bluuebunny/crossref_metadata_2025 huggingface dataset:
Triggering of erythropoietin production by hypoxia is inhibited by respiratory and metabolic acidosis
Authors: Eckardt K. U. , Kurtz A. , Bauer C.
Published: December 2017

Erythropoietin (EPO) production in response to hypoxic hypoxia is known to be attenuated by simultaneous hypercapnia. This study aimed to investigate whether this inhibitory effect of hypercapnia is 1) a direct effect of carbon dioxide or mediated by changes in pH or bicarbonate, 2) affects also carbon monoxide hypoxia, and 3) influences either the synthesis and release of EPO or the mechanisms by which hypoxia triggers an increase in EPO production rate. We found that EPO formation in mice exposed to normobaric hypoxia (8% O2) or to carbon monoxide (0.1%) was reduced by 30 and 42% when animals were simultaneously exposed to hypercapnia (7% CO2), by 35 and 38% when subjected to metabolic acidosis (NH4Cl), and unchanged when subjected to metabolic alkalosis (NaHCO3). In animals exposed to brief hypoxia (15 min) and subsequent normoxia (2 h), metabolic acidosis did not affect EPO levels when initiated after the hypoxic period. The results indicate that acidosis inhibits hypoxia-induced triggering of EPO formation independently of PCO2 and HCO3 levels. Because this inhibitory effect is also present during carbon monoxide hypoxia, it appears not solely due to potentiated hyperpnea. Alternatively, it may result from a facilitated intrarenal oxygen release or a direct effect at the EPO production sites.
Influence of serum glucose on glutamate decarboxylase activity in the ventromedial nucleus of rats
Authors: Beverly J. L. , Martin R. J.
Published: December 2017

Changes in the activity of glutamate decarboxylase (GAD), the rate-limiting enzyme in gamma-aminobutyric acid synthesis, in response to insulin-induced hypoglycemia were measured in several brain areas involved in glucoregulation. A 20% increase in GAD activity in the ventromedial nucleus (VMN) of rats was measured 30 min after injections of insulin. The increase was significantly correlated with the decrease in serum glucose (r = -0.74) and increased food intake (r = 0.44). The increase in VMN GAD activity was linear between 5 and 30 min after insulin injection and coincided with the decline in serum glucose. Pretreatment with a gastric preload of a 50% glucose solution attenuated the decline in serum glucose, the increase in food intake, and the increase in GAD activity. Inhibition of protein synthesis by puromycin did not block the decrease in glucose, but neither the increase in GAD activity in the VMN nor the increase in food intake in response to insulin was observed. The increase in VMN GAD activity also was present 6 h after insulin injection if rats were denied access to food. No consistent changes in GAD activity were measured in any brain area other than the VMN. The results of these trials suggest that the increase in VMN GAD activity is associated with the decrease in serum glucose and may be involved in the increased feeding associated with insulin administration.
Regulation of glycolysis in the pectoralis muscles of seasonally acclimatized American goldfinches exposed to cold
Authors: Marsh R. L. , Dawson W. R. , Camilliere J. J. , Olson J. M.
Published: December 2017

Regulation of glycolysis was assessed in winter- and summer-acclimatized goldfinches (Carduelis tristis). We exposed birds to a thermo-neutral temperature (30 degrees C), moderate cold (-15 degrees C), and severe cold (0 degrees C in an atmosphere of 21% O2-79% He), and then measured concentrations of glycogen, glycolytic intermediates, and citrate in the pectoralis muscles. Winter birds used less glycogen when exposed to moderate cold than did summer birds, confirming the carbohydrate sparing noted by Marsh and Dawson [Am. J. Physiol. 242 (Regulatory Integrative Comp. Physiol. 11): R563-R569, 1982]. However, depletion of muscle glycogen did not correlate with thermoregulatory failure in this study. Concentrations of glucose 6-phosphate and fructose 6-phosphate in the pectoralis muscles were approximately 1.9 and 0.3 mumol/g wet mass in birds exposed to thermoneutral temperatures. The levels of these intermediates fell 50-70% under conditions known to enhance flux through glycolysis as indicated by increased glucose turnover and glycogen depletion. This information identifies phosphofructokinase (PFK) as a major regulated step in glycolysis in these highly aerobic skeletal muscles. Winter birds maintained the inhibition of this step under conditions of moderate cold. However, concentrations of citrate, which have been hypothesized to be an important inhibitor of PFK, did not correlate with the observed pattern of inhibition. Therefore, if the enhanced beta-oxidative capacity of winter birds is important in the regulation of glycolysis, a mechanism other than the accumulation of citrate may be involved.
Suspension effects on rat femur-medial collateral ligament-tibia unit
Authors: Vailas A. C. , Zernicke R. F. , Grindeland R. E. , Li K. C.
Published: December 2017

To study the influence of a 2-wk absence of normal weight-bearing forces on dense fibrous connective tissues of growing animals, the geometrical and biomechanical characteristics were examined of femur-medial collateral ligament (MCL)-tibia units (FMT unit) of age-matched controls and tail-suspended young male rats. During the 2-wk suspension, the rate of longitudinal growth of MCL decreased significantly, but no differences were found in the cross-sectional area of the MCL of the two groups. The tensile stiffness of suspension FMT units was significantly less than control, and the proportional, maximum, and failure loads of FMT units were also significantly less for the suspended animals. The stresses in the suspension MCL at the proportional limit were significantly less than control values. These results indicated that a 2-wk absence of normal weight-bearing forces adversely affected the rate of longitudinal growth of MCL and the mechanical properties of the rat FMT unit.
Metabolic activation of efferent pathways from the rat area postrema
Authors: Gross P. M. , Wainman D. S. , Shaver S. W. , Wall K. M. , Ferguson A. V.
Published: December 2017

