bluuebunny/crossref_metadata_2025 huggingface dataset:
Ammonia movement and distribution after exercise across white muscle cell membranes in rainbow trout
Authors: Wang Y. , Heigenhauser G. J. , Wood C. M.
Published: December 2017

Manipulations of pH and electrical gradients in a perfused preparation were used to analyze the factors controlling ammonia distribution and flux in trout white muscle after exercise. Trout were exercised to exhaustion, and then an isolated-perfused white muscle preparation with discrete arterial inflow and venous outflow was made from the posterior portion of the tail. The tail-trunks were perfused with low (7.4)-, medium (7.9)-, and high (8.4)-pH saline, achieved by varying HCO3- concentration ([HCO3-]) at constant Pco2. Intracellular and extracellular pH, ammonia, CO2, K+, Na+, and Cl- were measured. Muscle intracellular pH was not affected by changes in extracellular pH. Increasing extracellular pH caused a decrease in the transmembrane NH3 partial pressure (PNH3) gradient and a decrease in ammonia efflux. When extracellular K+ concentration was increased from 3.5 to 15 mM in the medium-pH group, a depolarization of the muscle cell membrane potential from -92 to -60 mV and a 0.1-unit depression in intracellular pH occurred. Ammonia efflux increased despite a marked reduction in the PNH3 gradient. Amiloride (10(-4) M) had no effect, indicating that Na+/H(+)-NH4+ exchange does not participate in ammonia transport in this system. A comparison of observed intracellular-to-extracellular ammonia distribution ratios with those modeled according to either pH or Nernst potential distributions supports a model in which ammonia distribution across white muscle cell membranes is affected by both pH and electrical gradients, indicating that the membranes are permeable to both NH3 and NH4+. Membrane potential, acting to retain high levels of NH4+ in the intracellular compartment, appears to have the dominant influence during the postexercise period. However, at rest, the pH gradient may be more important, resulting in much lower intracellular ammonia levels and distribution ratios. We speculate that the muscle cell membrane NH3-to-NH4+ permeability ratio in trout may change between the rest and postexercise condition.
Thirst and fluid regulatory responses to hypertonicity in older adults
Authors: Stachenfeld N. S. , Mack G. W. , Takamata A. , DiPietro L. , Nadel E. R.
Published: December 2017

To assess the fluid regulatory responses in aging adults, we measured thirst perception and osmoregulation during and after infusion of hypertonic NaCl) saline in older (72 +/- 2 yr, n = 6) and younger (26 +/- n = 6) subjects. Hypertonic saline was infused at 0.1 min-1.kg-1 for 120 min. On a separate day, the same subjects were infused identically with isotonic saline as a control. After infusion and a 30-min equilibration period, the drank water ad libitum for 180 min. Hypertonic infusion led to graded increases in plasma osmolality (Posm; 18 +/- 2 and 20 +/- 2 mosmol/kgH2O) and percent changes plasma volume (16.2 +/- 1.9 and 18.0 +/- 1.2%) that were in older and younger subjects. Osmotically stimulated increases in thirst (94.8 +/- 18.9 and 88.3 +/- 25.6 mm), assessed on a line rating scale, and plasma arginine vasopressin concentration (6.08 +/- 1.50 and 4.51 +/- 1.37 pg/ml, for older younger, respectively) were also unaffected by age. subsequent hypervolemia, both groups of subjects sufficient water to restore preinfusion levels of Posm. Renal handling of free water and sodium was also unaffected by age during recovery from hypertonic saline infusion, but was significantly lower in older subjects during recovery from saline infusion, resulting in net fluid retention and a significant fall in Posm (6 mosmol/kgH2O). In contrast to earlier reports of a blunted thirst response to dehydration hypertonicity, we found that osmotically stimulated thirst and renal osmoregulation were intact in older adults after hypertonic saline infusion.
Characterization of the CCK-B/gastrin-like receptor in human colon cancer
Authors: Smith J. P. , Stock E. A. , Wotring M. G. , McLaughlin P. J. , Zagon I. S.
Published: December 2017

The gastrointestinal peptide, gastrin, tonically stimulates growth of human colon cancer cells in vivo and in vitro, and does so in a receptor-mediated fashion. This study defined the nature of gastrin binding in human colon cancer using [3H]L-365,260, a specific cholecystokinin B (CCK-B)/gastrin antagonist found to block gastrin's effects on growth. Following elucidation of optimal binding conditions (e.g., pH, time, and temperature) in log phase HT-29 human colon cancer cells, specific and saturable binding with a dissociation constant of 4.8 +/- 0.7 nM and a maximal binding capacity (Bmax) of 320 +/- 120 fmol/mg protein, consistent with a single binding site, was recorded. Binding was localized to the membrane fraction. Exposure to gastrin or receptor antagonist decreased and increased, respectively, the Bmax. Competition experiments indicated that L-365,260 was 25- and 200-fold more effective at displacing radiolabeled L-365,260 than gastrin and cholecystokinin, respectively. In contrast to log phase cells, the Bmax was decreased by 67 to 76% in confluent and postconfluent cultures. Binding activity was observed in other cell lines examined, as well as in xenografts and colon cancers obtained at surgery. Binding in normal human colonic mucosa was 10-fold less than in colon cancer. These results provide the first comprehensive identification and characterization of a CCK-B/gastrin-like receptor in human colon cancer.
Enhanced reproductive responses to melatonin in juvenile Siberian hamsters
Authors: Prendergast B. J. , Kelly K. K. , Zucker I. , Gorman M. R.
Published: December 2017

