Pharmacological evidence for involvement of the sympathetic nervous system in the increase in renin secretion produced by a low sodium diet in rats

To determine the degree to which increased sympathetic activity contributes to the increase in renin secretion produced by a low sodium diet, the beta-adrenergic blocking drug propranolol or saline vehicle was injected through indwelling jugular cannulas in rats fed a normal diet and rats fed a low sodium diet for 9 days. Plasma renin activity (PRA) and plasma renin concentration (PRC) were elevated by the low sodium diet, and these values were reduced 42-45% by propranolol, although they were still higher than in the normal diet controls. Plasma corticosterone was moderately elevated in cannulated rats on regular diet, compared to decapitated controls, but corticosterone did not differ between cannulated and decapitated rats on low salt diet; propranolol reduced plasma corticosterone. However, PRA and PRC were comparable in cannulated rats and decapitated controls on both the normal and the low sodium diets, and propranolol did not produce a significant reduction in PRA and PRC in rats fed the normal diet. This indicates that the effects of propranolol on PRA and PRC in the low sodium rats were not simply due to reduction of a stress-induced increase in renin secretion. The results indicate that increased sympathetic activity makes a substantial contribution to the increase in renin secretion produced by 9 days of dietary sodium restriction.     

Spermatogenesis in the prepuberty Wistar rat during protein-energy malnutrition followed by balanced refeeding

Protein-calorie malnutrition was induced by giving a 2% casein diet to a strain of post-weaning male Wistar rats from 26 to 56 days of age. They were then rehabilitated by a 15% casein diet till 86 days of age. Body and testis weights, diameter of seminiferous tubules and spermatogenetic score were compared to those of controls fed with the 15% casein diet. The unbalanced diet retarded growth by 30 days. Although rehabilitation of body and testis weights was incomplete, the spermatogenetic function equalled that of the controls at the end of the experiment. This aspect has been discussed.     

Adipose tissue development, growth, and food consumption in protein-malnourished rats.

Effects of protein malnutrition on adipose tissue development were studied in weanling male Sprague-Dawley rats fed isocaloric diets ad libitum containing either 22% (controls) or 8% (protein-malnourished rats) casein, and in rats pair-fed to the protein-malnourished rats with the 22% casein diet. After 32 days on the diet, protein-malnourished rats were 37% and pair-fed 67% the weight of the controls, while torso length was 37% and 73% of controls, respectively. Food consumption relative to body weight was greatest in protein-malnourished rats. Compared to control rats, the distal epididymal adipocyte number in the protein-malnourished rats was decreased in proportion to the decrease in body size and was more closely related to the protein intake than to the total calories consumed. After 32 days on diet, mean adipocyte number per 2 distal pads was 11.7 x 10(6) in controls and 4.3 x 10(6) in protein-malnourished rats. In pair-fed rats, cell number lagged behind controls at 4 and 11 days, but was normal at 32 days (11.4 x 10(6) cells). The distal epididymal pad adipocyte size and percent lipid were similar in all groups during the first 25 days of dietary treatment. Adipocyte size was increased significantly in controls at day 32 compared to the other two groups. At each time studied through day 25 on diet, epididymal pad weight was related to the adipose cell number rather than the cell size. It is concluded that severe restriction of dietary protein during the postweaning period of growth in rats results in decreased epididymal adipocyte proliferation and/or differentiation concomitant with generalized growth retardation, whereas isocaloric feeding of a diet of normal protein content is associated with only a transient delay in adipose tissue development.     

Lead induced testicular changes in protein malnourished rats

The effect of concurrent low protein (8% casein) diet and lead (Pb) exposure (1 mg/ml lead acetate in drinking water) on testes of weaned rats up to 90 days of age was investigated Histopathological examination of testes of lead treated rats maintained on low protein diet revealed marked pathological changes associated with greatly reduced succinic dehydrogenase, glucose-6-phosphate dehydrogenase and adenosine triphosphatase activity as revealed histochemically compared to lead treated rats fed normal protein diet. It was concluded that higher accumulation of lead may be responsible for altering the enzyme levels and inducing the testicular degeneration to a greater extent in low protein fed rats compared to their counterpart controls.     

