bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-day-like body weight changes do not prevent fat pad compensation after lipectomy in Siberian hamsters
Authors: Mauer M. M. , Bartness T. J.
Published: December 2017

Long-day (LD)-housed Siberian hamsters show compensatory increases in white adipose tissue (WAT) weight after lipectomy, whereas hamsters exposed to short days (SDs) for a long duration (22 wk) do not. We tested whether SD-induced body weight changes prevent fat pad compensation after lipectomy. In experiment 1, hamsters with lesions of the paraventricular nucleus of the hypothalamus (PVNx) rapidly increased body weight similarly to 22-wk SD-exposed hamsters. In experiment 2, LD-housed hamsters were food restricted for 22 wk and then pair fed with SD-housed hamsters for 12 wk to produce body weight changes mimicking those of ad libitum-fed SD-exposed animals. Epididymal WAT (EWAT) lipectomy (EWATx) of PVNx or food-restricted hamsters elicited compensatory increases in retroperitoneal and inguinal WAT (RWAT and IWAT) weights. Unlike other fat pads, EWAT was less affected by food restriction or PVNx than by SD exposure. In general, food restriction decreased adipocyte number, whereas SD exposure decreased adipocyte size. PVNx increased RWAT adipocyte size and IWAT adipocyte number. These results suggest that the lack of body fat compensation by EWATx hamsters exposed to SDs for a long duration is due to SD-associated responses other than body weight changes per se.
Feeding patterns of S. crassicaudata (Marsupialia:Dasyuridae): role of gender, photoperiod, and fat stores
Authors: Hope P. J. , Wittert G. A. , Horowitz M. , Morley J. E.
Published: December 2017

Little is known about feeding regulation in marsupials. Sminthopsis crassicaudata is a small nocturnal marsupial, whose tail contains approximately 25% total body fat. We have characterized the effect of gender, photoperiod, food deprivation, and tail removal (lipectomy) on food intake in S. crassicaudata. Males and females maintained in captivity on long-day (LD, 16:8-h light-dark cycle) and short-day (SD, 9:15-h light-dark cycle) light regimens were studied. Feeding patterns under LD and SD photoperiods were initially measured under conditions of ad libitum food supply and then in groups of animals exposed to 24- and 36-h periods of food deprivation. Feeding occurred predominantly in the dark. Females maintained on SD photoperiods for 5 wk ate less (P < 0.005) than females on LD or males on either SD or LD, but this reduction in food intake was not associated with a decrease either in body weight or tail width. After both 24- and 36-h fasts, total food intake in the subsequent 24 h increased (P < 0.001) up to 100% in all groups, with no gender or photoperiod effect. SD females, however, ate less (P < 0.05) than LD females in the first 6 h after refeeding. Tail width decreased (P < 0.05) in all groups of animals after the 36-h fast but only in LD animals after the 24-h fast (P < 0.05). Body weight decreased similarly in all groups of animals after fasting. The effect of tail removal was studied in LD males. The procedure, which was well tolerated, resulted in an initial decrease in body weight (P < 0.005), which recovered within 3 wk. On day 45 in the animals whose tails were removed, body fat was approximately 30% greater than body fat of controls (P < 0.02). No significant increase in food intake occurred after tail removal. These data demonstrate in Sminthopsis crassicaudata 1) a photoperiod and gender-dependent effect on food intake, 2) the ability to regulate the amount and distribution of total body fat, and 3) a dissociation between the regulation of food intake and changes in body fat stores, which suggest alterations in energy expenditure.
Neurogenic plasma exudation mediates grain dust-induced tissue injury in vivo
Authors: Gao X. P. , Von Essen S. , Rubinstein I.
Published: December 2017

The purpose of this study was to determine whether an aqueous extract of grain sorghum dust (GDE) elicits neurogenic plasma exudation in the oral mucosa in vivo. Using intravital microscopy, we found that GDE elicited significant, concentration-dependent leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the hamster cheek pouch (P < 0.05). The selective, nonpeptide neurokinin(1) (substance P) receptor antagonists, CP-96,345 and RP-67580, but not the 2R,3R enantiomer CP-96,344, significantly attenuated GDE-induced leaky site formation and increase in clearance of FITC-dextran (P < 0.05). Indomethacin had no significant effects on GDE-induced responses. CP-96,345 had no significant effects of adenosine-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch. We conclude that GDE elicits neurogenic plasma exudation from the oral mucosa in vivo. We suggest that this process is one mechanism whereby grain sorghum dust elicits immediate oral mucosa inflammation in vivo.
Chronic ANG II infusion and reflex control of norepinephrine and corticosterone in conscious rabbits
Authors: Brooks V. L. , Hatton D. C.
Published: December 2017

