bluuebunny/crossref_metadata_2025 huggingface dataset:
Graded and dynamic reflex summation of myelinated and unmyelinated rat aortic baroreceptors
Authors: Fan Wei , Schild John H. , Andresen Michael C.
Published: December 2017

Unmyelinated (C) and myelinated (A) baroreceptor (BR) axons are present in rat aortic depressor nerve (ADN). With graded ADN electrical activation and anodal conduction blockade, reflex responses in anesthetized rats were assessed as changes in mean arterial pressure (MAP) and heart rate (HR). We tested the hypothesis that C-type BR inputs are effective at low frequencies because they outnumber A-type. Anodal current ( I an) reversibly eliminated all MAP and HR responses to A-selective stimuli. High intensities activated all ADN axons (A+C) and decreased MAP at lower frequencies (<10 Hz) than were effective with A-selective stimulation. I anreduced only MAP responses to >10-Hz ADN stimulation. Burst patterns significantly augmented A- but not C-selective reflex responses despite identical numbers of shocks per second. A-selective stimuli failed to evoke significant bradycardia even at 200 Hz. Maximum intensity stimuli plus I an (C selective) evoked less bradycardia than without I an (A+C), indicating supra-additive summation unlike the occlusive summation for MAP responses. However, activation of reduced numbers of C-type BRs with all A-type BRs suggests a strong A to C interaction in reflex bradycardia responses. Surprisingly, I an block of A-type conduction eliminated all reflex bradycardia at such submaximal intensities despite C conduction and depressor responses. A- and C-type BRs act synergistically, and A-type activity is absolutely required in cardiac but not in depressor pathways. Thus greater numbers do not appear to account for C-type BR efficacy, and critical interactions between these two sensory subtypes appear to occur differentially across cardiac and systemic baroreflex effector pathways.
Activation of hypothalamic serotonin receptors reduced intake of dietary fat and protein but not carbohydrate
Authors: Smith Brenda K. , York David A. , Bray George A.
Published: December 2017

Systemic treatment with dexfenfluramine (dF), fluoxetine, or serotonin (5-hydroxytryptamine, 5-HT) recently was shown to suppress fat and occasionally protein but not carbohydrate intake in rats when a macronutrient selection paradigm was employed. These reports contrast with the prevailing literature, which for the past decade has described a role for serotonin neurotransmission in the modification of dietary carbohydrate consumption. To test the hypothesis that the suppression of fat selection and/or consumption by systemic serotonin agonists involves stimulation of central 5-HT receptors, a series of experiments was performed in nondeprived rats. In experiment 1, third cerebroventricular (3V) infusion of the nonselective 5-HT antagonist metergoline prevented the reduction in fat but not carbohydrate feeding caused by systemic dF. Furthermore, 3V metergoline alone increased fat intake. In experiments 2 and 3, 3V infusion of 5-HT1B/2C receptor agonistsd-norfenfluramine (dNF) or quipazine inhibited fat intake exclusively. Next, the infusion ofdNF or 5-HT into the region of the paraventricular nucleus (PVN) reduced both fat and protein intake ( experiments 4 and 5). Finally, in experiment 6, when rats were grouped by baseline diet preference, 5-HT infused into the PVN led to a dose-related decrease in fat intake in both carbohydrate- and fat-preferring rats. In contrast, there were no dose effects of 5-HT on carbohydrate or protein intake in either preference group. However, in fat-preferring rats, the highest dose of 5-HT reduced intake of all three macronutrient diets. These results demonstrate a selective effect of exogenous serotonergic drugs in the hypothalamus to reduce fat rather than carbohydrate intake and suggest that higher baseline fat intake enhances responsivity to serotonergic drugs.
Aminophylline alters the core temperature response to acute hypoxemia in newborn and older guinea pigs
Authors: Crisanti Kim C. , Fewell James E.
Published: December 2017

In newborns and adults of a number of species, exposure to acute hypoxemia produces a “regulated” decrease in core temperature, the mechanism of which is unknown. The present experiments were carried out on chronically instrumented newborn (5–10 days of age; n = 27) and older (25–30 days of age; n = 23) guinea pigs to test the hypothesis that adenosine mediates this regulated decrease in core temperature. During an experiment, core temperature was measured by biotelemetry from animals studied in a thermocline during a control period of normoxemia, an experimental period of normoxemia or acute hypoxemia (fraction of inspired oxygen 0.10), and during a recovery period of normoxemia after an intraperitoneal injection of 10 mg/kg aminophylline (i.e., a nonspecific adenosine antagonist) or vehicle. Core temperature decreased significantly during hypoxemia after vehicle in both newborn and older guinea pigs. After aminophylline, however, newborn guinea pigs failed to significantly decrease their core temperature, whereas older guinea pigs exhibited an attenuated yet significant core temperature decrease during hypoxemia. Our data support the hypothesis that adenosine plays an age-dependent role in mediating the regulated decrease in core temperature that occurs in newborn and older guinea pigs during acute hypoxemia.
Defective ACTH response to stress in previously stressed rats: dependence on glucocorticoid status
Authors: Martí Octavi , Andrés Rosa , Armario Antonio
Published: December 2017

