Renal nerves in renal adaptation to dietary sodium restriction

To assess the physiologic importance of the renal nerves in the renal mechanisms for the maintenance of body sodium balance, renal adaptation to normal and low sodium diet was evaluated in conscious Sprague-Dawley male rats before and 8 days after recovery from bilateral surgical-pharmacological renal denervation. Renal denervation was confirmed in every rat at the end of the study by absence of renal vasoconstriction to splanchnic nerve stimulation and loss of renal tissue norepinephrine content. Daily sodium balance, defined as the difference between dietary sodium intake and urinary sodium excretion, was positive with the normal sodium diet before and after bilateral renal denervation. Prior to bilateral renal denervation, changing to the low sodium diet was associated with a diminishingly negative sodium balance for 3 days that became progressively positive thereafter. After bilateral renal denervation, changing to the low sodium diet was associated with a continuous and progressively negative sodium balance. We conclude that intact renal innervation is required for normal renal sodium conservation and maintenance of body sodium balance during dietary sodium restriction.     

Effect of age on intestinal calcium absorption and adaptation to dietary calcium.

To study the reported decline in intestinal calcium absorption with age, calcium active transport, immunoreactive calcium protein (CaBP) content, and alkaline phosphatase activity were measured in the intestine of two strains of rats aged 3-wk--20 mo. Calcium active transport, as measured by everted gut sacs from Sprague-Dawley rats, was greatest at 3 wk, but it declined rapidly with no active transport demonstrable at 3 mo or thereafter. CaBP content closely paralleled the decline in active transport, but alkaline phosphatase activity increased as active transport decreased. Intestinal adaptation to dietary calcium was studied by feeding high- and low-calcium diets to Fischer 344 rats aged 1.5--12 mo. In 1.5-mo-old rats fed a low-calcium diet, there was an increase in calcium active transport, CaBP content, and alkaline phosphatase activity relative to animals fed a high-calcium diet. However, the magnitude of this intestinal adaptation decreased with age until there was only marginal adaptation by 12 mo. The observed changes in calcium active transport with age and diet may be explained by the parallel changes in the vitamin D-dependent CaBP content of the intestine.     

The effects of ageing and chronic dietary restriction on in vivo hepatic protein synthesis in the rat

Hepatic growth and protein synthesis in vivo was studied with age in ad libitum-fed and dietary restricted rats in which the mean and maximum lifespan was significantly extended. Livers from underfed rats showed significantly lower DNA, RNA and protein contents, and total protein synthesis. The fractional rate of synthesis although initially depressed by restricted feeding, showed no consistent trend with age when compared with control values. The lower fractional rate of synthesis observed in livers from dietary restricted rats at 7 weeks of age is attributable to a significant decrease in ribosomal capacity, with no effect on ribosomal activity being evident. Liver tissue from rats fed ad libitum demonstrated a progressive loss of translational efficiency with age which was delayed by chronic dietary restriction.     

The case for dietary calcium restriction in patients with atherosclerosis

An increasingly vast set of data is linking the process of vascular calcification to the metabolism of calcium and phosphorus. This phenomenon is already relatively well understood in renal failure patients. A similar phenomenon, however, could be taking place in the general population. This may indicate a need for a reassessment of calcium supplementation, including the ingestion of milk, not only in dialysis patients, but also in patients with preserved renal function. Given the fact that no clear prospective randomized evidence exists to show what may be the impact on prognosis of patients with atherosclerosis, caused by the ingestion of milk and milk derivatives, containing calcium and lactose, as is currently recommended to prevent bone disease in the general population, a case could be made to recommend restriction of such dietary products in atherosclerosis patients, until precise data have been obtained, in controlled, prospective studies, and especially so in patients with no evidence of osteoporosis. Such a case would not be a strong one at the present stage, but neither would be the opposite view. The recommendation that could be made at this stage would be that patients with significant atherosclerotic disease should be informed that the ingestion of milk, and calcium supplementation in general, has neither been conclusively proven to be safe, nor the opposite.     