Iron metabolism in Trypanosoma lewisi infection: serum iron and serum iron-binding capacity.

Progressive changes in iron levels, total iron binding capacity and hematocrit values in sera of rats infected with Trypanosoma lewisi are described. The host dietary group were: (1) complete or full complement; (2) iron-deficient, and (3) pair-fed or calorically restricted. The hematocrit values of T. lewisi-infected rats given the various diets were not significantly different from those of the controls. The decrease in total iron binding capacity (TIBC) of rats inoculated with T. lewisi and fed complete and pair-fed diets ranged up to 15% over uninfected controls. TIBC levels in rats fed an iron-deficient diet and inoculated with T. lewisi ranged up to 32% over uninfected controls. TIBC levels of deficient infected rats were significantly different from the controls from day 90 to infection to the end of the observation period. Serum iron (SI) values of non-infected rats regardless of dietary regimen showed significantly higher values than T. lewisi-infected animals between days 95 and 120. The average SI value, for this period, in adequately fed control rats was 204 +/- 7 microgram/100 ml as compared to 172 +/- 5 microgram/100 for trypanosome-infected rats. SI levels of rats on a pair-fed diet and infected with T. lewisi decreased to 17% over uninfected controls. SI levels of animals on an iron-deficient diet and infected with T. lewisi decreased up to 76% over uninfected controls.     

Prevention of adrenocortical hyperactivity by dietary casein in rats exposed to forced swimming stress

Adrenal weight, adrenal hydroxysteroid dehydrogenase activity and serum corticosterone level were significantly higher in rats fed with 5% casein diet after 7 days of swimming stress (45 min/day) as compared to their controls. All the parameters were similar to their control levels in rats receiving 20% casein diet and exposed to swimming stress. The results suggest that casein can play an important role in preventing adrenocortical hyperactivity in swimming stressed rats.     

Developmental physiology of cestodes. XIV. Roughage and carbohydrate content of host diet for optimal growth and development of Hymenolepis diminuta.

Diets of rats infected with Hymenolepis diminuta (CESTODA: Cyclophyllidea) were altered with respect to carbohydrate content and to roughage, and the effects on worm growth and development were studied. Compared to worms from rats fed a 56% glucose diet, those on a 56% starch diet were heavier at 10 and 15 days and had more immature proglottids at 5 days, mature prglottids at 10 days, and mature and gravid proglottids at 15 days postinfection. In addition, worms from rats fed the starch diet contained a higher carbohydrate concentration and a lower lipid concentration from those fed the glucose diet. Worms from rats fed diets with combinations of carbohydrates such as 51% starch-5% sucrose and 51% starch-5% lactose were not different from those fed the 56% starch diet. If rats were fed a pellet diet (Purina Laboratory Chow), the worms grew substantially larger than those from rats fed the 56% starch or combination diets. The differences could be overcome if a 6% roughage component were included in the 56% starch diet. Therefore, the starch-roughage diet here presented is recommended as the optimal defined diet for studies of the development of H. diminuta in the definitive host.     

Epididymal androgen binding protein in protein-calorie malnourished rats

Androgen binding protein (ABP) was measured at five-day intervals from 20 to 50 days of age in the epididymides of rats fed a low protein diet. The results were compared to findings made in age-matched controls fed a standard laboratory diet. ABP was consistently lower in the caputs of the malnourished rats throughout the entire study. Moreover, no significant changes were noted in caput ABP concentrations as these rats aged. In contrast, this protein was observed to increase during the course of the month-long experiment in those animals fed the standard laboratory diet. These findings indicate that dietary protein deficiency has a marked debilitative effect on Sertoli cell function.     

