Chow Pellets Research Articles

Angiotensin II mediates drinking elicited by eating in the rat

Captopril (CA) was used to block synthesis of endogenous angiotensin II (ANG II) in periphery and/or brain of adult male Sprague-Dawley rats in tests for drinking elicited by eating pelleted chow. Blockade of ANG II-converting enzyme (ACE) in periphery alone (using 0.5 mg/kg CA) increased drinking elicited by eating, whereas simultaneous blockade of ACE in periphery and brain (using subcutaneous 100 mg/kg CA or subcutaneous 0.5 mg/kg plus third ventricular 25 micrograms CA) decreased such drinking. The inhibitory effect of 100 mg/kg CA on water-to-food ratio was prevented by a dipsogenically subthreshold subcutaneous dose (5 micrograms/kg) of ANG II. Blockade of ACE in brain alone (third ventricular 25 micrograms CA) had no effect on food-related drinking. Pharmacological antagonism of ANG II (100 mg/kg CA) together with antagonism of histamine H1 and H2 receptors (using intraperitoneal dexbrompheniramine and cimetidine) were not additive in their inhibitory effects on drinking elicited by eating. Blockade of ACE (100 mg/kg CA) inhibited drinking elicited by subcutaneous histamine, but blockade of histamine receptors failed to inhibit drinking elicited by subcutaneous ANG II. These results support a role for endogenous ANG II under what appear to be physiological conditions for drinking behavior, i.e., when drinking is elicited by eating, and they suggest the working hypothesis of ANG II mediation of a histaminergic mechanism for food-related drinking in the rat.

High fat/sucrose feeding attenuates the hypertension of spontaneously hypertensive rats

To assess the caloric and cardiovascular effects of dietary obesity on an important animal model of hypertension research, 60-day-old male spontaneously hypertensive (SHR) rats were fed either Agway pelleted chow (Pellet), a diet enriched in fat and sucrose (HF/M), or alternated (Cycled) between 2-week periods of HF/M diet and Agway pelleted chow. After 14 weeks, HF/M feeding elevated the body weight of SHR rats by 15% over the body weight of pellet-fed control rats. This relative obesity was accompanied by heavier white (retroperitoneal) and brown (interscapular) fat pads, heavier heart weights, and tachycardia. Paradoxically, the systolic bood pressure levels of SHR rats fed the HF/M diet were reduced. Ruled out as an explanation for the blood pressure reduction was the relative polyunsaturated to saturated fat (P/S) rati of the diet. The hypertension of SHR rats may be due in part to the effects of an underlying metabolic problem that is counteracted by the effects of HF/M feeding; HF/M feeding not only elevated body weight but also reversed the hypoinsulinemia found in pellet-fed SHR rats. The Cycled group evidenced large up-and-down swings in caloric intake that coincided with HF/M and Pellet feeding; this produced modest staircase-like changes in body weight gain. Similar to the HF/M group, the systolic blood pressure level of the Cycled group was also reduced in comparison to the blood pressure level of the Pellet group. However, the Cycled group was found to be more responsive to the pressor effects of intravenous phenylephrine, an alpha-adrenergic agonist. This suggests that weight cycling superimposed on dietary obesity increased the sympathetic responsiveness of SHR rats perhaps making them more vulnerable to conditions that influence blood pressure level.

Dietary obesity and weight cycling: effects on blood pressure and heart rate in rats.

