bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal age influences the ability of rats to autoresuscitate from hypoxic-induced apnea
Authors: Fewell James E. , Smith Francine G. , Ng Vienna K. Y. , Wong Vanessa H. , Wang Yinghong
Published: December 2017

Failure to autoresuscitate from apnea by gasping has been suggested to have a role in sudden infant death. Little is known, however, about the factors that influence the ability of gasping to sustain life during acute hypoxia in the newborn. The present experiments were carried out on 105 rat pups to investigate the influence of postnatal age on the time to last gasp during a single hypoxic exposure and on the ability to autoresuscitate from primary apnea during repeated hypoxic exposures. On days 1–2, 5–6, 10–11, 15–16, and 19–20 postpartum, each pup was placed into a temperature-controlled chamber regulated to 37 ± 1°C and was exposed either to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N2-3% CO2), and the time to last gasp was determined, or repeated exposure to hypoxia was performed, and the ability to autoresuscitate from primary apnea was determined. Increases in postnatal age decreased the time to last gasp following a single hypoxic exposure and decreased the number of successful autoresuscitations following repeated hypoxic exposures. Thus our data provide evidence that postnatal age influences protective responses that may prevent death during hypoxia as may occur during episodes of prolonged sleep apnea.
Long-term orexigenic effects of AgRP-(83—132) involve mechanisms other than melanocortin receptor blockade
Authors: Hagan Mary M. , Rushing Paul A. , Pritchard Laurel M. , Schwartz Michael W. , Strack Alison M. , Van der Ploeg Lex H. T. , Woods Stephen C. , Seeley Randy J.
Published: December 2017

Overexpression of agouti-related peptide (AgRP), an endogenous melanocortin (MC) 3 and 4 receptor antagonist (MC3/4-R), causes obesity. Exogenous AgRP-(83—132) increases food intake, but its duration and mode of action are unknown. We report herein that doses as low as 10 pmol can have a potent effect on food intake of rats over a 24-h period after intracerebroventricular injection. Additionally, a single third ventricular dose as low as 100 pmol in rats produces a robust increase in food intake that persists for an entire week. AgRP-(83—132) completely blocks the anorectic effect of MTII (MC3/4-R agonist), given simultaneously, consistent with a competitive antagonist action. However, when given 24 h prior to MTII, AgRP-(83—132) is ineffective at reversing the anorectic effects of the agonist. These results support a critical role of MC tone in limiting food intake and indicate that the orexigenic effects of AgRP-(83—132) are initially mediated by competitive antagonism at MC receptors but are sustained by alternate mechanisms.
Naltrexone administered to central nucleus of amygdala or PVN: neural dissociation of diet and energy
Authors: Glass Michael J. , Billington Charles J. , Levine Allen S.
Published: December 2017

There is evidence that opioids may affect food consumption through mechanisms as diverse as reward or energy metabolism. However, these hypotheses are derived from studies employing peripheral or, more rarely, intracerebroventricular administration of drugs. Opioid receptors have a wide distribution in the central nervous system and include a number of regions implicated in food intake such as the hypothalamic paraventricular nucleus (PVN) and the central nucleus of the amygdala (ACe). It is not known whether local opioid receptor blockade in either of these regions will produce similar effects on food intake. To examine this issue, a chronic cannula was aimed at either the PVN or ACe of rats that were fed a choice of a high-fat and high-carbohydrate diet, which allows for the measurement of both preference and total energy consumption. Naltrexone influenced preferred and nonpreferred food consumption, depending on the site of administration. Consumption of both preferred and nonpreferred diets was suppressed after PVN naltrexone administration, whereas only preferred diet intake was reduced after ACe injection of naltrexone. The present evidence indicates that direct stimulation of different brain regions with naltrexone may be associated with diverse effects on diet selection, which may be accounted for by manipulation of specific functional neural circuitry.
Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input
Authors: Degtyarenko A. M. , Kaufman M. P.
Published: December 2017