The effect of previous exposure to stress on the pituitary-adrenal response to a further stress was characterized in rats with different glucocorticoid status: sham-operated rats (Sham), adrenalectomized (ADX) rats, and ADX rats supplemented with a low corticosterone (B) dose in the drinking saline (ADX + B). Previous exposure of Sham rats to 1 h of immobilization (Imo) reduced, 2 h later, the ACTH response to a second severe stressor (Imo) but not to a less severe stressor (tail shock). In ADX rats, previous Imo totally suppressed the ACTH response to Imo or to shock. In ADX + B rats the response to shock was blocked and that to Imo tended to be lower. These changes were not explained by depletion of adenohypophysial ACTH stores. After previous Imo, reduced response to corticotropin-releasing factor was observed in Sham and ADX + B, but not in ADX, rats. Taken together, the present results suggest that the reduced ACTH response of previously stressed rats to a second severe stress is observed in the presence and absence of glucocorticoids, but the main site at which such inhibition occurs might be critically dependent on the glucocorticoid status.
Low-frequency renal sympathetic nerve activity, arterial BP, stationary “1/f noise,” and the baroreflex
Authors: Burgess Don E. , Zimmerman Tabitha A. , Wise Marshall T. , Li Sheng-Gang , Randall David C. , Brown David R.
Published: December 2017

The object of this study is to quantify the very low frequency (i.e., <0.1 Hz) interactions between renal sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Six rats were instrumented for chronic recordings of SNA and ABP. Data were collected 24 h after surgery at 10 kHz for 2–5 h and subsequently compressed to a 1-kHz signal. The power spectra and ordinary coherence were calculated from data epochs up to 1 h in length. The very low frequency spectra for both variables were fitted to a constant times f −β. The peak magnitude squared of the coherence near 0.4 Hz was 0.82 ± 0.08, but the apparent linear coherence fell off quickly at lower frequencies so that it was close to zero for frequencies <0.1 Hz. Moreover, at these low frequencies β, as computed by a coarse grain spectral analysis, was significantly ( P < 0.01) different for SNA (0.66 ± 0.12) and ABP (1.12 ± 0.14). Assuming that SNA and ABP are stationary time series, the results of our classical spectral analysis would indicate that SNA and ABP are not linearly correlated at frequencies with a period more than ∼10 s. Accordingly, we tested for stationarity by computing the spectral coherence and found that SNA and ABP are not stationary “1/ f noise” within the frequency range from 0.02 to 2.0 Hz. Rather the SNA exerts control over the cardiovascular system through intermittent bursts of activity. Such intermittent behavior can be modeled by nonlinear dynamics.
A comparison of brain angiotensin II receptors during lactation and diestrus of the estrous cycle in the rat
Authors: Speth Robert C. , Barry William T. , Smith M. Susan , Grove Kevin L.
Published: December 2017

During lactation there are many dramatic alterations in the hypothalamic-pituitary (HP) axis, as well as an increased demand for food and water. The renin-angiotensin system (RAS) is one of the major mediators of the HP axis. This study examined the receptors for ANG II in the rat brain during lactation and diestrus. Compared with diestrus, lactating rats had significant decreases in ANG II receptor binding in several forebrain regions, most notably in the arcuate nucleus/median eminence, dorsomedial hypothalamic nucleus (DMH), and lateral hypothalamic area (LHA). In contrast, there was an increase in ANG II receptor binding in the preoptic area during lactation. These significant changes in ANG II binding in the brain during lactation support the hypothesis that changes in the RAS may contribute to the dramatic changes in the HP axis during lactation. In addition, the significant reduction in ANG II binding in the DMH and LHA may be indicative of a role in the regulation of food intake, a function only recently associated with the RAS.
Vesicoanal, urethroanal, and urethrovesical reflexes initiated by lower urinary tract irritation in the rat
Authors: Thor Karl B. , Muhlhauser Mark A.
Published: December 2017

Irritation of the urinary bladder causes activation of normally “silent” nociceptive primary afferent fibers. In the present study, it is reported that irritation of the urinary bladder or urethra with infusion of 0.5% acetic acid robustly activates motoneurons that innervate the striated muscle of the external anal sphincter via spinal reflex mechanisms. The activation of anal motoneurons following irritation of the bladder and urethra are termed vesicoanal and urethroanal reflexes, respectively. The reflexes can be mimicked by acute application of capsaicin to the bladder and urethra, and they show desensitization following prolonged topical application of capsaicin or following chronic systemic pretreatment with capsaicin. The reflexes can be demonstrated in chronic spinal cord-transected animals, indicating that the reflex pathways are organized within the spinal cord. The urethroanal reflex is also physiologically activated by urethral distension and/or increases in intraluminal pressure. In addition to activation of anal sphincter activity, slight distension, pressure increases, or instillation of 0.5% acetic acid into the urethra inhibited bladder contractions through activation of an inhibitory urethrovesical reflex. These reflexes are discussed in terms of clinical characteristics of urethritis and prostatitis. Anecdotally, it was discovered that the bladder can buffer acetic acid.
Strenuous resistive breathing induces proinflammatory cytokines and stimulates the HPA axis in humans
Authors: Vassilakopoulos Theodoros , Zakynthinos Spyros , Roussos Charis ,   (With the Technical Support of Michaelis Economou)
Published: December 2017

