Pubertal food intake, body length, weight, and composition in the well fed female rat

Pubertal age, food intake, body length, weight, and composition were determined by direct measurements in 29 well fed female rats studied from birth to first estrus. The average birth and weaning weights of the 12 early maturing rats were 6.99 +/- 0.13 g and 50.13 +/- 1.16 g, respectively, and did not differ significantly from those of the 11 late maturers (6.97 +/- 0.16 g and 49.72 +/- 1.42 g, respectively). Mean values for all pubertal measurements are included in Table 1. At puberty, the late maturing animals were heavier, longer, and had attained a greater quantity of total body water than the early maturers. Although both groups ate the same total amounts of food, late maturing rats at vaginal opening and at first estrus consumed relatively less food per 100 g body weight than did early maturers. Estrus was simultaneous with vaginal opening in 10 (83%) of early and 4 (36%) of the late maturing rats. Despite the similarity in the proportions of total body water, fat, and protein in early and late maturers, a regression analysis, shown in Figure 1, indicates a significant decrease in the proportion of body water (P less than 0.001), and a significant increase in the proportion of body fat (P less than 0.05) with increasing age at first estrus. The percentage of body protein does not change with increasing age at first estrus (regression coefficient = 0.13).     

Analysis of growth in five-sixths-nephrectomized rats

The present study was designed in an attempt to better define the pattern of growth in five-sixths-nephrectomized rats. Male Sprague-Dawley rats underwent two-stage (days 0 and 7) five-sixths nephrectomy (NX, n = 16) or sham surgery (SHAM, n = 9). At the time of sacrifice (day 21), renal failure (CRF) of NX rats was confirmed by elevated (p < or = 0.0001) serum concentrations (X +/- SEM) of urea nitrogen (SUN) (56 +/- 5 vs. 20 +/- 1 mg/dl) and creatinine (0.7 +/- 0.04 vs. 0.4 +/- 0.02 mg/dl) and reduced SUN (0.13 +/- 0.02 vs. 0.44 +/- 0.05 ml/min/100 g) and creatinine clearances (0.23 +/- 0.02 vs. 0.58 +/- 0.05 ml/min/100 g). As shown by lower cumulative gains of weight (41 +/- 6 vs. 74 +/- 4 g) and length (5.0 +/- 0.4 vs. 6.8 +/- 0.3 cm), NX rats grew subnormally. Detailed analysis of growth data revealed: (1) In spite of being identically matched in weight and length on day 0, at day 7, NX rats already weighed less than SHAM animals (147.1 +/- 2.3 vs. 153.4 +/- 1.9 g, p = 0.03). (2) From day 7 on, daily gain of weight was lower in the NX group only on days 8 (-6.08 +/- 0.52 vs. -1.60 +/- 0.69 g/100 g body weight) and 9 (-0.41 +/- 1.73 vs. 5.18 +/- 0.63 g/100 g body weight). (3) Following the early post-second-nephrectomy period, two subgroups of NX rats were clearly differentiated according to whether or not their daily growth rate was lower than that of SHAM animals. Maintained subnormal growth rate was observed in rats with severe CRF (SUN 73 +/- 5 mg/dl, range 54-90) but not in rats having milder uremia (42 +/- 3 mg/dl, range 31-51). Thus, growth in five-sixths-nephrectomized rats should be reported based on daily weight increments (g/100 g body weight). Subnormal growth can be attributed to CRF provided SUN is at least 3 times as high as normal while growth impairment of rats with less marked reduction of renal function is likely related to transient acute renal failure and postsurgical catabolic state.     

Toadfish serum as a binder for in vitro assay of vitamin B12

Fetal intrauterine growth retardation was induced in nine rats at 17 days' gestation by ligating the blood supply to one of the uterine horn. The 27 festuses from the uterine vessel ligated side were the intrauterine growth retarded fetuses (IUGR) and the 37 fetuses from the nonligated side were controls. The mean weight of the IUGR fetuses was 3.4 +/- 0.3 g which was significantly smaller (P less than 0.005) than the mean weight of the control fetuses, 4.0 +/- 0.3 g. Whole body histidine decarboxylase (HDC) activity was assayed by a radioisotope method. The HDC activity per g tissue was not correlated to body weight in the control fetuses. This is in contrast to the IUGR festuses in which the HDC per g tissue was significantly and inversely related to body weight (r - 0.48, P less than 0.001).     