The overconsumption of rich and palatable foods and "yo-yo" dieting are feeding patterns involved in obesity and possibly hypertension in humans. We therefore examined the effects of diet-induced obesity and weight cycling on the blood pressure and heart rate levels of 60-day-old male normotensive Sprague-Dawley (S-D) and spontaneously hypertensive (SHR) rats. Six months on a high-fat and high-sucrose diet (HF/M) produced a greater obesity in S-D rats than in SHR rats. The caloric intakes of S-D rats fed the HF/M diet were greater than the caloric intakes of pellet-fed controls, whereas those of SHR rats were similar. The obesity of both strains was associated with hyperinsulinemia, heavier white (retroperitoneal) and brown (interscapular) fat pads, heavier heart weights, and tachycardia. Despite these changes, diet-induced obesity failed to increase systolic blood pressure obtained under light ether anesthesia or mean arterial pressure in the conscious state. Paradoxically, the blood pressures of SHR rats fed HF/M diet were reduced perhaps as a result of the high polyunsaturated fat component of the diet. A second S-D dietary obese group was alternated between 2-wk periods of unrestricted HF/M diet and 50% restricted pellet chow. Although their body weights were similar to pellet-fed controls, three cycles of weight loss and weight regain resulted in the consumption of increased dietary fat, increased food efficiency, heavier fat pads, and hyperinsulinemia. Heart rate and to some extent blood pressure fluctuated with diet, being elevated during HF/M feeding and reduced during restricted pellet feeding. Although weight cycling intensified the physiological responses to food ingestion, we found that weight cycling in dietary obese S-D rats did not elevate blood pressure levels.

Effects of naltrexone on food preference and concurrent behavioral responses in food-deprived rats

Naltrexone (0.05–5.0 mg/kg, SC) was administered to food-deprived rats prior to a 15-min food-preference test. Total food intake and feeding duration was reduced following administration of the opiate antagonist. However, while naltrexone reduced the consumption of the initially-preferred chocolate-coated cookies, the ingestion of the nonpreferred standard laboratory chow pellets was significantly enhanced. These data cannot be explained in terms of a general anorexic effect and nonspecific suppression of feeding responses. Instead, they indicate that naltrexone reduced preference for the highly palatable cookies, so that a feeding response to the chow pellets emerged. Under the conditions of test-familiarity, naltrexone did not reduce grooming, locomotion or rearing duration. An increase in locomotion may have been secondary to the reduction in feeding. The results agree with previous data from animal and human studies in suggesting that endogenous opioid peptide activity is involved in the palatability of preferred foods.

Effect of Dietary Consistency and Incisor Trimming on the Morphology of the Craniofacial Complex in the Rat (<i>Rattus norvegicus</i>)

The purpose of this investigation was to examine histological changes in nasal septal cartilage due to alteration of dietary consistency and loss of incisor function. Sixteen female, weanling Sprague-Dawley rats (Rattus norvegicus), were subjected to one of the following feeding treatments: control rats (n = 7) received a standard pelleted chow; experimental rats (n = 9) received meal sufficient in calories and nutrients to sustain increases in body weight. The maxillary incisors of experimental rats were trimmed to the level of the gingiva on alternate days to minimize anterior occlusal loading associated with nonfeeding behaviors. Rats were killed at 13 weeks, the nasal septa prepared for histology and the dimensions of septal cartilage and mucoperichondrium were measured. Quantitative and qualitative comparisons between control and experimental rats revealed a lack of significant differences in size, shape and thickness of septal cartilage and mucoperichondrium. The results of this study provide support for the concept that postnatal growth of primary cranial cartilages is largely independent of extrinsic biomechanical forces.

The effect of liver denervation on the consumption of various diets by rats

Liver afferents have been proposed to influence food intake control, however, previous studies have shown that chow (pellet) intake is apparently not altered in total liver denervated rats. The present study explored whether total liver denervation could alter the rats' intake of various diets other than chow pellets. Total liver denervations were verified using staining histological and monoamine histofluorescence techniques. The denervated and sham operated rats were given short-term (4–6 days) exposure to four diets: (diet 1, chow plus a 32% w/v sucrose-water solution; diet 2, 1:1 mixture of powdered chow and granular glucose; diet 3, 33% w/w Crisco and powdered chow mixture and diet 4, a 5% w/v glucose-water solution plus chow. Body weight gains were not affected-by either surgery or diet exposure. Daily consumptions of the diets were similar in both groups, nevertheless, there was a trend for the denervated rats to consume slightly more of a high fat diet, which lends support for one hypothesized liver satiety mechanism. Also, the denervated rats consumed less (an average 5 kcal/day) of the 5% glucose solution (one hypothesis tested would predict an increase consumption of glucose by the denervated rats). Thus the liver may play a role, albeit small, through several ill defined mechanism(s) in the regulation of feeding.