We used the quantitative [14C]deoxyglucose method and autoradiography to evaluate metabolic activity in 47 individual cerebral structures or subregions that are part of neural pathways emanating from the brain stem circumventricular organ, area postrema. Electrical stimulation of the dorsocentral area postrema in halothane-ventilated rats produced hypotension and increased glucose metabolism by several structures within the ascending trajectories of efferent neural projections from the nucleus. Structures in the caudal medulla oblongata, including three subnuclei of the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and nucleus ambiguus-A1 noradrenergic region, had increases of metabolism during stimulation of 32-62%. Pontine activation occurred specifically in the locus coeruleus and lateral parabrachial nuclei (increases of 24-36%). Magnocellular and parvocellular subdivisions of the hypothalamic paraventricular nucleus, supraoptic and suprachiasmatic nuclei, and median eminence showed increases in metabolism of 22-34%. An 89% elevation of glucose metabolism by the pituitary neural lobe resulted. The findings are evidence for functional activation of specific structures within ascending neural pathways from area postrema to forebrain mechanisms regulating blood pressure and fluid balance.
Assessing the characteristic between length of hypoxic exposure and serum erythropoietin levels
Authors: Cahan C. , Hoekje P. L. , Goldwasser E. , Decker M. J. , Strohl K. P.
Published: December 2017

We examined the relationship between the duration of hypoxic exposure and serum erythropoietin (EPO) production. Adult male Long-Evans rats were exposed to hypobaric hypoxia (HH = 0.5 atm) for a period of 15 min to 20 days. Serum for EPO by radioimmunoassay was collected immediately, 1 or 2 h after HH exposure. A significant rise in EPO levels occurred 1 h after a 30-min HH exposure that was not sustained 2 h after termination. One hour of HH exposure resulted in increased EPO levels 1 h after termination of exposure and further increased levels 2 h after termination of exposure. With prolonged exposure, serum levels remained elevated at 6 and 20 days, despite the development of polycythemia. We concluded that the hypoxic stimulus for elevation of serum EPO could be as short as 30 min and that EPO levels remained elevated after chronic HH. The experimental data were consistent with a mathematical model in which stimulated EPO production was proportional to the time of HH stimulus.
Rainbow trout corpuscles of Stannius: stanniocalcin synthesis in vitro
Authors: Flik G. , Labedz T. , Neelissen J. A. , Hanssen R. G. , Wendelaar Bonga S. E. , Pang P. K.
Published: December 2017

In fresh-water rainbow trout, Oncorhynchus mykiss (formerly called Salmo gairdneri), experimentally induced mild hypercalcemia results in release of immunoreactive stanniocalcin from the corpuscles of Stannius (CS) and stimulated synthetic and releasing activities of the glands as measured in vitro. Pulse-chase experiments showed that stanniocalcin (STC) is a 56-kDa glycoprotein, processed from a 64-kDa precursor, prostanniocalcin (PSTC). PSTC and STC are homodimeric molecules that are readily split into monomers in the presence of reducing agents such as 2-mercaptoethanol. The monomeric form of PSTC and STC contains an approximately 5- to 6-kDa glycomoiety. Neither this sugar residue nor the NH2-terminal amino acid sequences of PSTC or STC proved to contain antigenic sites for the antiserum used in this study. Two-dimensional gel electrophoresis indicated the presence of several isoforms of PSTC and STC molecules that may reflect different stages of maturation of the (pro)hormone.
A direct effect of atrial peptide on arterioles of the terminal microvasculature
Authors: Sarelius I. H. , Huxley V. H.
Published: December 2017

Responses to atrial peptide (AP) were observed in cheek pouch arterioles of anesthetized golden hamsters (pentobarbital sodium, 70 mg/kg ip). Vessels for observation were selected on the basis of their functional status in relation to controlling the perfused capillary surface area. Local application of AP onto microvessels at a final concentration of from 7 X 10(-9) to 3 X 10(-8) M was achieved via micropipettes; responses were compared with those produced by application of vehicle only. Individual vessels were observed during control conditions and during vasoconstriction of the microvascular bed induced via either equilibration of the superfusate with 10% oxygen or addition to the superfusate of 5 X 10(-7) M norepinephrine (NE). Compared with responses induced by the vehicle in each condition, AP produced a statistically significant dilation during control conditions, and during raised PO2, but no statistically significant effect during NE exposure. Mean diameter changes were from a base line of 27.8 +/- 4.7 to 29.7 +/- 4.5 microns with vehicle and 33.2 +/- 4.4 microns with AP in controls; from 22.7 +/- 4.6 to 25.8 +/- 4.5 microns with vehicle and 30.1 +/- 4.7 microns with AP during raised PO2; and from 25.2 +/- 4.7 to 29.8 +/- 5.4 microns with vehicle and 33.5 +/- 4.9 microns with AP during NE exposure. The data show that arterioles of the terminal microvasculature can respond selectively to AP.
Intestinal absorption and metabolism of ascorbic acid in rainbow trout
Authors: Rose R. C. , Choi J. L.
Published: December 2017