Failure of NaHCO3 and KHCO3 to inhibit renin in the rat

To evaluate the contribution of chloride to NaCl- and KCl-induced renin inhibition, renin responses to NaCl or NaHCO3 and to KCl or KHCO3 loading were compared in NaCl-deprived rats. Sodium balance in animals drinking isotonic NaHCO3 and NaCl for 9 days did not differ (P greater than 0.40); K+ balance was less positive in NaHCO3-drinking animals (P less than 0.005). Plasma renin activity (PRA) in NaCl-loaded (16.5 ng/ml per h +/- 4.4 SE), but not in NaHCO3-loaded rats (57.2 +/- 9.8), was lower (P less than 0.005) than in NaCl-deprived controls (44.8 +/- 4.7). Renal renin content (RRC) of NaCl but not of NaHCO3-drinking animals was also decreased (P less than 0.02). Both PRA and RRC of KCl- but not of KHCO3-loaded rats (5 meq K+/10 g diet) were lower (P less than 0.01) than in NaCl-deprived controls. After acute intravenous expansion with isotonic NaCl or NaHCO3, increases of plasma volume and plasma K+ did not differ (P greater than 0.05). However, PRA of NaCl-expanded rats (11.8 +/- 3.8) was lower (P less than 0.05) than in NaHCO3-expanded animals (29.7 +/- 8.5). The failure of NaHCO3 and KHCO3 to inhibit renin suggests a role for chloride in mediating the renin responses to Na+ and K+.     

Mapping of a congenital microcoria locus to 13q31-q32

The growth and timing of female puberty in a seasonally breeding marsupial, the tammar wallaby, was examined in wild and captive animals. Puberty, defined as the time of first estrus and ovulation, can occur at any time of the year. Sixty percent of young wild females went through puberty in late October-November, 3 mo before the normal adult mating season in late January-February, but puberty was delayed in captive animals kept with a low ratio of males to females. During initial cycles, 19% of these captive animals were infertile as judged by failure to conceive. In the wild, puberty occurred well before the animals were fully grown (body weight 2.0+/-0.3 kg [mean+/-SD], n=23; adult females, 4.7+/-0.6 kg; n=34). Only 3% of animals with a body weight below 1.5 kg had ovulated. Thus, attainment of a minimum body weight was a key prerequisite associated with puberty. Progesterone concentrations in the peripheral plasma of prepubertal females were not significantly different from those of adult females during the nonbreeding season (prepubertal, 142+/-121 pg/ml, n=34; adult, 194+/-105 pg/ml, n=32, p > 0.05). However, there was a significant increase in progesterone (322+/-242 pg/ml, n=32, p < 0.05) in the postpubertal females (ovulating but still < 3.5 kg body weight) even though the corpus luteum was quiescent after its formation. There was no increase in plasma progesterone before the first estrus. These data confirm that estrus does not require a change in the progesterone:estradiol ratio, and that a "silent" ovulation does not precede the first estrus in this species, so that the onset of puberty coincides with the first behavioral estrus and ovulation, when the animals have reached a body weight of 2 kg. Although adult female tammars are strict seasonal breeders, with 6 mo of seasonal quiescence from the winter to the summer solstice, young females can go through puberty at any time of the year. The unique feature of the female tammar wallaby is that it does not become a seasonally breeding mammal until after puberty, when it has acquired a corpus luteum.     

