bluuebunny/crossref_metadata_2025 huggingface dataset:
Red blood cell life span in the ovine fetus
Authors: Brace Robert A. , Langendörfer Christiane , Song Tae-Bok , Mock Donald M.
Published: December 2017

Red cell life span within the fetal circulation has not been reported, although erythrocyte life span has been studied in the adult and newborn. The present study quantified red cell life span in 12 chronically catheterized fetal sheep at 97–136 days gestation (term = 150 days) with the use of autologous red cells labeled with [14C]cyanate. Cyanate forms a permanent covalent bond with hemoglobin and acts as a permanent red cell label. In the fetuses, blood14C activity decreased in a curvilinear fashion with time and reached 50% of the initial activity at 16.4 ± 1.6 (SE) days. In contrast,14C activity of autologous red cells in two adult ewes decreased linearly with time as expected, reached 50% of the initial14C activity in 59 days, and yielded life spans of 117 and 121 days. Computer modeling and parameter optimization taking into account growth and skewed life span distribution were used to analyze the14C disappearance curve in each fetus. The mean life span of all red cells in the fetal circulation was 63.6 ± 5.8 days. Mean red cell life span increased linearly from 35 to 107 days as fetal age increased from 97 to 136 days ( r = 0.83, P < 0.001). Life span of cells produced at the time of labeling was significantly greater than the mean life span. Fetal growth rate estimated from parameter optimization was 3.28 ± 0.72%/day; this compared well with the rate of 3.40 ± 0.14%/day calculated from fetal weights at autopsy. Mean corpuscular volume decreased as a function of gestational age, but the decrease was small compared with the large increase in red cell life span. We conclude the following: 1) red cell life span in the fetal circulation is short compared with the adult; 2) red cells in younger fetuses have shorter life spans than in near-term fetuses; 3) the curvilinear disappearance of labeled red cells in the fetus appears to be due primarily to an expanding blood volume with fetal growth; and 4) red blood cell life span in a growing organism will be significantly underestimated unless the expansion of blood volume with growth is taken into account.
Intraportal glucose infusion and pancreatic islet blood flow in anesthetized rats
Authors: Carlsson Per-Ola , Iwase Masanori , Jansson Leif
Published: December 2017

The aim of the study was to evaluate whether a selective increase in portal vein blood glucose concentration can affect pancreatic islet blood flow. Anesthetized rats were infused (0.1 ml/min for 3 min) directly into the portal vein with saline, glucose, or 3- O-methylglucose. The infused dose of glucose (1 mg · kg body wt−1 · min−1) was chosen so that the systemic blood glucose concentration was unaffected. Intraportal infusion of d-glucose increased insulin release and islet blood flow; the osmotic control substance 3- O-methylglucose had no such effect. A bilateral vagotomy performed 20 min before the infusions potentiated the islet blood flow response and also induced an increase in whole pancreatic blood flow, whereas the insulin response was abolished. Administration of atropine to vagotomized animals did not change the blood flow responses to intraportal glucose infusions. When the vagotomy was combined with a denervation of the hepatic artery, there was no stimulation of islet blood flow or insulin release after intraportal glucose infusion. We conclude that a selective increase in portal vein blood glucose concentration may participate in the islet blood flow increase in response to hyperglycemia. This effect is probably mediated via periarterial nerves and not through the vagus nerve. Furthermore, this blood flow increase can be dissociated from changes in insulin release.
Norepinephrine reuptake, baroreflex dynamics, and arterial pressure variability in rats
Authors: Bertram Delphine , Barrès Christian , Cheng Yong , Julien Claude
Published: December 2017

This study examined the effect of norepinephrine reuptake blockade with desipramine (DMI) on the spontaneous variability of the simultaneously recorded arterial pressure (AP) and renal sympathetic nerve activity (SNA) in conscious rats. Acute DMI administration (2 mg/kg iv) depressed AP Mayer waves (∼0.4 Hz) and increased low-frequency (<0.2 Hz) components of AP variability. DMI decreased renal SNA variability, especially due to the abolition of oscillations related to Mayer waves. To examine whether DMI-induced changes in AP and renal SNA variabilities could be explained by alterations in the dynamic characteristics of the baroreceptor reflex loop, the frequency responses of mean AP to aortic depressor nerve stimulation were studied in urethan-anesthetized rats. DMI accentuated the low-pass filter properties of the transfer function without significantly altering the fixed time delay. The frequency responses of iliac vascular conductance to stimulation of the lumbar sympathetic chain were studied in an additional group of anesthetized rats. DMI did not markedly alter the low-pass filter properties of the transfer function and slightly increased the fixed time delay. These results suggest that the DMI-induced decrease in the dynamic gain of the baroreceptor reflex is responsible for the decreased spontaneous renal SNA variability and the accompanying increased AP variability. The “slowing down” of baroreflex responses cannot be attributed to an effect of DMI at the vascular neuroeffector junction.
Dissociation of leptin secretion and adiposity during prehibernatory fattening in little brown bats
Authors: Kronfeld-Schor Noga , Richardson Christopher , Silvia Brian A. , Kunz Thomas H. , Widmaier Eric P.
Published: December 2017