Reproductive responses to melatonin (Mel) exposure were assessed in male Siberian hamsters gestated in long (16 h light/day; 16L) or short (8 h light/day; 8L) day lengths (DLs). Hamsters were maintained in constant light beginning at 14 days of age (day 14) and were infused for 3 successive days beginning on day 18, 25, or 32 with long (12 h/day) or short (6 h/day) durations of Mel or saline. Two weeks later, testis and body weights were determined. Responsiveness to Mel was enhanced in hamsters beginning shortly after weaning and was influenced by photoperiodic history. Gonadal growth in 16L hamsters was inhibited by 12-h Mel infusions initiated on day 18 or day 25, but infusions initiated on day 32 were ineffective. Hamsters gestated in 8L were not responsive to Mel treatments initiated on day 18, but discriminated 12-h from 6-h infusions at day 25 and manifested reduced gonadal growth after 12-h Mel infusions on day 32. Hamsters born in 8L to dams judged as photoinsensitive to short DLs did not respond to 12-h infusions on day 32 as inhibitory signals. We propose that maternal Mel secretion provides juvenile males with a photoperiodic history, which allows them to compare gestational with early postweaning Mel signals and thereby program seasonally appropriate developmental trajectories.
Cytochrome P-450-dependent HETEs: profile of biological activity and stimulation by vasoactive peptides
Authors: Carroll M. A. , Balazy M. , Margiotta P. , Huang D. D. , Falck J. R. , McGiff J. C.
Published: December 2017

The cytochrome P-450 pathway is capable of metabolizing arachidonic acid to omega- and subterminal hydroxylase metabolites, 16-, 17-, 18-, 19-, and 20-hydroxyeicosatetraenoic acids (P-450 HETEs). We have quantitated, by gas chromatography-mass spectrometry (GC/MS), endogenous HETEs exiting the rabbit isolated perfused kidney elicited by hormonal stimulation. Kidneys were perfused with Krebs-Henseleit solution containing indomethacin (2.8 microM) to prevent further metabolism of HETEs by cyclooxygenase. Phenylephrine (2-3 microM) was added to the perfusate to raise perfusion pressure to approximately 80 mmHg. Angiotensin II (ANG II), arginine vasopressin (AVP), and bradykinin (BK) were injected into the renal artery and perfusates collected throughout the vasoactive response. After addition of an internal standard, deuterated 19-HETE, perfusates were extracted and purified and P-450 HETEs were derivatized for GC/MS analysis. Under basal conditions, 16-, 18-, 19-, and 20-HETEs were released (range: 50-270 pg/ml), 19-HETE being the highest and fivefold greater than 16-HETE, the lowest. Injection of 50 ng ANG II increased by two- to sixfold P-450 HETE release associated with an increase of 40 +/- 11 mmHg in perfusion pressure. An equipressor dose of AVP (50 ng) did not release P-450 HETEs nor did a 5-micrograms dose of the vasodilator peptide BK, which decreased perfusion pressure by 22 +/- 6 mmHg. Authentic 19- and 20-HETE isomers resulted in dose-dependent dilation, as did 18(R)- and 16(R)-HETEs, whereas their enantiomers and 17-HETE isomers were without effect on perfusion pressure. The vasodilator effects of 18(R)- and 16(R)-HETEs, like 20- and 19-HETEs, were inhibited by indomethacin. Furthermore, P-450 HETEs exhibited both regio- and stereoselective inhibition of proximal tubule adenosine triphosphatase (ATPase) activity. The (S) enantiomers of 16- and 17-HETE potently inhibited activity, whereas their (R) isomers and other P-450 HETEs had negligible effects on ATPase activity. The quantity of HETEs released from the kidney, either under basal conditions or when stimulated by ANG II, and their biological profile suggest that subterminal HETEs may participate in renal mechanisms affecting vasomotion and tubular transport.
Siberian hamsters free run or become arrhythmic after a phase delay of the photocycle
Authors: Ruby N. F. , Saran A. , Kang T. , Franken P. , Heller H. C.
Published: December 2017

Body temperature (Tb) and locomotor activity were recorded telemetrically from male Siberian hamsters (Phodopus sungorus sungorus) that were 3 or 12 mo of age and maintained in a light-dark (LD) cycle of 16 h light/day for 2-4 mo. After 3 wk of Tb recording, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8-h LD cycle for the remainder of the experiment. Tb and activity rhythms of all animals were stably entrained to the LD cycle before the phase shift. After the phase shift, > or = 80% of the animals in each age group failed to reentrain and expressed free-running Tb rhythms with stable periods that ranged from 24.33 to 26.33 h; one hamster in each age group reentrained within several days. Tb became arrhythmic in 10% of all animals immediately after, and in 28% of free running animals several weeks after, the phase shift. Changes in tau and phase of activity rhythms closely paralleled Tb rhythms in individual hamsters. Daily mean Tb was unchanged, but Tb rhythm amplitude decreased by 25-50% in individual animals after the phase shift. We believe this to be the first report of neurologically intact animals failing to reentrain to a phase shift of the LD cycle. These phenomena are not readily explained by current knowledge of circadian systems and suggest that the entrainment process in Siberian hamsters differs markedly from that in other rodent species.
Evidence for the utilization of peptides for milk protein synthesis in the lactating dairy goat in vivo
Authors: Backwell F. R. , Bequette B. J. , Wilson D. , Metcalf J. A. , Franklin M. F. , Beever D. E. , Lobley G. E. , MacRae J. C.
Published: December 2017