Effects of ethanol intake on retinol concentration in the milk of lactating rats

The effect of the consumption of ethanol (5%) on retinol concentration in milk was studied in the rat on day 12 after delivery, together with the evolution of dam body weight and pup growth rate. Female Wistar rats receiving alcohol (5%) in drinking water during lactation (N = 7) were compared to normal controls fed ad libitum (N = 6). The mean maternal alcohol intake was 3.96 +/- 0.23 g/kg body weight per day. To determine retinol levels in milk we used the Bessey and Lowry method, modified by Araújo and Flores ((1978) Clinical Chemistry, 24:386-392). The pups were separated from dams for a 2-4-h period, after which the dams were injected intraperitoneally with anesthetic and oxytocin. The concentration of retinol in milk was 162.88 +/- 10.60 micrograms/dl in the control group and 60.02 +/- 8.22 micrograms/dl in the ethanol group (P < 0.05). The ethanol group consumed less food than the controls and lost a significant amount of weight during lactation. On days 8, 10 and 12, the body weight of the pups from rats given ethanol (13.46 +/- 0.43, 16.12 +/- 0.48 and 18.60 +/- 0.91 g, respectively) were significantly lower (P < 0.05) than the weight of pups from controls (15.2 +/- 0.44, 18.36 +/- 0.54, 20.77 +/- 0.81 g). These data show that ethanol intake during the suckling period, even at low concentrations, decreases the amount of retinol in milk and, therefore, the amount available to the pups.     

Fetal growth retardation and increased placental weight in the spontaneously hypertensive rat

Epidemiological studies have linked low birth weight and increased placental weight with increased risk of hypertension in adult life. It has been proposed that the cardiovascular changes which lead to hypertension are initiated in utero by processes associated with intrauterine growth retardation. The alternative possibility, that hypertension may result from genetic influences which also determine fetal and placental size, has had less support because birth weight is not determined genetically in humans. However, in the spontaneously hypertensive rat (SHR) essential hypertension is known to be transmitted genetically. Fetal and placental weights were, therefore, measured at Day 20 gestation in SHRs and compared with those in the normotensive Wistar Kyoto (WKY) control strain. Fetal weight (1.93 +/- 0.04 g) was significantly (P < 0.001) reduced in SHRs compared with WKY fetuses (2.23 +/- 0.01 g) but placental weight was heavier (P < 0.001) in SHRs (0.347 +/- 0.005 g) than in WKY rats (0.300 +/- 0.006 g) although litter size was not different. As expected, maternal blood pressure recorded under 1% halothane anaesthesia was higher (126 +/- 2.7 mm Hg) in SHR than WKY rats (100 +/- 2.1 mm Hg; 1 mm Hg = 133 Pa). In addition the concentration of maternal blood glucose in SHR was significantly (P < 0.001) higher (4.8 +/- 0.32 mM v. 3.7 +/- 0.11 mM) and the concentration of plasma insulin was significantly (P < 0.05) lower in SHRs (18.8 +/- 3.0 ng mL-1) than in WKY dams (29.4 +/- 3.1 ng mL-1). Thus, the data support human population studies which show an association between adult hypertension and a reduced fetal:placental weight ratio at birth. However, because hypertension in the SHR is genetically determined, these data suggest that fetal growth retardation and increased placental weight may also be determined genetically.     

Functional and morphologic maturation of superficial and juxtamedullary nephrons in the rat

The development of single nephron glomerular filtration rate (SNGFER) was studied in both superficial and juxtamedullary nephrons in rats in relation to concomitant morphologic maturation. These experiments were carried out in rats between 23 and 91 days of age (between 36 nad 275 g body weight) with the [14C]ferrocyanide infusion technique. 2. SNGFR of the superficial and juxtamedullary nephrons increased with body weight, glomerular volume and proximal tubular length. 3. The ratio SNGFR of the superficial (S) nephrons/SNGFR of the juxtamedullary (JM) nephrons rose from 0-60 in the 40-60 g rats to 0-84 in the adult rats, demonstrating the centrifugal functional maturation of the nephrons. 4. The S/JM ratio for both glomerular volume and tubular length was constant and averaged 0-72+/--0-12 and 0-81+/-0-05, respectively, indicating that while the increase in SNGFR was greater for S than for JM nephrons, this was not accompanied by concomitant disproportionate increases of glomerular volume and/or proximal tubular length between these nephron categories during development in the rat.     

