo dos Carboidratos , Glucose/metabolismo , Fígado/metabolismo , Sacarose/farmacologia , Uremia/metabolismo , Animais , Rim/metabolismo , Estado Nutricional , Ratos , Sacarose/administração & dosagem , Uremia/sangueRESUMO
Several experiments have shown that deterioration of renal parenchyma after reduction of functional mass is affected by the protein content of the diet. The respective role of proteins and that of other nutrients that vary with proteins were never clearly separated. Three groups of 9 uremic rats received diets differing exclusively in protein (casein) content, which was 8% (group 1), 16% (group 2), and 32% (group 3). Energy and minerals were maintained identical. Food intake was similar in groups 1 and 2 and was lower in group 3. Mortality rate remained closely related to protein intake. Of group 3 rats, 78% died within 10 weeks and 100% within 15 weeks. Of group 2 rats, 56% were dead at week 15, and 100% at week 30. Mortality occurred significantly later in group-1 rats fed the lowest protein diet. Histology of remnant kidneys showed severe glomerular and tubular damage, with no or little calcium deposits despite normal phosphorus diet and frequent hyperphosphatemia. These data suggest that protein intake, independent of any other nutrient, influences survival by accelerating the renal damage in rats with reduced kidney mass.
Assuntos
Injúria Renal Aguda/etiologia , Caseínas/efeitos adversos , Proteínas Alimentares/efeitos adversos , Glomerulonefrite/etiologia , Glomerulosclerose Segmentar e Focal/etiologia , Necrose Tubular Aguda/etiologia , Uremia/dietoterapia , Animais , Glomérulos Renais/patologia , Túbulos Renais/patologia , Masculino , Prognóstico , Ratos , Ratos Endogâmicos , Uremia/patologiaRESUMO
The effects of chronic metabolic acidosis (CMA) on zinc (Zn) bone content and urinary excretion were examined in the presence of normal or reduced renal function together with some aspects of calcium (Ca) metabolism. Four groups of rats were compared. All were fed a 30% protein and 9 mg Zn/100 g diet. Two were uremic (U): The first developed acidosis (UA), which was suppressed in the other (UNA) by NaHCO3 supplement. Two other groups had normal renal function: One was normal (CNA), and the other had NH4Cl in the drinking water and acidosis (CA). Femur total Zn and Ca content was markedly reduced by CMA and was not affected by uremia. Zn urinary excretion was increased by CMA and unaltered by uremia. Ca urinary excretion was markedly reduced in uremic rats, but was enhanced in both acidotic conditions. Urinary Ca and Zn showed a strong correlation in uremic and in control rats. Plasma parathormone and 1,25(OH)2D3 were unchanged by CMA. These data are in agreement with a direct primary effect of CMA on bone in releasing buffers. CMA induces bone resorption and a parallel decrease of mineral bone components, such as Ca and Zn, with little or no role of PTH, 1,25(OH)2D3 and of uremia itself.
Assuntos
Acidose/metabolismo , Reabsorção Óssea/metabolismo , Falência Renal Crônica/metabolismo , Zinco/metabolismo , Acidose/complicações , Acidose/urina , Animais , Reabsorção Óssea/etiologia , Cálcio/metabolismo , Cálcio/urina , Doença Crônica , Creatinina/sangue , Fêmur/anatomia & histologia , Fêmur/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/urina , Masculino , Hormônio Paratireóideo/sangue , Ratos , Ratos Endogâmicos , Ureia/sangue , Uremia/metabolismo , Uremia/urina , Zinco/urinaAssuntos
Proteínas de Ligação ao Cálcio/isolamento & purificação , Proteína G de Ligação ao Cálcio S100/isolamento & purificação , Pele/metabolismo , Animais , Cálcio/sangue , Eletroforese em Gel de Poliacrilamida , Imunodifusão , Imunoeletroforese , Masculino , Peso Molecular , Ratos , Proteína G de Ligação ao Cálcio S100/metabolismo , Pele/efeitos dos fármacos , Vitamina D/farmacologiaRESUMO
Several experimental studies have shown that the development of glomerular sclerosis during aging in rats is related to nutritional factors: it is impeded by overall food restriction, as well as by reduction of the protein, carbohydrate or sodium intake. It is enhanced by high protein or high sodium diets. In remnant kidneys, lesions develop that are similar to those in aging kidneys and that seem to be influenced by the same factors. Through several experiments, we have shown that the rapidity of the deterioration of renal function after subtotal nephrectomy is closely related to the protein intake and that the length of survival can be reduced by a high protein diet or increased by a low protein diet. The influence of protein intake remains clearly apparent when the intake of all other nutrients, particularly minerals, and of calories is strictly controlled. Low protein diets supplemented with essential amino acids resulting in increased appetite are of little benefit for survival, suggesting that the calorie intake or growth-related factors may be of significance. Prolonged survival observed with phosphorus (P) deficient diets compared to low or normal P diets is mainly due to decreased appetite. The optimal supply of protein, energy, sodium and other nutrients should be determined according, not only to nutritional status, but also to effects on the renal parenchyma.