Transport and metabolism of the reduced and oxidized forms of vitamin C were evaluated in trout intestine in vitro. Transepithelial fluxes of [14C]ascorbic acid were determined with the substrate present at 10 microM. The mucosa-to-serosa flux was fourfold greater than the serosa-to-mucosa flux with ascorbic acid present in both bathing solutions. Cellular accumulation of the reduced molecule occurred with a final tissue-to-medium ratio of 1.64. Ascorbic acid influx across the brush-border membrane was determined under conditions that inhibit transport of other nutrients. Influx was not reduced because of the presence of the D- or L-stereoisomeric form of glucose but was highly dependent on the presence of Na in the bathing medium. Brush-border influx was saturable with a Km of 220 microM. Short-term (8 min) exposure of intestinal loops to the oxidized form of vitamin C, dehydro-L-ascorbic acid, was followed by high-performance liquid chromatography analysis of the 14C label present in the tissue. Total uptake of substrate was greater from the serosal solution than from the mucosal solution; in either situation most of the 14C label was found in the reduced state. It is concluded that transport and metabolic capabilities are present in the trout intestine to absorb oxidized and reduced forms of vitamin C and to help regulate the redox potential of circulating ascorbic acid by recycling dehydro-L-ascorbic acid.
Inhibition of rostral VLM by baroreceptor activation is relayed through caudal VLM
Authors: Agarwal S. K. , Gelsema A. J. , Calaresu F. R.
Published: December 2017

Experiments were done to test the hypothesis that inhibition of neurons in the rostral ventrolateral medulla (RVLM) elicited by stimulation of the nucleus tractus solitarii (NTS) is relayed through the caudal ventrolateral medulla (CVLM). We recorded activity from 56 spontaneously firing units in the right RVLM of urethan-anesthetized and artificially ventilated rats. Eleven of these units were classified as cardiovascular neurons, because they were silenced by baroreceptor activation (1-3 micrograms phenylephrine iv) and showed rhythmicity of their spontaneous activity in synchrony with the cardiac cycle. Single pulses (0.1 ms, 30-75 microA) delivered 1/s to depressor sites in the ipsilateral NTS inhibited the activity of all these cardiovascular neurons. Microinjection of the glutamate antagonist kynurenic acid (0.15 M, 50 nl) into the ipsilateral CVLM blocked the inhibitory response of RVLM units to the administration of phenylephrine and increased the firing frequency of cardiovascular neurons in the RVLM by 43%. Moreover, kynurenic acid administration attenuated the inhibitory response of cardiovascular neurons in the RVLM to NTS stimulation. Finally, stimulation of the NTS that elicited depressor responses under control conditions produced a pressor response after kynurenic acid administration. The remaining 45 RVLM neurons were barosensitive but lacked cardiac cycle-related rhythmicity. These results provide direct evidence for the existence of a tonic inhibitory pathway from NTS to RVLM that is relayed through the CVLM probably by a glutamatergic projection from NTS to CVLM.
Central opioid modulation of fetal cardiovascular function: role of mu- and delta-receptors
Authors: Szeto H. H. , Zhu Y. S. , Cai L. Q.
Published: December 2017

To investigate the role of mu- and delta-receptors in opioid modulation of fetal cardiovascular function, we compared the effects on fetal heart rate (FHR) and fetal blood pressure (FBP) of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO, a mu-selective agonist), [D-Pen2,D-Pen5]-enkephalin (DPDPE, delta-selective agonist), and [D-Ala2,D-Leu5]-enkephalin (DADLE, a mixed mu- and delta-agonist) in 24 fetal lambs. All peptides were infused intracerebroventricularly at a constant rate for 1 h. Three to seven animals were studied at each of six dose levels ranging from 1.58 to 476 nmol/h. Saline infusion did not elicit any changes in FBP or FHR. DAGO caused a dose-dependent increase in FHR, with the peak response being 61.6 +/- 9.9% at the highest dose. The effects of DAGO on FBP were small (maximum being 11.1 +/- 3.4%) and did not reach statistical significance. In contrast, DPDPE did not induce any changes in either FHR or FBP over the same dose range, suggesting that delta-receptors do not play a role in opioid modulation of fetal cardiovascular function. The FHR response to DADLE was similar to DAGO in both dose-response and time-action characteristics. The finding that DADLE behaved like DAGO rather than DPDPE suggests that the opioid-induced fetal tachycardia may be mediated via mu 1-receptors. There was also evidence for rapid development of tolerance to the FHR response to both DAGO and DADLE, as demonstrated by the decline in FHR response by 45-50 min despite continuous peptide infusion.
Adaptation to temperature: phospholipid synthesis in hepatocytes of rainbow trout
Authors: Hazel J. R.
Published: December 2017

De novo phospholipid biosynthesis was assayed in isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) both fully acclimated to 5 or 20 degrees C and undergoing acclimation from one temperature extreme to the other. Incorporation of [14C]choline, [3H]ethanolamine, and [3H]serine into phosphatidyl-choline (PC), phosphatidylethanolamine (PE), or both, was followed to assess metabolic capacity. PE biosynthesis rates exceeded those for PC four- to fivefold. Methylation of PE accounted for 10 (20 degrees C)-17% (5 degrees C) of the synthetic capacity for PC, whereas 6 (20 degrees C-acclimated)-27% (5 degrees C-acclimated) of PE synthesis was derived from phosphatidylserine (PS) decarboxylation. Several factors may contribute to the altered proportions of PE and PC or unsaturated molecular species of phospholipids characteristic of thermally acclimated animals. 1) Activities of choline and ethanolamine phosphotransferase pathways were significantly higher, and decarboxylation activity lower, in 20 degrees C than in 5 degrees C-acclimated trout, resulting in maintained PE synthesis despite a general depression of lipid biosynthesis at cold temperatures. 2) PC biosynthesis depended more on temperature (Q10 = 2.6-3.0) than that of PE (Q10 = 1.8-2.2), causing the ratio of PC/PE synthesis to be positively correlated with temperature. 3) Contribution of methyltransferase pathway to the synthesis of PC was higher at 5 than 20 degrees C. 4) The percentage of ethanolamine incorporation recovered in PC increased threefold in the early stages of warm acclimation. However, not all adjustments in biosynthetic capacity (most notably a 10-fold stimulation of PC synthesis 2 days after transfer of warm-acclimated trout to 5 degrees C) influence membrane lipid composition, implicating other processes in the regulation of this parameter.
Noxious somatic stimuli excite neurosecretory vasopressin cells via A1 cell group
Authors: Day T. A. , Sibbald J. R.
Published: December 2017

