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Mechanism of altered B-cell response induced by changes in dietary protein type in mice.

The effect of 20 g/100 g dietary lactalbumin (L) or casein (C) diets or a nonpurified (NP) diet on the immune responsiveness of C57Bl/6J, C3H/HeJ and BALB/cJ mice has been investigated by measuring the response to the T cell-independent antigen, TNP-Ficoll. To investigate the possible influence of dietary protein type on the supply of B lymphocytes, bone marrow lymphocyte production has been examined by a radioautographic assay of small lymphocyte renewal and an immunofluorescent stathmokinetic assay of pre-B cells and their proliferation. The humoral response of all mice fed the L diet was found to be higher than that of mice fed the C diet or nonpurified diet. A similar pattern of dietary protein effect in (CBA/N X DBA/2J) F1 mice carrying the xid defect was observed following challenge with sheep red blood cells (SRBC). An even greater enhancing effect of dietary L was noted in normal (DBA/2J X CBA/N) F1 mice after immunization with SRBC, but in contrast, the normal large-scale production of B lymphocytes in mouse bone marrow was independent of the type of dietary protein. Dietary protein type did not affect blood level of minerals and trace metals. The free plasma amino acid profile essentially conformed to the amino acid composition of the ingested protein, suggesting that the changes in plasma amino acid profile might be a crucial factor in diet-dependent enhancement or depression of the B-cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelin-induced increased aldosterone activity mediates augmented distal nephron acidification as a result of dietary protein.

The hypothesis that increased dietary protein augments distal nephron acidification through endothelin-mediated increased aldosterone activity was tested. Munich-Wistar rats were studied after 3 wk of diets with 50% high protein (HiPro) and 20% control (CON) casein-provided protein, the latter comparable to standard diet. HiPro versus CON rats had higher distal nephron H+ secretion by in vivo microperfusion as shown previously. Perfusion with inhibitors of Na+/H+ exchange (EIPA, 10(-5) M), H+-ATPase (bafilomycin, 10(-7) M), and H+-K+-ATPase (Sch 28080 [10(-5) M] and ouabain [10(-3) M]) support that higher Na+/H+ exchange and higher H+-ATPase but not higher H+-K+-ATPase activity mediated increased H+ secretion in HiPro rats. Oral bosentan, an endothelin A/B receptor antagonist, decreased distal nephron H+ secretion in HiPro rats as a result of reduced Na+/H+ exchange and H+-ATPase activity as shown previously by the authors' laboratory. HiPro versus CON rats had higher plasma aldosterone (60.9 +/- 5.9 versus 42.2 +/- 4.4 pg/ml; P < 0.024) and higher urine aldosterone excretion (21.9 +/- 3.9 versus 10.5 +/- 2.8 ng/d; P < 0.04) in the absence but not presence of bosentan, consistent with endothelin-mediated increased aldosterone secretion. HiPro rats that did versus did not ingest the aldosterone antagonist spironolactone had lower distal nephron H+ secretion (29.2 +/- 3.3 versus 42.1 +/- 3.8 pmol/mm per min; P < 0.05) as a result of lower H+-ATPase activity without differences in Na+/H+ exchange or H+-K+-ATPase activity. The data support that dietary protein provided as casein increases distal nephron acidification through endothelin-stimulated Na+/H+ exchange and endothelin-stimulated aldosterone secretion that increases H+-ATPase activity.

Aldosterone↗

Increased endothelin activity mediates augmented distal nephron acidification induced by dietary protein.