Precursors for milk protein synthesis have been examined in lactating dairy goats using arteriovenous difference and isotope kinetic techniques. Certain amino acids, such as phenylalanine and histidine, are taken up by the mammary gland in quantities that are insufficient to account for their output in milk protein. Some amino acids have been shown to be present in significant quantities (10-30% of total non-protein-bound amino acids) as peptides (< 1,500 Da) in the arterial supply to the mammary gland, although methodological considerations make it difficult to accurately assess the extent of their uptake across the tissue bed. Indirect evidence for the utilization of peptides for milk protein synthesis in vivo has been obtained, however, by examination of the kinetics of milk casein labeling during long-term (24 h) systemic infusion of [1-13C]phenylalanine and [1-13C]leucine. Comparison of plateau enrichments for blood, plasma, and casein indicate that, although, for leucine, the plasma free pool seems to provide all the leucine for milk protein synthesis, sources other than the labeled plasma free amino acids contribute phenylalanine (10-20%) for casein biosynthesis. These findings raise questions relating to the type and source of amino acid precursors used by tissues for protein synthesis.
Alanyl-glutamine prevents muscle atrophy and glutamine synthetase induction by glucocorticoids
Authors: Hickson R. C. , Wegrzyn L. E. , Osborne D. F. , Karl I. E.
Published: December 2017

The aims of this work were to establish whether glutamine infusion via alanyl-glutamine dipeptide provides effective therapy against muscle atrophy from glucorticoids and whether the glucocorticoid induction of glutamine synthetase (GS) is downregulated by dipeptide supplementation. Rats were given hydrocortisone 21-acetate or the dosing vehicle and were infused with alanine (AA) or alanyl-glutamine (AG) at the same concentrations and rates (1.15 mumol.min-1.100 g body wt-1, 0.75 ml/h) for 7 days. Compared with AA infusion in hormone-treated animals, AG infusion prevented total body and fast-twitch muscle mass losses by over 70%. Glucocorticoid treatment did not reduce muscle glutamine levels. Higher serum glutamine was found in the AG-infused (1.72 +/- 0.28 mumol/ml) compared with the AA-infused group (1.32 +/- 0.06 mumol/ml), but muscle glutamine concentrations were not elevated by AG infusion. Following glucocorticoid injections, GS enzyme activity was increased by two- to threefold in plantaris, fast-twitch white (superficial quadriceps), and fast-twitch red (deep quadriceps) muscle/fiber types of the AA group. Similarly, GS mRNA was elevated by 3.3- to 4.1-fold in these same muscles of hormone-treated, AA-infused rats. AG infusion diminished glucocorticoid effects on GS enzyme activity to 52-65% and on GS mRNA to 31-37% of the values with AA infusion. These results provide firsthand evidence of atrophy prevention from a catabolic state using glutamine in dipeptide form. Despite higher serum and muscle alanine levels with AA infusion than with AG infusion, alanine alone is not a sufficient stimulus to counteract muscle atrophy. The AG-induced muscle sparing is accompanied by diminished expression of a glucocorticoid-inducible gene in skeletal muscle. However, glutamine regulation of GS appears complex and may involve more regulators than muscle glutamine concentration alone.
Lactate and metabolic H+ transport and distribution after exercise in rainbow trout white muscle
Authors: Wang Y. , Heigenhauser G. J. , Wood C. M.
Published: December 2017

An isolated-perfused tail-trunk preparation was employed to study the influence of transmembrane pH gradient and membrane potential on the transport and distribution of L(+)-lactate (Lac), metabolic H+ (delta Hm+), and related parameters in rainbow trout white muscle after exhaustive exercise. One resting [arterial pH (pHa) approximately 7.9] and four postexercise treatments (pHa approximately 7.4, 7.9, 8.4, and, high K+, pHa approximately 7.9, partially depolarized by 15 mM K+) were examined. Variations in HCO3- concentration (2-18 mM) at a constant PCO2 approximately 2 Torr were used to alter pHa. The elevated intracellular Lac (approximately 50 mM) remained unchanged after 60 min of perfusion because of very low rates of lactate efflux and oxidation. H+, HCO3-, and Lac- distributions were all well out of electrochemical equilibrium. Total CO2 efflux was reduced at high extracellular pH (pHe); alterations in the net driving force on HCO3- may have overshadowed the influence of PCO2 gradients in driving total CO2 efflux. Lac efflux and delta Hm+ flux were completely uncoupled. delta Hm+ flux reacted to both acid-base and electrochemical gradients as delta Hm+ efflux dropped and even reversed when pHe decreased, whereas partial depolarization in conjunction with depressed intracellular pH resulted in elevated delta Hm+ efflux. Lac efflux did not respond to changes in pHe. Changes in Lac efflux corresponded more closely to changes in the Lac- concentration gradient than in the lactic acid gradient. This study provides circumstantial evidence for the involvement of electroneutral mechanisms (i.e., Lac(-)-H+ cotransport and/or Lac-/anion exchange) in lactate efflux, but does not eliminate the possibility of an active transport mechanism contributing to the retention of Lac.
Molecular activity of sodium pumps in endotherms and ectotherms
Authors: Else P. L. , Windmill D. J. , Markus V.
Published: December 2017