Effect of dietary restriction and aging on polyploidy in rat liver

Liver polyploidy levels were compared as a function of age and diet in male Fischer 344 rats between 1 and 24 months of age. Dietary restriction was imposed on one group by reducing their food intake to 60% of ad libitum food intake. Histological sections of the livers of animals at each age and diet were examined. Diploid, tetraploid and octaploid nuclei were observed, and their size and frequency established. There were no differences in the diameter or volume of these size classes as a function of age or diet. An age-related decline in the percentage of diploid nuclei, coupled with an increase in the percentage of tetraploid and octaploid nuclei was observed in both groups. The major difference between the two groups was that the adult level of liver polyploidy was attained more slowly in the animals on dietary restriction as compared to the ad libitum fed controls. Polyploid cell formation in the liver is under the control of growth hormone, thyroid hormone and thymus, all of which might be influenced by dietary restriction.     

Changes in protein turnover and growth of the rat lung in response to ageing and long-term dietary restriction

The wet weight, protein, RNA and DNA contents of the lung were studied during normal ageing and chronic dietary restriction. The rate of normal lung growth gradually decreased between weaning and old age (105 weeks). However, unlike many other body tissues, there was little or no post-natal decline in the fractional rates of protein synthesis and breakdown. Dietary intervention severely retarded lung growth, particularly at the earliest stage (i.e. 4 weeks), studied. Here the suppression of protein synthesis was due to the combined effects of piece-meal feeding and the long-term effects of the reduced food supply.     

Tubular adaptation to Pi restriction in hypophysectomized rats

The renal tubule adapts its tubular transport capacity for inorganic phosphate (Pi) in response to a reduction in the Pi supply. In order to assess whether growth hormone plays a critical role in this adaptive response we have studied the change in the tubular handling of Pi which follows Pi restriction in hypophysectomized (HPX) rats and compared it to that occurring in intact counterparts. HPX and intact rats were maintained either on a 1.2 g/100 g phosphorus diet or fed a 0.2 g/100 g phosphorus diet for 3, 6 or 12 days. HPX rats received ACTH and thyroxine in doses which normalize their low glomerular filtration rate (GFR). Then the maximal net Pi reabsorption per volume of glomerular filtrate (max. TRPi/ml GFR) were determined during acute Pi infusion by clearance technique. The results indicate that HPX rats responded to Pi restriction by raising their tubular capacity to reabsorb Pi. However, the rapidity and the magnitude of the adaptive response was significantly less in HPX than in intact rats. The adaptation to Pi restriction was also observed in HPX rats after thyroparathyroidectomy. It is concluded that growth hormone and other pituitary hormones do not play a key role in the adaptive response to Pi restriction. The reduced adaptive response observed in HPX rats with intact thyroparathyroid glands could be due to the decreased Pi demand consecutive to impaired growth.     

Psychosocial stress, dietary calcium and hypertension in the spontaneously hypertensive rat

The interactive effects of psychosocial stress and diet on the development of hypertension were investigated in spontaneously hypertensive rats. Psychosocial stress, produced through manipulation of group housing conditions, was evaluated at three levels of dietary calcium and sodium: Low (0.1% Ca2+, 0.25% Na+), Intermediate (1.0% Ca2+, 0.45% Na+), and High (2.0% Ca2+, 1.0% Na+). After 13 weeks of exposure, stressed animals had higher blood pressure and lower serum ionized calcium than nonstressed animals across all diets. Likewise, animals on the low diet had higher blood pressures and lower ionized calcium values than animals on normal or high diets regardless of stress condition. The combination of stress and low diet produced the highest blood pressure and lowest serum ionized calcium values. The results suggest that stress both independently and in combination with dietary Ca2+ altered calcium metabolism. The interaction between psychosocial stress and dietary factors appears to contribute to reductions in serum ionized calcium and elevations in blood pressure in this experimental model of genetic hypertension.     