Hibernating animals deposit adipose tissue before hibernation to withstand long periods of reduced energy intake. Normally, adiposity is positively correlated with increased secretion from adipose tissue of the satiety hormone, leptin. During the prehibernatory phase of the little brown bat, Myotis lucifugus, body mass and adiposity increased to a maximum within 12 days. Leptin secretion from adipose tissue in vitro and plasma leptin, however, increased before the increase in adiposity, then significantly decreased when adiposity increased. Basal metabolic rate (BMR) decreased when plasma leptin was increasing. This was followed by an increase in nonshivering thermogenic capacity and brown adipose tissue mass. We conclude that in the early prehibernatory phase, BMR decreases despite increasing plasma leptin levels, suggesting a state of relative leptin resistance at that time. At later stages, adiposity increases as BMR continues to decrease, and plasma leptin becomes dissociated from adiposity. Thus, in M. lucifugus, hibernation may be achieved partly by removing the metabolic signal of leptin during the fattening period of prehibernation.
Impaired response of UCP family to cold exposure in diabetic (db/db) mice
Authors: Masaki Takayuki , Yoshimatsu Hironobu , Chiba Seiichi , Sakata Toshiie
Published: December 2017

Impaired activity of the uncoupling protein (UCP) family has been proposed to promote obesity development. The present study examined differences in UCP responses to cold exposure between leptin-resistance obese ( db/db) mice and their lean (C57Ksj) littermates. Basal UCP1 and UCP3 mRNA expression in brown adipose tissue was lower in obese mice compared with lean mice, but UCP2 expression in white adipose tissue (WAT) was higher. Basal skeletal muscle UCP3 did not change remarkably. The UCP family mRNAs, which were upregulated 12 and 24 h after cold exposure (4°C), were returned to prior levels 12 h after rewarming exposure (21°C) in lean mice. The accelerating effects of cold exposure on the UCP family were impaired in db/db obese mice. Together with these changes, WAT lipoprotein lipase mRNA was downregulated, and the concentration of serum free fatty acid was increased in response to cold exposure in the lean mice but not in db/db obese littermates. The impaired function of the UCP family and diminished lipolysis in response to cold exposure indicate that the reduced lipolytic activity may contribute to the inactivation of the UCP family in db/db obese mice.
Conditioned suppression of contact sensitivity is independent of sympathetic splenic innervation
Authors: Exton Michael S. , Elfers Alexandra , Jeong Woo-Young , Bull Diane F. , Westermann Jürgen , Schedlowski Manfred
Published: December 2017

The present study investigated the role of sympathetic innervation of the spleen in conditioned suppression of a contact hypersensitivity (CHS) reaction. Behavioral conditioning was achieved by pairing saccharin drinking solution (conditioned stimulus, CS) with injection of cyclosporin A (CsA, 20 mg/kg; unconditioned stimulus, UCS). Four days after sensitization of the animals by application of a 5% 2,4-dinitrochlorobenzene (DNCB) to abdominal skin, the animals were challenged by applying a 1% DNCB solution to the ear. The CHS response was monitored by measuring the degree of ear swelling. Saccharin re-presentation reduced ear swelling to a magnitude that approached that achieved by CsA treatment. Histological examination demonstrated that the conditioned reduction of ear swelling was produced by a reduced leukocyte infiltration of the ear. Prior sympathetic denervation of the spleen did not alter the conditioned suppression of the CHS response. These data indicate that behavioral conditioning using CsA produces alterations of CHS that, unlike conditioned prolongation of heart allograft survival, are independent of sympathetically regulated conditioned alterations in the spleen.
Effect of gender on vestibular sympathoexcitation
Authors: Ray Chester A.
Published: December 2017

Studies have suggested that premenopausal women are more prone to orthostatic intolerance than men. Additionally, it has been postulated that the vestibulosympathetic reflex is important in regulating postural-related changes in sympathetic activity. The purpose of the present study was to determine whether men and women differ in their sympathetic and cardiovascular responses to stimulation of the otolith organs elicited by head-down rotation (HDR). Heart rate (HR), arterial pressure, calf blood flow (CBF), and leg muscle sympathetic nerve activity (MSNA) were measured during 3 min of HDR in the prone posture in 33 women and 30 men. With the exception of HR (71 ± 2 and 63 ± 1 beats/min for women and men, respectively; P < 0.01), all baseline variables were not different between genders. There were no gender differences in responses to HDR. MSNA increased 72 ± 33 units (43%) in the men and 88 ± 15 units (59%) in the women during HDR ( P < 0.01). CBF decreased [−0.6 ± 0.1 (15%) and −0.5 ± 0.1 (19%) ml · min−1· 100 ml−1] and calf vascular resistance increased [8 ± 2 (21%) and 11 ± 3 (25%) units during HDR for men and women, respectively ( P < 0.01)]. Both in the men and women, HR increased 2 ± 1 beats/min ( P < 0.01). These results demonstrate that sympathetic activation during HDR in the prone posture is similar in men and women. Therefore, these findings suggest that the vestibulosympathetic reflex is not different between healthy men and women.
Amygdala-lesion obesity: what is the role of the various amygdaloid nuclei?
Authors: Rollins Bethany L. , King Bruce M.
Published: December 2017

