bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian rhythms of temperature and activity in obese and lean Zucker rats
Authors: Murakami D. M. , Horwitz B. A. , Fuller C. A.
Published: December 2017

The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.
Anoxic brain failure in an ectothermic vertebrate: release of amino acids and K+ in rainbow trout thalamus
Authors: Hylland P. , Nilsson G. E. , Johansson D.
Published: December 2017

The release of excitatory amino acids such as glutamate contributes greatly to anoxic and/or ischemic brain damage in mammals. However, for anoxia-intolerant ectothermic vertebrates, there has been no information on how anoxia affects extracellular amino acid levels, or how such changes relate temporally to major ion movements. We have investigated the effects of environmental anoxia on extracellular amino acid and K+ concentrations in rainbow trout thalamus in vivo at 15 degrees C, using microdialysis and K(+)-selective microelectrodes. Systemic blood pressure was also monitored. In separate experiments, endogenous neurotransmitter release was provoked by perfusing the microdialysis probe with a high-K+ Ringer solution, thereby establishing which amino acids are released by depolarization. Anoxia exposure resulted in the release of several amino acids, including glutamate, aspartate, gamma-aminobutyric acid (GABA), glycine, and taurine. GABA release appeared to be delayed compared with that of glutamate, for example. The loss of ion homeostasis (starting after 23 min) preceded the release of amino acids (starting after > or = 45 min). The amino acid release had no apparent effect on the rate of increase in extracellular K+. Thus, if these events are interrelated, the loss of ion homeostasis is likely to trigger the amino acid release but not vice versa.
Patterns of blood pressure variability in normotensive and hypertensive rats
Authors: Holstein-Rathlou N. H. , He J. , Wagner A. J. , Marsh D. J.
Published: December 2017

We sought patterns in mean arterial pressure of normotensive rats and alterations in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive Sprague-Dawley rats, spontaneously hypertensive rats (SHR), and Sprague-Dawley rats with two-kidney, one-clip renovascular hypertension (2K,1C). Time series analysis was by fast Fourier transform. Power spectra were divided into ultradian (frequencies > 1/day), circadian (frequency = 1/day), and infradian (frequencies < 1/day) domains. In the ultradian band from approximately 0.1 to 10 mHz the spectra were 1/f and without distinct peaks. The slopes were not significantly different among the groups and ranged from -1.03 to -1.61. At frequencies > 10 mHz, power continued to decrease but with a lower slope. A peak centered at approximately 100 mHz was present in both normotensive and 2K,1C rats but not in SHR. SHR had significantly more ultradian power than the others. The circadian rhythm modulated power in the ultradian band. Modulation was most prominent in normotensives, in which the ultradian activity was highest during the night when rats are active and lowest during the day; less pronounced in 2K,1C; and not detectable in SHR. There are regular patterns of blood pressure fluctuations and specific modifications to the patterns by different forms of hypertension.
Preoptic/anterior hypothalamic neurons: thermosensitivity in rapid eye movement sleep
Authors: Alam M. N. , McGinty D. , Szymusiak R.
Published: December 2017

The thermosensitivity of 15 warm-sensitive neurons (WSNs) and 19 cold-sensitive neurons (CSNs) from the medial preoptic/anterior hypothalamus (POAH) was tested during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by local POAH warming and cooling in freely moving cats. Thermosensitivity was quantified by three criteria, Q10, impulses per second per degree Celsius, and percent change per degree Celsius. Irrespective of the criterion used, WSNs did not exhibit a significant change in thermosensitivity during REM sleep compared with wakefulness and NREM sleep. In contrast, CSNs exhibited decreased mean thermosensitivity during REM sleep compared with wakefulness. CSNs as a group did not retain significant thermosensitivity in REM sleep. These findings are consistent with evidence that thermoeffector responses to cooling are lost in REM sleep, whereas some responses to warming are preserved.
Circadian locomotor rhythms in aged hamsters following suprachiasmatic transplant
Authors: Hurd M. W. , Zimmer K. A. , Lehman M. N. , Ralph M. R.
Published: December 2017

Circadian activity rhythms that have been eliminated by lesions of the suprachiasmatic nucleus (SCN) can be restored by fetal SCN grafts. Partial lesions of the host allow simultaneous expression of both donor and host rhythms. Because partial SCN ablation produces characteristic changes in activity rhythms that are similar to those that occur with age, including shortened period, reduced amplitude, and fragmentation, we investigated the extent to which fetal SCN grafts may be expressed by an animal whose activity rhythm exhibits these age-dependent changes. The results indicate that expression of a transplanted clock is possible in an unlesioned aged host. Grafts of fetal SCN into young hosts and cortical tissue grafts into intact aged hosts have no effect. In those aged animals that received SCN grafts, three patterns of expression emerged in the subsequent locomotor activity record: complete dominance of locomotor rhythmicity by the donor; relative coordination between donor and host rhythms; and spontaneous switching between host and donor phenotypes. The results suggest that the expression of rhythmicity by the grafted SCN may depend on the relative amplitude or strength of signals produced by the host and donor SCN.
Low doses of TRH analogue act in the dorsal motor nucleus to induce gastric protection in rats
Authors: Kato K. , Yang H. , Tache Y.
Published: December 2017

Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E2 (PGE2) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE2-, CGRP-, and nitric oxide-dependent mechanisms.
T4 depresses olfactory responses to L-alanine and plasma T3 and T3 production in smoltifying Atlantic salmon
Authors: Morin P. P. , Hara T. J. , Eales J. G.
Published: December 2017

During natural or induced smoltification, Atlantic salmon exhibit spring elevations in olfactory activity and plasma L-thyroxine (T4). To determine whether T4 influences olfactory activity, we administered T4 to late parr in early April and measured olfactory bulb electroencephalogram and olfactory epithelium electroolfactorogram responses to L-alanine nasal stimulation, plasma T4 and 3,5,3'-triiodo-L-thyronine (T3) levels, and hepatic and brain monodeiodination. T4 treatment raised plasma T4 to 15 ng/ml, simulating the smolt T4 surge, and depressed plasma T3 and electroencephalogram responses, without modifying electroolfactorogram responses. Decreased plasma T3 may be explained by inhibition of hepatic T4 outer-ring deiodination, generating T3, and stimulation of inner-ring deiodination, degrading T4 and T3. Brain T4 outer-ring deiodination was also strongly inhibited. In conclusion, creation of a high plasma T4 concentration simulating the natural smolt peak depressed olfactory bulb responses to L-alanine due to the high T4 concentration or the depressed T3 availability in brain induced by T4. T4 may terminate the period of heightened olfactory responsiveness during smoltification.
Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes
Authors: Williams G. , Becker L. , Bryant D. , Willis S. , Giroir B. P.
Published: December 2017

The production of nitric oxide (NO) via the inducible form of NO synthase (iNOS) is regulated by a complex network of cytokines and endogenous hormones. Among these, transforming growth factor-beta (TGF-beta 1) is known to suppress iNOS expression and NO production by many cell types. To determine the effect of TGF-beta 1 on NO production by skeletal muscle cells, we stimulated C2C12 myocytes with interferon-gamma (IFN) and interleukin-1 (IL-1) in the presence or absence of TGF-beta 1. In contrast to findings in macrophages, TGF-beta 1 markedly enhanced NO production by skeletal muscle cells. Increases in NO production reflected significant increases in iNOS immunoreactive protein and iNOS mRNA. Elevated iNOS mRNA levels associated with TGF-beta 1 treatment were not due to an alteration in mRNA stability, but rather reflected a significantly increased transcriptional rate of the iNOS gene. These findings indicate that TGF-beta 1 enhances iNOS expression in skeletal muscle cells and suggest that the regulation of NO production by TGF-beta 1 may depend on the cell type studied.
20-HETE is an endogenous inhibitor of the large-conductance Ca(2+)-activated K+ channel in renal arterioles
Authors: Zou A. P. , Fleming J. T. , Falck J. R. , Jacobs E. R. , Gebremedhin D. , Harder D. R. , Roman R. J.
Published: December 2017

The present study examined the effects of 20-hydroxyeicosatetraenoic acid (20-HETE) and 17-octadecynoic acid (17-ODYA), an inhibitor of the metabolism of arachidonic acid by P-450, on K(+)-channel activity in vascular smooth muscle cells (VSM) isolated from renal arterioles of the rat. Two types of K+ channels were characterized using inside-out excised membrane patches. One channel exhibited a large conductance (250.3 +/- 5 pS), was activated by membrane depolarization and elevations in cytoplasmic Ca2+ concentration, and was blocked by low concentrations (< 1 mM) of tetraethylammonium (TEA). The other K+ channel exhibited an intermediate conductance (46.3 +/- pS), was activated by membrane depolarization but not by changes in intracellular Ca2+ concentration, and was blocked by 4-aminopyridine (5 mM). Addition of 20-HETE to the bath (1-100 nM), reduced the frequency of opening of the large-conductance Ca(2+)-activated K+ channel recorded using cell-attached patches on VSM. It had no effect on the intermediate-conductance K+ channel: 17-ODYA (1 microM) increased the activity of the large-conductance Ca(2+)-activated K+ channel, and this effect was reversed by 20-HETE (10 nM). 20-HETE (1-1000 nM) reduced the diameter of isolated perfused small renal arteries of the rat by approximately 15% TEA (1 mM) blocked the vasoconstrictor response to 20-HETE (100 nM). These studies suggest that 20-HETE is an endogenously formed vasoconstrictor that acts in part by inhibiting the opening of the large-conductance Ca(2+)-activated K+ channel in renal arteriolar VSM.
Regulation of renal sympathetic nerve activity at birth
Authors: Mazursky J. E. , Segar J. L. , Nuyt A. M. , Smith B. A. , Robillard J. E.
Published: December 2017