Interleukin-1β (IL-1β) and interleukin-6 (IL-6), powerful stimulants of the hypothalamic-pituitary-adrenal (HPA) axis, increase in response to whole body exercise. Strenuous inspiratory resistive breathing (IRB), a form of clinically relevant “exercise” for the respiratory muscles, produces β-endorphin through a largely unknown mechanism. We investigated (in 11 healthy humans) whether strenuous IRB produces proinflammatory cytokines and β-endorphin in parallel with stimulation of the HPA axis, assessed by concurrent measurement of ACTH. Subjects underwent either severe [at 75% of maximal inspiratory pressure (Pmmax)] or moderate (at 35% of Pmmax) IRB. Plasma cytokines, β-endorphin, and ACTH were measured at rest ( point R), at the point at which the resistive load could not be sustained ( point F), and at exhaustion [15 min later ( point E)]. During severe IRB, IL-1β increased from 0.83 ± 0.12 pg/ml at point R to 1.88 ± 0.53 and 4.06 ± 1.27 pg/ml at points F and E, respectively ( P < 0.01). IL-6 increased from 5.30 ± 1.02 to 10.33 ± 2.14 and 11.66 ± 2.29 pg/ml at points F and E, respectively ( P = 0.02). ACTH and β-endorphin fluctuated from 20.87 ± 5.49 and 25.03 ± 3.97 pg/ml at point R to 22.97 ± 4.41 and 26.32 ± 3.93 pg/ml, respectively, at point F and increased to 46.96 ± 8.55 and 40.32 ± 5.94 pg/ml, respectively, at point E ( P< 0.01, point E vs. point F). There was a positive correlation between the IL-6 at point F and the ACTH and β-endorphin at point E ( r= 0.88 and 0.94, respectively; P < 0.01) as well as between the increase in IL-6 (between points R and F) and the increases in ACTH and β-endorphin (between points F and E, r= 0.91 and 0.92, respectively; P < 0.01). Moderate IRB did not produce any change. We conclude that severe IRB produces proinflammatory cytokines and stimulates the HPA axis in humans secondary to the production of cytokines (especially IL-6).
Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals
Authors: Zheng Huiyuan , Kelly Lisa , Patterson Laurel M. , Berthoud Hans-Rudolf
Published: December 2017

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.
Feeding status and bacterial LPS-induced cytokine and neuropeptide gene expression in hypothalamus
Authors: Gayle Dave , Ilyin Sergey E. , Plata-Salamán Carlos R.
Published: December 2017

This study determined the effects of feeding status on basal and lipopolysaccharide (LPS)-stimulated cytokine and neuropeptide gene expression in the hypothalamus. With the use of RNase protection assays, we measured mRNA levels of interleukin-1β (IL-1β), IL-1 receptor antagonist (IL-1RA), IL-1 receptor type I (IL-1RI), IL-1R accessory proteins (AcP I and II), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), glycoprotein 130 (Gp 130), leptin receptor (OB-R), neuropeptide Y (NPY), preprodynorphin, and proopiomelanocortin (POMC). Analyses were done in ad libitum-fed, fasted, and fasted and refed rats treated with the intracerebroventricular administration of physiological saline or LPS. The data show that food deprivation increases the basal mRNA expression of IL-1β, IL-1RA, TNF-α, IL-1RI, and IL-1R AcP I, whereas mRNA levels of POMC showed a decrease. Five hours of refeeding returned cytokine levels to those observed in the ad libitum-fed group. LPS administration induced a robust upregulation of IL-1β, TNF-α, and IL-1RI during all three feeding conditions. Acute food deprivation did not modulate LPS-induced changes in hypothalamic cytokine mRNA profiles. These findings show that 1) cytokine modulation occurs as an adaptive response to the stress of acute fasting and 2) acute fasting does not affect LPS-induced cytokine mRNA modulation in the hypothalamus. The data have implications to gram-negative infections associated with acute anorexia.
Novel TRH analog improves motor and cognitive recovery after traumatic brain injury in rodents
Authors: Faden Alan I. , Fox Gerard B. , Fan Lei , Araldi Gian Luca , Qiao Lixin , Wang Shaomeng , Kozikowski Alan P.
Published: December 2017

Thyrotropin-releasing hormone (TRH) and certain TRH analogs show substantial neuroprotective effects in experimental brain or spinal cord trauma but also have other physiological actions (autonomic, analeptic, and endocrine) that may be undesirable for the treatment of neurotrauma in humans. We developed a novel TRH analog (2-ARA-53a), with substitutions at the NH2-terminus and imidazole ring, that preserves the neuroprotective action of TRH-like compounds while decreasing or eliminating their autonomic, analeptic, and endocrine effects. Rats administered 2-ARA-53a (1.0 mg/kg, n = 17) intravenously 30 min after lateral fluid percussion brain injury showed marked improvement in motor recovery compared with vehicle-treated controls ( n = 14). Treatment of mice subjected to moderate controlled cortical impact brain injury, at the same dose and time after trauma ( n = 8), improved both motor recovery and cognitive performance in a water maze place learning task compared with vehicle-treated controls ( n = 8). In injured rats, no autonomic or analeptic effects were observed with this compound, and endocrine effects were significantly reduced with 2-ARA-53a, in contrast to those found with a typical NH2-terminal-substituted TRH analog (YM-14673). These findings demonstrate that the neuroprotective effects of TRH-related compounds can be dissociated from their other major physiological actions and suggest a potential role for dual-substituted TRH analogs in the treatment of clinical neurotrauma.
Effects of maturation on adrenergic neurotransmission in ovine cerebral arteries
Authors: Pearce William J. , Duckles Sue P. , Buchholz John
Published: December 2017