Adult height in girls with idiopathic true precocious puberty

GnRH analogs are used to suppress pituitary-gonadal activity in children with true precocious puberty. The indications for therapy in this situation are not established, as some girls have a slow evolutive form, and the capacity of GnRH analogs to preserve the adult height has not been evaluated. This study analyzes the growth and adult heights of 2 groups of girls with idiopathic true precocious puberty, 1 with a predicted height of 155 cm or less (group 1, 19 cases) and the other with a predicted height of more than 155 cm (group 2, 15 cases). Group 1 patients were treated with a long-acting GnRH analog (D-Trp6-GnRH), and group 2 patients were followed without therapy. Group 1 showed greater clinical signs of estrogenization, vaginal maturation index (P < 0.03), plasma estradiol (P < 0.0004), and ratio of LH/FSH peaks (P < 0.01) at the initial evaluation than did group 2. The mean target heights were similar (difference, 0.9 cm). In group 1, the adult height (159 +/- 1.1 cm) was greater than the predicted height before therapy (152 +/- 1.4 cm; P < 0.0001). The difference between the adult height and the predicted height before therapy (mean, 6.5 cm) correlated positively with the bone age advance (P < 0.01), negatively with the predicted height (P < 0.05), and positively with the difference between the target and predicted heights (P < 0.001) before therapy. In group 2, the adult height (162 +/- 1.4 cm) was similar to the predicted height at the initial evaluation (162.5 +/- 1.4 cm). Adult heights correlated with target height in group 1 and with predicted height at the initial evaluation in group 2. In conclusion, some girls with true precocious puberty and poor adult height prediction who are treated with GnRH analog achieve an adult height more comparable to their target height. However, the lack of effect on height in girls with predicted height at the onset of therapy similar to their target height and preservation of the growth potential in the slow evolutive forms suggest that these forms might not require immediate therapy. Careful follow-up before therapy may be a better way of evaluating their natural course.     

A biphasic developmental pattern of circulating leptin in the male rhesus macaque (Macaca mulatta)

To help elucidate the physiological role of leptin during somatic and sexual maturation, circulating concentrations of leptin were measured in 36 male rhesus monkeys of ages ranging from 0-20 yr. The body weight of these animals showed a steady increase of approximately 1 kg/yr during the first decade of life and reached a plateau at approximately 13 yr. In contrast, serum leptin concentrations showed a biphasic developmental pattern, which was highlighted by a strong negative correlation with body weight (r = -0.74, P < 0.001) before the onset of puberty (at approximately 3.5 yr) and by a strong positive correlation afterward (r = 0.77, P < 0.001). Overall, the developmental changes in serum leptin concentrations closely mimicked the expected developmental changes in serum testosterone concentrations (r = 0.62, P < 0.001), which were highly elevated at birth, fell to basal levels during the juvenile phase of development, and gradually rose again after the initiation of puberty. However, mean serum leptin concentrations during the peripubertal period itself (3-5 yr) were significantly lower (P < 0.01) than those observed during the first year of life or those observed in fully mature adults (i.e. > 7 yr) (3.5 +/- 0.3, 1.4 +/- 0.2, and 3.3 +/- 0.6 ng/ml, respectively). These data demonstrate that the role of leptin in energy homeostasis of primates is more than a simple linear relationship, being highly dependent upon the developmental age. Furthermore, the data do not support the hypothesis that leptin plays a major role in triggering the onset of puberty in primates, although the strong correlation between serum concentrations of leptin and testosterone suggests that the secretion of these two hormones may be causally linked.     

Patho-physiologic findings after chronic tryptophan deficiency in rats: a model for delayed growth and aging