The hypothesis that increased dietary protein augments distal nephron acidification and does so through an endothelin (ET-1)-dependent mechanism was tested. Munich-Wistar rats that ate minimum electrolyte diets of 50% (HiPro) and 20% (CON) casein-provided protein, the latter comparable to standard diet, were compared. HiPro versus CON had higher distal nephron net HCO(3) reabsorption by in vivo microperfusion (37.8 +/- 3.2 versus 16.6 +/- 1.5 pmol/mm per min; P < 0.001) as a result of higher H(+) secretion (41.3 +/- 4.0 versus 23.0 +/- 2.1 pmol/mm per min; P < 0.002) and lower HCO(3) secretion (-3.5 +/- 0.4 versus -6.4 +/- 0.8 pmol/mm per min; P < 0.001). Perfusion with H(+) inhibitors support that increased H(+) secretion was mediated by augmented Na(+)/H(+) exchange and H(+)-ATPase activity without augmented H(+),K(+)-ATPase activity. HiPro versus CON had higher levels of urine ET-1 excretion, renal cortical ET-1 addition to microdialysate in vivo, and renal cortical ET-1 mRNA, consistent with increased renal ET-1 production. Oral bosentan, an ET A/B receptor antagonist, decreased distal nephron net HCO(3) reabsorption (22.4 +/- 1.9 versus 37.8 +/- 3.2 pmol/mm per min; P < 0.001) as a result of lower H(+) secretion (28.4 +/- 2.4 versus 41.3 +/- 4.0 pmol/mm per min; P < 0.016) and higher HCO(3) secretion (-6.0 +/- 0.7 versus -3.5 +/- 0.4 pmol/mm per min; P < 0.006). The H(+) inhibitors had no additional effect in HiPro ingesting bosentan, supporting that ET mediated the increased distal nephron Na(+)/H(+) exchange and H(+)-ATPase activity in HiPro. Increased dietary protein augments distal nephron acidification that is mediated through an ET-sensitive increase in Na(+)/H(+) exchange and H(+)-ATPase activity.

Animals↗

Effect of pH, dietary proteins and trypsin inhibitors on the hydrolytic rate of human granulocyte colony-stimulating factor (G-CSF) by rat digestive enzymes.

The effects of pH, dietary proteins and trypsin inhibitors on the hydrolytic rate of recombinant human granulocyte colony-stimulating factor (G-CSF) by digestive enzymes were studied by in vitro incubation experiments. The bile obtained by cannulation into the rat common bile duct and the eluates obtained by infusing distilled water into the gastrointestinal tract were used as sources of digestive enzymes. Some proteins including dietary proteins such as casein and ovalbumin, and two kinds of trypsin inhibitors, chicken egg white and soybean ones, were used to examine the protective action on the hydrolysis of G-CSF by digestive enzymes. With an experiment using the digestive enzyme fluids obtained after centrifugation of bile by ultra-filters with a molecular weight (Mr) cut off of 30000, 10000 and 5000, the proteolytic activity to G-CSF decreased as the cut off Mr decreased. The enzyme solution obtained with a membrane with a Mr cut off of 5000 still had an enzyme activity against G-CSF. The protease activity was mainly ascribed to the pancreatic fluid, but the hepatic bile still had an enzyme activity. The hydrolytic rate of G-CSF was dependent on the pH of the enzyme fluid, and the intestinal fluid. The hydrolytic rate of G-CSF was studied at pHs of 1.68, 4.01, 6.86 and 9.18. Especially, as the pH decreased to 1.68, the hydrolytic rate of G-CSF considerably decreased. Some proteins including dietary proteins also affected the hydrolytic rate of G-CSF. The strength of the inhibitory effect of the proteins is the following order; ovalbumin greater than casein greater than mucin greater than keratin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function.

Dietary protein restriction has been reported to delay the need for renal replacement therapy in clinical trials and meta-analyses. However, less clear is what effect dietary protein has on the rate of decline in renal function. We pooled the results of 13 randomized controlled trials (n = 1,919 patients) and found that dietary protein restriction reduced the rate of decline in estimated glomerular filtration rate by only 0.53 mL/min/yr (95% confidence interval [CI], 0.08 to 0.98 mL/min/yr). We also used weighted regression analysis to determine the reasons for the differences in the results of these 13 randomized trials along with 11 other nonrandomized controlled trials (n = 2,248 patients). The effect of dietary protein restriction (glomerular filtration rate decline in treatment minus control) was substantially less in randomized versus nonrandomized trials (regression coefficient, -5.2 mL/min/yr; 95% CI, -7.8 to -2.5 mL/min/yr; P < 0.05) and relatively greater among diabetic versus nondiabetic patients (5.4 mL/min/yr; 95% CI, 0.3 to 10.5 mL/min/yr; P < 0.05), while there was a trend toward a greater effect with each additional year of follow-up (2.1 mL/min/yr; 95% CI, -0.05 to 4.2 mL/min/yr; P = NS). However, the number of diabetic patients studied was small and the duration of follow-up was short in most trials. No other patient or study characteristics altered the effect of dietary protein restriction on the rate of decline in renal function. Thus, although dietary protein restriction retards the rate of renal function decline, the relatively weak magnitude of this effect suggests that better therapies are needed to slow the rate of renal disease progression.

Diabetic Nephropathies↗

Effects of dietary protein in patients with chronic renal transplant rejection.