The present studies examine the hypothesis that multiple adrenergic neuroeffector mechanisms are not fully developed in fetal, compared with adult, ovine middle cerebral arteries. In arteries denuded of endothelium and pretreated with 1 μM atropine to block involvement of muscarinic receptors, 10 μM capsaicin to deplete sensory peptidergic neurons, and 10 μM nitro-l-arginine methyl ester (l-NAME) to block possible influences from nitric oxidergic innervation, transmural stimulation at 16 Hz increased contractile tensions to 9.5 ± 3.7% ( n = 6) of the potassium maximum in adult arteries. Corresponding values in fetal arteries, however, were significantly less and averaged only 1.1 ± 0.6% ( n =10). However, postsynaptic sensitivity to norepinephrine (NE) was similar in the two age groups; NE pD2 values (−log EC50) averaged 6.11 ± 0.12 ( n = 6) and 6.33 ± 0.09 M ( n = 9) in fetal and adult arteries, respectively. Similarly, NE content measured via HPLC was also similar in the two age groups and averaged 32.4 ± 5.0 ( n = 17) and 32.5 ± 3.9 ng/ng wet wt ( n = 13) in fetal and adult middle cerebral arteries, respectively. In contrast, stimulation-induced NE release was greater in fetal than in adult arteries, whether calculated as total mass released [883 ± 184 ( n = 17) vs. 416 ± 106 pg NE/mg wet wt ( n = 13)] or as fractional release [51.1 ± 5.3 ( n = 17) vs. 22.8 ± 3.8 pg/pg NE content per pulse × 10−6]. Measured as an index of synaptic density, neuronal cocaine-sensitive NE uptake was similar in fetal and adult arteries [1.55 ± 0.40 ( n = 10) and 1.84 ± 0.51 pmol/mg wet wt ( n = 7), respectively]. Overall, age-related differences in postsynaptic sensitivity to NE, NE release, and NE uptake capacity cannot explain the corresponding age-related differences in response to stimulation. The data thus suggest that total synaptic volume and cleft width, in particular, are probably greater and/or that adrenergic corelease of vasoactive substances other than NE is altered in fetal compared with adult middle cerebral arteries.
Different modulation of aromatase activity in frog testis in vitro by ACE and ANG II
Authors: Miano Antonino , Gobbetti Anna , Zerani Massimo , Quassinti Luana , Maccari Ennio , Murri Oretta , Amici Domenico , Bramucci Massimo
Published: December 2017

The aim of the present research was to study the role of angiotensin-converting enzyme (ACE) and ANG II in amphibian ( Rana esculenta) testicular steroidogenesis and prostaglandin production. Hormonal effects of ACE, ACE inhibitors, synthetic bullfrog ANG I, and [Val5]ANG II were determined in frog testis of prereproductive period. Production of 17β-estradiol, progesterone, androgens, and PGE2and PGF2αwas determined by incubating frog testes with ACE (2.5 mU/ml), captopril (0.1 mM), lisinopril (0.1 mM), [Val5]ANG II (1 μM), and synthetic bullfrog ANG I (1 μM). The analysis of the data showed an independent modulation of 17β-estradiol and androgen production by ACE and ANG II. The ACE pathway caused a decrease of 17β-estradiol production and an increase of androgen production in frog testes; on the other hand, the ANG II pathway increased 17β-estradiol production and decreased androgen production. The determination of testicular aromatase activity showed a positive regulation by ANG II and a negative regulation by ACE. As for prostaglandin production, only ANG II influenced PGF2α. These results suggest a new physiological role of ACE and ANG II in modulating steroidogenesis and prostaglandin production.
Dual effects of somatostatin analog octreotide on gastric emptying during and after intragastric fill
Authors: Smedh U. , Kaplan J. M. , Björkstrand E. , Uvnäs-Moberg K.
Published: December 2017

The effect of the somatostatin analog agonist octreotide (Oct) on gastric emptying of 12.5% glucose during and after intragastric fill was examined in nondeprived rats equipped with stainless steel gastric fistulas. The rate of intragastric infusion (1.0 ml/min) and the volumes delivered (6 or 12 ml) were within the ranges typically observed in rats normally ingesting the same stimulus. In experiment 1, a dose-related suppression of glucose emptying during 12-min infusions was obtained in response to Oct (0, 0.0014, 0.014, 0.14, and 1.4 nmol/kg sc) injected 60 min before the test. The highest dose tested yielded a 37% suppression of glucose solute emptying during fill. In experiment 2, the suppression of emptying during fill induced by Oct (1.4 nmol/kg) was reversed by 10 or 40 μg/kg of the somatostatin antagonist cyclo(7-aminoheptanoyl-Phe-d-Trp-Lys-Thr[Bzl]). The antagonist did not by itself affect emptying. Experiment 3 showed that the suppression of emptying obtained with 0.14 and 1.4 nmol/kg Oct had disappeared when the gastric sample was withdrawn 36 min after the termination of 12-min glucose infusions. Experiment 4 showed that the Oct-induced reductions in emptying during 6- and 12-min infusions, in fact, were reversed within 6 min after infusion offset. The point of transition between suppressed and increased emptying did not depend on time from injection or from infusion onset but was linked to the offset of the intragastric infusion regardless of its duration. The present findings support the notion that separable mechanisms govern gastric emptying during vs. after gastric fill.
Central administration of the somatostatin analog octreotide induces captopril-insensitive sleep responses
Authors: Beranek L. , Hajdu I. , Gardi J. , Taishi P. , Obál F. , Krueger J. M.
Published: December 2017