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 ± 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 ± 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 ± 0.07 mm, a value that was significantly ( P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.
Chemotransduction properties of nodose ganglion cardiac afferent neurons in guinea pigs
Authors: Thompson G. W. , Horackova M. , Armour J. A.
Published: December 2017

To determine the chemotransduction characteristics of ventricular sensory neurites associated with nodose ganglion afferent neurons, various chemicals were applied individually to epicardial sensory neurites associated with individual afferent neurons in anesthetized guinea pigs. The following ion channel-modifying agents were tested: barium chloride, cadmium chloride, calcium chloride, the chelating agent EGTA, nickel chloride, potassium chloride, tetraethylammonium chloride, and veratridine. An acidic solution (pH 6.0) and oxygen-derived free radicals (H2O2) were tested. The following chemicals were also tested: adenosine, α- and β-adrenergic agonists, angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), histamine, nicotine, the nitric oxide donor nitroprusside, substance P, and vasoactive intestinal peptide. A total of 102 cardiac afferent neurons was identified, of which ∼66% were sensitive to mechanical stimuli applied to their epicardial sensory fields. Application of individual ion channel-modifying agents to epicardial sensory fields modified most associated afferent neurons, with barium chloride affecting each neuron studied. Ventricular sensory neurites associated with most identified neurons were also responsive to the other tested chemicals, with hydrogen peroxide, adenosine, angiotensin II, bradykinin, CGRP, clonidine, and nicotine inducing responses from at least 75% of the neurons studied. It is concluded that 1) the ventricular sensory neurites associated with nodose ganglion afferent neurons transduce a much wider variety of chemical stimuli than considered previously, 2) these sensory neurites employ a variety of membrane ion channels in their transduction processes in situ, and 3) adrenergic agents influence on sensory neurites associated with cardiac afferent neurons suggests the presence of a cardiac feedback mechanism involving local catecholamine release by adjacent sympathetic efferent postganglionic nerve terminals.
Limb congestion enhances the synchronization of sympathetic outflow with muscle contraction
Authors: Mostoufi-Moab Sogol , Herr Michael D. , Silber David H. , Gray Kristen S. , Leuenberger Urs A. , Sinoway Lawrence I.
Published: December 2017

In this report, we examined if the synchronization of muscle sympathetic nerve activity (MSNA) with muscle contraction is enhanced by limb congestion. To explore this relationship, we applied signal-averaging techniques to the MSNA signal obtained during short bouts of forearm contraction (2-s contraction/3-s rest cycle) at 40% maximal voluntary contraction for 5 min. We performed this analysis before and after forearm venous congestion; an intervention that augments the autonomic response to sustained static muscle contractions via a local effect on muscle afferents. There was an increased percentage of the MSNA noted during second 2 of the 5-s contraction/rest cycles. The percentage of total MSNA seen during this particular second increased from minute 1 to 5 of contraction and was increased further by limb congestion (control minute 1 = 25.6 ± 2.0%, minute 5 = 32.8 ± 2.2%; limb congestion minute 1 = 29.3 ± 2.1%, minute 5= 37.8 ± 3.9%; exercise main effect <0.005; limb congestion main effect P = 0.054). These changes in the distribution of signal-averaged MSNA were seen despite the fact that the mean number of sympathetic discharges did not increase over baseline. We conclude that synchronization of contraction and MSNA is seen during short repetitive bouts of handgrip. The sensitizing effect of contraction time and limb congestion are apparently due to feedback from muscle afferents within the exercising muscle.
Activation of α2-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects
Authors: Stich Vladimir , De Glisezinski Isabelle , Crampes Francois , Hejnova Jindra , Cottet-Emard Jean-Marie , Galitzky Jean , Lafontan Max , Rivière Daniel , Berlan Michel
Published: December 2017