The present studies were designed to assess the contribution of onset of respiration, separation from the placenta, and a decrease in environmental temperature on the increase in renal sympathetic nerve activity (RSNA) that occurs at birth. In the first series of experiments, heart rate (HR), mean arterial blood pressure (MABP), and RSNA were recorded in chronically instrumented near-term fetal sheep (n = 12) before and during in utero ventilation (V), V + oxygenation (V + O), and V + O + umbilical cord occlusion (V + O + CO). RSNA increased by 49 +/- 16% during V alone (P < 0.05), whereas no additional changes were seen with V + O or V + O + CO. HR and MABP did not change with any intervention. In a second series of experiments (n = 10), changes in fetal HR, MABP, and RSNA in response to in utero cooling were recorded. Cooling of the fetal core temperature by -3.1 +/- 0.2 degree C produced a rapid and sustained increase in RSNA (330 +/- 155%), HR (25 +/- 11%), and MABP (10 +/- 2%) consistent with generalized sympathoexcitation. In a third series of studies (n = 3), we found that brain stem transection between the rostral pons and posterior hypothalamus abolishes the increases in RSNA seen at birth. These results suggest that cooling is a major contributor to the postnatal rise in RSNA and that brain centers at the level of or above the hypothalamus are involved in mediating sympathoexcitation at birth.
Eating-related increase of dopamine concentration in the LHA with oronasal stimulation
Authors: Yang Z. J. , Koseki M. , Meguid M. M. , Laviano A.
Published: December 2017

Previously, we showed that eating was associated with an increase in lateral hypothalamic area dopamine (LHA-DA) release, which returns to previous level when eating stops. We therefore hypothesize that LHA-DA release may be primarily contributed to by oronasal stimulation. To test our hypothesis, microdialysis was used to compare LHA-DA release during oral and intragastric feeding. A gastrostomy tube was inserted in 12 rats. After recovery from surgery, in vivo microdialysis was performed. Six rats were allowed to drink a liquid diet, whereas in another six rats the same liquid diet was infused at paired doses (volume = 4.8 +/- 0.6 ml; time = 5-10 min) through the gastrostomy tube into the stomach. Oral feeding increased baseline LHA-DA from 10.6 +/- 0.2 to 14.0 +/- 0.8 pg/10 microliters dialysate (P < 0.01) within 20 min. No significant change in measured LHA-DA occurred during intragastric feeding [baseline: 10.5 +/- 0.3 pg/10 microliters; postintragastric: 10.2 +/- 0.3 pg/10 microliters (P < 0.01 vs. oral feeding)], indicating that LHA-DA release occurs with oronasal stimulation.
Paraventricular nucleus efferents influence area postrema neurons
Authors: Smith P. M. , Ferguson A. V.
Published: December 2017

Extracellular single-unit recordings were obtained from area postrema neurons (AP), and peristimulus histograms were used to determine the effects of paraventricular nucleus (PVN) stimulation on these cells from anesthetized Sprague-Dawley rats. Of 91 AP cells tested, 30.8% responded to PVN stimulation with a short-latency (28.2 +/- 3.3 ms, mean +/- SE), short-duration (49.3 +/- 8.0 ms) excitation, whereas 8.6% were inhibited. In animals that had stimulation sites outside of PVN (non-PVN), only 4 of the 72 AP cells tested (5.6%) were influenced by stimulation. These excitatory effects of PVN stimulation on AP neurons were unaffected by V1-receptor blockade. Of 93 nucleus of the solitary tract (NTS) cells tested, 38.9% responded to PVN stimulation with a short-latency (18.5 +/- 2.4 ms), short-duration (48.8 +/- 9.6 ms) excitation and 22.2% with short-latency (20.75 +/- 4.1 ms), long-duration (204.4 +/- 44.9 ms) inhibitions. In contrast, non-PVN stimulation sites influenced only 19% of NTS neurons tested, all of which were excited. These data demonstrate that activation of PVN neurons elicits excitatory effects on the majority of AP neurons influenced. They further emphasize the potential significance of descending hypothalamic inputs in controlling neuronal activity in this circumventricular organ.
Photoperiod-dependent fat pad mass and cellularity changes after partial lipectomy in Siberian hamsters
Authors: Mauer M. M. , Bartness T. J.
Published: December 2017

Long day (LD)-housed Siberian hamsters show compensatory mass increases in nonexcised white adipose tissue (WAT) after partial lipectomy, whereas hamsters exposed to short days (SDs) for 22 wk do not. The purpose of this experiment was to determine the cellularity changes underlying lipectomy-induced WAT compensation and whether the duration of SD exposure affects this compensation. Male Siberian hamsters were epididymal (E) or inguinal (I) WAT lipectomized (x) or sham-lipectomized (Sham) and either remained in LDs or were transferred to SDs and killed 6 or 12 wk later. In LDs, lipectomized hamsters showed compensatory mass increases in retroperitoneal WAT (RWAT) due to hyperplasia. IWAT mass also was increased by approximately 40% in LD-housed EWATx hamsters because of nonsignificant increases in adipocyte size and number at weeks 6 and 12, respectively. SD-housed hamsters responded to lipectomy by delaying the SD-associated body fat loss so that RWAT mass was reduced only one-third as much in lipectomized as in Sham hamsters, and the IWAT adipocytes of EWATx hamsters were larger than in Sham hamsters at week 6. At week 12, there was little indication of fat pad compensation by SD-housed hamsters. Collectively, the results of the present experiment and our previous study (16) suggest that the inhibitory effect of SDs on fat pad compensation after lipectomy increases with prolonged SD exposure.
Endogenous angiotensin II inhibits natriuresis after acute volume expansion in the neonatal rat
Authors: Chevalier R. L. , Thornhill B. A. , Belmonte D. C. , Baertschi A. J.
Published: December 2017