The hypothesis that long-term increases in angiotensin II (ANG II) produce pressure-independent resetting of baroreflex control of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis was tested in rabbits by determining the effect of chronic ANG II infusion on reflex relationships between mean arterial pressure (MAP) and plasma concentrations of norepinephrine (NE) and corticosterone (CS). After 2 wk, ANG II increased MAP from 61 +/- 1 to 99 +/- 2 mmHg (P < 0.05) without altering heart rate or plasma NE concentration, but increased CS from 9.8 +/- 1.3 to 29.5 +/- 13.7 ng/ml (P < 0.05). Heart rate, NE, and CS baroreflex curves were all reset to a higher pressure level (P < 0.05) after 24 h, 1 wk, and 2 wk of ANG II. Forty minutes after stopping ANG II on the same days, MAP decreased, and curves were shifted back toward control (P < 0.05), indicating that ANG II was required for the resetting. Two findings suggest that the resetting action ofANG II is distinct from the pressor effect. First, although stopping ANG II reversed the hypertension as it reversed the resetting, reversal of the hypertension instead by prolonged infusion of nitroprusside along with ANG II did not have the same effect. Second, NE and heart rate baroreflex curves returned toward preinfusion positions after stopping ANG II (P < 0.05), even when the hypertension was nearly maintained by phenylephrine infusion. In conclusion, chronic increases in ANG II may have a global baroreflex resetting effect by a mechanism that is in part independent of the hypertension.
Enalapril and captopril enhance antioxidant defenses in mouse tissues
Authors: de Cavanagh E. M. , Fraga C. G. , Ferder L. , Inserra F.
Published: December 2017

This study was conducted to investigate a possible systemic effect of angiotensin-converting enzyme inhibitors (ACEi) on tissue antioxidant defenses. CF1 mice (4-mo-old females) were administered either water (control) or water containing enalapril (20 mg/l) or captopril (50 mg/l) during 11 wk. Neither enalapril nor captopril treatment had an effect on body mass or brain, kidney, or heart weight relative to controls. CuZn-superoxide dismutase (SOD) activity was increased by enalapril treatment in kidney medulla (27%), heart (24%), and erythrocytes (19%) and by captopril treatment in kidney medulla (43%) and heart (54%) relative to controls. Mn-SOD and catalase activities were unaffected by either treatment. Enalapril, but not captopril treatment, increased Se-glutathione peroxidase activity in renal medulla (19%). Nonenzymatic antioxidant defenses, evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (HICL), were enhanced in kidney cortex (48%) by enalapril and in brain by enalapril (44%) or captopril (36%) treatment relative to controls. As evaluated in vitro by HICL and thiobarbituric acid-reactive substances formation, captopril had a free radical scavenger activity, whereas neither enalapril nor lisinopril was effective. These results suggest that ACEi may protect tissues from oxidative damage by increasing enzymatic and nonenzymatic antioxidant defenses.
Brain angiotensinergic pathways mediate renal nerve inhibition by central hypertonic NaCl in conscious sheep
Authors: May C. N. , McAllen R. M.
Published: December 2017

The renal sympathetic responses to infusion of hypertonic solutions into the lateral cerebral ventricles were investigated in conscious sheep. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) containing 0.6 M NaCl, at 1 ml/h for 20 min, reduced renal sympathetic nerve activity (RSNA) by 81 +/- 5% (n = 6, P < 0.001). Plasma renin concentration also fell (P < 0.05), whereas arterial pressure increased by 6.4 +/- 0.7 mmHg (P < 0.01). Intracerebroventricular hypertonic sorbitol (0.9 M in CSF at 1 ml/h) had no effect. The AT1 receptor antagonist losartan (1 mg/h) abolished the plasma renin and arterial pressure responses to intracerebroventricular hypertonic saline and significantly reduced the fall in RSNA to 17 +/- 10% (P < 0.001). During intracerebroventricular hypertonic saline, the baroreflex relation of RSNA to diastolic pressure was shifted to the left and that to central venous pressure was abolished compared with control relations obtained by manipulating pressure with intravenous phenylephrine. These findings indicate that 1) RSNA is inhibited by a central mechanism that senses high sodium (or perhaps chloride) concentration rather than hypertonicity; 2) this inhibition occurs independently of reflexes from high- and low-pressure baroreceptors, although these may enhance the inhibition; and 3) inhibition of RSNA by hypertonic saline involves a central angiotensinergic pathway.
Cardiac sympathetic premotor neurons
Authors: Campos R. R. , McAllen R. M.
Published: December 2017

To locate premotor neurons controlling the cardiac sympathetic supply and to determine their relation to brain stem vasomotor pathways, the rostral ventrolateral medulla (RVLM) was mapped in seven chloralose-anesthetized cats, with the use of microinjections of sodium glutamate (5-10 nl, 0.1 M) to excite neuronal cell bodies. Cardiac sympathetic responses were recorded from the ipsilateral inferior cardiac nerve, while recordings were made simultaneously from postganglionic vasoconstrictor fibers to skeletal muscle (ipsilateral peroneal nerve). Baroreceptors were denervated to eliminate the reflex effects of blood pressure changes. Most of the 115 injected RVLM sites excited both sympathetic nerves. Inferior cardiac nerve activity increased by up to 395% (mean 105 +/- 86%, SD), and muscle vasoconstrictor activity increased by up to 487% (110 +/- 107%). Their relative response varied with injection site, however. For 16 of the most rostromedial injections, the inferior cardiac nerve-to-muscle vasoconstrictor response ratio exceeded that expected by two- to sevenfold; for 9 very caudolateral injections that ratio was strongly reversed, favoring muscle vasoconstrictors by two to fivefold. Intervening sites gave more equal responses. Overall, the response ratio varied systematically with injection site. These findings demonstrate that neurons with preferential or selective actions on the cardiac sympathetic outflow are present in the RVLM and are organized topographically. The simplest interpretation is that a population of selective cardiac sympathetic premotor neurons occupies a territory substantially overlapping, but centered rostromedially to, the population controlling vasoconstriction in muscle.
Analysis of responses to bradykinin in the rat hindquarters vascular bed
Authors: Nossaman B. D. , Kaye A. D. , Feng C. J. , Kang B. , Kadowitz P. J.
Published: December 2017