With the use of the microdialysis method, exercise-induced lipolysis was investigated in subcutaneous adipose tissue (SCAT) in obese subjects and compared with lean ones, and the effect of blockade of α2-adrenergic receptors (ARs) on lipolysis during exercise was explored. Changes in extracellular glycerol concentrations and blood flow were measured in SCAT in a control microdialysis probe at rest and during 60-min exercise bouts (50% of heart rate reserve) and in a probe supplemented with the α2-AR antagonist phentolamine. At rest and during exercise, plasma norepinephrine and epinephrine concentrations were not different in obese compared with lean men. In the basal state, plasma and extracellular glycerol concentrations were higher, whereas blood flow was lower in SCAT of obese subjects. During exercise, the increase of plasma glycerol was higher in obese subjects (115 ± 35 vs. 65 ± 21 μmol/l). Oppositely, the exercise-induced increase in extracellular glycerol concentrations in SCAT was five- to sixfold lower in obese than in lean subjects (50 ± 14 vs. 318 ± 53 μmol/l). The exercise-induced increase in extracellular glycerol concentration was not significantly modified by phentolamine infusion in lean subjects but was strongly enhanced in the obese subjects and reached the concentrations found in lean sujects (297 ± 46 μmol/l). These findings demonstrate that the physiological stimulation of SCAT adipocyte α2-ARs during exercice-induced sympathetic nervous system activation contributes to the blunted lipolysis noted in obese men.
Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice
Authors: Boundy Virginia A. , Cincotta Anthony H.
Published: December 2017

The genetically, seasonally, and diet-induced obese, glucose-intolerant states in rodents, including ob/ ob mice, have each been associated with elevated hypothalamic levels of norepinephrine (NE). With the use of quantitative autoradiography on brain slices of 6-wk-old obese ( ob/ ob) and lean mice, the adrenergic receptor populations in several hypothalamic nuclei were examined. The binding of [125I]iodocyanopindolol to β1- and β2-adrenergic receptors in ob/ ob mice was significantly increased in the paraventricular hypothalamic nucleus (PVN) by 30 and 38%, in the ventromedial hypothalamus (VMH) by 23 and 72%, and in the lateral hypothalamus (LH) by 10 and 15%, respectively, relative to lean controls. The binding of [125I]iodo-4-hydroxyphenyl-ethyl-aminomethyl-tetralone to α1-adrenergic receptors was also significantly increased in the PVN (26%), VMH (67%), and LH (21%) of ob/ ob mice. In contrast, the binding of [125I]paraiodoclonidine to α2-adrenergic receptors in ob/ ob mice was significantly decreased in the VMH (38%) and the dorsomedial hypothalamus (17%) relative to lean controls. This decrease was evident in the α2A- but not the α2BC-receptor subtype. Scatchard analysis confirmed this decreased density of α2-receptors in ob/ ob mice. Together with earlier studies, these changes in hypothalamic adrenergic receptors support a role for increased hypothalamic NE activity in the development of the metabolic syndrome of ob/ obmice.
Impact of NO on ET-1- and AM-induced inotropic responses: potentiation by combined administration
Authors: Kinnunen Pietari , Szokodi István , Nicholls M. Gary , Ruskoaho Heikki
Published: December 2017

We characterize herein the impact of myocardial nitric oxide (NO) synthesis on the inotropic response to two cardioactive peptides, endothelin-1 (ET-1) and adrenomedullin (AM). In the isolated perfused rat heart preparation, intracoronary infusion of AM (0.03 and 1 nmol/l) and ET-1 (0.08 and 1 nmol/l) for 30 min induced a dose-dependent, gradual increase in developed tension, the maximal responses being equal. Inhibition of myocardial NO synthase (NOS) by Nω-nitro-l-arginine methyl ester (l-NAME; 300 μmol/l) enhanced the inotropic response to ET-1 at a concentration of 1 nmol/l; meanwhile, the effect of AM was not augmented significantly. The inotropic response to simultaneous administration of low, equipotent doses of AM (0.03 nmol/l) and ET-1 (0.08 nmol/l) was significantly smaller than that of either peptide alone. This depressed response was more than overcome by concomitant administration of l-NAME. In conclusion, this study reveals that the maximal inotropic response to ET-1 can be augmented by inhibition of myocardial NOS, whereas it has only a minor impact on the effect of AM. The inotropic response to combined administration of low doses of AM and ET-1 is substantially suppressed by endogenous NO, whereas the individual effects of the peptides at these doses are not the subject of secondary modulation by NO.
Identification and regional distribution of the dopamine D1A receptor in the gastrointestinal tract
Authors: Vaughan Carl J. , Aherne Anna M. , Lane Eamon , Power Orla , Carey Robert M. , O'Connell Damian P.
Published: December 2017