The effects of intracerebroventricular injections of the long-lasting somatostatin analog octreotide (Oct) were studied on sleep and behavior in rats. Pyrogen-free physiological saline and Oct (0.001, 0.01, 0.1 μg) or vehicle were administered at light onset, and the electroencephalogram (EEG), motor activity, and cortical brain temperature were recorded during the 12-h light period. Plasma growth hormone (GH) concentrations were measured in samples taken at 30-min intervals after Oct. Oct (0.01 and 0.1 μg) suppressed non-rapid eye movement sleep (NREMS) for 1–2 h. NREMS intensity (delta EEG activity during NREMS) dose dependently increased in hour 3 postinjection and thereafter (0.1 μg). Plasma GH concentrations were suppressed after Oct (0.01 and 0.1 μg), but pulses of GH secretions occurred 90–120 min postinjection in each rat. Oct (0.1 μg) enhanced behavioral activity, including prompt drinking followed by grooming, scratching, and feeding. Intracerebroventricular injection of the angiotensin-converting enzyme inhibitor captopril (30 μg, 10 min before Oct), blocked these behavioral responses but not the Oct-induced sleep alterations. The changes in sleep after intracerebroventricular Oct suggest an intracerebral action site and might result from Oct-induced variations in the sleep-promoting activity of GH-releasing hormone.
Respiratory responses to thyrotropin-releasing hormone microinjected into the rabbit medulla oblongata
Authors: Mutolo Donatella , Bongianni Fulvia , Carfì Marco , Pantaleo Tito
Published: December 2017

We investigated the respiratory role of thyrotropin-releasing hormone (TRH) input to medullary structures involved in the control of breathing in anesthetized, vagotomized, paralyzed, and artificially ventilated rabbits. Microinjections (10–20 nl) of 1 or 10 mM TRH were performed in different regions of the ventral respiratory group (VRG), namely the rostral expiratory portion or Bötzinger complex (Böt. c.), the inspiratory portion, the transition zone between these two neuronal pools, and the caudal expiratory component. TRH microinjections were also performed in the dorsal respiratory group (DRG) and the area postrema (AP). Injection sites were localized by using stereotaxic coordinates and extracellular recordings of neuronal activity; their locations were confirmed by subsequent histological control. TRH microinjections in the Böt. c. and the directly caudally located region where a mix of inspiratory and expiratory neurons were encountered elicited depressant respiratory responses. TRH microinjections were completely ineffective at sites within the inspiratory and the caudal expiratory components of the VRG. TRH microinjections in either the DRG or the AP induced excitatory effects on inspiratory activity. The results show for the first time that TRH may exert inhibitory influences on respiration at medullary levels by acting on rostral expiratory neurons and that not only the DRG, as previously suggested, but also the AP may mediate TRH-induced excitatory effects on respiration.
Diurnal variations and sleep deprivation-induced changes in rat hypothalamic GHRH and somatostatin contents
Authors: Gardi J. , Obál F. , Fang J. , Zhang J. , Krueger J. M.
Published: December 2017

Previous reports indicate that hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep and is involved in sleep regulation. The aim of our experiments was to determine whether the GHRH and somatostatin contents of the rat hypothalamus have diurnal variations and whether they are altered by sleep deprivation (SD). Hypothalamic samples were collected at 10 time points during the 24-h light-dark cycle. SD started at light onset. Hypothalamic samples were obtained after 4 and 8 h of SD and after 1 and 2 h of recovery following 8 h of SD. The peptides were determined by means of radioimmunoassay. GHRH displayed significant diurnal variations with low levels in the morning (a transient rise occurred at 1 h after light onset), gradual increases in the afternoon (peak at the end of the light period and beginning of the dark period), and decreases at night. SD induced significant GHRH depletion, which persisted during recovery. The afternoon rise was delayed, and the nocturnal decline of somatostatin was more rapid than the changes in GHRH. Although the patterns of the diurnal variations in GHRH and somatostatin were similar, there was no significant correlation between them. SD did not alter somatostatin significantly. Comparisons of the present results with previously reported changes in hypothalamic GHRH mRNA suggest that periods of deep nonrapid eye movement sleep (first portion of the light period and recovery sleep after SD) are associated with intense hypothalamic GHRH release.
Role of lipid type on morphine-stimulated diet selection in rats
Authors: Glass Michael J. , Billington Charles J. , Levine Allen S.
Published: December 2017

Administration of morphine is said to increase fat consumption among rats allowed to self-select nutrients. However, fats represent a diverse group of molecules, differing in metabolic and sensory properties. Despite this, lipid has yet to be manipulated as a variable in drug-stimulated nutrient selection studies. To determine whether lipid source can impact daily and morphine-stimulated (1, 3, and 10 mg/kg) diet intake, rats were provided with a choice between a high-fat and high-carbohydrate diet in three regimens in which the source of fat was varied between vegetable shortening, lard, or corn oil. Daily and morphine-stimulated diet selections were determined under all conditions. Under daily feeding conditions, rats ate more of the high-lipid diet compared with the high-carbohydrate diet when vegetable shortening or lard was the main lipid alternative, but lipid and carbohydrate intake did not differ when corn oil was the main lipid alternative. When rats were stimulated with morphine, the percentage of lipid increased relative to baseline intake only when the lipid diets were the preferred alternatives (i.e., vegetable shortening or lard). When preference between lipid and carbohydrate diets was neutral (i.e., corn oil condition), morphine did not enhance lipid consumption. These results indicate that morphine increases consumption of total energy or preferred diets and not lipid per se.
Stimulation of NMDA and AMPA receptors in the rat nucleus basalis of Meynert affects sleep
Authors: Manfridi Alfredo , Brambilla Dario , Mancia Mauro
Published: December 2017