Long-Evans female rats three weeks, three months and 13-14 months of age were placed on tryptophan-deficient diets for periods ranging from a few months to nearly two years. Growth was interupted during the period of tryptophan-deficiency, but when the animals were returned to a complete diet, they gained weight and grew to normal size. Ability to reproduce, as indicated by litter production, was present at 17-28 months of age in rats which had been deprived of tryptophan, whereas no controls over 17 months of age produced any offspring. Other signs of delayed aging in the experimental group included, at advanced ages, greater longevity, as well as later onset in the appearance of obvious tumors, and better coat condition and hair regrowth. Many of these effects were also seen in pair-fed controls (fed a diet equal in amount to that eaten by the tryptophan-deprived rats, but with 1-tryptophan added). It is hypothesized that tryptophan deficiency delays growth, development and maturation of the central nervous system (CNS), in particular, by decreasing the levels of the neurotransmitter serotonin, for which tryptophan is the necessary precursor. In a parallel experiment, chronic treatment with d, 1-parachlorophenylalanine, an inhibitor of brain serotonin synthesis, from weaning until adulthood, also inhibited growth (body weight) and delayed sexual maturation (age of vaginal opening). These observations suggest that diets deficient in tryptophan or restricted in calories can affect maturation and aging by interfering with CNS protein synthesis, or neurotransmitter metabolism, or both.     

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume

Kidney weight and glomerular volume have been studied in groups of insulin-treated streptozotocin diabetic rats maintained at high, or nearly normal plasma glucose levels. Kidney weight and glomerular volume in these groups were compared to a non-diabetic control group. --Rats with nearly normal plasma glucose levels (95 +/- 35 to 182 +/- 20 mg/100 ml) had the same kidney weight as the non-diabetic controls, 1.04 +/- 0.14 and 1.07 +/- 0.09 g, respectively. In the rats with constant high plasma glucose (338 +/- 71 to 555 +/- 86 mg/100 ml) kidney weight was significantly increased, 1.73 +/- 0.20 g, compared to each of the two other groups. Glomerular volume was 0.559 millimicron3 in the diabetic animals with nearly normal plasma glucose, a value very close to that of the non-diabetic controls, 0.587 milimicron3. In animals with high plasma glucose concentrations glomerular volume was 0.775 millimicron3, 2 p less than 0.03 compared with both other groups. --The study indicates that good diabetic control for 6 months prevents the development of large kidneys and large glomeruli in dibatic rats.     

Production of less chronic nephrotoxicity by cyclosporine G than cyclosporine A in a low-salt rat model

Chronic tubulointerstitial nephropathy during long-term cyclosporine A (CsA) use has led to a search for equally effective but safer analogues. In this study we evaluated one of these analogues, cyclosporine G (CsG), in a rat model of chronic cyclosporine nephrotoxicity. CsG has immunosuppressive effects equivalent to CsA when dosed on a weight basis. Pair-fed Sprague-Dawley rats kept on a low-salt rice diet were given CsA 15 mg/kg, CsG 15 mg/kg, CsG 25 mg/kg, or vehicle subcutaneously. After 21 days, CsA animals had a lower glomerular filtration rate, measured by inulin clearance (0.16 +/- 0.04 ml/min/100 g) and higher serum creatinine (0.94 +/- 0.06 mg/dl) than CsG 15 mg/kg (GFR: 0.41 +/- 0.10 ml/min/100 g and serum creatinine: 0.68 +/- 0.09 mg/dl), CsG 25 mg/kg (GFR: 0.39 +/- 0.16 ml/min/100 g) or control rats (GFR: 0.62 +/- 0.06 ml/min/100 g; serum creatinine: 0.56 +/- 0.03 mg/dl), respectively (P < 0.05). The CsA group had considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), whereas both groups of CsG animals had more limited changes. Despite the same or larger doses of CsG on a weight basis, cyclosporine blood levels were significantly lower in CsG than CsA rats. We conclude that CsG, an analogue of cyclosporine with immunosuppressive activity equivalent to that of CsA, produced less nephrotoxicity in a model of chronic renal injury in rats, using both functional and structural parameters.     