Previous research has shown ectotherms to have markedly lower sodium pump metabolism than endotherms. Direct measurement of enzymatic activity of the sodium pump (Na(+)-K(+)-adenosinetriphosphatase) confirmed this difference. To determine the source of this difference, sodium pump density was measured with the use of [3H]ouabain binding. Ectotherms and endotherms were found to share similar sodium pump numbers. Approximate densities (in pmol/g) were 250 for skeletal muscle, 500 for liver, 900 for heart, and 8,000 for kidney and brain. Therefore, differences in sodium pump activity between endotherms and ectotherms were due to differences in turnover rates or molecular activities of sodium pumps. Molecular activities of sodium pumps (in ATP/min) of tissues from endotherms were between 6,000 and 12,000 and, for ectotherms, between 1,500 and 2,500. Exceptions were found that included the heart of Bufo marinus. In a single invertebrate species studied, Charax destructor, the sodium pumps of the heart had a low molecular activity characteristic of ectothermic tissues. These results suggest that during the evolution of endothermy there was a general increase in the molecular activity of the sodium pump.
Activation of GABAB receptors increases a potassium conductance in rat bulbospinal neurons of the C1 area
Authors: Li Y. W. , Guyenet P. G.
Published: December 2017

In anesthetized rats, iontophoresis of the gamma-aminobutyric acid (GABAB)-receptor agonist and antispastic drug baclofen inhibits the bulbospinal vasomotor neurons of the rostral ventrolateral medulla (RVLM). The present study was carried out to determine whether C1 adrenergic and other bulbospinal neurons of the RVLM have postsynaptic GABAB receptors. Retrogradely labeled RVLM bulbospinal neurons (n = 52) were recorded in 120-micron-thick slices from neonatal rat brain (3-10 days old). Most neurons (48/52) were tonically active (3 +/- 0.6 spikes/s). Twenty-six neurons were recovered histologically, and 18 of them were immunoreactive for tyrosine hydroxylase (TH). In current clamp, baclofen (0.3-10 microM) hyperpolarized RVLM bulbospinal cells in a dose-dependent manner (16 +/- 0.5 mV hyperpolarization by 3 microM baclofen; n = 19) and decreased input resistance by 40% (n = 10). In voltage clamp (1 microM tetrodotoxin present; holding potential: -40 to -60 mV), 3 microM baclofen induced an outward current of 21 +/- 2 pA (n = 29). This current exhibited inward rectification and reversed polarity close to the K+ equilibrium potential (external K+ from 2.5 to 10 mM). The current induced by baclofen was reduced 90% by 0.1-0.2 mM BaCl2 (n = 6) and was blocked reversibly by the selective GABAB-receptor antagonist CGP-55845A (0.5-1 microM; n = 6). All histologically verified TH-immunoreactive cells (n = 18) were sensitive to baclofen. In summary, RVLM bulbospinal neurons including C1 adrenergic cells possess GABAB receptors. Activation of these receptors increases an inwardly rectifying K+ conductance. This effect reduces the intrinsic firing frequency of RVLM vasomotor neurons "in vitro" and may contribute to the sympatholytic action of baclofen "in vivo."
Atrial natriuretic peptide and sodium homeostasis in compensated heart failure
Authors: Lohmeier T. E. , Mizelle H. L. , Reinhart G. A. , Montani J. P. , Hord C. E. , Didlake R. H.
Published: December 2017

The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.
Manipulation of potential perinatal zeitgebers for the juvenile circadian temperature rhythm in rats
Authors: Nuesslein-Hildesheim B. , Schmidt I.
Published: December 2017

We investigated the importance of pre- and postnatal maternal rhythmicity for the development and synchronization of the juvenile circadian core temperature (Tc) rhythm in rats by evaluating the Tc of artificially reared pups in six litters derived from mothers maintained in continuous bright light (LL) and impregnated after drinking behavior stopped showing circadian periodicity. Pups removed from their aperiodic mothers on postnatal day 9 and artificially reared for 3 days showed a free-running Tc rhythm whose amplitude (3.1 +/- 0.1 degrees C, n = 47) was only slightly smaller than that of control pups born to mothers maintained in a 12:12-h light-dark cycle. In four litters the acrophases were not much less synchronized than in the four control litters (mean vector lengths 0.79 +/- 0.05 vs. 0.94 +/- 0.04). In two litters synchronization among littermates was not significant. Additional experiments with cross-fostered pups showed that synchronization is not caused by the time of birth. We conclude that synchronization among littermates can develop even when maternal rhythmicity has been suppressed even before conception, possibly because the Tc decrease of several littermates happening to have similar phases at birth acts as zeitgeber.
Dietary sodium effects on renin and angiotensinogen gene expression in preweanling WKY and SHR
Authors: Kirby R. F. , Page W. V. , Johnson A. K. , Robillard J. E.
Published: December 2017