Effects of chronic amitriptyline and desipramine on food intake and body weight in rats

Long-term treatment with tricyclic antidepressant drugs (TCAs) can induce excessive body weight gain in a significant proportion of patients. Such weight gains, which appear to be largely independent of clinical improvement, are in many cases severe enough to interfere with continuation of treatment. In efforts to model this effect in experimental animals, seven experiments were performed in which two commonly used TCAs, amitriptyline and desipramine, were administered chronically to rats. Despite manipulations of drug dosages (2.5 mg−17 mg/kg), route of administration (intraperitoneal, subcutaneous, oral; daily injections vs. continuous release from osmotic pumps), diet composition and palatability (regular Purina Chow pellets or powder with or without added high fat and high carbohydrate sources; high vs. low protein diets) and animal sex and housing conditions (single vs. group housing), chronic TCA treatment was never observed to increase daily food intake or rates of body weight gain. Desipramine treatment invariably caused decreased food intake and weight loss. Amitriptyline treatment either caused no change in food intake and body weight or slightly reduced levels in comparison to vehicle-treated controls. However, both amitriptyline- and desipramine-treated rats showed a potentiation of acute caloric intake after a single systemic injection of the glucoprivic agent 2-deoxy-D-glucose. These results are considered against the background of human clinical observations. Possible reasons for the differences between human and animal data are discussed.

Effects of Nitrendipine on the Course of Experimental Immunologic Glomerulonephritis

To test whether calcium entry blockers (CEB) affect the course of progressive renal disease, we examined a standardized model of antiglomerular basement membrane glomerulonephritis (GN) in rats with and without oral administration of the CEB, nitrendipine (Nit). Nit was given in chow pellets at a daily dose of approximately 20 mg. Nephritic control rats received standard chow (Co). A time-course study over 4 weeks revealed the following; mean systolic blood pressure in GN/Nit rats remained below 115 mm Hg throughout, while GN/Co rats developed mild hypertension with peak values of 135 +/- 8 at 4 weeks (p less than 0.05). Urinary albumin excretion before induction of GN was 1.2 +/- 0.4 mg/24 h; at weeks 1 and 4, GN/Co had 249 +/- 34 and 306 +/- 50 mg/24 h, respectively. GN/Nit had less albuminuria, with 107 +/- 25 and 172 +/- 21 mg/24 h, respectively (p less than 0.05). Clearance experiments in anesthetized rats at 4 weeks revealed significantly better preservation of renal function in GN/Nit vs. GN/Co rats: (renal vascular resistance: 90.2 +/- 24 vs. 402.2 +/- 160 mm Hg/ml/min; clearance of para-aminohippurate: 1.388 +/- 0.151 vs. 0.598 +/- 0.368 ml/min/100 g; clearance of inulin: 0.570 +/- 0.123 vs. 0.141 +/- 0.077 ml/min/100 g; urinary sodium excretion: 1.417 +/- 0.554 vs. 0.188 +/- 0.081 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Feeding rats diets containing cheno- or ursodeoxycholic acid or cholestyramine modifies intestinal uptake of glucose and lipids.

We wished to test the hypothesis that variations in the luminal content of bile acid produced by feeding chenodeoxycholic acid (CDC), ursodeoxycholic acid (UDC) or cholestyramine (C) alter intestinal transport properties and morphology. Rats were fed standard chow pellets containing 0.5% CDC, 0.5% UDC or 2% C for a period of 2 weeks, and the in vitro uptake of glucose, cholesterol, bile acids and a homologous series of fatty acids was assessed. The food consumption was similar in animals fed chow, CDC, UDC and C, yet rats fed CDC or UDC gained less weight, and the weight of the jejunal and ileal mucosa was lower in animals fed CDC or C than in those fed chow or UDC. Ileal but not jejunal uptake of glucose was reduced in animals fed UDC, CDC or C. The active ileal uptake of bile acids was enhanced by UDC, CDC or C, whereas the jejunal passive permeability to bile acids was reduced by feeding C. Feeding C inhibited the jejunal and ileal uptake of cholesterol; C, UDC and CDC had a variable effect on the intestinal uptake of the fatty acids 10:0-18:0. The jejunal mucosal surface area was lower in groups fed CDC or UDC as compared with rats fed chow or C, and the ileal mucosal surface area was lower in rats fed CDC. However, the altered intestinal transport could not be explained by the altered morphology. Thus, (1) chronic variations in the intestinal luminal content of bile acids produced by the feeding of CDC, UDC or C resulted in alterations in the active and passive transport properties of the intestine, and (2) these changes differed between the jejunum and the ileum and were not explained simply by alterations in the animals' food intake or mucosal morphology. These studies suggest that chronic variations in the bile acids in the intestinal lumen may be one of the factors independently influencing the transport properties and mucosal surface area of the intestine. The long-term effect of changes in luminal bile acid content on intestinal function in man remains to be established.