The mechanism by which bradykinin (BK) decreases vascular resistance was investigated in the hindquarters vascular bed of the rat. Under conditions of controlled blood flow, BK produced dose-related decreases in hindquarters perfusion pressure when injected into the perfusion circuit in doses of 0.1-1.0 pg. Responses to BK were reproducible with respect to time, and HOE-140 (D-Arg, [Hyp3,Thi5,D-Tic7,Oic8] -BK), a kinin B2 receptor antagonist, decreased hindquarters vasodilator responses to the peptide. HOE-140 had no significant effect on responses to vasodilator agents, which act by a variety of pharmacologically distinct mechanisms. Nitric oxide synthase inhibitors N(omega)-nitro-L-arginine methyl ester or N(omega)-nitro-L-arginine benzyl ester did not decrease responses to BK in doses that decreased hindquarters vasodilator responses to acetylcholine. The cyclooxygenase inhibitors meclofenamate and indomethacin had no effect on responses to BK in doses that attenuated vasodilator responses to the prostaglandin precursor, arachidonic acid. Clotrimazole or 5,8,11,14-eicosatetraynoic acid (ETYA), cytochrome P-450 arachidonic acid metabolism inhibitors, in doses that attenuated vasodilator responses to arachidonic acid, had no effect on responses to BK. Glybenclamide or U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl), K+-ATP channel antagonists, in doses that attenuated responses to lemakalim, had no significant effect on responses to BK. Finally, des-Arg9-BK, a reported kinin B1 receptor agonist, decreased hindquarters perfusion pressure when injected in doses of 3-30 microg, and responses to the B1 agonist were attenuated by HOE-140. The observation that des-Arg9-BK, in high doses, induces modest HOE-140-sensitive responses suggests that kinin B1 receptors are not normally expressed in the hindquarters vascular bed of the rat. The present results indicate that BK dilates the hindquarters vascular bed by a kinin B2 receptor mechanism that is independent of the release of nitric oxide, cyclooxygenase, or P-450 metabolites of arachidonic acid or the activation of K+-ATP channels.
EEG delta power and auditory arousal in rested and sleep-deprived rabbits
Authors: Opp M. R. , Toth L. A. , Tolley E. A.
Published: December 2017

Slow-wave activity in the electroencephalogram is thought to reflect the depth or intensity of sleep. This hypothesis is primarily derived from studies of rats or humans. However, some characteristics of sleep of rabbits differ from those of rats or humans. To determine whether slow-wave activity (power density in the delta frequency band of 0.5-5.0 Hz) correlates with arousability in rabbits, we presented auditory stimuli (72-90 dB) to control or sleep-deprived animals during slow-wave sleep. The resulting behavioral responses, defined by changes in eye state and body posture, and the latency to return to sleep were used as measures of arousability. Behavioral responsiveness to auditory stimuli increased with increasing stimulus intensity in both control and sleep-deprived animals. Overall, however, sleep-deprived animals exhibited fewer postural changes and eye openings than did control rabbits. Sleep-deprived rabbits also more rapidly returned to sleep after the stimulus presentation than did control animals. Latency to return to sleep was correlated with delta power before stimulus presentation, but behavioral responsiveness was not. These data suggest that, in this rabbit model, delta power may not be predictive of behavioral arousability but may reflect sleep propensity.
Control of proximal tubule acidification by the endothelium of the peritubular capillaries
Authors: Amorena C. , Castro A. F.
Published: December 2017

Guanosine 3',5'-cyclic monophosphate (cGMP), a nitric oxide mediator, stimulates Na+/H+ exchange in brush-border vesicles of the renal cortex. The aim of the present work was to test whether the endothelium of the peritubular capillaries modulated the rate of proximal luminal acidification through the release of endothelium-derived nitric oxide (EDNO). Perfusion of the tubule lumen with dibutyryl cGMP increased net proton flux (J(H)). Two agents that elicit EDNO production, bradykinin (BK) and carbamylcholine (Cch), increased J(H) when added to the peritubular capillary perfusate. Bradykinin did not affect J(H) when the peritubular capillaries and the lumen were perfused with Na-free solution. Methylene blue (MB) and N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the elevation in J(H) by Cch and also decreased basal J(H). Bradykinin increased cGMP content of isolated proximal convoluted tubules, but only if they were coincubated with endothelial cells. This effect of BK was blocked by L-NAME. The results suggest that the endothelium of the peritubular capillaries affects proximal tubule acidification through changes of cGMP in proximal tubule cells, probably via stimulation of Na+/H+ exchanger.
Pressure, volume, and chemosensitivity in afferent innervation of urinary bladder in rats
Authors: Moss N. G. , Harrington W. W. , Tucker M. S.
Published: December 2017

Bladder afferent nerve activity was recorded from the pelvic and hypogastric nerves of rats anesthetized with pentobarbital sodium. Bladder filling with isotonic NaCl at a rate of 250 microl/min excited multiunit afferent activity in the hypogastric nerve by 190 +/- 38% over background at a pressure of 30 mmHg, whereas 150 meq/l KCl at the same filling rate excited hypogastric nerve activity by 498 +/- 103% (P < 0.0001). This difference was localized to a group of chemosensitive fibers that are excited by bladder filling with KCl in a concentration-dependent fashion but are insensitive to bladder filling with NaCl. Bladder filling with 200 meq/l KCl at different filling rates caused a bursting pattern of discharge in these fibers at consistent bladder volumes but with a pressure threshold that increased proportionately with filling rate. Other hypogastric bladder afferent fibers were activated to a similar extent by NaCl and KCl solutions. Chemoreceptive bladder afferent fibers were rare in the pelvic nerve (1 of 15 units), and multiunit preparations showed comparable excitations during bladder filling with NaCl and KCl solutions. The bursting activation of bladder chemoreceptive afferent nerves in hypogastric nerves could signal noxious overdistension and/or inflammation of the bladder.
Hemorrhage induces acute cardioadaptation to ischemia-reperfusion by an alpha1-adrenoceptor-mediated, protein synthesis-independent mechanism
Authors: Meldrum D. R. , Cleveland J. C. , Meng X. , Sheridan B. C. , Banerjee A. , Harken A. H.
Published: December 2017