The rate of linear deposition of bone tissue in the bone spongiosum of lactating rats on a low calcium diet

In the epiphysis and metaphysis of lactating rats, submitted to a Ca++ depletion for 10 and 30 days and a Ca++ repletion diet for 10 days, the density of spongiosa framework and the bone tissue linear accretion rate were compared with those of control rats. The distal metaphyses of femora of the rats fed a calcium free diet for 10 and 30 days lose 50% and 90% of the trabecular framework respectively, while the epiphysis of the same bone lose only 45% and 56%. The linear accretion rate in these regions increases by 7.9 and 24.7% in the epiphysis and by 11.3% and 75.6% in the metaphysis of rats fed a calcium-free diet for 10 and 30 days respectively. Our data indicate that the bone tissue linear accretion rate changes not only between the corresponding regions of control and experimental rats but, in the latter, also in different regions of the same bone. Moreover, the higher the bone loss is, the higher bone accretion rate will be. The correlation between the bone tissue linear accretion rate and the bone loss indicates that the same local factor - probably mechanical - controls the activity and distribution of osteoblasts and osteoclasts.     

Prenatal and postnatal protein restriction in the rat: effect on some parameters related to brain development, and prospects for rehabilitation.

Abstract— From the third day of pregnancy rats were fed a diet containing either 7% casein (experimental) or 24% casein (control). During lactation the control dams were fed the 24% casein diet and the experimental dams a 12% casein diet. From 25 to 50 days of age the experimental and control progeny were fed diets containing 7 and 24% casein, respectively. Between 50 and 120 days both groups were fed a diet containing 24% crude protein. Several indications of brain maturation in two brain areas were examined at various stages of development. In addition to retardation of brain growth, protein restriction led to myelin of an immature composition at 25 and 50 days of age. The immature composition was indicated by a low plasmalogen content at 25 days and by a high phospholipid and low galactolipid and plasmalogen contents at 50 days of age. The activity of the myelin marker enzyme, 2′3′-cyclic nucleotide 3′-phosphohydrolase (CNP), was significantly lower in the brains (excluding the cerebella) of malnourished rats at 21, 30 and 50 days. At all ages except at 50 days the activity of CNP in the cerebellum was higher in protein-deprived animals than in controls. The activity of glutamic acid decarboxylase (GAD) in the brains (excluding the cerebella) of protein-deprived rats was significantly lower at 21, 25 and 30 days but not at 50 and 65 days of age. As indicated by brain/body ratios, myelin composition and GAD activity, nutritional rehabilitation led to almost complete recovery of brain maturity, but the activity of CNP remained lower in the experimental group after rehabilitation.     

Control of urea synthesis and ammonia utilization in protein deprivation and refeeding.

Rats were fed a standard diet (20% protein) or a protein-free diet for up to 65 days. After 20 days on the protein-free diet some rats were refed the standard diet. By the 20th day the rats fed the protein-free diet showed a blood ammonia level approximately 70% higher than controls and urea excretion decreased approximately 20-fold. At this time the liver acetylglutamate decreased to approximately one-fifth of the initial and control levels, returning to normal after 3 days of refeeding the standard diet, with a concomitant increase in urea excretion. The protein-deficient diet resulted in decreased activities of liver enzymes related to ammonia metabolism. All enzyme activities assayed returned to normal values rapidly upon refeeding the standard diet, except hepatic carbamylphosphate synthetase, glutamine synthetase, and glutaminase, which took approximately 1 month to return to control values. The findings presented here are consistent with the view that urea production is controlled, at least under certain conditions, by acetylglutamate, the physiological activator of carbamylphosphate synthetase.     