Anatomic descriptions of amygdaloid lesions resulting in hyperphagia and obesity in rats, cats, and dogs have been inconsistent and often contradictory, frequently resulting in failures to replicate. The present study attempted to reconcile these differences by examining common areas of overlap among differently placed lesions in female rats. Small bilateral lesions of the most posterodorsal aspects of the amygdala resulted in substantial weight gains (mean = 45.4 g/10 days). The smallest lesions caused damage limited to the posterodorsal medial amygdaloid nucleus and the bed nucleus of the stria terminalis and were directly in the area where axons are collecting to form the stria terminalis. Larger lesions that extensively damaged the central and/or anterodorsal medial amygdaloid nuclei sometimes resulted in excess weight gains, as did very large lesions of the basolateral nuclei, but substantial weight gains occurred only when the lesions extended (unilaterally or bilaterally) into the posterodorsal amygdala. Examination of previously published brain sections indicated that the hyperphagia and obesity that have been observed after widely differing lesion placements in cats and dogs were also the result of damage to a common area of overlap (i.e., the bed nucleus and/or stria terminalis). In rats, the critical area producing weight gain has extensive reciprocal relations with the medial hypothalamus.
Differential stress responsivity in diet-induced obese and resistant rats
Authors: Levin Barry E. , Richard Denis , Michel Chantal , Servatius Richard
Published: December 2017

The relationship between stress and obesity was assessed in male rats selectively bred to develop either diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy, 31% fat diet for 3 wk followed by 2 wk on a hyperphagic liquid diet (Ensure). One-half of the rats of each phenotype were subjected to moderate daily, unpredictable stress (cage changing, exposure to conspecific, swim, and immobilization stress, intraperitoneal saline injection) during the 5 wk. Both stressed and unstressed DIO rats were 26% heavier and ate 27% more than comparable DR rats at onset and had 48% lower basal morning plasma corticosterone levels. Stressed DR rats gained less weight and had significant elevations of basal morning corticosterone but reduced basal sympathetic activity (24-h urine norepinephrine) over 5 wk compared with their unstressed DR controls. Terminally, there was a 35% increase in the paraventricular nucleus corticotropin-releasing hormone mRNA expression. On the other hand, stressed DIO rats showed only a transient early increase in open-field activity and a terminal increase in basal corticosterone levels as the only effects of stress. Thus DIO rats are hyporesponsive to chronic stress compared with DR rats. This is in keeping with several other known differences in hypothalamopituitary and autonomic function in this model.
Circadian rhythms of body temperature and activity levels during 63 h of hypoxia in the rat
Authors: Bishop B. , Silva G. , Krasney J. , Salloum A. , Roberts A. , Nakano H. , Shucard D. , Rifkin D. , Farkas G.
Published: December 2017

The hypothermic response of rats to only brief (∼2 h) hypoxia has been described previously. The present study analyzes the hypothermic response in rats, as well as level of activity (La), to prolonged (63 h) hypoxia at rat thermoneutral temperature (29°C). Mini Mitter transmitters were implanted in the abdomens of 10 adult Sprague-Dawley rats to continuously record body temperature (Tb) and La. After habituation for 7 days to 29°C and 12:12-h dark-light cycles, 48 h of baseline data were acquired from six control and four experimental rats. The mean Tb for the group oscillated from a nocturnal peak of 38.4 ± 0.18°C (SD) to a diurnal nadir of 36.7 ± 0.15°C. Then the experimental group was switched to 10% O2 in N2. The immediate Tb response, phase I, was a disappearance of circadian rhythm and a fall in Tb to 36.3 ± 0.52°C. In phase II, Tb increased to a peak of 38.7 ± 0.64°C. In phase III, Tb gradually decreased. At reoxygenation at the end of the hypoxic period, phase IV, Tb increased 1.1 ± 0.25°C. Before hypoxia, La decreased 70% from its nocturnal peak to its diurnal nadir and was entrained with Tb. With hypoxia La decreased in phase I to essential quiescence by phase II. La had returned, but only to a low level in phase III, and was devoid of any circadian rhythm. La resumed its circadian rhythm on reoxygenation. We conclude that 63 h of sustained hypoxia 1) completely disrupts the circadian rhythms of both Tb and La throughout the hypoxic exposure, 2) the hypoxia-induced changes in Tb and La are independent of each other and of the circadian clock, and 3) the Tb response to hypoxia at thermoneutrality has several phases and includes both hypothermic and hyperthermic components.
Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension
Authors: Lohmeier Thomas E. , Lohmeier Justin R. , Haque Atif , Hildebrandt Drew A.
Published: December 2017