Hemorrhage and resuscitation (H-R) has been recognized as an exclusively destructive process that results in multiple organ dysfunction. Although it is well established that endogenous adaptation mechanisms exist, it is unknown whether H-R induces endogenous adaptive/protective mechanisms. Furthermore, alpha1-adrenoceptors and de novo protein synthesis have been variably implicated in myocardial adaptation responses. This study tests the hypothesis that H-R results in myocardial adaptation by a mechanism mediated by alpha1-adrenoceptors and requiring de novo protein synthesis. The aims of the present study were to determine 1) whether H-R stress results in acute cardioadaptation to subsequent global, normothermic ischemia-reperfusion (I-R); 2) whether H-R-induced endogenous adaptation is mediated by alpha1-adrenoceptors; and 3) whether H-R-induced endogenous adaptation requires de novo protein synthesis. Rats were hemorrhaged and resuscitated, sham operated, or neither, with and without prior alpha1-adrenoceptor or protein synthesis inhibition. Hearts were then isolated and subjected to a second insult consisting of global, normothermic I-R (20 min ischemia-40 min reperfusion). The results show that antecedent H-R improved post-I-R left ventricular developed pressure, compliance, coronary flow, and decreased reperfusion creatine kinase loss (P < 0.05, analysis of variance with Bonferroni-Dunn). H-R-induced adaptation was abolished by prior alpha1-adrenoceptor blockade (prazosin, 0.5 mg/kg ip); however, inhibition of de novo protein synthesis (cyclohexamide, 1.0 mg/kg ip) did not affect H-R-induced acute adaptation. This study constitutes the initial demonstration that H-R induces endogenous cardioadaptation, which is mediated by an alpha1-adrenergic signaling pathway, but does not require de novo protein synthesis.
Effect of exposure to hypoxia from birth on aldosterone in rabbits: role of unesterified fatty acids
Authors: Raff H. , Jankowski B. M. , Goodfriend T. L. , Baker J. E. , Papanek P. E.
Published: December 2017

Hypoxia and fluid and electrolyte disturbances are serious risks to normal postnatal development. Because a decrease in inspired O2 (hypoxic hypoxia) inhibits aldosterone synthesis in the adult and aldosterone controls water and electrolyte balance, we studied adrenocortical function in rabbits exposed to normobaric normoxia or hypoxic hypoxia (fraction of inspired O2 0.09) from birth. At 21 days of age, rabbits were anesthetized, the adrenals were rapidly removed, and the adrenal capsules containing mostly zona glomerulosa cells were separated. Cells were dispersed with collagenase and studied in vitro. Hypoxia in vivo resulted in a 73% decrease in basal aldosterone release and a 86% decrease in adenosine 3',5'-cyclic monophosphate-stimulated aldosterone release in vitro. We hypothesized that increased unesterified fatty acids could be partly responsible for inhibition of aldosterone synthesis. Total serum unesterified fatty acids in hypoxic kits were significantly increased (298 +/- 14 micromol/l) compared with normoxic kits (184 +/- 31 micromol/l). When cells from hypoxic rabbits were washed with fatty acid-free albumin and studied under conditions devoid of fatty acids, aldosterone production was partially restored. Corticosterone production was not affected by washing. Washing had no effect on aldosterone synthesis by cells from normoxic rats. Finally, exposing washed zona glomerulosa cells to oleic acid (10-50 microM) inhibited aldosteronogenesis. We conclude that exposure to hypoxia from birth attenuates aldosterone production in part due to an increase in levels of unesterified fatty acid levels.
Ca2+ uptake by cardiac sarcoplasmic reticulum at low temperature in rat and ground squirrel
Authors: Liu B. , Belke D. D. , Wang L. C.
Published: December 2017

The Ca2+ uptake by isolated cardiac sarcoplasmic reticulum (SR) was compared between Richardson's ground squirrels and rats at 37, 25, 15, and 5 degrees C. The rate of SR Ca2+ uptake in ground squirrels was significantly higher than in rats over the temperature range. This marked species difference was observed over a Ca2+ concentration range from 0.1 to 10 microM. The Arrhenius plot for Ca2+ uptake was linear for ground squirrels between 37 and 5 degrees C but showed a depression from linearity for rats at 5 degrees C. This temperature sensitivity was also reflected in rat SR Ca2+-adenosinetriphosphatase activity. Analysis of [3H]ryanodine binding in SR suggests that more Ca2+ release channels are in an open state at low temperatures in rats than in ground squirrels. Together, these results suggest that species differences in the response of SR to low temperature may account for the rise in cytosolic free Ca2+ in cold-sensitive species and may be responsible, at least in part, for the inability of cold-sensitive hearts to function at low temperature.
Rates of local cerebral protein synthesis in fetal and neonatal sheep
Authors: Abrams R. M. , Burchfield D. J. , Sun Y. , Smith C. B.
Published: December 2017