Cerebral energy levels during trimethaphan-induced hypotension in the rat: effects of light versus deep halothane anesthesia

Hypotension may be expected to produce less perturbation of metabolism in the brain when cerebral metabolic rate is lowered by deep anesthesia. Male Wistar rats having unilateral carotidartery ligation were exposed to mean arterial pressure (MAP) of 40 torr for 22 min by an intravenous infusion of trimethaphan during anesthesia with halothane, 0.6 or 2 per cent, in oxygen. Cortical tissue metabolite levels on the side of the ligated carotid artery were more abnormal in rats receiving halothane, 0.6 per cent, than in those receiving halothane, 2 per cent. Values at halothane, 0.6 per cent, were adenosine triphosphate (ATP), 1.71 +/- 0.05 (+/-SEM) mumol/g, phosphocreatine (PCr) 1.97 +/- 0.07 mumol/g. and lactate 16.5 +/- 5.1 mumol/g; corresponding values at halothane, 2 per cent, were ATP 2.27 +/- 0.02, PCr 4.02 +/- 0.23, and lactate 4.75 +/- 0.9 mumol/g. ATP and PCr values were significiantly lower (P less than 0.05) and the lactate value was significantly higher with halothane, 0.6 per cent, than with halothane 2 per cent. Cerebral oxygen consumption decreased 47 per cent in rats anesthetized with halothane, 2 per cent. Preservation of cortical metabolite levels in deeply anesthetized animals suggests a protective effect of cerebral metabolic depression.     

Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit

Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We describe the early growth mechanics of fetal lungs and type II pneumocytes after tracheal ligation (TL). Fetal rabbits underwent TL at 24 days gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and were sacrificed at time intervals ranging from 1 to 5 days after TL. Lung growth was measured by stereological volumetry and bromodeoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein A and BrdU immunohistochemistry and computer-assisted morphometry. Nonoperated littermates served as controls. TL resulted in dramatically enhanced lung growth (lung weight/body weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001, unpaired Student's t-test). Post-TL lung growth was characterized by a 3-day lag-phase typified by relative stagnation of growth, followed by distension of airspaces, increased cell proliferation, and accelerated architectural and cellular maturation by postligation days 4 and 5. During the proliferation phase, the replicative activity of type II cells was markedly increased (type II cell BrdU labeling index was 10.0 +/- 4.1% in TL versus 1.1 +/- 0.3% for controls at 29 DGA; P < 0.02), but their numerical density decreased (3.0 +/- 0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2 in controls at 29 DGA; P < 0.02), suggesting accelerated terminal differentiation to type I cells. In conclusion, post-TL lung development is characterized by a well defined temporal pattern of lung growth and maturation. The rabbit model lends itself well to study the regulatory mechanisms underlying accelerated fetal lung growth after TL.     

Induction of macrophage migration inhibitory factor messenger ribonucleic acid in rat forebrain by reperfusion

To evaluate the impact of uremia and associated caloric restriction on physiologically pulsatile growth hormone (GH) release, we used deconvolution analysis of spontaneous plasma GH profiles in 5/6-nephrectomized male rats (NX, N = 9). Three different normal renal function sham-operated groups were used: rats fed a normal diet ad libitum (SAL, N = 9); NX pair-fed rats (SPF, N = 6); NX rats pair-fed for protein ingestion but calorically supplemented up to the energy intake of SAL (SPF+, N = 8). Severe renal failure was confirmed by much higher (P < 0.001) BUN in NX than sham groups. NX rats were growth retarded as shown by reduced (P < 0.01) weight and length gains as compared with sham animals. Deconvolution analysis (mean +/- SEM) of plasma samples obtained every 10 minutes over 6 hours, and 14 to 16 days after second stage nephrectomy showed that NX rats had a longer GH t(1/2) (17.0 +/- 1.8 vs. 11.6 +/- 0.8 min), less GH mass secreted per burst (48 +/- 15 vs. 95 +/- 16 ng/ml/pulse), lower secretory pulse amplitude (1.9 +/- 0.5 vs. 5.8 +/- 0.9 ng/ml/min), and a reduced total GH secretion (240 +/- 69 vs. 400 +/- 56 ng/ml/6 hr) than SAL rats. Corresponding data were not significantly different between NX and SPF, or between SAL and SPF+ groups. In summary, stunted rats with chronic renal failure exhibit a prolonged GH t(1/2) and suppression of GH secretory pattern burst mass. Control data from rats with normal renal function suggest that the amplitude-specific depression of GH secretion may be attributed, at least in part, to chronic renal failure-associated calorie deficiency.     