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng · kg−1 · min−1. In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 ± 4 mmHg and 1.04 ± 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30–35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys ( day 5 Den/Inn sodium = 0.51 ± 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion ( day 5 Den/Inn sodium = 2.02 ± 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.
Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms
Authors: Balkan Börk , Li Xue
Published: December 2017

The incretin glucagon-like peptide-1 (GLP-1)-(7—36) amide is an important factor in prandial glucose homeostasis. Findings that GLP-1 is rapidly inactivated led to the hypothesis that the target of GLP-1 is close to the site of release. To investigate whether the target tissue is located in the hepatoportal system, we administered GLP-1 with glucose into the portal vein of rats and compared this with peripheral GLP-1 administration (jugular vein) and studied the effects of blockers of the nervous system. Portal GLP-1 augmented the insulin response to a portal glucose bolus by 81% ( P < 0.01) and markedly improved the glucose disposal rate ( P < 0.05). Peripheral administration of GLP-1 produced a similar augmentation of the insulin response (88%) and of the glucose disposal rate. However, only the effect of portal GLP-1 on insulin secretion was blocked by the ganglionic blocker chlorisondamine. The data suggest that prandial β-cell stimulation by GLP-1 is evoked via a neural reflex triggered in the hepatoportal system. Because absorbed nutrients and GLP-1 first appear in the portal system, this mechanism may constitute a major pathway of GLP-1 action during meals.
Synergy ofl-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise
Authors: Wideman Laurie , Weltman Judy Y. , Patrie James T. , Bowers Cyril Y. , Shah Niki , Story Shannon , Veldhuis Johannes D. , Weltman Arthur
Published: December 2017

We investigated the ability of exercise, a multipathway, potent, physiological stimulus for GH release, to alter the synergistic interaction of l-arginine (A) and GH-related peptide (GHRP)-2 (G) observed at rest and the ability of gender to further modulate this putative interaction. Subjects (9 men and 9 early follicular phase women) completed 30 min of constant load aerobic exercise in combination with intravenous infusions of saline (S), A (30 g over 30 min), G (1 μg/kg bolus), or both (AG) in separate study sessions in randomly assigned order. Measures of GH release were logarithmically transformed for statistical analysis. Similar to rest, exercise maintained the rank order (AG > G > A > S) of effective stimulation of GH release for the key response measures in men or women, a gender disparity in the time to reach the maximal serum GH concentration, the calculated endogenous GH half-life, and the observed effect of preinfusion (basal) serum GH concentrations on determining secretagogue responsiveness. Exercise potentiated the individual stimulatory actions of A and G, while blunting the relative magnitude of the synergistic (supra-additive) interaction observed at rest. We infer from the present data that 1) exercise is likely to induce release of both GHRH and somatostatin, 2)l-arginine may facilitate the effect of exercise by limiting somatostatin release, 3) GHRP-2 could further enhance the stimulatory impact of exercise by opposing central actions of somatostatin and/or heightening endogenous GHRH release, and 4) gender strongly controls the relative but not absolute magnitude of A/G synergy both at rest and after exercise.
Differential effects of inhaled nitric oxide and hyperoxia on pulmonary dysfunction in newborn guinea pigs
Authors: Gries Delores M. , Tam Elizabeth K. , Blaisdell Jodi M. , Iwamoto Lynn M. , Fujiwara Naomi , Uyehara Catherine F. T. , Nakamura Kenneth T.
Published: December 2017

This study tested the hypothesis that inhaled nitric oxide (NO) and combined NO and hyperoxia will result in less pulmonary dysfunction and delay onset of respiratory signs compared with hyperoxia-exposed newborn guinea pigs (GPs). GPs were exposed to room air ( n = 14), 95% O2( n = 36), 20 parts per million (ppm) NO ( n = 14), or combined 20 ppm NO and 95% O2(NO/O2, n = 13) for up to 5 days. Data evaluated included latency interval for onset of respiratory distress, pressure volume curves, lung histology, and bronchoalveolar lavage (BAL) polymorphonuclear cells (PMNs), proteolytic activity, and total protein. NO-exposed GPs did not develop respiratory distress and had no evidence of pulmonary dysfunction. O2-exposed GPs developed respiratory distress after 1–5 days (median 4.0) vs. 3–5 days (median 5.0) for NO/O2exposure ( P < 0.05). BAL from O2-exposed GPs showed increased PMNs compared with NO/O2-exposed GPs. O2- and NO/O2-exposed GPs had comparable reduced lung volumes, lung histology, and increased BAL proteinase activity and total protein. In summary 1) O2exposure resulted in multiple measures of pulmonary dysfunction in newborn GPs, 2) 5-day exposure to NO produced no noticeable respiratory effects and pulmonary dysfunction, and 3) short-term exposure (≤5 days) to NO/O2delayed onset of respiratory distress and neither exacerbated nor attenuated pulmonary dysfunction compared with O2exposure alone.
Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey
Authors: Fitts Robert H. , Desplanches Dominique , Romatowski Janell G. , Widrick Jeffrey J.
Published: December 2017