Activation of nociceptive somatic afferents excites hypothalamic neurosecretory cells and stimulates the release of vasopressin. To investigate the possibility that relevant afferent information is relayed through the A1 norepinephrine cell group of the caudal ventrolateral medulla, single-unit recording experiments were performed in pentobarbital sodium-anesthetized rats. The effects of somatic nerve stimulation, application of noxious somatic stimuli, and A1 region stimulation on the activity of putative vasopressin-secreting neurosecretory cells of the supraoptic nucleus were compared. The predominant effect of femoral and sciatic nerve stimulation on these cells was excitation, 54% (n tested = 113) displaying a marked increase in discharge probability, which had a mean onset latency of 72 +/- 3 ms and a mean duration of 114 +/- 9 ms. Almost all cells (96%) responding to somatic nerve stimulation were also excited by pinching of the ipsilateral or contralateral hindlimb paw, and the majority (84%) displayed a matching but shorter latency response to A1 region stimulation (mean onset 35 +/- 4 ms, duration 55 +/- 9 ms). A1 region injections of the inhibitory neurotransmitter gamma-aminobutyric acid reversibly blocked the effects of both somatic nerve stimulation (n = 14) and paw pinch (n = 9) on putative vasopressin cells. These results indicate that excitation of vasopressinergic neurosecretory cells by noxious somatic stimuli requires activation of neurons of the caudal ventrolateral medulla and hence are consistent with the proposal of a role for the A1 norepinephrine cell group.
Renal responses to graded hemorrhage in conscious pig
Authors: Sondeen J. L. , Gonzaludo G. A. , Loveday J. A. , Deshon G. E. , Clifford C. B. , Hunt M. M. , Rodkey W. G. , Wade C. E.
Published: December 2017

We developed a conscious pig model with a chronically instrumented kidney to measure renal blood flow (RBF), glomerular filtration rate (GFR), and excretory functions during hemorrhage. Seven to 10 days before experimentation, pigs were splenectomized, arterial and venous catheters were implanted, an ultrasonic flow probe was placed on the renal artery, and a pyelostomy was performed for nonocclusively placing a ureteral catheter. Measurements were taken before hemorrhage, and at hemorrhage volumes of 7, 14, 21, and 28 ml/kg (equivalent to 10.5, 21, 31, and 42% of the estimated blood volume), or at corresponding time points for controls. RBF was decreased by 30% when 21% of the blood (14 mg/kg) was removed, before arterial pressure, GFR, or urine flow or excretion was changed. At volumes of hemorrhage greater than 14 ml/kg, there were progressive decreases in RBF, GFR, urine flow rate, osmotic and electrolyte excretion, and arterial pressure. Thus pigs, like humans, respond to hypovolemia with an early redistribution of blood flow away from the kidney.
Control of interbreath interval in the African lungfish
Authors: Pack A. I. , Galante R. J. , Fishman A. P.
Published: December 2017

We have performed studies to examine the effect of variations in intrapulmonary pressure on the interval between lung breaths in the African lungfish. Studies were performed in two different preparations. In the first we produced changes in lung pressure using a controlled-infusion pump. Increases in intrapulmonary pressure prolonged the interval between lung breaths. At a pressure of 2.5 cmH2O the average interval was 2.6 +/- 1.8 min (mean +/- SD); at 5.0 cmH2O, 8.1 +/- 3.5 min; and at 7.5 cmH2O, 16.2 +/- 3.8 min. Inflations of the lung early in the interbreath interval had less of an effect on its duration than inflations later in the interval. In the second preparation we used a system in which gas flowed continuously through both lungs. Intrapulmonary pressure was varied by changing outlet pressure and O2 concentration by changing the composition of the gas mixture. This allowed separate control of both O2 concentration and intrapulmonary pressure. At a fixed O2 concentration intrapulmonary pressure increased the duration of the interval between lung breaths. At a fixed pressure, reductions in O2 concentration shortened the interval. There was no significant interactive effect of O2 and pressure. Lung inflation did not alter the frequency of gill ventilation. These results imply that a reflex highly similar to the Hering-Breuer expiratory-promoting reflex was already present in the African lungfish.
Short-term hormonal responses to food intake in peripubertal female rats
Authors: Bronson F. H. , Heideman P. D.
Published: December 2017