Dopamine (DA) is regarded as an important modulator of enteric function. Recent experiments have suggested that newly cloned DA receptor subtypes are widely expressed in peripheral organs, including the gastrointestinal tract. In the present studies, the D1A receptor subtype was identified in rat gut regions through localization of receptor protein by means of light microscopic immunohistochemistry and Western blot analysis and receptor mRNA by RT-PCR and in situ amplification and hybridization (3SR in situ). D1A receptor immunoreactivity was shown to have a diverse distribution in the gastrointestinal tract, being present in the gastroesophageal junction, stomach, pylorus, small intestine, and colon. The receptor has a transmural distribution present in both epithelial and muscle layers as well as in blood vessels and lamina propria cells of different gastrointestinal regions. Western blot analysis demonstrated a single 50-kDa band for esophagus, stomach, duodenum, jejunum, and colon. The in situ hybridization signal was localized to the same sites revealed by D1A receptor immunoreactivity. RT-PCR revealed an appropriate sized signal in similar regions. This study is the first to identify expression of the central D1A receptor throughout the normal mammalian gastrointestinal tract.
Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction
Authors: Hopper Richard A. , Forrest Christopher R. , Xu Huai , Zhong Anguo , He Wei , Rutka James , Neligan Peter , Pang Cho Y.
Published: December 2017

Protein kinase C (PKC) inhibitors, chelerythrine (Chel, 0.6 mg) and polymyxin B (Poly B, 1.0 mg), and PKC activators, phorbol 12-myristate 13-acetate (PMA, 0.05 mg) and 1-oleoyl-2-acetyl glycerol (OAG, 0.1 mg), were used as probes to investigate the role of PKC in mediation of ischemic preconditioning (IPC) of noncontracting pig latissimus dorsi (LD) muscles against infarction in vivo. These drugs were delivered to each LD muscle flap (8 × 12 cm) by 10 min of local intra-arterial infusion. It was observed that LD muscle flaps sustained 43 ± 5% infarction when subjected to 4 h of global ischemia and 24 h of reperfusion. IPC with three cycles of 10 min ischemia-reperfusion reduced muscle infarction to 25 ± 3% ( P < 0.05). This anti-infarction effect of IPC was blocked by Chel (42 ± 7%) and Poly B (37 ± 2%) and mimicked by PMA (19 ± 10%) and OAG (14 ± 5%) treatments ( P < 0.05), given 10 min before 4 h of ischemia. In addition, the ATP-sensitive K+ (KATP) channel antagonist sodium 5-hydroxydecanoate attenuated ( P < 0.05) the anti-infarction effect of IPC (37 ± 2%), PMA (44 ± 17%), and OAG (46 ± 9%). IPC, OAG, and Chel treatment alone did not affect mean arterial blood pressure or muscle blood flow assessed by 15-μm radioactive microspheres. Western blot analysis of muscle biopsies obtained before (baseline) and after IPC demonstrated seven cytosol-associated isoforms, with nPKCɛ alone demonstrating progressive cytosol-to-membrane translocation within 10 min after the final ischemia period of IPC. Using differential fractionation, it was observed that nPKCɛ translocated to a membrane compartment other than the sarcolemma and/or sarcoplasmic reticulum. Furthermore, IPC and preischemic OAG but not postischemic OAG treatment reduced ( P < 0.05) muscle myeloperoxidase activity compared with time-matched ischemic controls during 16 h of reperfusion after 4 h of ischemia. Taken together, these observations indicate that PKC plays a central role in the anti-infarction effect of IPC in pig LD muscles, most likely through a PKC-KATPchannel-linked signal-transduction pathway.
Effects of posture on gastric emptying and satiety ratings after a nutritive liquid and solid meal
Authors: Spiegel Theresa A. , Fried Harry , Hubert Christine D. , Peikin Steven R. , Siegel Jeffry A. , Zeiger Louis S.
Published: December 2017