Chemoprevention of colorectal neoplasms. Ascorbic acid and beta-carotene.

The organospecific, 1,2-dimethylhydrazine-induced rat tumor model was used to test tumor formation in groups of animals receiving regular chow, powdered chow with 7%/wt ascorbic acid supplement, pelleted chow with 1%/wt beta-carotene supplement, and pelleted chow with placebo beadlets. Following a 16-week induction period, animals were killed and tumor formation was recorded. Tumor formation in the ascorbic acid supplement group was found to be significantly less than the control group. The beta-carotene group showed no difference in tumor formation compared with the placebo-beadlet control group. Tumor incidence was generally the same between the two control groups, and the ascorbic acid group had significantly fewer tumors than the beta-carotene group. In sum, ascorbic acid supplements in high doses significantly decreased tumor formation, whereas beta-carotene supplements in moderately high doses had no effect on tumor formation in this model.

Intake of a liquid diet after 2-deoxy-D-glucose injections in rats

The effects of a liquid diet after 2-deoxy-D-glucose (2DG) were examined following water deprivation, after food deprivation, and at longer post-injection intervals when animals reportedly are hypophagic as a function of drug treatment. Water deprived rats were unable to increase their post-drug feeding when ingesting the liquid diet; and in food deprived subjects, intake patterns of liquid diet and of lab chow pellets were essentially identical after 2DG. The tendency of a 750 mg/kg dosage to produce a longer-term hypophagic reaction was more evident in animals given pellets instead of the liquid diet. While previous studies have found the liquid diet to promote 2DG-induced feeding in lesioned subjects, the present data demonstrate that such facilitation effects do not invariably occur during post-drug conditions in which animals are inhibited in their intake.

Glucagon satiety: Diurnal variation after hepatic branch vagotomy or intraportal alloxan

Hepatic vagotomized and hepatic portal alloxan-injected rats and their controls were tested for glucagon satiety at three time points during the circadian photoperiod: 6 hr into the light cycle with no food deprivation using a palatable liquid food; at the onset of the dark cycle after 6 hr food deprivation using pelleted rat chow; and 3 hr into the dark cycle after 9 hr food deprivation using pelleted chow. Glucagon failed to suppress intake in hepatic vagotomized and alloxan-treated rats when tests were conducted during the light cycle or at the onset of the dark cycle. In contrast, in tests conducted 3 hr into the dark cycle, glucagon suppressed food intake significantly in both hepatic vagotomized and alloxan-treated rats. Glucagon suppressed food intake significantly in controls in all tests. These results indicate that the hepatic vagus is not the sole mediator or glucagon satiety. Moreover, the fact that alloxan-treated rats and hepatic vagotomized rats responded in a similar manner to glucagon at all testing times suggests that hepatic portal alloxan treatment damages hepatic vagal fibers.

Inhibition of the development of radiation-induced leukemia in mice by reduction of food intake.