Effect of previous dietary history of calcium intake on the skeleton and calcium absorption in the rat

1. Rats were fed either a high or a low calcium diet for 6 weeks. Thereafter all were given the low calcium diet, and the time during which differences persisted between the two groups in apparent absorption of calcium and urinary excretion of calcium has been studied. The apparent absorption of calcium is the same in the two groups after 15 days but the differences in urinary excretion of calcium persist longer.2. Faecal endogenous calcium and true absorption of calcium have been measured by an isotope dilution technique. The fall in apparent absorption of calcium seen in rats fed a high calcium diet is in part due to a fall in true absorption. Faecal endogenous calcium is also increased in these animals.3. The amount of calcium and phosphate in the bones is increased by feeding a high calcium diet and decreased by feeding a very low phosphate diet. Femur, humerus, caudal vertebrae and calvaria are equally affected by the different diets.4. There are strong inverse correlations between absorption of calcium and the percentage of calcium in the bones. This suggests that absorption of calcium may be regulated by the degree of bone mineralization.5. Rats were fed diets with different calcium phosphate ratios for 6 weeks. Thereafter all were given a low calcium diet with a calcium: phosphorous ratio of 1 and absorption and urinary excretion of calcium were studied. The effects of the different diets may be explained by their effect on calcium status and bone mineralization.     

The distribution and exchange of brain calcium in vivo in the rat

Summary Calcium exhibits a heterogenous distribution among the various brain areas studied. The pituitary gland contains 25.97 meq./kg of wet tissue, followed by the pons containing 9.91 meq. and the hypothalamus 5.35 meq. The calcium content in the other areas is as follows: 4.23 meq. in medulla, 4.0 meq. in cerebral white matter, 3.60 meq. in cerebellum and about 3.0 meq./kg of wet tissue in the cerebral cortex. No difference in calcium concentration was found between the right and left corresponding brain areas.The distribution of brain calcium between the extracellular and cellular compartments was derived, and indicates that the concentration of cellular calcium is several-fold that in the extracellular space.Three hours after intraperitoneal injection of ⁴⁷Ca Cl₂, the maximum uptake of ⁴⁷Ca was reached in all tissues except the pituitary gland where maximum uptake occurred 1 h after injection. The radioactive calcium in the brain was resolved into two components: A fast component having a short half time ranging between 0.5 and 4.25 h and a relatively slow component having a half time of 4.5–18 h.In the pituitary gland, pons, hypothalamus and medulla the calcium exchanges partially with serum calcium whereas, in cerebellum, cerebral cortex and white matter of cerebrum, tissue calcium is completely exchangeable.     

Dendritic calcium accumulation associated with direction-selective adaptation in visual motion-sensitive neurons in vivo

Motion adaptation in directionally selective tangential cells (TC) of the fly visual system has previously been explained as a presynaptic mechanism. Based on the observation that adaptation is in part direction selective, which is not accounted for by the former models of motion adaptation, we investigated whether physiological changes located in the TC dendrite can contribute to motion adaptation. Visual motion in the neuron's preferred direction (PD) induced stronger adaptation than motion in the opposite direction and was followed by an afterhyperpolarization (AHP). The AHP subsides in the same time as adaptation recovers. By combining in vivo calcium fluorescence imaging with intracellular recording, we show that dendritic calcium accumulation following motion in the PD is correlated with the AHP. These results are consistent with a calcium-dependent physiological change in TCs underlying adaptation during continuous stimulation with PD motion, expressing itself as an AHP after the stimulus stops. However, direction selectivity of adaptation is probably not solely related to a calcium-dependent mechanism because direction-selective effects can also be observed for fast moving stimuli, which do not induce sizeable calcium accumulation. In addition, a comparison of two classes of TCs revealed differences in the relationship of calcium accumulation and AHP when the stimulus velocity was varied. Thus the potential role of calcium in motion adaptation depends on stimulation parameters and cell class.     