Compared with the adult, the neonatal renal natriuretic response to acute volume expansion (VE) is attenuated. To test the hypothesis that antinatriuresis is mediated by endogenous angiotensin I (ANG II), Sprague-Dawley rats were given losartan, an ANG II type 1 (AT1)-receptor inhibitor (40 mg.kg-1.day-1) from birth to 14-17 days. Control littermates received saline vehicle. Anesthetized rats underwent acute saline VE for measurement of mean arterial blood pressure (MAP), plasma aldosterone concentration (Paldo), plasma atrial natriuretic peptide (PANP), glomerular filtration rate (GFR), sodium excretion (UNaV), potassium excretion (UKV), and urine guanosine 3',5'-cyclic monophosphate excretion (UcGMPV). Losartan increased basal urine flow fivefold, UNaV 10-fold, and UKV twofold. Acute VE induced marked diuresis, natriuresis, and kaliuresis in the losartan but not in the saline group. This occurred without change in Paldo and PANP and despite lower MAP, GFR, and UcGMPV. In addition, losartan did not affect release of cGMP from isolated glomeruli stimulated by ANP or sodium nitroprusside. We conclude that the limited renal response to acute VE in the neonate results from stimulation of tubular Na reabsorption by ANG II acting on the AT1 receptor.
Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control
Authors: Stanley B. G. , Willett V. L. , Donias H. W. , Dee M. G. , Duva M. A.
Published: December 2017

To determine whether endogenous lateral hypothalamic (LH) glutamate and its N-methyl-D-aspartate (NMDA) receptors might participate in the stimulation of natural eating, LH injection of the NMDA antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was tested in adult male rats for suppressive actions on feeding elicited by 1) NMDA, kainic acid or D, L-alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) injected into the LH; 2) food deprivation; and 3) the onset of the nocturnal period. D-AP5 (10-100 nmol) reduced by 72-90% the approximately 10-g eating response elicited by NMDA (10 nmol) without affecting the quantitatively similar eating responses elicited by kainic acid (1.0 nmol) or AMPA (1.0 nmol). This treatment also suppressed deprivation-induced eating by as much as 61% and nocturnal eating by as much as 40%. To determine its long-term effects, D-AP5 (50 nmol) was injected bilaterally into the LH twice a day for 8 consecutive days. This treatment caused up to 65% reductions in daily food intake and body weight loss of up to 13 g/day. These findings, showing behaviorally selective suppressions of eating and body weight by D-AP5, argue that endogenous LH glutamate acts to regulate natural eating and body weight and that NMDA receptors participate in these functions.
cGMP-dependent protein kinase inhibitors block light-induced phase advances of circadian rhythms in vivo
Authors: Mathur A. , Golombek D. A. , Ralph M. R.
Published: December 2017

Synchronization of circadian rhythms is thought to be accomplished primarily through daily phase delays and advances of the endogenous circadian clock that, in mammals, is located in the hypothalamic suprachiasmatic nucleus (SCN). In the SCN, numerous second messenger pathways may participate in photic signal transduction. In these studies, the involvement of cyclic nucleotide-dependent kinases was examined in vivo using inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP)- and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent kinase (PKA and PKG, respectively). In constant dark, selective and nonselective inhibitors of PKG injected near the SCN of hamsters had no effect on phase delays produced by light pulses given in the early subjective night (early in the animals' active period) but significantly attenuated phase advances induced late in the subjective night. PKA inhibition had no effect at either time point. In addition, cGMP agonists had no effect on rhythmicity in the absence of light. The results suggest that PKG activity is necessary, but not sufficient, for normal photic responsiveness and that PKA activity is not required. The phase dependence of the effect of PKG inhibition supports the notion that photic entrainment is influenced by biochemical pathways that differentially regulate sensitivity in a phase-dependent manner.
Melatonin rhythm is not shifted by lights that suppress nocturnal melatonin in humans under entrainment
Authors: Hashimoto S. , Nakamura K. , Honma S. , Tokura H. , Honma K.
Published: December 2017

Effects of a single light exposure on the circadian rhythm in plasma melatonin were, examined in young males to obtain the threshold of light intensity for suppressing the nocturnal melatonin level on the one hand and to understand the relationship between the light-induced phase shift of melatonin rhythm and the melatonin suppression on the other hand. Eight subjects spent 3 days in an experimental living facility where light intensity was set below 200 lx and were exposed to light for 3 h in the early morning on the 2nd day. The same procedure was repeated five times in each subject with an interval of at least 3 wk, and one of five light intensities was tested in each trial. As a result, nocturnal melatonin level was not suppressed by light of 200 lx but significantly suppressed by light of intensity > or + 500 lx. On the other hand, the circadian melatonin rhythm was not shifted by any light intensity up to 10,000 lx. It is concluded that the threshold of light intensity for suppressing the melatonin level is located between 200 and 500 lx in young Japanese males, and the threshold for phase shifting the circadian melatonin rhythm was much greater than that for suppressing the nocturnal melatonin level in humans under entrained conditions.
Cardiac output in Xenopus laevis tadpoles during development and in response to an adenosine agonist
Authors: Tang Y. Y. , Rovainen C. M.
Published: December 2017