The influence of altered dietary sodium on angiotensinogen and renin gene expression was examined in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Artificial rearing was used to increase or decrease dietary sodium intake during the preweanling period. In normally reared control animals, renal renin and liver angiotensinogen mRNA decreased between 6 and 30 postnatal days of age. In contrast, in the central nervous system, angiotensinogen mRNA increased between 6 and 30 days of age, and renin mRNA remained stable. Dietary sodium manipulation between postnatal days (PD) 6 and 18 significantly influenced renal renin gene expression, with low-sodium diet increasing renin mRNA on PD12 and PD18 and high-sodium diet decreasing renin mRNA on PD18. Liver angiotensinogen mRNA decreased for animals on either diet on PD12 and PD18. Brain angiotensinogen and renin mRNA were not affected by dietary sodium levels. There were no strain-related differences in the response to high and low dietary sodium. These results demonstrate that 1) the peripheral and central renin-angiotensin systems do not have a common ontogenetic pattern of development, 2) they are independently regulated in response to dietary sodium variations, and 3) young WKY and SHR share very similar ontogenetic patterns of angiotensinogen and renin gene expression.
Reorganization of the innervation of the vas deferens after sympathetic decentralization
Authors: Kihara K. , Kakizaki H. , de Groat W. C.
Published: December 2017

Reorganization of autonomic efferent pathways to the rat vas deferens was noted after chronic (30 days) sympathetic decentralization produced by hypogastric nerve (HGN) transection. In normal rats, electrical stimulation of the HGN elicited an increase in vasal pressure (VP) bilaterally, whereas pelvic nerve (PN) stimulation did not alter VP. However, after unilateral HGN transection, stimulation of the PN on the transected side but not on the normal side increased VP. The decentralized vas exhibited larger VP responses to stimulation of the contralateral HGN in comparison with the normal vas. After bilateral HGN transection, PN-induced VP responses were elicited at lower stimulus intensities than in rats with unilateral transections. PN-induced VP responses were blocked by hexamethonium and prazosin but were not altered by atropine. Distension of the vas lumen occurred after decentralization. PN-induced VP responses were not detectable in extremely distended vas. These data indicate that, after degeneration of sympathetic preganglionic axons, decentralized adrenergic ganglion cells are reinnervated by parasympathetic or sympathetic preganglionic pathways and that the reinnervation influences vasal function.
Age-related changes in the responsiveness of apolipoprotein A1 to thyroid hormone
Authors: Mooradian A. D. , Wong N. C. , Shah G. N.
Published: December 2017

To determine the age-related changes in the effect of thyroid hormone on apolipoprotein A1 (ApoA1) gene expression, male Fischer 344 rats at 4 (young) and 26 (aged) mo of age were studied. Hyperthyroidism was induced with daily intraperitoneal injections of 3,5,3'-triiodothyronine (15 micrograms/100 g body wt) for 10 days. Hypothyroidism was induced with 0.025% methimazole in drinking water for 4 wk. Hyperthyroidism was associated with increased serum ApoA1 levels in young rats [7.52 +/- 0.41 vs. 3.67 +/- 0.30 optical density (OD); P < 0.01]. The increase in aged rats (6.5 +/- 0.87 vs. 5.14 +/- 0.09 OD) did not reach statistical significance. Hypothyroidism was not associated with significant changes in serum ApoA1 levels in either young or aged rats. Hyperthyroidism was associated with a 2.5-fold increase in ApoA1 mRNA in young rats and a 1.7-fold increase in aged rats. Hypothyroidism was associated with a 3.6-fold reduction in ApoA1 mRNA in young rats, but there was no significant change in aged hypothyroid rats. Mobility shift assays indicated that the binding of transacting factors to ApoA1 promoter increased in hyperthyroid young rats but not in hyperthyroid aged rats. It is concluded that aging in rats is associated with reduced ApoA1 responsiveness to thyroid hormones. This altered responsiveness could partly be the result of changes in the binding activity of nuclear factors to the ApoA1 promoter.
Beta 3-adrenoceptor in guinea pig brown and white adipocytes: low expression and lack of function
Authors: Atgie C. , Tavernier G. , D'Allaire F. , Bengtsson T. , Marti L. , Carpene C. , Lafontan M. , Bukowiecki L. J. , Langin D.
Published: December 2017

In the guinea pig, cold acclimation induced a conversion of unilocular to multilocular adipocytes in interscapular (IS) and retroperitoneal (RP) fat depots but not in the epididymal (EP) fat pad. The conversion was associated with an increase in mitochondriogenesis and the appearance of the uncoupling protein. The maximal lipolytic responses to norepinephrine and dibutyryl adenosine 3',5'-cyclic monophosphate were decreased in IS cells, unchanged in RP cells, and increased in EP cells, suggesting a site-specific regulation of lipolysis at the postreceptor level. beta 3-Adrenergic agonists were not lipolytic regardless of the depot and the thermal environment of the animal. These agents did not inhibit glucose transport and lipogenesis, as was previously reported for rodents. Cloning and sequencing of the guinea pig beta 3-adrenoceptor gene revealed a slightly higher amino acid sequence similarity with the human than with the rodent beta 3-adrenoceptors. beta 3-Adrenoceptor transcripts were present at a very low level in guinea pig adipocytes, and mRNA levels did not increase to a significant extent after cold acclimation. The guinea pig thus differs from rodents by an absence of beta 3-adrenergic effects and by low beta 3-adrenoceptor expression in brown and white adipose tissues.
Food hoarding is increased by pregnancy, lactation, and food deprivation in Siberian hamsters
Authors: Bartness T. J.
Published: December 2017