These studies focused on the phenomenon of "catch-up" pubertal development. Circulating levels of several hormones were characterized in 8-wk-old female rats whose growth and reproductive development had been blocked before puberty by restricting their food intake. Some of these females were fed ad libitum for 24 h to initiate rapid pubertal development. Blood levels of luteinizing hormone (LH) and growth hormone (GH) were suppressed by food restriction and then partially restored to adult diestrus levels by 24 h of ad libitum feeding. Prolactin titers were also suppressed by food restriction but not significantly elevated by 24 h of ad libitum feeding. Circulating levels of follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were unaffected by either treatment. It is concluded that GH could play an active supplementary role to LH in eliciting catch-up pubertal development but that FSH and TSH could play only passive roles at best. The role of prolactin remains uncertain. On a finer time scale, when food-restricted females were examined in relation to the time of day at which they were fed, most showed high-amplitude LH pulses 2-4 h after eating but rarely at any other time. Thus under some conditions LH secretion can be modulated by food intake on an almost hour-by-hour basis. Overall, blood levels of corticosterone were generally but not always inversely correlated with the frequency of LH pulsing in these experiments. Finally, the present results argue against the concept that puberty is dependent on a critical whole body characteristic.(ABSTRACT TRUNCATED AT 250 WORDS)
Parasympathetic impairment of baroreflex control of heart rate in Dahl S rats
Authors: Whitescarver S. A. , Ott C. E. , Kotchen T. A.
Published: December 2017

To test the hypothesis that impaired baroreflex control of heart rate in Dahl salt-sensitive (S) rats is due to an impairment of the parasympathetic limb of the bradycardic response, baroreflex sensitivity was evaluated in conscious, chronically instrumented Dahl S and salt-resistant (R) animals. Sensitivity was impaired in Dahl S rats when bolus doses of phenylephrine were administered (0.863 +/- 0.042 vs. 1.43 +/- 0.055 ms/mmHg), but it was not different than in R rats when tested with sodium nitroprusside. When the sensitivities before and after blocking the parasympathetic nervous system with atropine were compared, it was revealed that 82% of the reflex bradycardia resulting from bolus doses of phenylephrine was due to the parasympathetic nervous system, whereas the majority (73%) of the bradycardia induced by 5-min infusions of phenylephrine was due to withdrawal of sympathetic tone. Neither baroreflex sensitivity to infusions of phenylephrine (73% sympathetic) or to infusions after atropine (100% sympathetic) were significantly different between S and R rats. Therefore, the impairment of the heart rate reflex in Dahl S rats is due to an impairment of the parasympathetic limb of the response. In addition, a high-salt diet before the development of hypertension did not alter baroreflex sensitivity in either Dahl S or R rats.
Effects of temperature on nervous system: implications for behavioral performance
Authors: Montgomery J. C. , Macdonald J. A.
Published: December 2017

Temperature change has a major impact on the function of the nervous system and its components, including altering synaptic gain and changing synaptic and conduction delays. Although many animals are subject to changes in body temperature, the degree of temperature change actually experienced by many poikilotherms is not well documented. The fact that many animals continue to exhibit coordinated sensorimotor function during changes in body temperature indicates that some form of temperature compensation has occurred within the nervous system. Compensations may occur automatically (opposing effects of temperature offsetting each other), they may be an inherent property of closed-loop systems, or they may be effected by more sophisticated control mechanisms such as those of the vertebrate cerebellum.
Muscle temperature of mammals: cooling impairs most functional properties
Authors: Faulkner J. A. , Zerba E. , Brooks S. V.
Published: December 2017

Our purpose was to study the effect of a decrease in skeletal muscle temperature on single and repeated shortening, isometric, and lengthening contractions of mammalian skeletal muscles. Fast extensor digitorum longus muscles of mice were studied in situ and in vitro at 25 and 35 degrees C. No difference in isometric force was observed, but maximum and sustained powers were reduced by 40 and 62%, respectively. With cooling, maximum power absorption, which is proportional to the external work required to lengthen the muscle, increased significantly at each velocity of lengthening from 0.5 to 4.0 optimum fiber length/s. The 10 degrees C decrease in muscle temperature produced a decrease in power that was primarily a result of the decrease in the velocity of shortening, whereas the increase in power absorption was likely due to an increase in the number of strongly bound cross bridges resulting from a decreased rate of detachment. During voluntary exercise at decreased muscle temperatures, maximum and endurance performances are inevitably impaired by the decreases in maximum and sustained power of individual motor units.
Capsaicin desensitization induces atrophy of brown adipose tissue in rats
Authors: Cui J. , Zaror-Behrens G. , Himms-Hagen J.
Published: December 2017

Interscapular brown adipose tissue (BAT) of capsaicin-desensitized (Cap-Des) rats is atrophied, having a lower wet weight, a reduced total protein content, and as little as 10% of the normal content of uncoupling protein (UCP). Because the mitochondrial concentration of UCP, relative to other mitochondrial proteins, is not altered in Cap-Des rats, it is concluded that most of the mitochondria of BAT of Cap-Des rats have been lost. Consistent with this interpretation is a reduction of almost 40% of the overall thermogenic response to infused norepinephrine by anesthetized Cap-Des rats. Feeding a palatable diet had a delayed thermogenic effect and no trophic effect on BAT of Cap-Des rats. Food selection and intake were normal in Cap-Des rats, and diet-induced weight gain was the same as in control rats. Exposure of Cap-Des rats to cold for 1 or 7 days exerted a normal thermogenic effect on BAT but a delayed trophic effect. The cold-induced increase in thyroxine 5'-deiodinase in BAT occurred normally. Cap-Des rats were hypothermic at 1 day but normothermic by 7 days of cold exposure. The concentration of thyroid hormones in their blood was normal. It is suggested that the depletion of sensory neuropeptides in BAT presumed to be brought about by Cap-Des results either in loss of a trophic influence on mitochondriogenesis in BAT or in lack of an inhibitory influence on mitochondrial breakdown in BAT and leads to atrophy of BAT in rats living at 26 degrees C and an impaired response to stimulation by diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in turtle brain neurotransmitters and related substances during anoxia
Authors: Nilsson G. E. , Alfaro A. A. , Lutz P. L.
Published: December 2017