We have reported previously that the incidence of tumors induced in Sprague-Dawley rats by total-body gamma-ray irradiation can be considerably reduced by restriction of food intake [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598]. In experiments reported here we investigated the influence of reduced food intake on the development of radiation-induced leukemia in C3H(f) mice. The incidence of spontaneous leukemia in mice of this strain does not exceed 0.5%, but it can be considerably increased by total-body x-irradiation. In our study, two groups of C3H(f) mice were submitted to fractionated total-body gamma-irradiation (150 rads, five times at weekly intervals; 1 rad = 0.01 gray). The first group received a full ad lib diet (4.5-5.4 g of Purina Rodent Lab Chow pellets per day, each). In this group 31 out of 58 females (53.4%) and 24 out of 50 males (48%) developed leukemia at an average age of 8 months. In the second group, consisting of sisters and brothers of the first group, and submitted to the same gamma-irradiation but receiving a restricted diet (2 g of Purina Lab Chow pellets each, followed by 3 g on alternate days), only 2 out of 55 females (3.6%), and 1 out of 36 males (2.8%), developed leukemia at an average age of 9 and 12 months, respectively. Leukemia in both groups was predominantly of the lymphatic or lymphoblastic form, the leukemic cells infiltrating most organs, particularly the thymus, mesenteric and peripheral lymph nodes, spleen, liver, kidneys, and bone marrow; in most instances the peripheral blood was also leukemic.

Noradrenergic innervation of the paraventricular nucleus: Specific role in control of carbohydrate ingestion

Acute injections of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN) have been shown to elicit eating in satiated rats. The present report examines the effects of acute and chronic PVN infusion of NE on intake of various liquid and mixed solid diets and on selection of the pure macronutrients, carbohydrate, protein, and fat. The results demonstrate that noradrenergic stimulation of the PVN (40 nmoles of NE) reliably enhances ingestion of pure sucrose diets (liquid and solid) and also of sweet and non-sweet milk solutions. Saccharin intake, in contrast, is unaffected. In preference tests, rats injected with NE show a greater increase in consumption of sucrose cubes compared with lab chow pellets, but exhibit an equivalent preference for sweet and non-sweet carbohydrate-rich diets. Tests with the three pure macronutrients similtaneously available reveal, after NE injection, a strong and selective increase in consumption of carbohydrate, with little or no change in intake of fat and, in some cases, a suppression of protein intake. This clear preference for carbohydrate can be seen with chronic NE infusion (5 nmoles every 30 min over a 14-day period), as well as after acute NE injection (40 nmoles), and also with long-term (24-hr) as well as short-term (1-hr) food intake measurements. This and other evidence suggests that the PVN noradrenergic system may play a specific and unique role in the control of carbohydrate ingestion.

Periodic water availability is not a potent zeitgeber for entrainment of circadian locomotor rhythms in rats

Entrainment of tilt-cage measured circadian activity rhythms to a 2 hr daily period of water availability was assessed in rats fed either an oil-chow mash, which rats readily consume in the absence of water, or dry pellet chow, which rats less readily consume in the absence of water. Four of 6 pellet fed rats but only 2 of 14 mash fed rats exhibited entrainment to water access. Periodic water availability, unlike periodic food availability, thus does not appear to be a potent zeitgeber for circadian activity rhythms in the rat. The entrainment that does occur in some rats may result from shifting of food intake to coincide with the availability of water.

Role of dietary iron in maturation of rat small intestine at weaning.

The weanling process is characterized by the transition from a liquid diet poor in iron (rat milk) to a solid diet high in iron (chow pellets). To examine the effects of iron content of the weanling diet on terminal maturation of rat small intestine, suckling pups, nursed by iron-sufficient mothers, were weaned by day 16 onto a solid basal diet that was either deficient [low-iron diet (LID): 0.5 mg iron/100 g solid] or high [high-iron diet (HID) controls: 30 mg iron/100 g solid] in iron. The animals were studied during or at the end of the 4th postnatal wk. By day 17 rats weaned onto the LID exhibited an initial rise in jejunal sucrase activity as did their controls, but the activity plateau of the enzyme was reduced to a level 60% of the controls. On day 28 iron-deprived rats were anemic and showed significant decreases (P less than 0.01 compared with HID rats) in the activity of jejunal sucrase (-57%), neutral lactase (-83%), and maltase (-46%), whereas villus height, crypt depth, mucosal mass parameters, ileal acid beta-galactosidase activity, mucosal protein, and DNA synthesis rates were equivalent in LID and HID groups. The concentration of the secretory component, a glycoprotein synthesized by the intestinal crypt cell, was markedly depressed (P less than 0.01 vs. controls) in the jejunum (-54%) and ileum (-79%) of iron-deprived rats. When D-[1-14C]glucosamine was injected intraperitoneally, incorporation of the label into jejunal and ileal brush-border proteins was two to three times lower for iron-deficient rats than for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventromedial hypothalamic knife-cut lesions in rats resistant to dietary obesity.