To study the effects of posture and meal structure on gastric emptying and satiety, nine women ingested tomato soup and then immediately or 20 min later an egg sandwich, when seated and when supine. The lag time was not different, but the half-emptying time of the sandwich was 32% longer ( P < 0.01) and the emptying rate after the lag phase was 39% slower ( P < 0.01) when the subjects were supine than when they were seated. The half-emptying time of the soup was 50% longer ( P < 0.01) when the subjects were supine and ingested the soup immediately before the sandwich than in the other three conditions. Postprandial hunger ratings recovered more slowly ( P < 0.01) when the subjects ingested the soup 20 min before the sandwich than when they ingested the soup immediately before the sandwich. These results suggest that posture did not affect the intragastric distribution of the sandwich but affected propulsion of the meal into the intestine and that postprandial satiety was enhanced by the cumulative effect over time of a 20-min “head start” in stimulation of intestinal receptors by emptying of the soup.
Taurine secretion in primary monolayer cultures of flounder renal epithelium: stimulation by low osmolality
Authors: Benyajati Siribhinya , Renfro J. Larry
Published: December 2017

Transepithelial taurine fluxes determined in short-circuited monolayer cultures of flounder renal proximal cells in Ussing chambers revealed net taurine secretion. Both unidirectional secretory and reabsorptive taurine fluxes exhibited saturation kinetics contributed by two distinct saturable transepithelial taurine transport systems operating at different taurine concentration ranges. The taurine secretory system operating below 0.5 mM had lower affinity but higher capacity than the reabsorptive system, whereas the one operating at high concentrations (0.5–3.0 mM) had higher affinity but the same capacity as the corresponding reabsorptive system. Exposure (2 h) of the cultures to hyposmotic medium in the presence of taurine increased taurine secretory flux twofold with no effect on the reabsorptive flux. The hyposmolality-induced increase in taurine secretion was associated with a decreased peritubular taurine efflux and a concurrent increased luminal taurine efflux; the latter occurred via a pathway that was not affected by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid but inhibited by probenecid. The culture response in hyposmotic medium mimics the in vivo response of the intact marine fish kidney to dilution.
Systolic pressure predicts plasma vasopressin responses to hemorrhage and vena caval constriction in dogs
Authors: Thrasher Terry N. , Keil Lanny C.
Published: December 2017

We have proposed that the reflex increase in arginine vasopressin (AVP) secretion in response to hypovolemia is due to arterial baroreceptor unloading. If arterial pressure is the key to the mechanism, the slope relating plasma AVP to arterial pressure should be the same in response to hemorrhage, a model of true hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC), a model of central hypovolemia. We tested this hypothesis in conscious, chronically instrumented dogs ( n = 8). The mean coefficient of determination ( r 2) values obtained from the individual regressions of log AVP onto systolic pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were 0.953 ± 0.009 and 0.845 ± 0.047, respectively. Paired comparisons indicated a significant difference between the means ( P < 0.05), hence, SP was used in subsequent analyses. The mean slopes relating the log of plasma AVP to SP in response to hemorrhage and IVCC were −0.034 ± 0.003 and −0.032 ± 0.002, respectively, and the means were not significantly different ( P = 0.7). The slopes were not altered when the experiments were repeated during acute blockade of cardiac receptors by intrapericardial procaine. Finally, sinoaortic denervation ( n = 4) markedly reduced the slope in both the hemorrhage and IVCC treatments. We conclude that baroreceptors monitoring arterial pressure provide the principal reflex control of AVP secretion in response to hypovolemia.
Macrophage migration inhibitory factor antagonizes hydrocortisone-induced increases in cytosolic IκBα
Authors: Daun Jane M. , Cannon Joseph G.
Published: December 2017