Food hoarding by male Siberian hamsters (Phodopus sungorus sungorus) is increased only when body mass (fat) is decreased. Pregnancy and lactation result in marked decreases in lipid reserves (approximately 50%) in female Siberian hamsters. Therefore, the present experiments addressed the following questions: 1) Is food hoarding increased after food deprivation in female Siberian hamsters? and 2) How do food hoarding and food intake change during pregnancy, lactation, and their combination? During measurements in a simulated burrow system food hoarding increased after a 32-h fast (approximately 2- to 3-fold) to a level similar to that seen previously in males and was markedly increased during pregnancy (approximately 12- to 18-fold, lactation, and concurrent pregnancy and lactation (approximately 10- to 25-fold for each of the latter 2 conditions). Postfast food intake was not different from prefast baseline measures. Food intake was increased only during the last few days of pregnancy and was elevated throughout lactation. These impressive increases in the level of food hoarding during pregnancy, lactation and their combination suggest that food hoarding may play an important role in supplying easily accessible energy to subserve these reproductive conditions.
Posttranscriptional mechanisms regulate ontogenic changes in rat renal sodium-phosphate transporter
Authors: Taufiq S. , Collins J. F. , Ghishan F. K.
Published: December 2017

The present investigation sought to characterize the relationship between ontogeny and Na(+)-P(i) transporter expression in the rat kidney. Results showed that the maximal reaction rate (nmol.mg protein-1.10 s-1) of Na(+)-P(i) transport was highest in 21-day-old rats (2.26 +/- 0.26), was lower in 42- to 45-day-old rats (1.44 +/- 0.19) and 4-mo-old rats (0.78 +/- 0.15), and was lowest in 14-day-old rats (0.50 +/- 0.16) (P = 0.0009, n = 3). The Michaelis constants (mM Pi) were not significantly different in the four age groups. Northern blot analysis revealed that the abundance of Na(+)-P(i) transporter mRNA was similar in all four age groups (n = 5). Western blot analysis demonstrated the highest immunoreactive protein signal in the 21-day-old rat (Na(+)-P(i)/beta-actin = 4.15 +/- 1.16), followed by decreasing protein levels in 42-day-old rats (2.13 +/- 0.22), 4-mo-old rats (0.85 +/- 0.25), and 14-day-old rats (0.75 +/- 0.37) (P = 0.022, n = 5). Immunohistochemical analysis of kidney cortex in the four age groups showed specific staining of only apical membranes in all samples. We conclude that posttranscriptional mechanisms play a role in regulating this transporter during rat ontogeny.
Lactation alters the effects of conditioned stress on immune function
Authors: Shanks N. , Kusnecov A. , Pezzone M. , Berkun J. , Rabin B. S.
Published: December 2017

During lactation, endocrine function is altered and stress responses are dampened. Stress effects on immune function are partially determined by endocrine factors; therefore, we assessed whether stress similarly alters immune function during lactation. Sprague-Dawley rats were conditioned by exposure to a tone paired with foot shock (2 sessions, 16 shocks each) prior to breeding or were left undisturbed. Lactating (day 10) (Lac) and nonlactating diestrous virgin controls (C) were killed immediately after reexposure to the tone or removal from their home cage. Plasma corticosterone stress responses were dampened in Lac relative to C animals. Peripheral blood lymphocyte proliferation to T cell receptor antibody stimulation was reduced to a similar extent in both experimental groups. Conditioned stress reduced splenocyte proliferation and increased nitrite accumulation in C animals, but not in Lac animals. Mesenteric lymph node lymphocyte proliferation was significantly increased after stress in Lac compared with C animals. Both plasma interleukin-6 (IL-6) and phytohemagglutinin-stimulated splenic IL-6 production were increased in Lac animals compared with C animals after stress exposure. These data indicate that stress-induced alterations may be determined by different regulatory mechanisms within immune compartments and that these effects depend on the physiological state of the organism.
A source of adenosine involved in cardiovascular responses to defense area stimulation
Authors: St Lambert J. H. , Thomas T. , Burnstock G. , Spyer K. M.
Published: December 2017

We have investigated the source of central adenosine important in modulating the cardiovascular response to hypothalamic defense area (HDA) stimulation in alpha-chloralose-anesthetized rats. Microinjections of an ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP (alpha,beta-meADP), were made into caudal nucleus of the solitary tract (cNTS) and rostral ventrolateral medulla (RVLM), and its effects on HDA-evoked responses were observed. Stimulation of HDA evoked an increase in arterial pressure and a secondary rise in arterial pressure after stimulation ceased. There was also an increase in heart rate and hindlimb blood flow. alpha,beta-meADP had no effect on resting levels of arterial pressure, heart rate, and hindlimb blood flow when injected into the cNTS or RVLM. alpha,beta-meADP also had no effect on the HDA-evoked tachycardia and increase in muscle blood flow. However, alpha,beta-meADP reduced the primary increase in arterial pressure evoked by HDA stimulation when microinjected into the cNTS. In contrast, alpha,beta-meADP reduced the secondary increase in arterial pressure when microinjected into the RVLM. From these results, we suggest that at least part of the adenosine released centrally during HDA stimulation is derived extracellularly from ATP metabolism.
Regulation of ingestion by CRF and bombesin-like peptides: distinct meal-related peptide level changes
Authors: Plamondon H. , Merali Z.
Published: December 2017