Dietary protein restriction reduces proteinuria and slows the progression of renal failure in a variety of renal diseases in native kidneys. Such beneficial effects may be mediated by the multiple renal effects of dietary protein including those on glomerular capillary hemodynamics and the renin-angiotensin system. The role of dietary protein restriction in the management of chronic renal transplant rejection is, however, unclear. This study was therefore undertaken to examine the effects of dietary protein restriction in patients with chronic rejection. Fourteen patients with biopsy proven chronic rejection, who had been on a self-selected home diet of 1.0 +/- 0.1 g protein/kg/day, were randomly assigned, using a crossover design to two 11-day periods, one on a low protein diet (0.55 g/kg/day) and the other on a high protein diet (2 g/kg/day). The effect of these diets on renal hemodynamics, proteinuria, plasma renin activity, and nutritional status was examined. The low protein diet was associated with a significant improvement in glomerular permselectivity in all patients as evidenced by a significant fall in the fractional clearance of albumin and IgG and reduction in 24-hour urinary excretion of total protein, albumin and IgG without any change in blood pressure, glomerular filtration rate, or renal plasma flow. Compared to the proteinuria at the beginning of each diet, a high protein diet did not increase but a low protein diet significantly decreased the proteinuria. The low protein diet was also associated with a significant reduction in plasma renin activity, suggesting that part of the beneficial effect of protein restriction was related to the suppression of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Physiological and biochemical responses to dietary protein in the omnivore passerine Zonotrichia capensis (Emberizidae).

We studied the physiological, biochemical and morphological responses of the omnivore sparrow Zonotrichia capensis, a small opportunistic passerine from Central Chile acclimated to high- and low-protein diets. After 4 weeks of acclimation to 30% (high-protein group) or 7% (low-protein group) dietary casein, we collected urine and plasma for nitrogen waste production and osmometry analysis, and measured gross renal morphology. Plasma osmolality and hematocrit were not significantly affected by dietary treatment, but urine osmolality was higher in the high-protein group than in the low-protein group. Kidney and heart masses were higher in animals acclimated to the high-protein diet. Mean total nitrogen waste was significantly higher in the high-protein group, but the proportions of nitrogen excreted as uric acid, urea and ammonia were unaffected by diet. Our data suggest that the response of Z. capensis to an increase in dietary protein content is through greater amounts of total nitrogen excretion and hypertrophy of kidney structures, without any modification of the proportion of excretory compounds.

Ammonia↗

Effects of dietary protein content, addition of nonessential amino acids and dietary methionine to cysteine balance on responses to dietary sulphur-containing amino acids in broilers.

1. Two experiments were conducted with male broiler chicks from 2 to 5 weeks of age to determine the effect of dietary protein content and amino acid balance on the response to dietary sulphur-containing amino acids (SAA) in terms of performance and carcase quality. 2. In experiment 1, 5 graded amounts of a DL-methionine and L-cysteine (1:1 by weight) mixture were added to basal diets containing 197 or 233 g crude protein/kg. The diets containing 197 g protein/kg were fed with or without the further addition of 36 g crude protein/kg from nonessential amino acids. The amino acid balance of all diets was kept constant for all essential amino acids except the SAA. In experiment 2, 5 graded amounts of SAA from either a crystalline source (DL-methionine or a mixture of DL-methionine and L-cysteine) or from intact proteins were added to a diet containing 208 g protein/kg. 3. At each protein concentration there were significant responses to the SAA addition in weight gain, food conversion efficiency, and carcase quality. Non-linear exponential regression analyses were used to describe bird responses to SAA concentration. The broiler chick's requirement for SAA increased with increasing dietary protein concentrations ranging from 197 to 259 g protein/kg. 4. The utilisation of SAA differed also with differences in origin (crystalline or peptide-bound), and methionine:cysteine balances. Compared to DL-methionine, a 1:1 mixture of DL-methionine and L-cysteine was only 81% or 86% as effective in supporting growth or food conversion, respectively. SAA from added protein was even less effectively utilised. 5. The addition of nonessential amino acids tended to decrease food intake without affecting SAA utilisation. 6. Slaughter yield and breast meat yield were clearly increased while fat deposition was clearly decreased, by SAA addition. The response in breast meat yield suggested an important economic benefit for further meat processing. Nitrogen retention was significantly enhanced by SAA supplementation from crystalline sources, and this led to reductions of up to 30% in the amount of nitrogen excreted per kg weight gain.