We test the hypothesis that the heart and arteries enlarge with increased cardiac output (CO) during development and volume overload. Transparent albino tadpoles of Xenopus laevis at stages 43-50 were anesthetized in 0.3-0.5 mM benzocaine. Areas and radii [maximum and minimum radius (Rmax and Rmin, respectively)] of the ventricle were measured in digitized video frames during the cardiac cycle. Stroke volume (SV) and CO were calculated from Rmax and Rmin. Maximal velocities of 3.4-microns fluorescent beads were measured in the aortic arches. Arterial pressure was estimated by the Landis method. During normal development, the radii of the ventricle and aortic arch diameters increased with lengths of tadpoles, and SV (0.7 microliters/g) and CO (70 microliters.g-1.min-1) with wet weights. Volume overload was induced by a vasodilatory adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) in the aquarium water. Acute (0.5-4 h) NECA significantly increased Rmax and heart rate. Chronic (> 1 wk) NECA significantly increased both Rmax and Rmin. SV and CO increased more than two times, blood pressures decreased, and specific vascular conductances increased more than five times. It is concluded that NECA increases CO in Xenopus tadpoles through a combination of increased filling and accelerated growth.
An interleukin-1 receptor fragment inhibits spontaneous sleep and muramyl dipeptide-induced sleep in rabbits
Authors: Takahashi S. , Kapas L. , Fang J. , Seyer J. M. , Wang Y. , Krueger J. M.
Published: December 2017

Interleukin-1 (IL-1) is hypothesized to be involved in physiological sleep regulation and in sleep responses occurring during infectious disease. If this hypothesis is correct, then inhibition of endogenous IL-1 should reduce both normal sleep and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-induced sleep. MDP is a somnogenic substance derived from bacterial cell walls. We report here the effects of a synthetic IL-1 receptor fragment corresponding to amino acid residues 86-95 of the human type I IL-1 receptor (IL-1RF) on spontaneous sleep and IL-1 beta- and MDP-induced sleep and fever in rabbits. Two doses of the IL-1RF (25 and 50 micrograms) were injected into normal rabbits intracerebroventricularly (icv). Both doses significantly decreased spontaneous non-rapid eye movement sleep (NREMS) across a 22-h recording period. Pretreatment of rabbits with 25 micrograms of IL-1RF blocked the somnogenic actions of 10 ng icv IL-1. Similarly, central pretreatment of animals with 25 micrograms IL-1RF significantly attenuated the NREMS-promoting and REMS-suppressive actions of 150 pmol MDP injected centrally. The increase in NREMS and decrease in REMS induced by systemic injection of 12.5 micrograms/kg MDP were also significantly suppressed by central administration of 50 micrograms IL-1RF. In contrast, the febrile response induced by either intracerebroventricularly or intravenously injected MDP were not significantly affected by IL-1RF. These results support the hypothesis that endogenous, brain-derived IL-1 contributes to the maintenance of normal sleep and may mediate sleep responses to systemic as well as central bacterial infections.
Immediate acceptance of minerals and HCl by calcium-deprived rats: brief exposure tests
Authors: Coldwell S. E. , Tordoff M. G.
Published: December 2017

We conducted two experiments to test the hypothesis that calcium consumption by calcium-deprived rats is unlearned and guided by oral cues. In experiment 1, we gave 23.5-h water-deprived control and calcium-deprived rats 30-min tests with water and various taste solutions. Relative to controls, calcium-deprived rats licked significantly less water and more 300 mM Ca.lactate in the first minute, more 50 mM HCl and 125 mM HCl in the first 10 min, and more 75 mM CaCl2, 150 mM CaCl2, and 300 mM CaCl2 by the end of the 30-min session. There was no difference between the groups at any time in lick rates for sodium solutions, quinine hydrochloride, sucrose octaacetate, or saccharin. In experiment 2, we gave 23-h water-deprived control, calcium-deprived, and sodium-deprived rats 10-min tests. During the first minute, calcium-deprived rats licked more than did control and sodium-deprived rats for 100 mM CaCl2, 100 mM FeCl2, and 20 mM Pb.acetate. Sodium-deprived rats licked more than did control and calcium-deprived rats for 600 mM NaCl and less than did controls for 200 mM L-histidine. At the end of the 10-min session, sodium-deprived rats had higher lick rates for 100 mM FeCl2 than did control rats. There were no differences between the groups in lick rates for 1 mM quinine hydrochloride, 100 mM SrCl2, or 20 mM citric acid. The results suggest that calcium-deprived rats use innate oral factors to guide consumption of calcium and other solutions.
Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds
Authors: Fincher E. F. , Johannsen L. , Kapas L. , Takahashi S. , Krueger J. M.
Published: December 2017

Excess sleep and fever are central nervous system (CNS) facets of the acute phase response; these responses are induced by microbial products, such as muramyl peptides, via their ability to enhance cytokine production. Although peripheral macrophages are known to digest bacteria, thereby releasing muramyl peptides that, in turn, stimulate cytokine production, it was unknown whether CNS phagocytes such as microglia also had this capacity. Primary cultures of microglia were allowed to phagocytize and digest Staphylococcus aureus radiolabeled with a cell wall-specific marker. Radiolabeled low molecular weight substances released into the culture medium were partially purified and tested for the ability to induce excess sleep, fever, and cytokine production. These substances increased non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature after intracerebroventricular injection into rabbits. They also induced interleukin-1, tumor necrosis factor, and the interleukin-1 receptor antagonist production in human monocytes. Results suggest that microglia perform fundamental macrophage functions and further implicate microglia as resident immunocompetent cells.
Expression of sarcoplasmic reticulum Ca(2+)-ATPase isoforms in marlin and swordfish muscle and heater cells
Authors: Tullis A. , Block B. A.
Published: December 2017