The effects of ventromedial hypothalamic (VMH) knife-cut lesions on food intake and body weight of S 5B/Pl rats, which are normally resistant to obesity when eating a high-fat diet, were examined in two experiments. In the first experiment body weight increased only slightly after VMH knife-cut lesions when animals were fed pelleted laboratory chow or a 10% corn oil diet. When eating the 30% corn oil diet, however, body weight increased in the VMH knife-cut rats. In the second experiment VMH knife-cut lesions produced a small weight gain in rats fed the 10% fat diet; this manipulation also increased food intake and disrupted the normal diurnal feeding pattern. Changes in the weight of the liver, interscapular brown adipose tissue, and white adipose tissue paralleled the changes in body weight. Plasma insulin increased in the rats eating the 30% corn oil diet ad libitum but not in the VMH-lesioned animals pair fed to the sham-operated rats. Incorporation of 3H from 3H2O into lipid was significantly increased in white fat of animals with VMH knife cuts. Similar results were obtained from incubation of adipose tissue in vitro with insulin and radioactively labeled glucose. These studies show that hypothalamic knife-cut lesions can remove the resistance of the S 5B/Pl rats to obesity when they are fed a high-fat diet.

Stimulation of gastric prostaglandin synthesis by refeeding in the rat. Role in protection of gastric mucosa from damage.

The purpose of the present study was to determine whether feeding stimulates prostaglandin (PG) synthesis in the gastric mucosa and whether this might play a role in the defensive mechanism of the gastric mucosa. The effect of refeeding on the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs and on the generation of prostaglandin in the gastric mucosa was investigated. In the fasted rat aspirin and indomethacin produced many lesions in the corpus, but few or no lesions in the antrum. Refeeding of chow pellets before aspirin or indomethacin significantly decreased the corpus lesions, but provoked lesions in the antrum. When each drug was given before the refeeding, the protection against corpus lesions by refeeding was reduced and the lesions in the antrum were significantly increased. Mucosal generation of 6-keto-PGF 1 alpha (a stable metabolite of PGI2) and PGF2 alpha was measured ex vivo by the method of Whittle. The generation of 6-keto-PGF1 alpha and PGF2 alpha in the fasted rat deprived of food for 24 hr was 1761 +/- 170 and 217 +/- 7 ng/min/g tissue in the corpus mucosa, and 2958 +/- 217 and 453 +/- 33 ng/min/g tissue in the antral mucosa, respectively. Refeeding of chow pellets significantly increased the generation of both prostaglandins in the antral mucosa and of PGF2 alpha in the corpus mucosa, but did not affect the generation of PGI2 in the corpus mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effect of butylated hydroxytoluene against induction of gastric cancer by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in wistar rats

The effects of butylated hydroxytoluene (BHT) on the incidence and histology of gastric cancers induced by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in Wistar rats. Oral administration of 1.0% BHT in regular chow pellets during treatment with MNNG for 25 weeks significantly reduced the incidence of gastric cancers in experimental week 40. BHT had no influence on the histological type of adenocarcinomas induced in MNNG-treated rats. BHT alone induced slight glandular hyperplasia, but not moderate glandular hyperplasia or gastric cancer.

The lee obesity index vindicated?

Correlations are reported for rats between the Lee Obesity Index and percent body fat. At weaning, rats were divided into 4 groups: supermarket diet and ovariectomy, supermarket diet and sham surgery, Lab Chow pellets and ovariectomy, and Lab Chow pellets and sham surgery. Four other groups received the treatments as adults. Eighteen and fifteen weeks later, respectively, the rats were measured for Onesity Index and were sacrificed for carcass analysis. The Obesity Index correlated well with percent body fat for animals made obese by diet; but it was not generally reliable for ovariectomized rats or for pellet fed sham operated controls. The Percent body fat also correlated well with body weight and with a simple weight/length ratio for rats made obese by diet. Thus, while the Obesity Index can reliably predict percent body fat, it may be no better at doing this than are some simpler measures.