The nucleus basalis of Meynert (NBM), a heterogeneous area in the basal forebrain involved in the modulation of sleep and wakefulness, is rich in glutamate receptors, and glutamatergic fibers represent an important part of the input to this nucleus. With the use of unilateral infusions in the NBM, the effects of two different glutamatergic subtype agonists, namely N-methyl-d-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) hydrobromide, on sleep and wakefulness parameters were determined in freely moving rats by means of polygraphic recordings. NMDA (5 nmol) and AMPA (0.4 nmol) induced an increase in wakefulness and an inhibition of slow-wave sleep. AMPA, but not NMDA, also caused a decrease in desynchronized sleep. These AMPA- and NMDA-mediated effects were counteracted by a pretreatment with the specific NMDA antagonist 2-amino-5-phosphonopentanoic acid (20 nmol) and the specific AMPA antagonist 6,7-dinitroquinoxaline-2,3-dione (2 nmol), respectively. The results reported here indicate that 1) the NBM activation of both NMDA and AMPA glutamate receptors exert a modulatory influence on sleep and wakefulness, and 2) AMPA, but not NMDA receptors, are involved in the modulation of desynchronized sleep, suggesting a different role for NBM NMDA and non-NMDA receptors in sleep modulation.
Central nervous system regulation of reflex responses to hypotension during fetal life
Authors: Wood Charles E. , Tong Haiyan
Published: December 2017

The ability of the fetus to survive, grow, and successfully complete the transition from fetal to neonatal life is critically dependent on the appropriate regulation of fetal blood pressure, blood volume, and fluid dynamics. This is a short review of the physiological mechanisms controlling the fetal cardiovascular system, focusing mainly on the neural and endocrine elements in the schema of cardiovascular function and control. The fetal cardiovascular system is arranged anatomically to provide for perfusion of the umbilical-placental circulation, the organ of gas exchange of the fetus, and to largely bypass the lungs. Fetal blood volume and pressure, maintained at levels that are appropriate for this function, are influenced by neural and endocrine control mechanisms, which are similar to, but quantitatively different from, the adult animal. Baroreceptors and chemoreceptors located in the carotid sinuses and aortic arch sense changes in blood pressure and blood gases and comprise the afferent limb of the major reflexes that maintain normal fetal blood pressure and volume. Fetal hypotension stimulates reflex decreases in fetal heart rate, which are apparently mediated by chemoreceptor input. Arginine vasopressin responses to hypotension are most likely mediated by baroreceptor input. Recent evidence suggests that the reflex responses to hypotension in the fetus are modulated by paracrine or endocrine factors. For example, baroreceptor or chemoreceptor reflex pathways are modulated by the endogenous production of prostanoids and by the preparturient changes in fetal plasma estrogen concentration.
Shivering and digestion-related thermogenesis in pigeons during dark phase
Authors: Rashotte Michael E. , Saarela Seppo , Henderson Ross P. , Hohtola Esa
Published: December 2017

The pigeon's main source of regulated heat production, shivering, is especially likely to be used for thermoregulation during the dark phase of the day when there is little heat from locomotor activity. However, food stored in the pigeon's crop is digested during the night, and digestion-related thermogenesis (DRT) will provide heat that should decrease the need for shivering to maintain body temperature (Tb). We investigated the conditions under which DRT alters the occurrence of nocturnal shivering thermogenesis in pigeons. In fasting experiments, in which DRT was minimal, variations in pectoral shivering were closely related to the kinetics of nocturnal Tb when the ambient temperature (Ta) was moderate (21°C). In that case, shivering was low while Tb fell at the beginning of the night, moderate during the nocturnal plateau in Tb, and strong during the prelight increase in Tb. Similar kinetics of nocturnal Tb occurred when Ta = 28°C, but shivering was negligible throughout the dark phase. In restricted feeding experiments, nocturnal DRT was varied by providing different amounts of food late in the light phase. When Ta = 21°C, 11°C, and 1°C, nocturnal Tb and O2consumption were directly related to the amount of food ingested. However, nocturnal shivering tended to decrease as the food load increased and was significantly reduced at the higher loads. Because nocturnal shivering did not become more efficient in producing heat as the size of the food load increased, we conclude that nocturnal DRT decreased the need for shivering thermogenesis.
Regulatory features of transcription in isolated mitochondria fromArtemia franciscanaembryos
Authors: Eads Brian D. , Hand Steven C.
Published: December 2017

Optimal conditions were developed for an in organello transcriptional run-on assay using mitochondria isolated from Artemia franciscana embryos to investigate potential regulatory features of RNA synthesis under conditions of anoxia-induced quiescence. Transcription is not dependent on oxidative phosphorylation for maximal activity when exogenous ATP is available. Bona fide transcription products, as assessed by hybridization with specific mitochondrial cDNAs from A. franciscana, are produced in an inhibitor-sensitive manner. Transcription rate measured at pH 7.9 is reduced 80% when pH is lowered to 6.3, a pH range that mimics the in vivo change seen on exposure of embryos to anoxia. The proton sensitivity of mitochondrial RNA synthesis may provide a mechanism to depress this significant energy expenditure during quiescence. The influence of nucleotide concentration on kinetics is complicated by an interdependence among nucleotide species. ATP inhibition observed at subsaturating UTP concentrations is relieved when UTP is at saturating, physiologically relevant levels. Taken together, these data suggest that local (versus nuclear mediated) control is important in dictating mitochondrial transcription during rapid modulations in gene expression, such as those observed under anoxia-induced quiescence.
Thermocyclic entrainment of lizard blood plasma melatonin rhythms in constant and cyclic photic environments
Authors: Firth Bruce T. , Belan Ingrid , Kennaway David J. , Moyer Robert W.
Published: December 2017