Strain variation in the response of body temperature to dietary restriction

Dietary restriction (DR, also referred to as calorie restriction, energy restriction, and food restriction) retards senescence and increases longevity in mammals. DR also lowers mean body temperature (T(b)), and thus mean T(b) might be useful as a covariate of DR-induced life extension. Indeed, lower T(b) could itself underlie some of the beneficial life-extension effects that occur during DR. To assess the relationship between lower T(b) during DR and life extension, we asked whether significant strain variation exists in the T(b) response of mice being fed 60% ad libitum (AL). Individually-housed, female mice from 28 strains, representing a genealogically diverse sample of the classical inbred strains, were directly compared. The mean T(b)s in response to DR exhibited highly significant strain variation, ranging from 1.5 degrees C below normal to a phenomenal 5 degrees C below normal. This variation was not explained by differences in loss of thermoregulation, AL adiposity, sensitivity to a nonadaptive hypothermia, motor activity, thermal arousal, absolute food intake, or efficacy of nutrient extraction. The variation in strain mean T(b) was also present in the absence of torpor. This strain variation could be used to critically test whether lower T(b) is a covariate of life extension during DR.     

Adaptive response of ileal mucosa to malnutrition in the rat: role of polyamines

Mucosal disaccharidases and ornithine decarboxylase activities were measured in malnourished, preweaning (19 days), post weaning (24 days) and young adult (37 days) rats. Malnutrition resulted in decreased body weight, intestinal weight, DNA and protein content. Mucosal Prot/DNA ratios were elevated in the ileal segments of the 24 and 37 day rats. Preweaned malnourished rats had significantly enhanced lactase specific activity in both jejunal and ileal segments. Adult malnourished rats showed enhanced jejunal lactase and sucrase activities which were not accompanied by elevated ornithine decarboxylase values. Mucosal sucrase and ornithine decarboxylase specific activities were significantly elevated in the ileal segment of the 24 and 37 day old malnourished rats. Studies of adult rats showed that these increased specific activities were located in the mature enterocytes at the villus tip, and persisted during a 24 h diurnal cycle. DFMO administration for 4 days completely inhibited mucosal ornithine decarboxylase and abolished the rise of ileal sucrase activity. We concluded that the intestinal response to reduced food intake is age related and differs in the jejunum and ileum: ornithine decarboxylase and polyamines are involved in ileal adaptation to malnutrition in postweaned and adult rats.     

The morphogenesis of cyclohexylamine-induced testicular atrophy in the rat: in vivo and in vitro studies

Male Wistar strain rats were fed a diet providing an intake of 0 or 400 mg cyclohexylamine (CHA)/kg body weight/day for 1, 3, 7, 9, or 13 weeks. At the end of the appropriate feeding period the rats were perfused-fixed with Karnovsky's fixative. The weights of the fixed testes were recorded and the testes, epididymides, and spermatic cord were sampled and processed into methacrylate resin. Histopathological examination of the testes showed changes after 3 weeks of CHA administration. The most frequent and consistent lesion consisted of a focal, basal vacuolation of the Sertoli cell cytoplasm associated with the local loss of spermatocytes and spermatogonia. After a 7-week administration, the Sertoli cell vacuolation was extensive, while the germ cell population showed mild to moderate degeneration and depletion. After longer periods of treatment the lesion was more severe and affected a greater number of tubules leading to general disruption of the germinal epithelium. Cocultures of Sertoli and germ cells were prepared from the testes of Wistar strain rats and exposed to (CHA) or its metabolite 4-aminocyclohexanol (4ACH) at concentrations ranging from 0.1 to 10 mM for periods of 24-72 hr. The cultures were fixed, stained, and examined by light microscopy. Cultures exposed to CHA or 4ACH showed morphological changes comparable with those seen in vivo. Sertoli cell vacuolation was the earliest change with progressive germ cell degeneration and exfoliation from the Sertoli cell monolayer. At equimolar concentrations, CHA produced more marked changes than 4ACH. These results suggest that CHA itself acts directly on the testis and that its primary cellular target is the Sertoli cell.