During gestation there is likely to be a constantly changing rate of protein synthesis in the brain that may exhibit regional specificity. With the use of the quantitative autoradiographic L-[1-(14)C]leucine method for the determination of local rates of leucine incorporation into cerebral protein (lCPS(Leu)), we have sought to characterize this important process. lCPS(Leu) was measured in nine fetal sheep (118-139 days gestational age) and five newborn lambs (1-5 days of age). In other experiments, the fraction of leucine in the precursor pool for protein synthesis in the brain derived from the arterial plasma was determined to be 0.57 +/- 0.04 (mean +/- SE) in one fetus and two lambs. This value was used in the calculation of lCPS(Leu) in 35 regions of the central nervous system, pineal body, and whole brain. Regardless of age, lCPS(Leu) was highest in the pineal body, brain stem, and hypothalamic nuclei and lowest in white matter. In sensorimotor cortex, corona radiata, pyramidal tracts, and whole brain, lCPS(Leu) was positively correlated with prenatal age (P < or = 0.05). These increases in lCPS(Leu) probably reflect myelination in the cerebrum, which is known to occur in late gestation.
Antioxidant status and lipid peroxidation after short-term maximal exercise in trained and untrained humans
Authors: Ortenblad N. , Madsen K. , Djurhuus M. S.
Published: December 2017

The purpose of this study was to measure resting muscle and blood antioxidant status in untrained (n = 8) and jump-trained (n = 8) humans and to evaluate free radical-mediated muscle damage after a strenuous jump test consisting of six bouts of 30-s continuous jumping separated by 2 min of rest. Resting muscle antioxidant activities [superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), and manganese SOD] were significantly higher in jump-trained compared with untrained subjects. Blood antioxidant enzyme activities and muscle catalase, however, were not different between the two groups. Creatine kinase activities increased significantly (P < 0.0001) after the jump test in untrained individuals, but remained unchanged in the jump trained. Plasma and muscle malonaldehyde (MDA) after the jump test were not significantly different from rest. These data suggest that jump training is associated with elevated activities of SOD and the coupled enzymes GPX and GR in muscle tissue, but other antioxidants remain unchanged. High-intensity jump exercise induces muscle enzyme leakage in untrained humans, but muscle lipid peroxidation, measured as changes in MDA, was not different in the two groups despite the varied muscle antioxidant enzyme levels.
Energy budget in free-living animals: a novel approach based on the doubly labeled water method
Authors: Kam M. , Degen A. A.
Published: December 2017

We provide a theoretical and practical model for the calculation of energy balance of free-living animals using the doubly labeled water method. Energy expenditure, metabolizable energy intake, and body energy balance (energy retention, negative or positive) of animals are estimated using CO2 production, water influx, and dietary habits. This model accounts for CO2 produced from the 1) oxidation of dietary substrates, 2) catabolism of body tissue, and 3) deposition of body energy. We examined the model using data from studies on five homeotherms reported in the literature. The ratios between daily energy expenditure using our model and that presented in the reports ranged between 0.76 and 1.18. Metabolizable energy intakes were as low as 43% of energy expenditure in negative energy-balanced hummingbirds and as high as 245% of energy expenditure in positive energy-balanced koala bears. This model is the first that allows theoretical calculation of all energy budget components, including energy retention, in free-living animals using the doubly labeled water method.
Food intake alters muscle protein gain with little effect on Na(+)-K(+)-ATPase and myosin isoforms in suckled rats
Authors: Fiorotto M. L. , Davis T. A.
Published: December 2017

Biochemical maturation accompanies the rapid accretion of skeletal muscle in early life. We wished to determine whether changes in muscle protein accretion, induced by variations in food intake, altered the biochemical maturation of the soleus and the extensor digitorum longus (EDL) muscles. Rat pups were suckled in litters of 4, 10, or 16 to induce differences in food intake. At 21 days of age, muscle protein and DNA were quantitated and biochemical maturation was assessed from measurement of [3H]ouabain-binding site abundance and myosin isoform composition. Differences in food intake produced a twofold range in body and muscle weights and protein and DNA contents. Protein accretion was more sensitive to nutrient intake in the soleus than in the EDL. Serum 3-5,3'-triiodothyronine (T3) and insulin concentrations decreased with a reduction in food intake. Total ouabain-binding sites were not altered in either muscle and were independent of muscle size. Differences in myosin isoform composition were more pronounced for the soleus than the EDL, but were relatively small in magnitude. These results demonstrate that, whereas postnatal muscle protein accretion and circulating hormone concentrations are sensitive to food intake, the biochemical maturation is resilient. The immature muscle does not exhibit the fiber type-specific responses to malnutrition typical of mature muscle.
Growth of artificially fed infant rats: effect of supplementation with insulin-like growth factor I
Authors: Philipps A. F. , Anderson G. G. , Dvorak B. , Williams C. S. , Lake M. , Lebouton A. V. , Koldovsky O.
Published: December 2017