We assessed how chronic exposure to 6-h cryophase temperatures of 15°C in an otherwise 33°C environment entrains the rhythm of blood plasma melatonin rhythms in lizards ( Tiliqua rugosa) subjected to constant dark (DD), constant light (LL), and to 12:12-h light-dark cycles (12L:12D). The peak of the melatonin rhythm was entrained by the cryophase temperature of the thermocycle in DD and LL, irrespective of the time at which the cryophase temperature was applied. Comparable thermocycles of 6 h at 15°C imposed on a 12L:12D photocycle, however, affected the amplitude and phase of the melatonin rhythm, depending on the phase relationship between light and temperature. Cold pulses in the early light period and at midday resulted, respectively, either in low amplitude or nonexistent melatonin rhythms, whereas those centered in or around the dark phase elicited rhythms of high amplitude. Supplementary experiments in 12L:12D using two intermittent 6-h 15°C cryophases, one delivered in the midscotophase and another in the midphotophase, elicited melatonin rhythms comparable to those in lizards subjected to constant 33°C and 12L:12D. In contrast, lizards subjected to 12L:12D and a 33°C:15°C thermocycle, whose thermophase was aligned with the photophase, produced a threefold increase in the amplitude of the melatonin rhythm. Taken together, these results support the notion that there is an interaction between the external light and temperature cycle and a circadian clock in determining melatonin rhythms in Tiliqua rugosa.
Relation between complement and the febrile response of guinea pigs to systemic endotoxin
Authors: Li S. , Sehic E. , Wang Y. , Ungar A. L. , Blatteis C. M.
Published: December 2017

We reported recently that the complement (C) system may play a role in the febrile response of guinea pigs to intravenous lipopolysaccharide (LPS) administration because C depletion abolished the LPS-induced rise in core temperature (Tc). The present study was designed to investigate further the relation between C reduction [induced by cobra venom factor (CVF); 20, 50, 100, and 200 U/animal iv] and the fever of adult, conscious guinea pigs produced by LPS injected intravenously (2 μg/kg) or intraperitoneally (8, 16, 32 μg/kg) 18 h after CVF; control animals received pyrogen-free saline. Serum C levels were measured as total hemolytic C activity before and 18 h after CVF injection and expressed as CH100units. In other experiments, serum C levels were determined at various intervals after the intravenous and intraperitoneal injections at different doses of LPS alone. LPS produced fevers generally of similar heights but of different onset latencies and durations, depending on the dose and route of administration. CVF caused dose-related reductions in serum C, from ∼1,136 U to below detection. These reductions proportionately attenuated the fevers induced by intraperitoneal LPS, but not by intravenous LPS. Intravenous and intraperitoneal LPS per se caused reductions in serum C of 25 and 40%, respectively, indicating activation of the C cascade. These decreases were transient, however, occurring early during the febrile rise ∼30 min after LPS injection. These data thus support the notion that the C system may be critically involved in the febrile response of guinea pigs to systemic, particularly intraperitoneal, LPS.
Regulation of l-methionine and l-lysine uptake in chicken jejunal brush-border membrane by dietary methionine
Authors: Soriano-García Juan F. , Torras-Llort Mònica , Moretó Miquel , Ferrer Ruth
Published: December 2017

In the chicken intestine,l-methionine is transported by systems that are specific for neutral amino acids (L- and B-like) and by systems that can also transport cationic amino acids (y+m and b0,+-like). These four uptake pathways have been investigated in brush-border membrane vesicles from the jejunum of chickens fed a diet enriched with 0.4%l-methionine. Methionine supplementation from the 1st to the 6th wk of age has no effect on body weight or on the efficiency of food utilization. The kinetic analysis of l-methionine influx across the transport systems specific for neutral amino acids shows, for system L, no dietary effect on the Michaelis constant ( K m) and a 30% reduction in maximal velocity ( V max); for system B it shows a decrease in K m (30%) and in V max (51%). Transport systems shared by cationic and neutral amino acids show no dietary effect on b0,+ activity and a significant reduction in y+m V max, similar forl-methionine andl-lysine, both in the absence and in the presence of Na+(l-methionine, 30 and 26% reduction; l-lysine, 19 and 28% reduction, respectively). The downregulation induced byl-methionine supplementation may be an adaptive response to reduce the risk of intoxication by dietary excess of l-methionine. These results support the view that the toxicity of the supplemented substrate can be an important factor in the regulation of amino acid transport by dietary content.
Restricted fetal growth and the response to dietary cholesterol in the guinea pig
Authors: Kind Karen L. , Clifton Peter M. , Katsman Arkadi I. , Tsiounis Maria , Robinson Jeffrey S. , Owens Julie A.
Published: December 2017