Animal Feed↗

[Protein utilization of mixed feed rations in lactating pigs with reference to the essential amino acid content of the feed proteins. 3. Report. Correlation between the protein metabolism data and the amino acid content of the dietary protein].

Protein utilization data were established in N balance trials with lactating sows fed various dietary proteins. The data obtained were compared with the amino acid indices of the dietary proteins and regression equations were established for the relations existing between these data. Additionally, simple and multiple regressions were calculated for relationships between the levels of N balance and the levels of crude protein intake, digestible crude protein, lysine per kg of milk production or lysine and all the other essential amino acids per 10 g of milk N. A relation was found between the level of daily lysine intake and all the other essential amino acids and the level of productive N utilization.

Amino Acids, Essential↗

Dietary protein and atherogenesis.

Different dietary proteins determine different serum cholesterol levels if fed in a semisynthetic diet to some, but not all, animal species. In one species, the rabbit, this metabolic response is elicited without adding high sucrose or cholesterol supplements that have to be added to rat or pig diets in order to cause a similar response. Eleven out of 13 studies show that casein and soy protein do not induce different serum cholesterol levels in normal man. More important, protein-induced differences of serum cholesterol concentrations have not been reported when appropriate nutritional methodology has been applied. We conclude that no protein-induced hypercholesterolemia is observed in primates, particularly not in the human species. Dietary recommendations urging the general public to reduce consumption of animal protein because of a higher atherogenicity are not supported by the present data. The biochemical basis of the metabolic responses has been studied by many investigators, but no convincing unifying concept has yet been identified. The recent observation of higher serum thyroxine concentrations following soy protein consumption (and vegetable protein in general) when compared to casein shed new light on this problem. This endocrine response explains a wide array of metabolic features of soy-fed rodents: the lower hepatic VLDL secretion, the higher hepatic HMG-CoA reductase activity, the higher hepatic apo B, E receptor activity, the higher fecal bile acid excretion, and finally the lower serum cholesterol concentrations.

Animals↗

Dietary protein regimen prior to renal ischemia significantly affects the postischemic uremic response.

Recently we reported that maintaining rats on restricted dietary protein regimens prior to renal ischemia will significantly improve postischemic survival rates. This effect required a week or more of maintenance on a restricted protein diet prior to the renal insult and appeared to be independent of the postischemic dietary protein regimen. The present study was designed to evaluate the role of systemic toxicity in this protection. Adult male Sprague-Dawley rats were pair-fed by weight on restricted or high isocaloric protein diets for 8-10 days prior to 45 min of renal ischemia induced by renal pedicle clamping. When placed on a normal dietary protein regimen immediately following ischemia, the rats preconditioned to restricted dietary protein exhibited significantly less acidosis, less hyperkalemia, lower blood urea nitrogen values, and improved survival rates compared with rats preconditioned on a high dietary protein regimen. In order to separate the possible effects of prior dietary protein regimen on acute tubular necrosis suffered during renal ischemia from its effects on the uremic response, bilateral nephrectomies were performed on rats preconditioned for 14 days to low, normal, and high dietary protein regimens. Although all of the rats were placed on the same dietary protein regimen immediately following bilateral nephrectomy, those that had previously been on a lower dietary protein regimen exhibited a significantly reduced uremic response and lived longer. These findings indicate that dietary protein regimen prior to renal ischemia is a risk factor which can have a significant lingering effect on the severity of postischemic systemic toxicity.

Animals↗

Influence of dietary protein level, amino acid supplementation, and dietary energy levels on growing-finishing pig performance and carcass composition.