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine secreted by several cell types, including mononuclear and pituitary cells. It has also been shown to counteract cortisol-induced inhibition of inflammatory cytokine secretion. The purpose of this study was to determine whether MIF antagonized the effect of hydrocortisone on the NF-κB/IκB signal transduction pathway in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells. Physiological doses of hydrocortisone (50–200 ng/ml) diminished both the LPS-stimulated decrease in cytosolic IκBα levels and the subsequent increase in nuclear NF-κB DNA binding. In the presence of both LPS and hydrocortisone, 1 ng/ml of MIF antagonized the effects of hydrocortisone, resulting in decreased cytosolic IκBα levels ( P < 0.05) and increased nuclear NF-κB DNA binding ( P < 0.05). In the absence of hydrocortisone, MIF had no effect on LPS-induced decreases in IκBα. In the absence of LPS, MIF inhibited hydrocortisone-induced increases in IκBα ( P = 0.03). Thus the mechanism by which MIF antagonizes the effect of hydrocortisone on the NF-kB/IκB signal transduction pathway is through inhibiting the ability of hydrocortisone to increase cytosolic IκBα.
Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat
Authors: Rajab P. , Fox J. , Riaz S. , Tomlinson D. , Ball D. , Greenhaff P. L.
Published: December 2017

Prolonged treatment with the β2-adrenoceptor agonist clenbuterol (1–2 mg · kg body mass−1· day−1) is known to induce the hypertrophy of fast-contracting fibers and the conversion of slow- to fast-contracting fibers. We investigated the effects of administering a lower dose of clenbuterol (250 μg · kg body mass−1· day−1) on skeletal muscle myosin heavy chain (MyHC) protein isoform content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar rats were administered clenbuterol ( n = 8) or saline ( n = 6) subcutaneously for 8 wk, after which the extensor digitorum longus (EDL) and soleus muscles were removed. We demonstrated an increase of type IIa MyHC protein content in the soleus from ∼0.5% in controls to ∼18% after clenbuterol treatment ( P < 0.05), which was accompanied by an increase in the total adenine nucleotide pool (TAN; ∼19%, P < 0.05) and energy charge [E-C = (ATP + 0.5 ADP)/(ATP + ADP + AMP); ∼4%; P < 0.05]. In the EDL, a reduction in the content of the less prevalent type I MyHC protein from ∼3% in controls to 0% after clenbuterol treatment ( P < 0.05) occurred without any alterations in TAN and E-C. These findings demonstrate that the phenotypic changes previously observed in slow muscle after clenbuterol administration at 1–2 mg · kg body mass−1· day−1are also observed at a substantially lower dose and are paralleled by concomitant changes in cellular energy metabolism.
Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats
Authors: Vallès Astrid , Martí Octavi , García Arantxa , Armario Antonio
Published: December 2017

A single exposure to severe stressors has been shown to cause anorexia in the next 24 h, but the duration of such alterations is not known. Male Sprague-Dawley rats were subjected to different stressors, and food intake was measured for several days after stress. In experiment 1, 2 h of immobilization (Imo) and lipopolysaccharide (LPS) administration (1,000 μg/kg) caused a marked anorexia in the 24 h after stress, which persisted on poststress day 3. In experiment 2, changes in food intake after LPS and Imo were followed until total recovery. As in experiment 1, LPS caused initially a greater degree of anorexia than Imo, but normal food intake recovered much faster (poststress day 3 vs. poststress day 9). Changing the period of exposure to Imo between 20 min and 6 h ( experiment 3) only slightly modified the pattern of response to the stressor. When different doses of LPS (50, 250, and 1,000 μg/kg) were tested in experiment 4, a dose-dependent effect on food intake was observed, the greatest doses causing the most marked and lasting effect. The present results showed stressor-specific lasting changes in food intake caused by a single exposure to some stressors, the effect of a severe psychological stressor such as Imo being more lasting than that of LPS, despite a lower initial anorexia. A severe psychological stressor and a physical stressor such as LPS appear to change food intake in different ways.
Weight cycling-induced alteration in fatty acid metabolism
Authors: Sea Man-Mei , Fong Wing Ping , Huang Yu , Chen Zhen-Yu
Published: December 2017