Bombesin (BN) and corticotropin-releasing factor (CRF) have both been shown to induce satiety in rats when injected centrally. The present study assessed temporal changes in the utilization of BN- and CRF-like peptides in relationship to feeding status, fluctuations that may indicate the physiological participation of these peptides in the regulation of feeding. Alterations in the endogenous levels of CRF- and BN-like peptides associated with the initial spontaneous meal of the nocturnal cycle were determined in 15 hypothalamic and extrahypothalamic brain nuclei in the following three groups of rats: 1) a preprandial group consisting of rats killed before feeding, 2) a prandial group consisting of rats killed during the meal, and 3) a postprandial group consisting of rats killed 8-12 min after the meal. Findings revealed site-specific changes in BN and CRF content during the course of a meal. During ingestion, levels of BN were significantly elevated at the paraventricular, arcuate, and dorsomedial nuclei of the hypothalamus and reduced at the nucleus accumbens. In the case of CRF, feeding-related alterations were observed at the lateral (LH) and ventromedial (VMH) hypothalamic nuclei and at the central nucleus of the amygdala (Ce). At the LH, CRF content decreased after feeding compared with preprandial levels. At the VMH, CRF levels were significantly elevated both before and after food intake compared with prandial levels. In contrast, at the Ce marked increases in CRF concentrations were observed during ingestion. These data demonstrate, for the first time, site-specific fluctuations of BN and CRF in relationship to the animal's feeding status and suggest that these peptides may play a role in the regulation of food intake.
Interleukin-1 beta potentiates bradykinin-induced macromolecular efflux from hamster oral mucosa
Authors: Gao X. P. , Rubinstein I.
Published: December 2017

The purpose of this study was to determine whether interleukin-1 beta (IL-1 beta) elicits macromolecular efflux from the in situ oral mucosa and whether it amplifies that evoked by bradykinin. Using intravital microscopy, we found that suffusion of recombinant human IL-1 beta (50 ng/ml) had no significant effects on leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) from the hamster cheek pouch. However, it significantly potentiated bradykinin-induced macromolecular efflux (P < 0.05). The potentiating effects of IL-1 beta on bradykinin-induced responses were abrogated by a bradykinin B2-receptor antagonist and by a recombinant human IL-1-receptor antagonist. They were not mediated by substance P, prostaglandins, or changes in vasomotor tone. IL-1 beta had no significant effects on adenosine-induced macromolecular efflux. Collectively, these data indicate that IL-1 beta potentiates bradykinin-induced macromolecular efflux from the in situ hamster oral mucosa in a specific fashion. We suggest that this interaction could play a role in the pathogenesis of oral mucosa inflammation.
NMDA as well as non-NMDA receptors in phrenic nucleus mediate respiratory effects of carotid chemoreflex
Authors: Chitravanshi V. C. , Sapru H. N.
Published: December 2017

An in vivo model was used to identify the transmitter/receptor mechanisms in the phrenic nucleus that mediate carotid chemoreceptor responses. Adult male Wistar rats, anesthetized with urethan, were fixed in a stereotaxic instrument, and the blood pressure and heart rate were monitored. The rats were immobilized and artificially ventilated to maintain the end-tidal CO2 at 4.5-5%. The vagus nerves were bilaterally sectioned, and a pneumothorax was produced. Activity was recorded from one of the phrenic nerves. The spinal cord was exposed from C1 to T1 vertebral level. The dorsal and ventral rootlets of spinal nerves C3, C5, and C6, ipsilateral to the phrenic nerve from which electrical activity was recorded, were sectioned; the dorsal and ventral roots of spinal nerve C4 were left intact. Thus the phrenic nerve bursts recorded in this preparation represented output from a portion of the phrenic nucleus located in the ipsilateral C4 spinal segment. Carotid chemoreceptor stimulation by N2 inhalation increased the amplitude as well as the frequency of phrenic nerve bursts. Microinjections (50 nl) of a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist (D(-)-2-amino-7-phosphonoheptanoic acid, AP-7, 50-100 mM) into the phrenic nucleus decreased the N2-induced increase in amplitude, but not the frequency, of phrenic nerve bursts. Likewise microinjections of a specific non-NMDA receptor antagonist (1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulfonamid e, NBQX, 0.5-1 mM) into the phrenic nucleus decreased the N2-induced increase in phrenic nerve burst amplitude. When AP-7 and NBQX were microinjected into the phrenic nucleus sequentially within an interval of 5 min, a drastic reduction in the N2-induced increase in phrenic nerve burst amplitude was observed. These observations suggest that both NMDA and non-NMDA receptors located in the phrenic nucleus are involved in the mediation of phrenic nerve responses to the carotid chemoreceptor stimulation.
Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific
Authors: Leeuwenburgh C. , Hollander J. , Leichtweis S. , Griffiths M. , Gore M. , Ji L. L.
Published: December 2017