Two experiments were conducted to determine the effects of feeding reduced-CP, AA-supplemented diets at two ambient temperatures (Exp. 1) or three levels of dietary NE (Exp. 2) on pig performance and carcass composition. In Exp. 1, 240 mixed-sex pigs were used to test whether projected differences in heat increment associated with diet composition affect pig performance. There were 10 replications of each treatment with four pigs per pen. For the 28-d trial, average initial and final BW were 28.7 kg and 47.5 kg, respectively. Pigs were maintained in a thermoneutral (23 degrees C) or heat-stressed (33 degrees C) environment and fed a 16% CP diet, a 12% CP diet, or a 12% CP diet supplemented with crystalline Lys, Trp, and Thr (on an as-fed basis). Pigs gained at similar rates when fed the 16% CP diet or the 12% CP diet supplemented with Lys, Trp, and Thr (P > 0.10). Pigs fed the 12% CP, AA-supplemented diet had a gain:feed similar to pigs fed the 16% CP diet when housed in the 23 degrees C environment but had a lower gain:feed in the 33 degrees C environment (diet x temperature, P < 0.01). In Exp. 2, 702 gilts were allotted to six treatments with nine replicates per treatment. Average initial and final BW were 25.3 and 109.7 kg, respectively. Gilts were fed two levels of CP (high CP with minimal crystalline AA supplementation or low CP with supplementation of Lys, Trp, Thr, and Met) and three levels of NE (high, medium, or low) in a 2 x 3 factorial arrangement. A four-phase feeding program was used, with diets containing apparent digestible Lys levels of 0.96, 0.75, 0.60, and 0.48% switched at a pig BW of 41.0, 58.8, and 82.3 kg, respectively. Pigs fed the low-CP, AA-supplemented diets had rates of growth and feed intake similar to pigs fed the high-CP diets. Dietary NE interacted with CP level for gain:feed (P < 0.06). A decrease in dietary NE from the highest NE level decreased gain:feed in pigs fed the high-CP diet; however, gain:feed declined in pigs fed the low-CP, AA-supplemented diet only when dietary NE was decreased to the lowest level. There was a slight reduction in longissimus area in pigs fed the low-CP diets (P < 0.08), but other estimates of carcass muscle did not differ (P > 0.10). These data suggest that pigs fed low-CP, AA-supplemented diets have performance and carcass characteristics similar to pigs fed higher levels of CP and that alterations in dietary NE do not have a discernible effect on pig performance or carcass composition.

Amino Acids↗

The influence of dietary protein and carbohydrate on the principal oxidative biotransformations of estradiol in normal subjects.

Dietary protein, when substituted for carbohydrate or fat, can increase cytochrome P-450-dependent drug oxidation rates in humans. Endogenous estrogens, as well as drugs, are also metabolized by cytochrome P-450 and other enzymes in the hepatic endoplasmic reticulum. Therefore, it was of interest to determine whether variations in diet can alter the major metabolic pathways for estrogens, as assessed by radiometric methods. Eight normal men were fed a high protein diet (44% of calories as protein, and 35% as carbohydrate for 2 weeks), followed by a high carbohydrate diet (70% of calories as carbohydrate and 10% as protein) for an additional 2 weeks. The fat and total energy contents of the two diets were equal. The percent oxidation of [2-3H]estradiol, measured as 3H2O released, which is an in vivo measure of 2-hydroxylation of endogenous estrogen, was greater in all eight men during the high protein dietary period than during the high carbohydrate dietary period (44 +/- 3% and 33 +/- 3%, respectively, means +/- SE, P less than 0.005). In contrast, 16 alpha-hydroxylation of estrogen, as measured using [16 alpha-3H]estradiol, did not change significantly. Our findings demonstrate that dietary components can alter estradiol oxidation in humans and that the 2- and 16 alpha-hydroxylases for estrogen are under separate regulatory control. The influences of specific nutrients on estrogen metabolism may have potential significance for diseases in which these hormones may play a role in clinical expression.

Antipyrine↗

Dietary protein and cardiovascular risk.

The relations between dietary protein and cardiovascular risk were first considered through their impact on blood cholesterol. Half a century after the first reports of an hypocholesterolemic effect of plant proteins, this subject is still a mater of debate, notably because of the difficulty in distinguishing between an independent effect of proteins and that of phytochemicals present in proteins preparations. In addition, many questions still have to be answered as to how the proteins may affect cholesterol metabolism. This review also describes the recent advances in new areas of research that have recently gained attention. Dietary proteins may affect cardiovascular risk through their effect on homocysteine, glutathione and nitric oxide. Although most of the data now available are still inconclusive, incoming results on these topics may prove important to appraise the role that the amount and/or the nature of dietary proteins play in the onset of cardiovascular disease.

Blood Pressure↗

Kinetic constants of lactase of the small intestine of growing rats fully recovered from protein depletion, in relation to dietary protein and lactose concentration.