Insulin-like growth factor I (IGF-I), a potent mitogenic peptide, is present in considerable quantities in most mammalian milks, but its importance for the neonate is unknown. To test the hypothesis that milk-borne IGF-I is an important factor in the regulation of neonatal growth, as well as that of the gastrointestinal tract, rat pups were fed a rat milk substitute (RMS) devoid of growth factors via gastrostomy. These animals were compared with those given RMS supplemented with recombinant human IGF-I added at a concentration of 500 ng/ml. Animals given RMS + IGF-I gained mere weight than controls, although skeletal growth as represented by elongation of the tail was no different. Animals fed RMS + IGF-I had increased brain and liver wet weights as well as increased liver and small intestine protein contents. Serum IGF-I concentrations in the IGF-I-supplemented group were more than twofold above RMS controls and were similar to dam-fed rat pups. Semiquantification of serum IGF-binding proteins (IGFBP) in these animals documented that in IGF-I-supplemented pups the amount of 38- to 40-kDa molecular mass IGFBP species was also greater than in RMS controls. The rate of migration of enterocytes from crypts in duodenum and proximal jejunum was greater in IGF-I-supplemented animals than in rats fed RMS alone. These studies suggest that milk-borne IGF-I is important in modulation of somatic and gastrointestinal tract growth in the neonatal rat.
Loss of body fat in lean parabiotic partners of ob/ob mice
Authors: Harris R. B.
Published: December 2017

The objective of this experiment was to confirm whether changes in serum leptin and leptin expression were consistent with it being the "lipostatic" factor implicated by earlier parabiosis studies. Lean (+/?) and obese (ob/ob) female C57B1/6J-ob mice were parabiosed (lean-ob/ob) at 7 wk of age. Controls were ob/ob-ob/ob and lean-lean pairs, and single lean and ob/ob mice. Pairs were maintained for 50 days. In ob/ob members of lean-ob/ob pairs serum insulin was normalized, food intake was suppressed, and body fat was reduced by 14%. Lean partners of ob/ob mice had a reduced rectal temperature and experienced a 37% reduction in body fat. Despite loss of fat, serum leptin and adipose leptin mRNA expression were unchanged in lean partners of ob/ob mice. These results suggest that, in lean-ob/ob parabiotic pairs, the ob/ob mouse responds to leptin originating in the lean parabiont, whereas the lean partner responds to a circulating signal, originating in the ob/ob mouse, that maintains leptin expression at inappropriate levels for the degree of adiposity of the lean animal.
Identification of brown fat and mechanisms for energy balance in the marsupial, Sminthopsis crassicaudata
Authors: Hope P. J. , Pyle D. , Daniels C. B. , Chapman I. , Horowitz M. , Morley J. E. , Trayhurn P. , Kumaratilake J. , Wittert G.
Published: December 2017

The presence of brown adipose tissue (BAT) in marsupials is controversial because attempts to identify mitochondrial uncoupling protein (UCP) have been unsuccessful. Sminthopsis crassicaudata is a small nocturnal marsupial with an interscapular pad of adipose tissue. Electron microscopy revealed this tissue to have characteristics typical of BAT. GDP binding and UCP detection by immunoblot confirmed BAT. Expression of UCP was increased by cold exposure. When animals were placed from 28 to 15 degrees C, body temperature (Tb) decreased by 1.7 degrees C within 30 min and a further 1.0 degree C by 90 min (P < 0.001) before stabilizing at these lower levels. When animals were returned to 28 degrees C, Tb increased within 30 min (P < 0.001) and returned to basal by 120 min. When animals were maintained at 15 degrees C with ad libitum food for 12 days, Tb (P < 0.05), tail width (P < 0.04), and O2 consumption (P < 0.01) all decreased. The respiratory quotient increased (P < 0.001), indicating a change from fat to carbohydrate utilization. Food intake was unchanged, and body weight increased on day 1 (P < 0.01) before returning to baseline on day 3, remaining stable thereafter. These data suggest that although BAT is present in the marsupial S. crassicaudata, it may not be necessary for thermogenesis, at least in the short term. S. crassicaudata utilizes a plasticity in Tb and a change in substrate utilization to maintain energy balance and body composition without the need for an increase in metabolic rate or food consumption and without the need for torpor.
Mechanism for changes in vasopressin during acute exposure at 3 atm abs air
Authors: Torii R. , Sagawa S. , Wada F. , Nagaya K. , Endo Y. , Yamazaki F. , Nakamura T. , Claybaugh J. R. , Shiraki K.
Published: December 2017

Plasma arginine vasopressin (AVP) concentration is reduced in human subjects during prolonged saturation dive exposures of 4 atmospheres absolute (atm abs) and greater. The objectives of the present study were to determine if AVP would be reduced in eight male subjects during a 1-h exposure of 3 atm abs air and, if so, to determine the mechanisms responsible for the AVP response. Assessments of transmural central venous pressure (central venous pressure-esophageal pressure) and cardiac volume measurements were made to evaluate the possible role of cardiopulmonary receptors on the AVP response. Also, plasma osmolality (P(osmol)), venous blood gases, and mean corpuscular volume (MCV) were determined to evaluate potential effects of osmoreceptor and other fluid shifts on AVP release. AVP decreased (P < 0.05) by 0.5 microU/ml at 3 atm abs, whereas the transmural central venous pressure and cardiac volume remained unchanged throughout the experimental periods. A significant reduction (P < 0.05) in P(osmol) (by approximately 3 mosmol/kgH2O) was detected at 3 atm abs. Therefore, we conclude that the reduction in P(osmol) may cause the reduction in AVP during exposure to 3 atm abs pressure. The reduction in P(osmol) without water intake requires the postulation of an internal source of water. We propose that the threefold increase (P < 0.01) in venous PO2 and concomitant decrease (P < 0.05) in venous MCV suggest that the red blood cell may contribute to hypotonicity at 3 atm abs.
Effects of alpha-adrenergic stimuli on mesenteric collecting lymphatics in the rate
Authors: Benoit J. N.
Published: December 2017