Sodium balance of hyper- and hypo-natriophilic rats under basal conditions and during sodium deprivation

Sodium and water balance was determined in two strains of Wistar rats selectively bred for high (hypernatriophilic, HR) or low salt preference (hyponatriophilic, HO) under basal conditions and during sodium deprivation. Male rats from each stain were selected for an average ingestion of 1.5% NaCl solution of more than (HR) or less than (HO) 4 ml 100 g body weight (-1) day (-1), during a 10-day period. HR rats (N = 17) presented markedly higher sodium intake under basal conditions (2.983 +/- 0.316 mEq 100 g body weight (-1) day (-1)) than HO rats (N = 12; 0.406 +/- 0.076 mEq 100 g body weight (-1) day (-1); Mann-Whitney test, P < 0.01). Water (HR: 8.6 +/- 0.57; HO: 7.7 +/- 0.32 ml 100 g body weight (-1) day (-1)) and sodium balances (HR: 0.936 +/- 0.153; HO: 0.873 +/- 0.078 mEq 100 g body weight (-1) day (-1)) were similar in both strains, despite a higher sodium and total fluid (HR: 16.3 +/- 1.06; HO: 10.8 +/- 0.49 ml 100 g body weight (-1) day (-1); P < 0.01) ingestion in HR rats. During sodium deprivation HR rats (N = 13) exhibited a sodium balance similar to that of HO rats (N = 13) (HR: -0.159 +/- 0.011; HO: -0.129 +/- 0.019 mEq 100 g body weight (-1) day (-1)), and, in addition, an adequate suppression of natriuresis (HR: 0.049 +/- 0.011; HO: 0.026 +/- 0.004 mEq 100 g body weight (-1) day (-1)). These data show that HR rats present hypernatriophilia as a primary trait, since their sodium-conserving mechanisms are intact. Therefore, these rats provide an adequate model to study factors that determine innate sodium preference.     

Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats

In the past, there has been considerable concern that treatment with active vitamin D might accelerate progression independent of hypercalcemia and hypercalcuria. Nevertheless, 1,25(OH)2D3 has known antiproliferative properties and has also been shown to inhibit renal growth. Since glomerular growth is a permissive factor for the development of glomerulosclerosis, we reasoned that 1,25(OH)2D3 might even attenuate progression. To test this working hypothesis we performed two experiments of 8 and 16 weeks duration, respectively, to compare subtotally nephrectomized (SNX) rats treated with ethanol and SNX treated with 1,25(OH)2D3. Control animals were sham operated and pair-fed with SNX animals. 1,25(OH)2D3 (3 ng/100 g body wt/day) was administered by osmotic minipump. 1,25(OH)2D3 had no significant effect on systolic blood pressure and only a transient effect on weight gain. SNX reduced the number of glomeruli (left kidney) from an average of 3.3 x 10(4) to 1.2 x 10(4) per kidney. Mean glomerular volume was 3.87 +/- 0.71 x 10(6) microns 3 in sham operated animals and significantly (P < 0.05) higher (10.1 +/- 1.75 x 10(6) microns 3) in untreated animals 16 weeks after SNX. Glomerular volume was significantly (P < 0.05) less in 1,25(OH)2D3 treated SNX [10.1 +/- 1.75 in ethanol vs. 7.04 +/- 1.78 in 1,25(OH)2D3 treated SNX]. In parallel, there was significantly (P < 0.01) less glomerulosclerosis [glomerulosclerosis index 1.16 +/- 0.14 in the ethanol treated SNX vs. 0.80 +/- 0.16 in SNX treated with 1,25(OH)2D3] in the eight week experiment. Albuminuria was significantly (P < 0.01) lower in 1,25(OH)2D3 treated than in ethanol treated SNX (mean 0.785 mg/24 hr, range 0.43 to 1.80, vs. 3.75 mg/24 hr, 1.29 to 14.2). The morphological data were directionally analogous in a second 16 week experiment. Only slight changes of the vascular sclerosis index and tubulointerstitial index were seen in SNX and were not affected by 1,25(OH)2D3 further. To prove that the effect of 1,25(OH)2D3 was independent of PTH, parathyreoidectomized SNX rats without or with 1,25(OH)2D3 treatment were examined seven days post-SNX. PCNA staining showed suppression of cell proliferation. Furthermore, in situ hybridization for transforming growth factor-B (TGF-beta) showed less vascular and tubular expression in 1,25(OH)2D3 treated rats. We conclude that 1,25(OH)2D3 has antiproliferative actions during the compensatory growth of nephrons in response to subtotal nephrectomy. These effects are independent of PTH. The data document that 1,25(OH)2D3 reduces renal cell proliferation and glomerular growth as well as glomerulosclerosis and albuminuria as indicators of progressive glomerular damage.     