The superior rectus muscles of marlin, swordfish, sailfish, and spearfish are modified for generating heat rather than force. This study focuses on the sarcoplasmic reticulum calcium-adenosinetriphosphatase (SR Ca(2+)-ATPase) to gain further insight into the muscle fiber type origin of the billfish “heater cell.” Direct sequencing and immunolocalization demonstrated that marlin and swordfish epaxial swimming muscles express two forms of the SR Ca(2+)-ATPase in a fiber type-specific manner; red slow-twitch skeletal and cardiac muscles express the same SERCA2 message, whereas white fast-twitch skeletal muscles express a SERCA1 message. Thus the expression pattern of the SR Ca2+ pump is similar in both billfish and tetrapod muscles. Molecular and immunological studies revealed that billfish heater tissue and superior rectus muscle express both fast and slow SR Ca2+ pump isoforms. Immunohistochemical results suggest that heater cells and most extraocular muscle fibers express the fast SR Ca2+ pump. Expression of the fast SR Ca(2+)-ATPase by heater cells has implications for heater cell origin and thermogenic control.
Chemoreflex and endocrine components of cardiovascular responses to acute hypoxemia in the llama fetus
Authors: Giussani D. A. , Riquelme R. A. , Moraga F. A. , McGarrigle H. H. , Gaete C. R. , Sanhueza E. M. , Hanson M. A. , Llanos A. J.
Published: December 2017

We tested the hypothesis that the llama fetus has a blunted cardiovascular chemoreflex response to hypoxemia by investigating the effects of acute hypoxemia on perfusion pressure, heart rate, and the distribution of the combined ventricular output in 10 chronically instrumented fetal llamas at 0.6-0.7 gestation. Four llama fetuses had the carotid sinus nerves sectioned. In the intact fetuses, there was a marked bradycardia, an increase in perfusion pressure, and a pronounced peripheral vasoconstriction during hypoxemia. These cardiovascular responses during hypoxemia in intact fetuses were accompanied by a pronounced increase in plasma vasopressin, but not in plasma angiotensin II concentrations. Carotid denervation prevented the bradycardia at the onset of hypoxemia, but it did not affect the intense vasoconstriction during hypoxemia. Plasma vasopressin and angiotensin II levels were not measured in carotid-denervated fetuses. Our results do not support the hypothesis that the carotid chemoreflex during hypoxemia is blunted in the llama fetus. However, they emphasize that other mechanisms, such as increased vasopressin concentrations, operate to produce an intense vasoconstriction in hypoxemia. This intense vasoconstriction in the llama fetus during hypoxemia may reflect the influence of chronic exposure to the hypoxia of high altitude on the magnitude and gain of fetal cardiovascular responses to a superimposed acute episode of hypoxemia.
Hemodynamic and renal effects of cross-linked hemoglobin infusion
Authors: Cases A. , Stulak J. M. , Katusic Z. , Villa E. , Romero J. C.
Published: December 2017

It is well known that hemoglobin binds nitric oxide (NO) and produces a pronounced vasoconstriction in isolated arteries. However, it is debatable whether such an effect takes place in whole animals, because hemoglobin also catalyzes the formation of prostaglandins from arachidonic acid. Short-term studies were performed to evaluate the effects induced by intravenous infusion of cross-linked hemoglobin (XL-Hb) on blood pressure (BP) and renal, iliac, and mesenteric flows, and on renal function in six anesthetized dogs. A similar volume-matched expansion with 6% dextran was used as a control (n = 6). Glomerular filtration rate (GFR), urinary flow, and total and fractional sodium excretion were measured before and after XL-Hb or dextran infusion to evaluate possible renal function changes. XL-Hb administration resulted in a 29% elevation in BP and a significant decrease of blood flow (30-37%) to the three vascular beds. XL-Hb did not alter GFR or sodium excretion, despite the increase in BP. In contrast, the administration of dextran did not significantly alter BP but induced a significant increase (6-13%) of blood flow in the three vascular beds. These changes were accompanied by threefold increases in urinary flow and sodium excretion without alterations in GFR. The binding effect of XL-Hb on NO was studied in isolated renal arteries in organ chambers. These in vitro studies showed that XL-Hb blunted the endothelium-mediated vasodilator response to calcium ionophore A-23187 and to acetylcholine. Our results demonstrate that XL-Hb administration is followed by hypertension, vasoconstriction, and blunted natriuresis. All these effects are compatible with the scavenging effect on NO attributed to XL-Hb.
Possible nicotinic receptor-mediated modulation of synaptic transmission in nucleus of the solitary tract
Authors: Shiraki T. , Toyoda A. , Sugino H. , Hori A. , Kobayashi S.
Published: December 2017