The present study examined the effects of alpha 1- and alpha 2-adrenergic stimuli on rat mesenteric collecting lymphatics in vivo. Sprague-Dawley rats were anesthetized, and the mesentery was prepared for intravital microscopic study. Mesenteric collecting lymphatic diameter was continuously monitored by using a computerized video tracking system, and indexes of lymphatic pumping (e.g., contraction frequency, stroke volume, ejection fraction, and muscle shortening velocity) were determined from the diameter record. Contractile activity was monitored before and during the administration of various adrenergic agonists and antagonists. The receptor antagonists prazosin (alpha 1) and yohimbine (alpha 2) did not significantly alter baseline diameter or contractile activity, which suggests that lymphatics possess no basal adrenergic tone. Norepinephrine and phenylephrine (01-1.0 microM) produced dose-dependent increases in frequency and decreases in diameter. Lymphatic pump flow increased in direct proportion to frequency, because stroke volume did not change. The changes in lymphatic pumping produced by 1 microM norepinephrine were completely blocked by prazosin or phentolamine and only partially blocked by yohimbine. The alpha 2-adrenoceptor agonist (alpha-methyl-norepinephrine) produced no changes in lymphatic activity. This latter observation suggests that a role for postjunctional alpha 2-adrenoceptors in modulating mesenteric lymphatic smooth muscle is unlikely. The results of these studies support the existence of alpha-adrenoceptors on lymphatic smooth muscle. It is concluded that conditions characterized by increased sympathetic outflow may augment lymphatic function through alpha 1- but not alpha 2-adrenoceptors.
Functional and structural changes in the thick ascending limb of Henle's loop in rats with liver cirrhosis
Authors: Jonassen T. E. , Marcussen N. , Haugan K. , Skyum H. , Christensen S. , Andreasen F. , Petersen J. S.
Published: December 2017

Five weeks after common bile duct ligation (CBL), Wistar rats had histologically verified liver cirrhosis with sodium retention but without ascites. Plasma concentrations of vasopressin and aldosterone were normal. Glomerular filtration rate was unchanged, although renal plasma flow was increased. A test dose of furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%) and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated controls. Stereological examination of kidneys demonstrated a 47% increase in the volume of the inner stripe of the outer medulla, with a 55% increase in the volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic Wistar rats relative to controls. CBL produced a similar degree of liver cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and structural renal changes observed in cirrhotic Wistar rats were absent in vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a permissive action of vasopressin for the adaptive changes in TALH in rats with experimental liver cirrhosis. Our results are consistent with the hypothesis that increased sodium chloride reabsorption in the TALH may contribute to the early sodium retention that precedes ascites formation in rats with secondary biliary liver cirrhosis.
Enhanced responsiveness of cardiac vagal chemosensitive endings to bradykinin in heart failure
Authors: Schultz H. D. , Wang W. , Ustinova E. E. , Zucker I. H.
Published: December 2017

There is good evidence that the cardiopulmonary and arterial baroreflexes are blunted in chronic heart failure (HF). Other evidence, however, suggests that the cardiac chemoreflex is enhanced during HF. In the present study, we sought to determine whether HF alters the sensitivity of cardiac vagal chemosensitive endings to bradykinin (BK), an endogenous mediator that activates ventricular C fiber afferents. We measured the activity of cardiac vagal single fibers and compared the afferent responses to left atrial injections of BK and capsaicin in sham-operated and pacing-induced HF dogs. The capsaicin-sensitive endings did not respond to changes in cardiac pressures evoked by vascular snares and were C fiber endings (0.8-2.1 m/s). Most were located in the left heart. There was no difference in rate or pattern of resting discharge of the cardiac vagal fibers between HF and sham groups (1.5 +/- 0.5 vs. 1.3 +/- 0.3 impulses/s, respectively). The afferent response to BK (0.001-1 microgram/kg), but not capsaicin (1-10 micrograms/kg), was greater in HF compared with sham dogs. Captopril (2 mg/kg i.v.) significantly enhanced resting discharge (P < 0.05) from cardiac chemosensitive vagal afferents in HF but not sham dogs. The afferent response to BK in both groups was significantly (P < 0.05) and similarly enhanced. Indomethacin (5 mg/kg i.v.) significantly inhibited resting discharge (P < 0.05) and nearly abolished the afferent responses to lower doses of BK in HF, but did not affect resting discharge and less effectively attenuated responses to BK in sham dogs. Responses to capsaicin did not differ between HF and sham animals. From these results, we conclude that 1) resting discharge from cardiac vagal chemosensitive endings is not altered in HF, 2) these vagal endings exhibit an enhanced sensitivity to exogenous BK but not to capsaicin in the HF state, 3) angiotensin-converting enzyme activity inhibits resting discharge from these afferents in HF, and 4) the cyclooxygenase system contributes to the enhanced BK responsiveness of cardiac chemosensitive endings in HF.
Prevention of diet-induced obesity in transgenic mice overexpressing skeletal muscle lipoprotein lipase
Authors: Jensen D. R. , Schlaepfer I. R. , Morin C. L. , Pennington D. S. , Marcell T. , Ammon S. M. , Gutierrez-Hartmann A. , Eckel R. H.
Published: December 2017