Cellular injury and carcinogenesis. The effect of a protein-free high-carbohydrate diet on the metabolism of dimethylnitrosamine in the rat

1. Rats fed on a protein-free high-carbohydrate diet for 7 days metabolized dimethylnitrosamine at only 55% the rate of rats fed on a commercial diet. 2. Dimethylnitrosamine was metabolized by liver slices from rats fed on the protein-free diet at less than half the rate attained by slices from rats fed on a commercial diet. But kidney slices from these rats metabolized dimethylnitrosamine at the same rate as kidney slices from rats on a commercial diet. 3. Methylation by dimethylnitrosamine (70mg/kg body wt.) of N-7 of guanine of the liver RNA and DNA of rats fed on a protein-free diet was only slightly higher than in rats fed on a normal diet given 27mg/kg body wt. In contrast, the methylation by dimethylnitrosamine of guanine in kidney nucleic acids of these rats was three times that in the rats fed on a normal diet. 4. In rats fed on a protein-free diet the incidence of kidney tumours produced by a single dose of dimethylnitrosamine is increased.     

Eicosanoid synthesis and ornithine decarboxylase activity in mammary tumors of rats fed varying levels and types of N-3 and/or N-6 fatty acids

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10 mg dose of 7,12-dimethylbenz(a) anthracene (DMBA). Three weeks later they were placed on diets containing either 20% corn oil (CO), 20% primrose oil (PO), 20% black currant seed oil (BCO), 20% borage oil (BO), 15% menhaden oil plus 5% corn oil (15% MO + 5% CO), 10% menhaden oil plus 10% corn oil (10% MO + 10% CO), 5% menhaden oil plus 15% corn oil (5% MO + 15% CO) or 10% menhaden oil plus 10% borage oil (10% MO + 10% BO). Incidences of mammary tumors at 16 weeks post-DMBA were 80% in rats fed the CO diet, 84% in rats fed PO diet, 67% in rats fed BCO diet, 88% in rats fed BO diet, 60% in rats fed 15% MO + 5% CO diet, 67% in rats fed 10% MO + 10% CO diet, 83% in rats fed 5% MO + 15% CO diet, and 92% in rats fed 10% MO + 10% BO diet. Tumor multiplicity was lowest in PO-fed rats and highest in BO-fed rats. The tumor burden per tumor-bearing rat was lowest in rats fed the 15% MO + 5% CO, and 10% MO + 10% CO, diets and highest in those fed 20% BCO diet. Although body weight at 16 weeks post DMBA was not significantly different among the dietary groups, food intake was significantly greater in rats fed a diet containing 20% BO, or 5% MO + 15% CO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Course of minimal oxygen consumption in the young rat during protein energy malnutrition followed by return to a balanced diet

Growth and resting oxygen consumption (VO2 minimal) were studied on two strains of six post-weaning male rats during 60 days. The first strain was fed with a balanced diet (15% casein) for 60 days, the second received a 2% casein diet for 30 days, and then the balanced diet for the remaining 30 days. The 2% casein diet completely stopped the body weight and VO2 minimal increases. When return to a balanced diet, these parameters show an evolution similar to that of controls of the same body weight. The VO2 minimal had the same kind of evolution as body weight and was well correlated with growth speed. The protein restriction involves a strong and temporary reduction of the VO2 minimal, which will correspond to a nutritional stress.     

Effect of dietary polyunsaturated fat and 7,12-dimethylbenz(a)-anthracene on rat splenic natural killer cells and prostaglandin E synthesis

Summary Dietary polyunsaturated fat has been shown to stimulate mammary tumorigenesis induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA). Studies were undertaken to investigate the effect of polyunsaturated fat and DMBA on splenic natural killer (NK) activity and prostaglandin E (PGE) synthesis. In a first experiment, splenic NK activity at 33, 55, 75, and 110 days of age was measured in Sprague-Dawley rats fed 0.5% low fat (LF), 5% normal fat (NF), or 20% high fat (HF) corn oil diets from 23 days of age. At 55 days of age, half of the rats from the 75 and 110 day age groups were given 5 mg DMBA. Ten days after the initiation of the diets splenic NK activity against YAC-1 lymphoma was decreased from 50% cytotoxicity in rats fed NF diet to 21% cytotoxicity in rats fed HF diet, but was not affected by LF feeding. No difference in NK activity was observed among the groups at the later time periods. DMBA had no effect on NK activity at 20 or 55 days after its administration. In a second experiment, where DMBA (15 mg/rat) was given to half of the rats at 50 days of age and NF or HF diets were started 3 days later, NK activity was 35% in rats fed NF diet and 21% in rats fed HF diet, 5 days after the diets were started. No difference in NK activity in rats fed either diet was observed at later time periods. DMBA decreased both NK activity and spleen cellularity transiently. In both experiments, PGE synthesis by spleen cells cultured for 18 h was not affected by dietary fat intake, but was slightly increased 3 days after DMBA administration. Results from these experiments suggest that the stimulation of DMBA-induced mammary tumorigenesis by polyunsaturated fat and by DMBA itself may possibly be mediated by a transient decrease in splenic NK cell activity.This work was supported by grants CA-35641, CA-33240, CA-13038 and Core Grant CA-24538 from the National Cancer Institute     