Signal transmission from afferent nerves to neurons in the nucleus of the solitary tract (NTS) may be mediated partially by nicotinic acetylcholine receptors (nAChRs). Here, we investigated nAChR-mediated signal transmission using rat NTS slices. First, we characterized nAChRs by obtaining patch-clamp recordings from NTS neuronal cell bodies. Under whole cell voltage-clamp conditions at -60 mV, application of nicotine induced an inward current, and this effect was blocked by hexamethonium. In outside-out patch recordings, nicotine was seen to induce a hexamethonium-sensitive single-channel current. Second, we investigated nAChR-mediated signal transmission. Fast synaptic transmission mediated by nAChRs was not detected. The action of diffusible acetylcholine (ACh) on nAChRs was then tested using the outside-out patches excised from NTS neurons as probes for ACh. When the patch was placed at a distance of 20-30 microm from the cell body, single-channel currents were recorded, and these were inhibited by hexamethonium. The frequency of channel opening was increased by high-extracellular potassium concentration solution suggesting the voltage-dependent release ofACh that acts on nAChRs. These results suggested that nAChR-mediated signal transmission from sensory afferents to NTS neurons is in part mediated by diffusible ACh.
Environmental induction of photononresponsiveness in the Siberian hamster, Phodopus sungorus
Authors: Gorman M. R. , Zucker I.
Published: December 2017

In seasonally breeding rodent species, a fraction of the population is unresponsive to short day lengths (DL) and remains reproductively competent during winter. We previously observed that incidence of nonresponsiveness to short days was affected by photoperiodic history. Here we tested whether exposure to long DL (18 h light/day; 18L) renders animals unresponsive to short DL (10L). Hamsters, maintained from birth in 10L, were transferred at week 6 to 18L or 14L. Ten weeks later (week 16), groups were transferred to 10L for 10 wk. All hamsters maintained in short DL from birth had undeveloped testes at week 6. At week 26, however, 92% of hamsters previously kept in 18L failed to undergo complete gonadal regression in 10L, compared with only 10% of hamsters previously in 14L. Entrainment of locomotor activity in 10L in nonresponsive hamsters resembled that typically observed under long DL. Exposure to 18L may induce nonresponsiveness by altering interactions of component circadian oscillators that mediate gonadal regression in short DL.
Acute administration of a tryptophan-free amino acid mixture decreases 5-HT release in rat hippocampus in vivo
Authors: Stancampiano R. , Melis F. , Sarais L. , Cocco S. , Cugusi C. , Fadda F.
Published: December 2017

The effect of oral administration of a tryptophan-free amino acid mixture or the same mixture containing tryptophan (Trp) on hippocampal serotonin (5-HT) extracellular levels was studied using in vivo brain microdialysis of freely moving rats. During chloral hydrate anesthesia rats were implanted with dialysis probes in the dorsal hippocampus, and experiments were performed 24 h later. In vehicle-treated rats, the extracellular levels of 5-hydroxyindolacetic acid (5-HIAA) and 5-HT did not change during 240 min after ingestion. Oral administration of the Trp-free amino acid mixture significantly decreased basal 5-HT and 5-HIAA output 100 min after ingestion (65 and 81% of basal value, respectively) and remained at this level for another 140 min. The amino acid mixture containing Trp failed to significantly change basal extracellular levels of 5-HT, but enhanced that of 5-HIAA by approximately 134%. Moreover, in rats receiving the Trp-free amino acid mixture, the increase of hippocampal 5-HT release induced by d-fenfluramine (206%) was smaller than that released by the same drug in rats receiving the nutritionally balanced amino acid mixture (271%). Thus these results show that removal of Trp from the balanced amino acid mixture decreases spontaneous and d-fenfluramine-induced release of 5-HT in the hippocampus. In conclusion, our study supports the hypothesis that the mood-lowering effect observed in man after ingestion of a Trp-free amino acid mixture is associated with diminished 5-HT release in the brain.
Opioids in the nucleus of the solitary tract are involved in feeding in the rat
Authors: Kotz C. M. , Billington C. J. , Levine A. S.
Published: December 2017

We evaluated the effect of selective opioid peptides and naltrexone on feeding when injected into the nucleus of the solitary tract (NTS). Doses of 0, 1, 2, 4, and 8 nmol of [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-agonist), dynorphin A-(1-17) (DynA-(1-17), kappa-agonist), and [D-Ser2]leucine enkephalin-thr, (delta-agonist) were injected into the NTS in satiated male rats, and food intake was measured at 1, 2, and 4 h. Only DAMGO significantly increased feeding above control levels at doses of 2, 4, and 8 nmol. Doses of 10 and 50 microg naltrexone in the NTS significantly decreased 18-h deprivation-induced feeding. These data suggest that NTS opioid receptors (primarily mu) may be involved in the regulation of feeding.
Raising at thermoneutrality prevents obesity and hyperphagia in BAT-ablated transgenic mice
Authors: Melnyk A. , Harper M. E. , Himms-Hagen J.
Published: December 2017