Transgenic (Tg) FVB/N mice were produced that overexpress human lipoprotein lipase (LPL) in skeletal muscle using the muscle creatine kinase promoter and enhancers. It was hypothesized that, by overexpressing LPL in muscle, high fat feeding-induced obesity would be prevented by diverting lipoprotein-derived triglyceride fatty acids away from storage in adipose tissue to oxidation in muscle. Mice were examined both at 6 wk of age before high fat (HF) feeding and at 19 wk of age after 13 wk of HF (46.1% fat) or high carbohydrate (HC) feeding (11.5% fat). At 6 wk in heterozygous Tg mice, LPL was increased 11-fold in white muscle and 2.5-fold in red muscle, but not in cardiac muscle or spleen, brain, lung, kidney, or adipose tissue. Plasma triglycerides (mg/dl) were lower in Tg mice (87 +/- 7 vs. 117 +/- 7, P < 0.0001), and glucose increased (201 +/- 9 vs. 167 +/- 8 mg/dl, P = 0.029). There were no differences in body weight between Tg and nontransgenic (nTg) mice; however, carcass lipid content (% body wt) was significantly decreased in male Tg mice at 6 wk (7.5 +/- 1.0 vs. 9.0 +/- 1.0%, P = 0.035). Body composition was not different in female Tg mice at 6 wk. Overall, when Tg mice were fed either a HC or HF diet for 13 wk, plasma triglycerides (P < 0.001) and free fatty acids (P < 0.001) were decreased, whereas plasma glucose (P = 0.01) and insulin (P = 0.05) were increased compared with nTg mice. HF feeding increased carcass lipid content twofold in both male (10.3 +/- 1.1 vs. 21.4 +/- 2.6%, HC vs. HF, P < 0.001) and female nTg mice (6.7 +/- 0.9 vs. 12.9 +/- 1.8%, P = 0.01). However, the targeted overexpression of LPL in skeletal muscle prevented HF diet-induced lipid accumulation in both Tg male (10.2 +/- 0.7 vs. 13.5 +/- 2.2%, HC vs. HF, P = NS) and female Tg mice (6.8 +/- 0.6 vs. 10.1 +/- 1.4%, P = NS). The potential to increase LPL activity in muscle by gene or drug delivery may prove to be an effective tool in preventing and/or treating obesity in humans.
Ethanol disrupts and decreases the regulated body temperature differentially in C57BL/6J and DBA/2J mice
Authors: Crawshaw L. I. , Wallace H. L. , Crabbe J. C. , Ramos C. , Duerr J. , O'Connor C. S.
Published: December 2017

Two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), were evaluated for effects of ethanol on thermoregulation. Continuous recording of core temperature (Tc) from undisturbed animals at an ambient temperature (Ta) of 27 degrees C indicated Tc was similar for both strains during active (approximately 38.0 degrees C) and inactive (approximately 36.7 degrees C) periods. Ethanol-injections of 1.5, 2.5, 3.5, and 4.5 g/kg in an environment where Ta rose and fell at 6-min intervals, reaching extremes of 14 and 42 degrees C, produced dose-dependent falls in Tc for both strains. The changes in Ta produced fluctuations in Tc under all conditions. The amplitude of these fluctuations in Tc was used as a measure of physiological disruption. Dose-dependent increases in disruption were found for both strains. At a constant 26 degrees C Ta, ethanol produced dose-related increases in tail temperature. Responses after ethanol administration were different for B6 and D2 mice. The results indicate regulated temperature is similar for B6 and D2 strains. Regulated temperature is decreased more by ethanol for B6 mice, whereas disruption of thermoregulation by ethanol is greater for D2 mice.
Effects of small intestinal nutrient infusion on appetite and pyloric motility are modified by age
Authors: Cook C. G. , Andrews J. M. , Jones K. L. , Wittert G. A. , Chapman I. M. , Morley J. E. , Horowitz M.
Published: December 2017

The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are unknown. The aims of this study were to evaluate the effects of aging on small intestinal regulation of appetite and pyloric motility. Eight healthy older (age 65-75 yr) and seven healthy young (age 20-34 yr) male subjects received isocaloric (2.9 kcal/min) intraduodenal infusions of lipid and glucose for 120 min, each on separate days. During the intraduodenal infusions, perceptions of hunger, desire to eat, and fullness were assessed by visual analog scales. Pyloric motility (isolated pyloric pressure waves and tonic pyloric pressure) was measured by manometry during the intraduodenal lipid infusion. On each day, after completion of the intraduodenal nutrient infusion the subject was offered a buffet meal and food intake was quantified. Before intraduodenal nutrient infusions, sensations of hunger (P < 0.01) and desire to eat (P < 0.05) were less in the older compared with the young subjects. In the young, intraduodenal lipid suppressed hunger to a greater extent than intraduodenal glucose (P < 0.05). In older persons, neither intraduodenal nutrient infusion suppressed hunger. Intraduodenal lipid and glucose increased fullness in both age groups (P < 0.05 for both), with no significant difference between the two nutrients. There was no significant difference in food intake from the buffet meal between the elderly and young subjects. Intraduodenal lipid infusion stimulated phasic pyloric pressure waves in both age groups (P < 0.01 for both), and this response was greater (P < 0.05) in older persons. There was an increase (P < 0.01) in tonic pyloric pressure during intraduodenal lipid infusion that was not significantly different between the two age groups. We conclude that the effect of small intestinal lipid infusion on hunger is attenuated, and the stimulation of phasic pyloric pressure waves increased in healthy older persons compared with healthy young males. Increased feedback from small intestinal nutrients does not appear to be responsible for the physiological anorexia of aging.