Epidemiological studies suggest that retarded growth before birth is associated with increased plasma total and low-density lipoprotein (LDL) cholesterol concentrations in adult life. Thus perturbations of prenatal growth may permanently alter cholesterol metabolism. To determine directly whether restriction of prenatal nutrition and growth alters postnatal cholesterol homeostasis, the plasma cholesterol response to cholesterol feeding (0.25% cholesterol) was examined in adult guinea pig offspring of ad libitum-fed or moderately undernourished mothers. Maternal undernutrition (85% ad libitum intake throughout pregnancy) reduced birth weight (−13%). Plasma total cholesterol was higher prior to and following 6 wk cholesterol feeding in male offspring of undernourished mothers compared with male offspring of ad libitum-fed mothers ( P< 0.05). The influence of birth weight on cholesterol metabolism was examined by dividing the offspring into those whose birth weight was above (high) or below (low) the median birth weight. Plasma total cholesterol concentrations prior to cholesterol feeding did not differ with size at birth, but plasma total and LDL cholesterol were 31 and 34% higher, respectively, following cholesterol feeding in low- compared with high-birth weight males ( P < 0.02). The response to cholesterol feeding in female offspring was not altered by variable maternal nutrition or size at birth. Covariate analysis showed that the effect of maternal undernutrition on adult cholesterol metabolism could be partly accounted for by alterations in prenatal growth. In conclusion, maternal undernutrition and small size at birth permanently alter postnatal cholesterol homeostasis in the male guinea pig.
Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease
Authors: Heunks Leo M. A. , Viña Jose , van Herwaarden Cees L. A. , Folgering Hans T. M. , Gimeno Amparo , Dekhuijzen P. N. Richard
Published: December 2017

In the present study, we hypothesized that exhaustive exercise in patients with chronic obstructive pulmonary disease (COPD) results in glutathione oxidation and lipid peroxidation and that xanthine oxidase (XO) contributes to free radical generation during exercise. COPD patients performed incremental cycle ergometry until exhaustion with ( n = 8) or without ( n = 8) prior treatment with allopurinol, an XO inhibitor. Reduced (GSH) and oxidized glutathione (GSSG) and lipid peroxides [malondialdehyde (MDA)] were measured in arterial blood. In nontreated COPD patients, maximal exercise (∼75 W) resulted in a significant increase in the GSSG-to-GSH ratio (4.6 ± 0.9% at rest vs. 9.3 ± 1.7% after exercise). In nontreated patients, MDA increased from 0.68 ± 0.08 nmol/ml at rest up to 1.32 ± 0.13 nmol/ml 60 min after cessation of exercise. In contrast, in patients treated with allopurinol, GSSG-to-GSH ratio did not increase in response to exercise (5.0 ± 1.2% preexercise vs. 4.6 ± 1.1% after exercise). Plasma lipid peroxide formation was also inhibited by allopurinol pretreatment (0.72 ± 0.15 nmol/ml preexercise vs. 0.64 ± 0.09 nmol/ml 60 min after exercise). We conclude that strenuous exercise in COPD patients results in blood glutathione oxidation and lipid peroxidation. This can be inhibited by treatment with allopurinol, indicating that XO is an important source for free radical generation during exercise in COPD.
Relationship between intracranial pressure and cervical lymphatic pressure and flow rates in sheep
Authors: Silver I. , Li B. , Szalai J. , Johnston M.
Published: December 2017

Previous reports from our group demonstrated that about one-half of the total volume of cerebrospinal fluid (CSF) removed from the cranial vault in sheep is transported into extracranial lymphatics, especially cervical lymphatic vessels in the neck. In this study, we tested the hypothesis that an elevation of intracranial pressure (ICP) would increase cervical lymphatic pressure and lymph flow rates in anesthetized sheep. Catheters were inserted into both lateral ventricles, the cisterna magna, cervical lymphatics, and the jugular vein. A ventriculo-cisternal perfusion system was employed to regulate ICP. Mean ( P = 0.008), peak ( P = 0.007), and baseline ( P = 0.013) cervical lymphatic pressures increased as ICP was elevated from 10 to 70 cmH2O in 20-cmH2O increments. Similarly, cervical lymph flow rates increased ( P < 0.001), with flows at 70 cmH2O ICP observed to be approximately fourfold higher than those at 10 cmH2O ICP. No changes were observed in mesenteric lymph flow rates (vessels not expected to drain CSF). We conclude that cervical lymphatic vessels play an important role in the transport of CSF from the cranial vault when ICP is elevated.
Two circadian rhythms in the human electroencephalogram during wakefulness
Authors: Aeschbach Daniel , Matthews Jeffery R. , Postolache Teodor T. , Jackson Michael A. , Giesen Holly A. , Wehr Thomas A.
Published: December 2017

The influence of the circadian pacemaker and of the duration of time awake on the electroencephalogram (EEG) was investigated in 19 humans during ∼40 h of sustained wakefulness. Two circadian rhythms in spectral power density were educed. The first rhythm was centered in the theta band (4.25–8.0 Hz) and exhibited a minimum ∼1 h after the onset of melatonin secretion. The second rhythm was centered in the high-frequency alpha band (10.25–13.0 Hz) and exhibited a minimum close to the body temperature minimum. The latter rhythm showed a close temporal association with the rhythms in subjective alertness, plasma melatonin, and body temperature. In addition, increasing time awake was associated with an increase of power density in the 0.25- to 9.0-Hz and 13.25- to 20.0-Hz ranges. It is concluded that the waking EEG undergoes changes that can be attributed to circadian and homeostatic (i.e., sleep-wake dependent) processes. The distinct circadian variations of EEG activity in the theta band and in the high-frequency alpha band may represent electrophysiological correlates of different aspects of the circadian rhythm in arousal.