Transgenic mice with ablation of brown adipocytes induced by brown adipocyte-specific expression of diphtheria toxin A chain (DTA) driven by the uncoupling protein (UCP) promoter (UCP-DTA mice) become obese and hyperphagic (Lowell, B. B., V. S. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. P. Kozak, and J. S. Flier. Nature 366: 740-742, 1993). A deficit in energy expenditure for brown adipose tissue (BAT) thermogenesis in these mice is presumed to contribute to the development of obesity. The objective of the present study was to obviate any deficit in BAT thermogenesis by raising transgenic and control mice at thermoneutrality (35 degrees C), where both would have equally inactive BAT, to see whether this would prevent the obesity and the hyperphagia. Transgenic and control mice were raised from weaning (3 wk of age) to 8 wk of age at either 24 or 35 degrees C. Raising at 35 degrees C completely prevented development of obesity of UCP-DTA mice, as indicated by their normal carcass fat, normal weights of four major white adipose tissue depots, and normal size of white adipocytes. As seen before, transgenic mice raised at 24 degrees C had excess weight gain by 6 wk of age and by 8 wk had doubled carcass fat, an obesity characterized by increased white adipocyte size with no increase in number of adipocytes. The treatment also prevented hyperphagia of UCP-DTA mice, consistent with the hypothesized role of BAT thermogenesis in control of thermoregulatory feeding (Himms-Hagen, J. Proc. Soc. Exp. Biol. Med. 208: 159-169, 1995). UCP-DTA mice thus differ from genetically obese mice (ob/ob, db/db) for which raising at thermoneutrality is known not to prevent either the obesity or the hyperphagia. Both the obesity and the hyperphagia of UCP-DTA mice appear to be due to their deficit in BAT thermogenesis.
Acute hypoxia stimulates renin secretion and renin gene expression in vivo but not in vitro
Authors: Ritthaler T. , Schricker K. , Kees F. , Kramer B. , Kurtz A.
Published: December 2017

This study aimed at examining the influence of acute hypoxia on renin secretion and renin gene expression in the kidney. To this end, male Sprague-Dawley rats were exposed to severe hypoxic stress (8% O2) or to carbon monoxide (0.1% CO) for 6 h, and plasma renin activity (PRA) and renal renin mRNA levels were determined. PRA values increased from 3 to 13 and 10 ng angiotensin I x h(-1) x ml(-1), and renin mRNA levels increased by 120 and 100% during hypoxia and CO, respectively. Lowering the PO2 from 150 to 20 or 7 mmHg in the gas atmosphere of primary cultures of renal juxtaglomerular cells had no influence on renin secretion and renin gene expression after 6 and 20 h. Our findings thus suggest that both arterial and venous hypoxia can be powerful stimulators of renin secretion and renin gene expression in vivo. Because renal denervation did not prevent stimulation of the renin system by hypoxia, the effect could be indirectly mediated via the baroreceptor-macula densa mechanism. Another potential mediator of the effect could be circulating catecholamines, since we found that plasma norepinephrine increased from 0.7 to 1.5 and 2.4 ng/ml and plasma epinephrine increased from 0.3 to 1.4 and 2.7 ng/ml during hypoxia and CO inhalation, respectively.
Detrusor-sphincter dyssynergia induced by cold stimulation of the urinary bladder of rats
Authors: Cheng C. L. , Chai C. Y. , de Groat W. C.
Published: December 2017

Instillation of cold water into the urinary bladder has been used as a diagnostic test to evaluate neurogenic dysfunctions of the lower urinary tract (LUT). This study examined the effects of cold stimulation on the LUT of urethan-anesthetized rats. Urinary bladder pressure and external urethral sphincter (EUS) electromyogram (EMG) were recorded during cystometrograms in which body- or room-temperature saline was infused continuously into the bladder and voided through the urethra. Subsequent infusion of cold saline (6-8 degrees C) into the bladder increased by approximately 100% the duration and amplitude of supraspinal reflex bladder contractions, increased baseline bladder pressure, increased the pressure threshold for inducing micturition, and increased EUS EMG activity. Blocking EUS activity by transecting the pudendal nerves or by administering a neuromuscular blocking agent markedly reduced or eliminated the effect of cold stimulation. Capsaicin pretreatment suppressed the effect of cold stimulation. It is concluded that cold temperatures stimulate capsaicin-sensitive C fiber bladder afferents that reflexly activate the EUS, producing detrusor and sphincter dyssynergia and increasing urethral outlet resistance. This in turn increases the amplitude and duration of bladder contractions during voiding.
Comparison of ANP binding and sensitivity in brains from hypertensive and normotensive rats
Authors: Grove K. L. , Goncalves J. , Picard S. , Thibault G. , Deschepper C. F.
Published: December 2017

We compared the abundance and sensitivity of atrial natriuretic peptides (ANP) receptors in the brains of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats and examined the effect of blood pressure on the abundance of brain ANP receptors in several other experimental rat models. Brain slices from SHR generated more guanosine 3',5'-cyclic monophosphate in response to ANP than brain slices from WKY rats. No differences were found in brain particulate guanylate cyclase activity in both strains of rats. In rat brain homogenates, we observed that ANP bound in a specific and saturable fashion to samples from WKY rats, but not in samples from SHR. In vitro receptor autoradiography revealed that ANP binding was reduced in the subfornical organ, the choroid plexus, and the paraventricular nucleus of SHR compared with WKY rat brains. Correction of hypertension in SHR or induction of hypertension in other strains did not affect ANP binding in any of these brain regions. Altogether, our data suggest that the increased sensitivity of SHR brains to the action of ANP may be a consequence of factors other than the abundance of receptors and that it is not secondary to the elevation of blood pressure.