Learning is improved by a soybean oil diet in rats

A semi-synthetic diet containing 20% polyunsaturated fat (soybean) oil was fed to young male hooded rats for 21 days. These animals exhibited improved performance on an environmentally-cued testing paradigm which is thought to reflect cognitive learning skills (i.e., Place Navigation Water Task). Other rats fed the same base diet but containing 20% saturated fat (lard) showed no such improvement compared to chow-fed (4.5% mixed fat) controls. The animals fed soybean oil also exhibited a transient resistance to extinguish this learning. This improved learning could not be explained by changes in general motor activity, basal body temperature, energy consumption, body weight, or in the brain activity of choline acetyltransferase, the marker enzyme for cholinergic neurons. These findings constitute the first evidence that short-term variations in the quality of dietary fat can enhance mammalian learning.     

Effect of short-term exercise training on muscle glycogen in resting conditions in rats fed a high fat diet.

It has been reported that exercise training increases muscle glycogen storage in rats fed a high carbohydrate (CHO) diet in resting conditions. The purpose of this study was to examine whether a 3-week swimming training programme would increase muscle glycogen stores in rats fed a high-fat (FAT) diet in resting conditions. Rats were fed either the FAT or CHO diet for 7 days ad libitum, and then were fed regularly twice a day (between 0800 and 0830 hours and 1800 and 1830 hours) for 32 days. During this period of regular feeding, half of the rats in both dietary groups had swimming training for 3 weeks and the other half were sedentary. The rats were not exercised for 48 h before sacrifice. All rats were killed 2 h after their final meal (2030 hours). The glycogen contents in red gastrocnemius muscle, heart and liver were significantly higher in sedentary rats fed the CHO diet than in those fed the FAT diet. Exercise training clearly increased glycogen content in soleus, red gastrocnemius and heart muscle in rats fed the CHO diet. In rats fed the FAT diet, however, training did not increase glycogen content in these muscles or the heart. Exercise training resulted in an 87% increase of total glycogen synthase activity in the gastrocnemius muscle of rats fed the CHO diet. However, this was not observed in rats fed the FAT diet. The total glycogen phosphorylase activity in the gastrocnemius muscle of the rats of both dietary groups was increased approximately twofold by training.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxic effects of 2-methyl-4-dimethylaminoazobenzene in normal and partially hepatectomized rats