The effect of endurance training on glutathione (GSH) status and antioxidant enzyme system was investigated in skeletal muscle, heart, and liver of female Sprague-Dawley rats pair fed an isocaloric diet. Ten weeks of treadmill training (25 m/min, 10% grade for 2 h/day, 5 days/wk) increased citrate synthase activity in the deep vastus lateralis (DVL) and soleus muscles by 79 and 39%, respectively (P < 0.01), but not in the heart or liver. In DVL, GSH content was increased 33% (P < 0.05) with training, accompanied by a 64% (P < 0.05) increase in glutamate content but no change in cysteine. Trained rats showed a 62 and 27% higher GSH peroxidase (GPX) and superoxide dismutase (SOD) activity, respectively (P < 0.05), in DVL compared with control rats. In contrast, GSH content and glutathione reductase (GR) activity in soleus declined with training (P < 0.05), whereas activities of GPX and SOD remained unchanged. Training did not alter GSH status in the liver or plasma but significantly decreased the GSH-to glutathione disulfide ratio in the heart. In addition, GR activity in the liver and GSH sulfur-transferase activity in the heart and DVL were significantly lower in the trained vs control rats DVL muscle had threefold higher gamma-glutamyl transpeptidase activity compared with other tissues; however no significant alteration was observed in the activity of gamma-glutamyltranspeptidase or gamma-glutamylcysteine synthetase in the liver, heart, or skeletal muscle. These data indicate that endurance training can cause tissue- and muscle fiber-specific adaptation of antioxidant systems and that GSH homeostasis in extrahepatic tissues may be determined by utilization and uptake of GSH via the gamma-glutamyl cycle.
The role of menopause in the development of chronic mountain sickness
Authors: Leon-Velarde F. , Ramos M. A. , Hernandez J. A. , De Idiaquez D. , Munoz L. S. , Gaffo A. , Cordova S. , Durand D. , Monge C.
Published: December 2017

The objective of this study was to investigate the role of menopause in the appearance of the physiopathological sequence that leads to chronic mountain sickness (CMS) in a high-altitude female population. The females studied are 30-54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru; 4,300 m). The sample was divided into postmenopausal and premenopausal groups for comparison. Blood oxygen saturation (SaO2), excessive erythrocytosis [EE, measured by the level of hematocrit (Het)], peak expiratory flow rates (PEFR), and a score that represents the main signs and symptoms of CMS (CMSscore) were measured. Postmenopausal women had higher Het (50.2 +/- 4.04 vs. 47.4 +/- 4.13%, P < 0.001), lower SaO2 (81.9 +/- 4.12 vs. 84.7 +/- 3.14%, P < 0.001) and PEFR values (489 +/- 101 vs. 534 +/- 90 l/min, P < 0.02), and slightly higher CMSscore (19.1 +/- 3.37 vs. 17.9 +/- 3.48, P < 0.06) than premenopausal women. The prevalence of women with EE (EE = Hct > 56%) was found to be 8.8%. Forty-five percent of the postmenopausal subjects presented a high CMSscore (> 21), whereas only 22% of the premenopausal subjects presented this high value (P < 0.02). We can therefore conclude that menopause may represent a contributing factor for the development of CMS.
AV3V neurons that send axons to hypothalamic nuclei respond to the systemic injection of IL-1beta
Authors: Ota K. , Katafuchi T. , Takaki A. , Hori T.
Published: December 2017

The single neuron activity in the anteroventral region of the third ventricle (AV3V) was extracellularly recorded in urethan and alpha-chloralose anesthetized rats. Electrical stimulation of the medial preoptic area (mPOA) and the paraventricular nucleus (PVN) revealed a reciprocal neural connection between the AV3V and these hypothalamic nuclei with an ipsilateral preponderance. All the AV3V neurons, which were antidromically activated by the stimulation of the mPOA or the PVN, altered their activity after the systemic injection of interleukin (IL)-1beta. On the other hand, only about 60% of the AV3V neurons that showed orthodromic responses were affected by IL-1beta. In seven of nine AV3V neurons that were electrophysiologically identified to send their axons to the mPOA or the PVN, the recombinant human IL-1beta-induced excitation and inhibition were attenuated by a local application of sodium salicylate through multibarreled micropipettes. These results suggest that the AV3V neurons alter their activity in response to the blood-borne IL-1beta, at least in part, through a local synthesis of prostanoids and then send the information to the mPOA and PVN.
Role of adrenoceptors in the hypertensive response to feeding in the conscious calf
Authors: Bowman E. C. , Roderick G. P. , Bloom S. R. , Edwards A. V.
Published: December 2017

Ingestion of milk during suckling causes hypertension and tachycardia in young, unweaned animals of many species, but these responses are most pronounced in the calf. The present study was undertaken to assess the extent to which this phenomenon depends on activation of adrenoceptors in these animals. Mean basal heart rate was 100 +/- 8 beats/min and mean basal aortic blood pressure was 92 +/- 5 mmHg. The rise in heart rate during feeding was almost completely suppressed after propranolol (2-4 mg/kg iv), which also significantly reduced the rise in blood pressure from 67 +/- 4 to 44 +/- 3 mmHg (P < 0.005). Additional pretreatment with phentolamine (1.0 mg/kg and < or =0.1 mg x min(-1) x kg(-1) iv) virtually eliminated the rise in blood pressure during feeding; it rose by only 8 +/- 4 mmHg (P < 0.001). Section of both splanchnic nerves also significantly reduced the rise in blood pressure during feeding, especially after pretreatment with propranolol. Neither section of the splanchnic nerves nor the administration of the blocking agents significantly affected the rises in plasma insulin and pancreatic polypeptide that occurred after feeding. There was no detectable rise in plasma neuropeptide Y concentration in response to feeding. The hypertensive response to direct electrical stimulation of the peripheral end of a splanchnic nerve and to intra-arterial injections of norepinephrine were completely abolished after combined pretreatment with atropine, propranolol, and phentolamine after the ipsilateral adrenal vein had been tied off. It is concluded that the cardiovascular changes that occur during feeding in these animals are attributable very largely, if not entirely, to activation of adrenoceptors.