Epidemiological studies have suggested that repeated weight cycling over time may increase the risk of coronary heart disease. The mechanism involved remains poorly understood, but the change in lipid metabolism during weight cycling has been offered as a possible explanation. The present study investigated the effect of weight cycling on the size and fatty acid composition of rat fat pads as well as serum cholesterol, triglyceride, glucose, insulin, and glucagon in rats. Two consecutive weight cycles were induced by 40% energy restriction followed by ad libitum refeeding of either a moderate-fat (MF; 22% energy) or a high-fat (HF; 45% energy) diet. The lipogenic enzymes, including fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, pyruvate kinase, and lipoprotein lipase in the weight-cycled (WC) rats fed only the HF diet, yielded an overshoot of activities at the end of two weight cycles. These changes were accompanied by an 80% increase in the size of the adipocyte and a 40–50% increase in the size of perirenal and epididymal fat tissues in HF-WC rats. Regardless of whether the rats were fed the HF or MF diet, all WC rats showed a gradual reduction in linoleic and α-linolenic acid and an increase in palmitic, palmitoleic, and stearic acid in total body lipid. It is concluded that weight cycling in rats may promote body fatness if an HF diet is consumed and can significantly alter whole body fatty acid balance irrespective of whether they consumed an MF or HF diet. Most importantly, the weight cycling led to an overshoot or fluctuation of serum cholesterol, triglyceride, glucose, insulin, and glucagon. If weight cycling is associated with an increased risk of cardiovascular disease, then, part of the mechanism may involve the changes in these risk factors.
Pavlov and integrative physiology
Authors: Smith Gerard P.
Published: December 2017

Ivan Petrovich Pavlov was the first physiologist to win the Nobel Prize. The Prize was given in 1904 for his research on the neural control of salivary, gastric, and pancreatic secretion. A major reason for the success and novelty of his research was the use of unanesthetized dogs surgically prepared with chronic fistulas or gastric pouches that permitted repeated experiments in the same animal for months. Pavlov invented this chronic method because of the limitations he perceived in the use of acute anesthetized animals for investigating physiological systems. By introducing the chronic method and by showing its experimental advantages, Pavlov founded modern integrative physiology. This paper reviews Pavlov's journey from his birthplace in a provincial village in Russia to Stockholm to receive the Prize. It begins with childhood influences, describes his training and mentors, summarizes the major points of his research by reviewing his book Lectures on the Work of the Digestive Glands, and discusses his views on the relationship between physiology and medicine.
Water stimulation of the posterior oral cavity induces inhibition of gastric motility
Authors: Kobashi Motoi , Mizutani Masatoshi , Matsuo Ryuji
Published: December 2017

The response of gastric motility to the administration of water and saline in the larynx and epiglottis was investigated in urethan-chloralose anesthetized rats. Administration of water inhibited motility of the distal stomach, but 0.15 M NaCl did not induce the inhibitory response. Bilateral sectioning of the superior laryngeal nerve (SLN) abolished the inhibitory response induced by water. Bilateral cervical vagotomies abolished the inhibitory responses, although spinal transection did not affect the inhibitory response. These inhibitory responses have been observed in immobilized animals. The degree of inhibition by water and hypotonic saline was negatively correlated with the sodium concentration. In contrast, the degree of inhibition to hypertonic saline was positively correlated with the sodium concentration. The proximal stomach also showed a reduction in intragastric pressure in response to the administration of water. These findings suggest that water-responsive afferent neurons in the SLN suppress gastric motility via the vagal efferent nerve.
IL-1 is a mediator of increases in slow-wave sleep induced by CRH receptor blockade
Authors: Chang Fang-Chia , Opp Mark R.
Published: December 2017