In order to obtain a more precise definition of the conditions under which 2-methyl-4-dimethylaminoazobenzene (2-Me-DAB) and liver cell proliferation play a role in the initiation of hepatocarcinogenesis, the toxicity of 2-Me-DAB for normal and partially hepatectomized rats was investigated. Continuous feeding of a basal low protein, low riboflavin diet supplemented with 2-Me-DAB was found to be highly toxic for male albino rats. All animals fed on such a diet died before 200 days. Sham operation and partial hepatectomy (PH) at 30 days of 2-Me-DAB feeding reduced the median survival time from 122 days to 107 and 94 days, respectively. Transfer to the basal diet after 30 days of 2-Me-DAB feeding and PH prolonged the median survival time to 216 days while 97% of the rats returned to the normal complete diet after the same treatments survived for more than 300 days. 2-Me-DAB was not necrogenic and there was no evidence of reparative proliferation or hepatic tumor formation in any group. Feeding rats with the 2-Me-DAB containing diet for 1 month delayed and strongly inhibited the mitotic response of the liver to the stimulus of partial hepatectomy. This is the result of a blockage of the cells in G1 as revealed by the fact that only 1% of the hepatocytes became labeled when 2-Me-DAB fed animals were injected with tritiated thymidine prior to sacrifice at 24 h post-hepatectomy, as compared to 40% in rats fed the normal or the control basal diet. This inhibitory effect of 2-Me-DAB is reversible however since rats returned to the normal diet for 1 or 2 months after 2-Me-DAB feeding showed percentages of mitoses and labeling indices comparable to those of control animals following PH. The number of abnormal mitoses was high (13%) in regenerating livers of rats fed 2-Me-DAB and the lesions responsible for this effect are apparently not repaired since 2-Me-DAB fed rats partially hepatectomized after being transferred to the normal diet for 1 or 2 months showed the same number of mitotic irregularities. The present results suggest that assays with 2-Me-DAB as 'pure initiator' or agent of selective toxicity should be pursued in attempts to improve existing experimental models of hepatocarcinogenesis.     

Exaggerated response to mild stress in rats fed high-fat diet

It has been suggested that high-fat (HF) diet exaggerates the stress-induced release of glucocorticoids due to activation of the hypothalamic-pituitary-adrenal (HPA) axis. In an initial experiment, in which rats were fed HF diet for 4 days, we found that HF-fed controls stopped gaining weight, indicating that they were hyperresponsive to the mild stress of tail bleeding but responded the same as low-fat (LF)-fed rats to the more severe stress of restraint. A second experiment confirmed these results when rats fed a HF diet for 4 days showed an exaggerated corticosterone release in response to an intraperitoneal injection of saline and movement to a novel cage, compared with LF-fed rats. Experiment 3 tested the same parameters as experiment 2 but interchanged the diets. This allowed us to differentiate between the effects of the dietary fat and the novelty of the diet. Additionally, this experiment determined whether hyperresponsiveness to mild stress in HF-fed rats was sustained during a prolonged exposure to diet. The results confirmed that a HF diet, not novelty, exaggerated the endocrine stress response after 9 days on the diet but that the effect was no longer present after 23 days on the diet. The hyperresponsiveness of the HPA axis in HF-fed rats is similar to that observed in animals that have been exposed to a significant chronic or acute stress, suggesting that the HF diet may initially be perceived as a stressor.     

Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet

We previously reported an exaggerated endocrine and weight loss response to stress in rats fed a high-fat (HF) diet for 5 days. Others report blunted stress-induced anxiety in rats made obese on a HF diet. Experiments described here tested whether sensitivity to stress-related peptides was changed in obese and nonobese HF-fed rats. Third ventricle infusion of corticotropin-releasing factor (CRF) in rats made obese on HF diet (40% kcal fat) produced an exaggerated hypophagia, which is thought to be mediated by CRF(2) receptors. Obese rats responded to a lower dose of CRF for a longer time than rats fed a low-fat (LF) diet (12% kcal fat). CRF-induced release of corticosterone, which is thought to be mediated by CRF(1) receptors, was not exaggerated in obese HF-fed rats. In contrast, rats fed HF diet for 5 days showed the same food intake and corticosterone response to CRF as LF-fed rats. CRF mRNA expression in the paraventricular nucleus of the hypothalamus was stimulated by mild stress (ip saline injection and placement in a novel cage) in LF-fed rats but not in rats fed HF diet for 5 days because of a nonsignificant increase in expression in nonstressed HF-fed rats. In addition, nonstressed levels of urocortin (UCN) I mRNA expression in the Edinger-Westphal nucleus were significantly inhibited in HF-fed rats. These data suggest that rats that have become obese on a HF diet show a change in responsiveness to stress peptides, whereas the increased stress response in nonobese HF-fed rats may be associated with changes in basal CRF and UCN I mRNA expression.