The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 ± 1, 46 ± 2, and 59 ± 2 μm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 ± 0.01 to 0.31 ± 0.02 (CS group) and 0.32 ± 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m2), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m2) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca2+ sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m2) in the Sol type I and MG type II fibers.
Tumor necrosis factor-α impairs contraction but not relaxation in carotid arteries from iNOS-deficient mice
Authors: Gunnett Carol A. , Heistad Donald D. , Loihl Angela , Faraci Frank M.
Published: December 2017

We used mice deficient in expression of inducible NO synthase (iNOS −/−) to directly examine the role of iNOS in impaired vasoconstrictor responses following tumor necrosis factor-α (TNF-α). In iNOS +/+ mice, contraction of carotid arteries in response to prostaglandin F2α(PGF2α) was impaired following TNF-α (100 μg/kg ip)( n = 10, P < 0.01). In contrast to responses in wild-type mice, contraction to low concentrations of PGF2αwere normal, but maximum contraction to PGF2αwas impaired in arteries from iNOS −/− mice treated with TNF-α [0.35 ± .0.02 g ( n = 8) following vehicle and 0.25 ± 0.02 g ( n = 7) following TNF-α ( P < 0.05)]. Aminoguanidine, a relatively selective inhibitor of iNOS, partially restored contraction to PGF2αin vessels from iNOS +/+ mice but had no effect in iNOS −/− mice injected with TNF-α, suggesting that a mechanism(s) other than iNOS contributes to impaired responses. In contrast to contractile responses, relaxation of the carotid artery in response to acetylcholine and nitroprusside was not altered following TNF-α in iNOS +/+ or iNOS −/−mice. Responses of carotid arteries from iNOS −/− mice and effects of aminoguanidine suggest that both iNOS-dependent and iNOS-independent mechanisms contribute to impaired contractile responses following TNF-α.
Effect of central CO2 drive on lung inflation responses of expiratory bulbospinal neurons in dogs
Authors: Tonkovic-Capin Mislav , Zuperku Edward J. , Stuth Eckehard A. , Bajic Jurica , Dogas Zoran , Hopp Francis A.
Published: December 2017

The purpose of these studies is to better understand the nature of the reflex interactions that control the discharge patterns of caudal medullary, expiratory (E) bulbospinal neurons. We examined the effect of central chemodrive inputs measured as arterial CO2 tension (PaCO2 ) during hyperoxia on the excitatory and inhibitory components of the lung inflation responses of these neurons in thiopental sodium-anesthetized, paralyzed dogs. Data from slow ramp inflation and deflation test patterns, which were separated by several control inflation cycles, were used to produce plots of neuronal discharge frequency ( F n) versus transpulmonary pressure (Pt). Pt was used as an index of the activity arising from the slowly adapting pulmonary stretch receptors (PSRs). Changes in inspired CO2 concentrations were used to produce PaCO2 levels that ranged from 20 to 80 mmHg. The data obtained from 41 E neurons were used to derive an empirical model that quantifies the average relationship for F n versus both Pt and PaCO2 . This model can be used to predict the time course and magnitude of E neuronal responses to these inputs. These data suggest that the interaction between PaCO2 and PSR-mediated excitation and inhibition of F n is mainly additive, but synergism between PaCO2 and excitatory inputs is also present. The implications of these findings are discussed.
PDGF-β receptor expression and ventilatory acclimatization to hypoxia in the rat
Authors: Alea Oscar A. , Czapla Marc A. , Lasky Joseph A. , Simakajornboon Narong , Gozal Evelyne , Gozal David
Published: December 2017

Activation of platelet-derived growth factor-β (PDGF-β) receptors in the nucleus of the solitary tract (nTS) modulates the late phase of the acute hypoxic ventilatory response (HVR) in the rat. We hypothesized that temporal changes in PDGF-β receptor expression could underlie the ventilatory acclimatization to hypoxia (VAH). Normoxic ventilation was examined in adult Sprague-Dawley rats chronically exposed to 10% O2, and at 0, 1, 2, 7, and 14 days, Northern and Western blots of the dorsocaudal brain stem were performed for assessment of PDGF-β receptor expression. Although no significant changes in PDGF-β receptor mRNA occurred over time, marked attenuation of PDGF-β receptor protein became apparent after day 7 of hypoxic exposure. Such changes were significantly correlated with concomitant increases in normoxic ventilation, i.e., with VAH ( r: −0.56, P < 0.005). In addition, long-term administration of PDGF-BB in the nTS via osmotic pumps loaded with either PDGF-BB ( n = 8) or vehicle (Veh; n = 8) showed that although no significant changes in the magnitude of acute HVR occurred in Veh over time, the typical attenuation of HVR by PDGF-BB decreased over time. Furthermore, PDGF-BB microinjections did not attenuate HVR in acclimatized rats at 7 and 14 days of hypoxia ( n = 10). We conclude that decreased expression of PDGF-β receptors in the dorsocaudal brain stem correlates with the magnitude of VAH. We speculate that the decreased expression of PDGF-β receptors is mediated via internalization and degradation of the receptor rather than by transcriptional regulation.
Development of a compartmental model of human zinc metabolism: identifiability and multiple studies analyses
Authors: Miller Leland V. , Krebs Nancy F. , Hambidge K. Michael
Published: December 2017