Assuntos
Falência Renal Crônica/etiologia , Fenômenos Fisiológicos da Nutrição , Envelhecimento , Animais , Dieta Redutora , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Glomerulonefrite/imunologia , Camundongos , Nefrectomia , Fósforo/deficiência , Ratos , Sódio/administração & dosagemRESUMO
The renal functional reserve (RFR), the increase in glomerular filtration rate (GFR) induced by a protein load, seems to be diminished or even lost in renal failure. Our experimental study was undertaken to determine whether the RFR is lost beyond a given level of nephron reduction, using different protein loads. In the first two studies, RFRs were evaluated during an oral protein load consisting in a high-protein diet (30% casein) compared to a low-protein diet (7% casein). Each diet was given to SD rats (200 g) either for three weeks immediately after nephrectomy (Nx) or for four days one month after Nx. Nx was subtotal and consisted in removal of 65 to 85% of the mass of the renal parenchyma. The GFR evaluated by inulin clearance measurements increased considerably after a prolonged (+188%) or short-lived (+35%) oral protein load if less than 70% of the renal mass had been removed. Beyond this threshold of nephron amputation, the high-protein diet had no effect on the GFR, despite an increase in the residual renal mass (+200% in moderate and severe Nxs). In a third study, the GFR was measured one month after Nx and the effects of an infusion of amino acids (vamine) or of a placebo were compared, each rat serving as his own control. Extent of Nx was 0%, 50%, 65-70%, and 80%. Regardless of the extent of nephron reduction, the GFR increased under vamine, but interindividual variations in each group were marked (+5 to +70%).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Taxa de Filtração Glomerular/fisiologia , Néfrons/fisiologia , Aminoácidos/administração & dosagem , Aminoácidos/farmacologia , Animais , Proteínas Alimentares/farmacologia , Eletrólitos , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucose , Hipertrofia , Infusões Intravenosas , Falência Renal Crônica/fisiopatologia , Nefrectomia , Néfrons/efeitos dos fármacos , Soluções de Nutrição Parenteral , Placebos , Ratos , Soluções , Fatores de TempoRESUMO
The many published studies of experimental chronic renal failure (CRF) include a few findings which are similar to those reported in children with the naturally occurring disease. Experimental CRF has proved a useful model for investigating changes in eating behaviors: lack of appetite for sweet foods and selection of foods with high protein contents was comparable to behaviors exhibited by children. Optimal protein intake was found to be close to the minimum recommended intake for "optimal" growth (different from maximum growth in rats). Excessive protein intake had detrimental effects on renal function and growth with conventional dehydrated feeds, but water intake may have a greater impact than blood urea nitrogen and acidosis. A 50% reduction in protein intake with adequate amounts of essential amino acids ensured normal growth and slowed progression of renal lesions. Replacement of protein by mixtures of ketoanalogs was more likely to be responsible for growth failure; where similar growth rates were achieved, there was no evidence of a beneficial effect on renal lesions. Diets with high sucrose contents were poorly tolerated by CRF rats and were associated with fructose "intolerance" and reduced liver energy stores.
Assuntos
Proteínas Alimentares/administração & dosagem , Crescimento , Falência Renal Crônica/tratamento farmacológico , Aminoácidos Essenciais/administração & dosagem , Animais , Nitrogênio da Ureia Sanguínea , Carboidratos da Dieta/administração & dosagem , Modelos Animais de Doenças , Comportamento Alimentar , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Ratos , Equilíbrio HidroeletrolíticoRESUMO
The nutritional effects of low-protein diets are difficult to assess in humans. Normal and uraemic growing rats were therefore fed: a moderately low-protein (12%) reference diet (diet R), two 5% casein diets, one supplemented with essential amino acids (AA) (diet A) and the other with their keto acids (diet K), and a 7% casein diet isonitrogenous with diet K (diet L). Appetite and growth of both uraemic and control rats were identical on diets R and A and were reduced on diets K and L. Stunting was prominent in rats fed diet L and more severe than in those on diet K. Diet K induced marked anorexia in controls. This effect was smaller in uraemic rats, which were all anorectic, regardless of the diet. Plasma essential AA were similar in rats on diets R and A but low in control rats fed diets L and K. In particular, diet K did not improve the branched-chain AA levels although it produced better growth than diet L. Plasma and muscle threonine were surprisingly elevated in rats on the semi-synthetic diets A and K, despite identical or lower consumptions. Regardless of the diet, uraemia resulted in unchanged or increased plasma essential AA, despite reduced appetite and stunting. Uraemia caused a marked rise in some non-essential AA. Muscle essential AA, except for threonine, were essentially unaltered and did not correlate with growth or uraemia.
Assuntos
Aminoácidos Essenciais/metabolismo , Proteínas Alimentares/administração & dosagem , Músculos/metabolismo , Uremia/metabolismo , Aminoácidos Essenciais/administração & dosagem , Animais , Peso Corporal , Caseínas/administração & dosagem , Creatinina/sangue , Creatinina/urina , Ingestão de Alimentos , Cetoácidos/administração & dosagem , Masculino , Nefrectomia , Proteinúria/urina , Ratos , Ratos Endogâmicos/crescimento & desenvolvimentoRESUMO
To determine what levels of chronic metabolic acidosis affect growth in uremia, we compared two groups of uremic rats receiving a 30% protein diet. This diet induced acidosis in A rats (n = 52; pH: 6.9-7.35) which was prevented by the addition of NaHCO3 in the diet of B rats (n = 52; pH: 7.38-7.46). A rats were separated into five groups by increasing severity of acidosis and were matched with B rats of similar renal function. Comparison between A and B rats showed: (1) no difference in food intake; (2) a reduction of weight gain only for severe acidosis with pH around 7.20 or less; (3) a reduction of length gain which was observed for less severe acidosis than reduction of weight gain, but which did not exist for marginal acidosis (pH > 7.25).