The effect of dietary composition on the kinetic constants of intestinal lactase was studied using rats depleted of protein by feeding protein-free diet from the weanling stage to 34 days of age and subsequently allowed to recover on diets containing 11.5 or 17% of protein calories (P%) and different levels of lactose (L%; 1, 15, 27 and 37%). After four days of refeeding, rats were decapitated and lactase activity was determined at different substrate concentrations by the method of Dahlqvist using homogenate of intestinal mucosa. Maximum velocity (Vmax) and Michaelis constant (Km) were calculated according to Eisenthal and Cornish-Bowden. At both levels of P%, Vmax tended to increase with the dietary lactose concentration. With diets containing 37% lactose, at P% 11 Vmax was about 60% of that at P% 17.0 Km tended to increase with L% in groups given the 17.0% protein calorie diets, but no difference was observed between groups fed at the lower level of protein. These results can be explained on the basis of interactions between dietary protein at different concentrations and inducer substrate which results in changes in isoenzyme patterns.

Animals↗

Effects of dietary protein restriction on the fractional rates of protein synthesis in perfused rat hindlimb.

The effects of dietary protein restriction on protein synthesis were investigated in perfused rat hindlimb. The fractional rate of protein synthesis was measured with [3H]phenylalanine in young adult (7-week-old) rats fed a low protein (5% casein) diet and a protein-free diet for 3 weeks. The low protein diet (LPD) allowed a moderate gain in body weight. The fractional rate of protein synthesis fell to 70% of the control value in LPD group and further fell to less than a half in the protein-free diet (PFD) group. Thus, the protein synthesis rate decreased as the dietary protein content was reduced. The fall of protein synthesis was mainly accompanied by the reduction of RNA activity (mg protein/mg RNA/day) rather than RNA concentration (RNA/protein). The rate of protein breakdown was calculated by subtracting growth rate from protein synthesis rate. The breakdown rate was decreased in LPD group and increased slightly in PFD group. From the low rates of protein synthesis and breakdown, it appears that dietary protein restriction, at least allowing a gain in body weight, makes the turnover rate slow down. The overall changes in protein synthesis obtained in the perfused hindlimb are consistent with the reported results in vivo.

Animals↗

Update: dietary protein and microbial protein contribution.

Factors influencing microbial protein synthesis in the rumen have been reviewed several times in recent years. Original publications in the past 3 yr have reported microbial and feed protein nitrogen contribution postruminally when feeding a variety of dietary proteins. Ammonia is a satisfactory source of nitrogen for growth of the majority of rumen species, but substitution of intact protein for urea (source of ammonia) usually stimulates microbial protein production. Protein sources such as soybean meal appear to possess properties (perhaps rate of degradability) that optimize microbial growth in vivo. Protein sources more undegradable than soybean meal, when fed as the major nitrogen source, sometimes reduce microbial growth. However, nondegradable proteins may compensate for less microbial protein by supplying intact dietary protein postruminally, so the amino acids potentially available may be equal to or greater than those available when readily degradable protein is fed. Soybean meal may reduce microbial growth in diets containing grass silage at protein exceeding 16.8%. Various measurements of microbial and intact dietary protein postruminally show that the contribution of each can be manipulated. Accuracy of quantitative predictions of postruminal contribution depends on several factors that require more research.

Animals↗

Effect of dietary protein on renin and angiotensinogen gene expression after renal ablation.

High dietary protein increases renin mRNA and likely contributes to the increased plasma renin activity (PRA) in the normal rat. In experimental renal ablation, dietary protein influences renal growth and injury. This study was undertaken to examine the effect of dietary protein on the renin-angiotensin system after reduction of renal mass. Male Sprague-Dawley rats were subjected to 1 1/3 nephrectomy (1 1/3 NX) and maintained for 7 days on a low-protein (6%) diet, at which time they were stratified according to serum creatinine to either continue on the low-protein diet or were switched to a high-protein (40%) diet. Two weeks after stratification renal renin mRNA was higher on the 40% compared with the 6% protein diet, angiotensinogen mRNA was lower in the high-protein group, and no change occurred in renal actin mRNA. The magnitude of this dietary protein-induced increase in renin mRNA with high-protein diet was greater in the 1 1/3 NX group compared with that observed in sham-operated rats (320 vs. 60%). PRA and tissue renin activity were also elevated on the high-protein diet after 1 1/3 NX. When three levels of dietary protein intake were examined after 1 1/3 NX, the high-protein (40%) diet was associated with increased renal renin mRNA compared with both the intermediate-protein (20%) and low-protein (6%) diets. In conclusion, a high-protein diet induced activation of the renin-angiotensin system. This activation may explain some of the detrimental effects of dietary protein on the course of chronic renal failure.

Angiotensinogen↗