A compartmental model of zinc metabolism has been developed from stable isotope tracer studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously, and the resulting enrichment was measured in plasma, erythrocytes, urine, and feces for as long as 3 wk. Data from total zinc measurements and model-independent calculations of various steady-state parameters were also modeled with the kinetic data. A structure comprised of 14 compartments and as many as 25 unknown kinetic parameters was developed to adequately model the data from each of the individual studies. The structural identifiability of the model was established using the GLOBI2 identifiability analysis software. Numerical identifiability of parameter estimates was evaluated using statistical data provided by SAAM. A majority of the model parameters was estimated with sufficient statistical certainty to be considered well determined. After the fitting of the model and data from the individual studies using SAAM/CONSAM, results were submitted to SAAM extended multiple studies analysis for aggregation into a single set of population parameters and statistics. The model was judged to be valid based on criteria described elsewhere.
Functional morphology of the avian medullary cone
Authors: Casotti Giovanni , Lindberg Kimberly K. , Braun Eldon J.
Published: December 2017

The organization of the renal medulla of the Gambel's quail, Callipepla gambelii, kidney was examined to determine the number of loops of Henle and collecting ducts and the surface area occupied by the different nephron segments as a function of distance down the medullary cones. Eleven medullary cones were dissected from the kidneys of four birds, and the tissue was processed and sectioned for light microscopy. In addition, individual nephrons were isolated on which total loop thin descending segment and thick prebend segment lengths were measured. The results show no correlation between the absolute number of loops of Henle and the length of the medullary cones. The number of thick and thin limbs of Henle and collecting ducts decrease exponentially with distance toward the apex of the cones and the rate of decrease is similar for cones of different lengths. Initially there is a rapid decrease in the number of thin limbs of Henle, indicating that most nephrons do not penetrate the cones a great distance. Thick descending limbs of Henle (prebend segment) ranged in length from 50 to 770 μm, and there was little correlation with the total length of the loop of Henle. However, the length of the thin limb of Henle correlated well with total loop length. The cell surface areas of the limbs of the loop of Henle and the collectng ducts decreased toward the apex of the cones.
Central angiotensin receptor blockade impairs thermolytic and dipsogenic responses to heat exposure in rats
Authors: Mathai M. L. , Hübschle T. , McKinley M. J.
Published: December 2017

The effect of central angiotensin AT1 receptor blockade on thermoregulation and water intake after heat exposure was investigated. Rats were placed in a chamber heated to 39 ± 1°C for 60 min and then returned to their normal cage (at 22°C), and water intake was measured for 120 min. Artificial cerebrospinal fluid (5 μl) was injected intracerebroventricularly 60 min before heat exposure in five control rats. Colonic temperature increased from 37.22 ± 0.21 to 40.68 ± 0.31°C after 60 min. In six rats injected intracerebroventricularly with 10 μg of the AT1antagonist losartan, colonic temperature increased from 37.41 ± 0.27 to 41.72 ± 0.28°C after 60 min. This increase was significantly greater than controls ( P < 0.03). Losartan-treated rats drank 1.1 ± 0.4 ml of water compared with 5.9 ± 0.77 ml ( P < 0.002) drank by control animals, despite a similar body weight loss in the two groups. Central losartan did not inhibit the drinking response to intracerebroventricular carbachol in heated rats, suggesting that losartan treatment did not nonspecifically depress behavior. We conclude that central angiotensinergic mechanisms have a role in both thermoregulatory cooling in response to heat exposure and also the ensuing water intake.
Na+/Ca2+-exchange activity regulates contraction and SR Ca2+content in rainbow trout atrial myocytes
Authors: Hove-Madsen Leif , Llach Anna , Tort Lluis
Published: December 2017