Effects of cardiomyoplasty on cardiac growth in rats

BACKGROUND AND AIM OF THE STUDY: Cardiomyoplasty (CMP) has been proposed as a treatment for pediatric patients, but restriction of cardiac growth by the muscle wrap is a potential source of concern. This possibility was investigated in an immature animal model. METHODS: Six-week-old rats (body weight 203.8 +/- 5.4 g, mean +/- SEM) underwent either left thoracotomy with CMP (group I, n = 7), or thoracotomy without CMP (group II, n = 8). A third group (group III, n = 7) served as untreated controls. Final measurements were made 20 weeks later after body weights had reached a plateau. RESULTS: Preoperative body weights were not significantly different between the groups. At elective sacrifice, the body weights of animals that underwent surgery did not differ significantly (group I, 558.0 +/- 21.5 g and group II, 617.3 +/- 20.3 g), but were significantly less than those of control animals (727.6 +/- 13.3 g, p < 0.001 and p < 0.01, respectively). Cardiac ventricular weights in the CMP group were significantly less than those of control animals (group I, 1.21 +/- 0.06 g; group III 1.45 +/- 0.04 g; p < 0.01), but were not statistically different from those of the sham thoracotomy group (group II, 1.36 +/- 0.05 g). Mean left ventricular end-diastolic volumes were similar in all groups (group I, 0.67 +/- 0.07 mL; group II, 0.66 +/- 0.07 mL; and group III, 0.69 +/- 0.10 mL; p = ns). CONCLUSIONS: A major surgical procedure impairs growth in juvenile rats. no evidence emerged from this study for additional restriction of cardiac development due to cardiac wrapping. However, studies that include stimulated muscle wraps are needed before CMP should be considered for the pediatric age group.     

The role of estrogen in bone growth and maturation during childhood and adolescence

Twenty years ago it was believed that pubertal growth was stimulated by testicular androgen in boys and by adrenal androgen in girls. Estrogen, which was used to inhibit growth in excessively tall girls, was not thought to have growth-promoting effects. We hypothesized that estrogen has a biphasic effect on epiphyseal growth, with maximal stimulation at low levels. We showed that the administration of low doses of estrogen, corresponding to a serum estradiol level of about 4 pg/ml (15 pmol/l) caused more than a 60% increase over the prepubertal growth rate in both boys and girls. To test the hypothesis that estrogen is the principal mediator of the pubertal growth spurt in boys, we administered the aromatase inhibitor, testolactone, to boys with familial male-limited precocious puberty. Testolactone produced near normalization of both growth velocity and bone maturation, despite levels of serum testosterone that remained within the adult male range. The observation that low levels of estrogen stimulate growth and bone maturation suggested that estrogen might explain the more rapid epiphyseal maturation of prepubertal girls compared to boys. To determine whether prepubertal girls have higher estrogen levels than prepubertal boys, we developed an ultrasensitive recombinant cell bioassay for estrogen with a sensitivity of 0.02 pg/ml (0.07 pmol/l) estradiol equivalents. Prepubertal girls had approximately eight-fold higher levels of serum estradiol than did prepubertal boys (0.6 +/- 0.6 pg/ml (SD) (2.2 +/- 2.2 pmol/l) vs 0.08 +/- 0.2 pg/ml (0.29 +/- 0.73 pmol/l), P < 0.05). We concluded that the pubertal growth spurt of both sexes is driven primarily by estrogen, and that the more rapid epiphyseal maturation of prepubertal girls (vs boys) may be explained by their higher estradiol levels.