Freshwater turtles (Pseudemys scripta elegans) were exposed to 0.5-13 h of anoxia at 25 degrees C, whereupon the brain concentrations of 14 amino acid and monoamine neurotransmitters and related substances were measured. Monoamines are of particular interest, because their synthesis and (in part) degradation require molecular oxygen. During anoxia, the level of the inhibitory transmitter gamma-aminobutyric acid (GABA) increased (2.3-fold after 13 h) and the level of the excitatory transmitter Glu fell. Furthermore, anoxia caused increases in the levels of Ala (14 times after 13 h), Tau, Gly, and Ser, whereas the Gln level fell. The increase in Ala is likely to inhibit pyruvate kinase, thereby mediating the decreased rate of glycolysis seen after prolonged anoxia. The increased level of Tau might protect the turtle brain against Ca2(+)-mediated anoxic damage. The monoamine metabolites almost vanished within a few hours of anoxia, indicating a halt in monoamine synthesis and breakdown, and the dopamine level fell. Nevertheless, serotonin, norepinephrine, and epinephrine levels were maintained during 13 h of anoxia, at levels extremely high compared with mammals, suggesting adaptive mechanisms such as stockpiling. It is hypothesized that the pattern of change in levels of amino acids (notably GABA and Glu) and monoamines is of functional significance, because it promotes the decrease in brain activity and energy consumption seen in anoxic turtles.
Energy expenditure and subsequent nutrient intakes in overfed young men
Authors: Roberts S. B. , Young V. R. , Fuss P. , Fiatarone M. A. , Richard B. , Rasmussen H. , Wagner D. , Joseph L. , Holehouse E. , Evans W. J.
Published: December 2017

We investigated the mechanisms of body weight regulation in young men of normal body weight leading unrestricted lives. Changes in total and resting energy expenditure, body composition, and subsequent voluntary nutrient intakes in response to overeating by 4,230 +/- 115 (SE) kJ/day (1,011 +/- 27 kcal/day) for 21 days were measured in seven subjects consuming a typical diet. On average, 85-90% of the excess energy intake was deposited (with 87% of this amount in fat and 13% in protein on average). There was no detectable difference between individuals in susceptibility to energy deposition. The resting metabolic rate, averaged for fasting and fed states, increased during overfeeding (mean +/- SE, 628 +/- 197 kJ/day, P less than 0.01), but at least some of this amount was obligatory expenditure associated with nutrient assimilation. No significant increase in energy expenditure for physical activity or thermoregulation resulted from overfeeding. Thus energy expenditure did not substantially adapt to increased energy intake. However, significant decreases in voluntary energy intake (1,991 +/- 824 kJ/day, P less than 0.05) and fat intake (48 +/- 11 g/day, P less than 0.01) followed overeating, indicating that adaptive changes in nutrient intakes can contribute significantly to body weight regulation after overeating.
Paraventricular hypothalamic adrenoceptors and energy metabolism in exercising rats
Authors: Scheurink A. J. , Steffens A. B. , Gaykema R. P.
Published: December 2017

The role of adrenoceptors in the paraventricular nucleus (PVN) in the exercise-induced changes in plasma norepinephrine (NE), epinephrine (E), corticosterone, free fatty acids (FFA), and blood glucose was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min. Before, during, and after swimming, blood samples were withdrawn through a permanent heart catheter for determination of E, NE, corticosterone, FFA, and glucose, In control rats receiving artificial cerebrospinal fluid through permanent bilateral cannulas into the PVN, the levels of all blood components increased during exercise. Infusion of the alpha-adrenoceptor antagonist phentolamine into the PVN completely reduced the exercise-induced increases in blood glucose and plasma corticosterone concentrations. Plasma NE, E, and FFA were not affected. Infusion of the beta-adrenoceptor antagonist timolol into the PVN reduced blood glucose and plasma NE concentrations. Plasma E, corticosterone, and FFA remained unchanged. It is concluded that alpha- and beta-adrenergic receptors in the PVN are involved in the central nervous regulation of blood glucose levels during exercise, partly by influencing sympathetic outflow. alpha-Adrenoceptors in the PVN play an important role in the release of corticosterone during exercise.
Effects of antiglucocorticoid RU 486 on development of obesity in obese fa/fa Zucker rats
Authors: Langley S. C. , York D. A.
Published: December 2017

The effects of RU 486 (mitepristone), an antagonist of type II glucocorticoid receptors (GR), on the development of obesity in young 5-wk-old obese fa/fa rats has been investigated. After 15 days of treatment, body composition of obese RU 486-treated rats was similar to that of lean-vehicle rats. Analysis of body composition changes showed that RU 486 effectively reversed the obesity. It stopped fat deposition in obese rats but increased protein deposition to the level of lean-vehicle rats. RU 486 prevented the development of hyperphagia and reduced gross energetic efficiency in the obese rats but had little effect on lean rats. Brown adipose tissue mitochondrial GDP binding was increased in obese rats but was reduced in lean rats by RU 486 treatment. RU 486 also reduced the elevated activity of hippocampal glycerophosphate dehydrogenase, a glucocorticoid-responsive enzyme, of obese rats to the level of lean rats. The evidence suggests that abnormal activity of glucocorticoid GR receptors or abnormal cellular responsiveness to corticosterone receptor complexes may be important in the development of obesity in the fa/fa rat.
Fetal endocrine responses to prolonged hypoxemia in sheep
Authors: Hooper S. B. , Coulter C. L. , Deayton J. M. , Harding R. , Thorburn G. D.
Published: December 2017