We have used the whole cell configuration of the patch-clamp technique to measure sarcolemmal Ca2+transport by the Na+/Ca2+exchanger (NCX) and its contribution to the activation and relaxation of contraction in trout atrial myocytes. In contrast to mammals, cell shortening continued, increasing at membrane potentials above 0 mV in trout atrial myocytes. Furthermore, 5 μM nifedipine abolished L-type Ca2+current ( ICa) but only reduced cell shortening and the Ca2+carried by the tail current to 66 ± 5 and 67 ± 6% of the control value. Lowering of the pipette Na+concentration from 16 to 10 or 0 mM reduced Ca2+extrusion from the cell from 2.5 ± 0.2 to 1.0 ± 0.2 and 0.5 ± 0.06 amol/pF. With 20 μM exchanger inhibitory peptide (XIP) in the patch pipette Ca2+extrusion 20 min after patch break was 39 ± 8% of its initial value. With 16, 10, and 0 mM Na+in the pipette, the sarcoplasmic reticulum (SR) Ca2+content was 47 ± 4, 29 ± 6, and 10 ± 3 amol/pF, respectively. Removal of Na+from or inclusion of 20 μM XIP in the pipette gradually eliminated the SR Ca2+content. Whereas ICawas the same at −10 or +10 mV, Ca2+extrusion from the cell and the SR Ca2+content at −10 mV were 65 ± 7 and 80 ± 4% of that at +10 mV. The relative amount of Ca2+extruded by the NCX (about 55%) and taken up by the SR (about 45%) was, however, similar with depolarizations to −10 and +10 mV. We conclude that modulation of the NCX activity critically determines Ca2+entry and cell shortening in trout atrial myocytes. This is due to both an alteration of the transsarcolemmal Ca2+transport and a modulation of the SR Ca2+content.
Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors
Authors: Brabham Tiffini , Phelka Andrew , Zimmer Carrie , Nash Aleda , López Juan F. , Vázquez Delia M.
Published: December 2017

The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 μg/ml) or tap water (Veh) from gestational day 15until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.
Carotid and aortic baroreflexes of the rat: II. Open-loop frequency response and the blood pressure spectrum
Authors: Dworkin Barry R. , Tang Xiaorui , Snyder Alan J. , Dworkin Susan
Published: December 2017

To determine the relationship between blood pressure (BP) variability and the open-loop frequency domain transfer function (TF) of the baroreflexes, we measured the pre- and postsinoaortic denervation (SAD) spectra and the effects of periodic and step inputs to the aortic depressor nerve and isolated carotid sinus of central nervous system-intact, neuromuscular-blocked (NMB) rats. Similar to previous results in freely moving rats, SAD greatly increased very low frequency (VLF) (0.01–0.2 Hz) systolic blood pressure (SBP) noise power. Step response-frequency measurements for SBP; interbeat interval (IBI); venous pressure; mesenteric, femoral, and skin blood flow; and direct modulation analyses of SBP showed that only VLF variability could be substantially attenuated by an intact baroreflex. The −3-dB frequency for SBP is 0.035–0.056 Hz; femoral vascular conductance is similar to SBP, but mesenteric vascular conductance has a reliably lower and IBI has a reliably higher −3-dB point. The overall open-loop transportation lag, of which ≤0.1 s is neural, is ≈1.07 s. Constrained algebraic solution, over a range of frequencies, of the pre- and postSAD endogenous noise spectra and the independently determined relative frequency and absolute lag measurements was used to calculate the absolute gain for the open-loop TF. The average gain at 0.02 Hz, the frequency of maximum sensitivity, was 1.47 (95% confidence interval = ±0.48), which agrees well with estimates for the dog reversible sinus. We found that, in the NMB rat, the effects of SAD on the BP noise spectrum were accounted for by the open-loop properties of the baroreflex.
Validation of the doubly labeled water method in rats during isolation and simulated weightlessness
Authors: Blanc Stéphane , Géloën Alain , Pachiaudi Christiane , Gharib Claude , Normand Sylvie
Published: December 2017

Total energy expenditure (TEE) of rats during simulated microgravity is unknown. The doubly labeled water method (DLW) reliably measures TEE, but the results depend on the methods of calculation. These methods were validated and appraised by indirect calorimetry in eight rats during isolation (7 days) and simulated microgravity (10 days). There were no effects on CO2 production in the method used to derive constant flux rates as in the regression models. rCO2 estimates were dependent on the assumed fractionation processes, the derivation of constant flux rate methods, and the selected pool models. Use of respiratory or food quotients did not influence TEE estimations, which were similar during isolation and simulation. During either isolation with growth or simulation with a stabilized mass, the one-pool model of Speakman (Speakman JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) resulted in the more reliable validation (0.8 ± 2.2 and 2.2 ± 3.4% vs. calorimetry, respectively). However, during simulation, agreement was also observed with the single pool model of Lifson (Lifson N, Gordon GB, and McClintock R. J Appl Physiol7: 704–710, 1955) (−2.5 ± 2.5%), and two two-pool models [Schoeller (Schoeller DA. J Nutr 118: 1278–1289, 1988) (0.5 ± 3.1%) and Speakman (Speakman, JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) (−1.9 ± 2.7%)]. This latter finding seems linked to the stable body mass and to fractionation consideration close to the single-pool model of Speakman. During isolation or simulated microgravity, the other equations underestimated TEE by 10–20%.
Attenuation of sleep propensity, core hypothermia, and peripheral heat loss after temazepam tolerance
Authors: Gilbert Saul S. , Burgess Helen J. , Kennaway David J. , Dawson Drew
Published: December 2017