Our aim was to characterize the pattern of release of epinephrine, norepinephrine, arginine vasopressin (AVP), cortisol (hydrocortisone), and prostaglandin E2 (PGE2) into the fetal circulation during prolonged reductions in uterine blood flow (RUBF). In five sheep RUBF was induced for 24 h, whereas in another five sheep (controls) uterine blood flow was not reduced. Fetal arterial oxygen saturation was decreased from 60.5 +/- 3.6 to 20.3 +/- 1.6% after 2 h of RUBF and remained significantly reduced for the entire RUBF period. The incidence of fetal breathing movements (FBM) and fetal arterial pH were reduced from 36.7 +/- 4.5 min/h and 7.36 +/- 0.01 to 4.3 +/- 1.8 min/h and 7.13 +/- 0.02, respectively, after 2 h of RUBF, but both had returned to control levels after 14 h. Fetal plasma AVP and epinephrine concentrations were increased from 4.4 +/- 0.5 pg/ml and 0.19 +/- 0.05 ng/ml to 333.8 +/- 41.5 pg/ml and 1.5 +/- 0.6 ng/ml, respectively, after 2 h and then declined to near control levels after 12 h of RUBF. Fetal plasma norepinephrine and cortisol concentrations were increased from 1.3 +/- 0.4 and 4.0 +/- 2.2 ng/ml to 6.1 +/- 1.8 and 13.5 +/- 4.1 ng/ml, respectively, after 2 h of RUBF, and both remained significantly elevated throughout the remainder of the RUBF period. Fetal plasma PGE2 concentrations progressively increased (from 1.9 +/- 0.4 to 8.8 +/- 1.7 nmol/l at 12 h) as the duration of RUBF increased and were still significantly elevated after 24 h. The time course for the increase in PGE2 during RUBF was very similar to the increases in arterial pH and in the incidence of FBM.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of dietary limiting amino acid in prepyriform cortex on meal patterns
Authors: Beverly J. L. , Gietzen D. W. , Rogers Q. R.
Published: December 2017

Microinjection of the dietary limiting essential amino acid (DLAA) into the prepyriform cortex (PPC) increased intake of a diet having an imbalance among the essential amino acids (imbalanced diet) from 50-55% of baseline, when artificial cerebrospinal fluid (aCSF) was injected, to 70-75% of baseline. The increase in intake of the imbalanced diet by DLAA injection became apparent after 3-6 h and was maintained throughout the dark period. Meal size, meal duration, and the number of meals returned to normal after bilateral injections of the DLAA into the PPC of rats fed the imbalanced diet. Injection of the DLAA 30 min before the onset of the dark phase increased intake of imbalanced diet to 70% of baseline intake. When injections of threonine or isoleucine were made 6 and 3 h, respectively, prior to onset of the dark phase, intake of imbalanced diet increased to 85% of baseline intake. Results suggest that some form of processing of the injected DLAA within the PPC is necessary to increase the intake of imbalanced diets.
Calorimetric study of the energetics of pregnancy in golden hamsters
Authors: Quek V. S. , Trayhurn P.
Published: December 2017

The energetics of pregnancy have been assessed in the golden hamster, using continuous whole body indirect calorimetry to determine energy expenditure throughout gestation. Energy intake was unchanged during pregnancy, either on a daily or cumulative basis. The total energy expenditure per animal was, however, significantly higher (14%) in pregnant hamsters than in virgin control animals. The increase in total expenditure was the result of increases in daily energy expenditure over the last one-third of gestation (mean increase 21%), the period during which the energy costs associated with fetal growth are highest. The respiratory quotient (RQ) of the control hamsters was approximately 0.95, but in the pregnant group there was a progressive reduction over the second half of gestation, and by parturition the RQ had fallen to 0.80. The changes in RQ indicate that there is a switch toward the oxidation of fat, away from the oxidation of carbohydrate, in the later stages of pregnancy. Measurements of body lipid suggest that the fall in RQ in the second half of pregnancy is the result of a net utilization of maternal fat reserves; 42% of maternal body lipid was lost during pregnancy, with most of the loss occurring over the final one-third of gestation. Because energy expenditure is increased (relative to virgin controls) without any change in energy intake, it is evident that the efficiency of energy utilization (energy gain per unit of energy intake) is not increased during pregnancy in the golden hamster.
Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues
Authors: Vallerand A. L. , Perusse F. , Bukowiecki L. J.
Published: December 2017

The effects of cold exposure on the net rates of 2-[3H]deoxy-D-glucose uptake (Ki) in rat peripheral tissues were investigated comparatively in warm- and cold-acclimated animals to determine whether cold acclimation induces regulatory alterations in glucose metabolism. Acute exposure of warm-acclimated (25 degrees C) rats to cold (48 h at 5 degrees C) markedly increased the Ki values in red and white skeletal muscles (2-5 times), in the heart (8 times), in several white adipose tissue (WAT) depots (4-20 times), and in brown adipose tissue (BAT) (110 times). After cold acclimation (3 wk at 5 degrees C), the Ki values further increased in the heart (15 times) and WAT (up to 29 times) but decreased in BAT (36 times). Remarkably, glucose uptake was still increased in muscles of cold-exposed/cold-acclimated animals (that do not shiver), demonstrating that enhanced glucose uptake may occur in muscles in the absence of shivering thermogenesis (or contractile activity). When cold-acclimated rats were returned to the warm for 18 h, the Ki values of all tissues, except WAT, returned to control levels. Cold exposure synergistically potentiated the stimulation of tissue glucose uptake induced by a maximal effective dose of insulin (0.5 U/kg iv) in warm- as well as in cold-acclimated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurogenesis of respiratory rhythm and pattern: emerging concepts
Authors: Feldman J. L. , Smith J. C. , Ellenberger H. H. , Connelly C. A. , Liu G. S. , Greer J. J. , Lindsay A. D. , Otto M. R.
Published: December 2017

We present three hypotheses related to the nervous system control of breathing in mammals: 1) that neural mechanisms controlling breathing change with state and that the relationship between mechanisms in different states can be described in terms of either modulation or a basic transformation of properties, or both; 2) that the mechanisms generating respiratory rhythm and pattern are separate; and 3) that conditional pacemaker cell activity is the basis for respiratory rhythm in highly reduced states.
Role of calcium channels and protein kinase C for release of norepinephrine and neuropeptide Y
Authors: Haass M. , Forster C. , Richardt G. , Kranzhofer R. , Schomig A.
Published: December 2017

The role of calcium for the release of norepinephrine (NE, determined by high-pressure liquid chromatography) and neuropeptide Y (NPY, determined by radioimmunoassay) was investigated in guinea pig perfused hearts with intact sympathetic innervation. In the presence of extracellular calcium (1.85 mM), electrical stimulation of the left stellate ganglion (12 Hz, 1 min) induced a closely related release of NE and NPY with the molar ratio of approximately 400-600 (NE) to 1 (NPY). The stimulation-evoked overflow of both transmitters was dependent from the extracellular calcium concentration and was almost completely suppressed by calcium-free perfusion. The corelease of both transmitters was not affected by the L-type calcium channel blocker felodipine (1-10 microM). However, the overflow of NE and NPY was markedly attenuated by the unselective calcium antagonist flunarizine (1-10 microM) and completely prevented by the neuronal (N-type) calcium channel blockers omega-conotoxin (1-100 nM) and cadmium chloride (10-100 microM), indicating a key role for N-type calcium channels in the exocytotic release of transmitters from cardiac sympathetic nerve fibers. Possibly due to unspecific actions, such as interference with sodium channels or uptake1-blocking properties, the phenylalkylamines verapamil (0.01-10 microM) and gallopamil (1-10 microM) reduced NPY overflow with only a minor effect on NE overflow. The stimulation-induced transmitter release was increased up to twofold by activation of protein kinase C (phorbol 12-myristate 13-acetate, 3 nM-3 microM) and completely suppressed by inhibition of protein kinase C (polymyxin B, 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Neurons controlling cardiovascular responses to emotion are located in lateral hypothalamus-perifornical region
Authors: Smith O. A. , DeVito J. L. , Astley C. A.
Published: December 2017

We did four experiments to determine whether the lateral hypothalamus-perifornical (LH/PF) region is the source of neuronal cell bodies responsible for producing the cardiovascular (CV) responses associated with emotion or the defense reaction. Of particular concern was whether the paraventricular nucleus (PVN) plays a role in the generation of these CV responses. Mapping the hypothalamus with electrical stimulation showed that the CV pattern of responses was never produced by stimulating the PVN and was invariably produced by stimulating the LH/PF region. Complete electrolytic destruction of the PVN and subsequent axonal degeneration did not change the CV pattern of responses elicited by LH/PF stimulation, whereas any encroachment of the lesion on the LH/PF region decreased the magnitude of the CV responses. Injection of the neuroexcitotoxin ibotenic acid (Ibo) into the PVN did not affect responses to LH/PF stimulation, whereas Ibo injection into the LH/PF region eliminated or severely attenuated the CV responses. Retrograde labeling of cells from the thoracic cord and the ventrolateral reticular formation revealed a scattered group of cells in the LH/PF region that may be the cells controlling the CV responses. These results point directly to the LH/PF region as the source of the cell bodies responsible for the autonomic responses associated with emotion or defense reactions.
Baroreflex sensitivity in the canine model of obesity-induced hypertension
Authors: Wehberg K. E. , West D. B. , Kieswetter C. , Granger J. P.
Published: December 2017

Studies have demonstrated abnormalities in baroreflex function in various models of hypertension. The purpose of this study was to examine baroreflex sensitivity in the canine model of obesity-induced hypertension. Baroreflex sensitivity was determined by the relative changes in heart rate (HR) in response to changes in mean arterial pressure (MAP) induced by sodium nitroprusside (Nitro) and phenylephrine (Pe). Studies were performed in conscious lean dogs (n = 10) and obese dogs fed a high-fat diet for 6 wk (n = 8). Body weight averaged 18.1 +/- 0.3 kg in the lean dogs and 26.5 +/- 0.5 kg in the obese dogs. Associated with the 46% increase in body weight in the obese dog group were significant increases in MAP (120.7 +/- 3.0 vs. 102.8 +/- 1.5 mmHg) and HR (132.7 +/- 8.5 vs. 96.4 +/- 3.3 beats/min). Administration of Nitro (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in comparable reductions in MAP in the lean and obese dogs. The reflex increases in HR were significantly greater in the obese animals only with a dose of 5.0 micrograms.kg-1.min-1 of Nitro (55.5 +/- 7.7 vs. 32.0 +/- 7.5 beats/min). Administration of Pe (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in significantly greater increases in MAP in the obese dogs (17.8 +/- 4.6 vs. 4.9 +/- 2.6, 37.1 +/- 4.4 vs. 19.6 +/- 2.7, and 72.7 +/- 7.5 vs. 51.5 +/- 7.1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)