If changes in thermoregulation mediate sleepiness induced by sedative/hypnotics, then a reduction in the soporific efficacy (tolerance) of these agents may be accompanied by a concomitant reduction in their thermoregulatory effects. We compared the thermoregulatory and soporific effects of acute temazepam (30 mg at 1400) in 11 young male subjects before and immediately after 7 consecutive days of temazepam (30 mg). Subjects lay supine (0800–2030), while foot (Tft) and rectal (Tc) temperatures were recorded. Sleep onset latency (SOL) was measured hourly using 20-min multiple sleep latency tests. Relative to placebo, temazepam significantly reduced both Tc and SOL (−0.31°C and 14.1 min) while increasing Tft (3.39°C). A significant tolerance developed after the week of temazepam, with a mean reduction in soporific efficacy of 4.0 ± 0.8 min. This was accompanied by a concomitant attenuation in both Tc(−0.16°C) and Tft (1.44°C). Furthermore, SOL was temporally related to Tft and the maximum rate of decline in Tc before and after tolerance. Together, these results indicate that the thermoregulatory system may be functionally involved in the regulation of sleepiness.
Comparison of heat and cold stress to assess thermoregulatory dysfunction in hypothyroid rats
Authors: Gordon Christopher J. , Becker Peggy , Padnos Beth
Published: December 2017

How borderline impairment of thyroid function can affect thermoregulation is an important issue because of the antithyroidal properties of a many environmental toxicants. This study compared the efficacy of heat and cold stress to identify thermoregulatory deficits in rats subjected to borderline and overt hypothyroidism via subchronic exposure to propylthiouracil (PTU). After 3 wk of exposure to PTU in the drinking water (0, 2.5, 5, 10, and 25 mg/l), rats were subjected to a heat stress challenge (34°C for 2.5 h). After one more week of PTU treatment, the same rats were subjected to a cold stress challenge (7°C for 2.5 h). Core temperature (Tc) was monitored by radiotelemetry. Baseline Tc during the light phase was reduced by treatment with 25 mg/l PTU. The rate of rise and overall increase in Tcduring heat stress was attenuated by PTU doses of 10 and 25 mg/l. Cold stress resulted in a 1.0°C increase in Tc regardless of PTU treatment. The rate of rise in Tc during the cold stress challenge was similar in all PTU treatment groups. There was a dose-related decrease in serum thyroxine (T4) at PTU doses ≥5 mg/l. Serum triiodothyronine (T3) was reduced at PTU doses of 5 and 25 mg/l. Serum thyroid-stimulating hormone (TSH) was marginally elevated by PTU treatment. Overall, heat stress was more effective than cold stress for detecting a thermoregulatory deficit in borderline (i.e., 10 mg/l PTU) and overtly hypothyroid rats (i.e., 25 mg/l PTU). A significant thermoregulatory deficit is manifested with a 78% decrease in serum T4. A thermoregulatory deficit is more correlated with a reduction in serum T4 compared with T3. Serum levels of TSH are unrelated to thermoregulatory response to heat and cold stress.
Heat-stress-induced hyperthermia alters CSF osmolality and composition in conscious rabbits
Authors: Frosini Maria , Sesti Casilde , Palmi Mitri , Valoti Massimo , Fusi Fabio , Mantovani Piero , Bianchi Loria , Della Corte Laura , Sgaragli Giampietro
Published: December 2017

Amino acids have received increased attention with regard to their thermoregulatory effects and possible role as neurotransmitters within the thermoregulatory system. The purpose of the present work was to evaluate in conscious rabbits the changes in cerebrospinal fluid (CSF) concentration of taurine, GABA, aspartate, and glutamate during exposure to high ambient temperature (50 min, 40°C) to investigate their involvement in heat stress (HS). CSF and plasma osmolality and CSF concentrations of some cations and proteins were also determined. HS animals underwent transient hyperthermia and thereafter fully recovered. This was accompanied by a significant rise in CSF and plasma osmolality, CSF protein, calcium, taurine, and GABA. Artificial CSF osmolality measurements after addition of CaCl2 or taurine demonstrated that the increased CSF osmolality after HS is accounted for, only in part, by the increased concentrations of either calcium and taurine. It is suggested that, during HS, taurine and GABA are released in the extracellular space of brain tissues in higher amounts, possibly to counteract the resulting hyperthermia.
Inhibition of TNF-α production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline
Authors: Porter M. H. , Hrupka B. J. , Altreuther G. , Arnold M. , Langhans W.
Published: December 2017

Cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-α production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 μg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 μg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-α production by more than 95% and IL-1β production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-α production was reduced by ∼90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-α (150 ug/kg body wt). The results suggest that suppression of TNF-α production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-α plays a major role in the anorexia associated with bacterial infection.