We hypothesize that corticotropin-releasing hormone (CRH), a regulator of the hypothalamic-pituitary-adrenal (HPA) axis, is involved in sleep-wake regulation on the basis of observations that the CRH receptor antagonist astressin, after a delay of several hours, reduces waking and increases slow-wave sleep (SWS) in rats. This delay suggests a cascade of events that begins with the HPA axis and culminates with actions on sleep regulatory systems in the central nervous system. One candidate mediator in the brain for these actions is interleukin (IL)-1. IL-1 promotes sleep, and glucocorticoids inhibit IL-1 synthesis. In this study, central administration of 12.5 μg astressin into rats before dark onset reduced corticosterone 4 h after injection and increased mRNA expression for IL-1α and IL-1β but not for IL-6 or tumor necrosis factor-α in the brain 6 h after injection. To determine directly whether IL-1 is involved in astressin-induced alterations in sleep-wake behavior, we then pretreated rats with 20 μg anti-IL-1β antibodies before injecting astressin. The increase in SWS and the reduction in waking that occur after astressin are abolished when animals are pretreated with anti-IL-1β. These data indicate that IL-1 is a mediator of astressin-induced alterations in sleep-wake behavior.
Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women
Authors: Brooks-Asplund E. M. , Cannon J. G. , Kenney W. L.
Published: December 2017

Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body temperature (Tb) at a lower level than women not receiving hormone replacement therapy (untreated) and women using estrogen plus progesterone therapy (E + P), but it is not clear if reproductive hormones alter Tbby directly acting on central thermoregulatory centers or indirectly via a secondary mediator(s). The purpose of the present investigation was to examine the possible involvement of pyrogenic cytokines and cyclooxygenase (COX) products (e.g., prostaglandins) in the regulation of Tbin three groups of postmenopausal women (8 ERT, 7 E + P, and 8 untreated). We measured ex vivo secretion of cytokine agonists [tumor necrosis factor (TNF)-α and interleukin (IL)-1β and -6] and modifiers (IL-2 soluble receptor, IL-1 receptor antagonist, soluble TNF receptor type I, soluble TNF receptor type II, soluble IL-6 receptor, and soluble glycoprotein 130) from peripheral blood mononuclear cells and thermoregulatory responses at rest and during 1 h of passive whole body heating in the postmenopausal women before and after 3 days of placebo or aspirin (50 mg · day−1· kg−1). With and without aspirin, the ERT group had a lower baseline rectal temperature (Tre; 0.44°C, P < 0.004) and a reduced Tbthreshold for cutaneous vasodilation (0.29°C and 0.38°C, P < 0.01) compared with the untreated and E + P groups, respectively. In the placebo condition, waking morning oral temperature (Tor) correlated with ex vivo secretion of the proteins associated with IL-6 bioactivity. Aspirin caused significant reductions in waking Torin the E + P group and in baseline Trein the untreated group. However, the difference in thermoregulation brought about by steroid hormone treatment could not be explained by these relatively modest apparent influences by cytokines and COX products. Therefore, the altered thermoregulation induced by reproductive steroid therapy appears to occur via a mechanism distinct from a classic infection-induced fever.
Regulation of uterine and umbilical amino acid uptakes by maternal amino acid concentrations
Authors: Thureen Patti J. , Anderson Susan M. , Hay William W.
Published: December 2017

We tested the hypothesis that decreased fetal amino acid (AA) supply, produced by maternal hypoaminoacidemia (low AA) during hyperglycemia (HG), is reversible with maternal AA infusion and regulates fetal insulin concentration ([I]). We measured net uterine and umbilical AA uptakes during maternal HG/low AA concentration ([AA]) and after maternal intravenous infusion of a mixed AA solution. After 5 days HG, all maternal [AA] except glycine were decreased >50%, particularly essential [AA] ( P < 0.00005). Most fetal [AA] also were decreased, especially branched-chain AA ( P < 0.001). Maternal AA infusion increased net uterine uptakes of Val, Leu, Ile, Met, and Ser and net umbilical uptakes of Val, Leu, Ile, Met, Phe, and Arg but did not change net uteroplacental uptake of any AA. Fetal [I] increased 55 ± 14%, P < 0.001, with correction of fetal [AA], despite the lack of change in fetal glucose concentration. Thus generalized maternal hypoaminoacidemia decreases uterine and umbilical uptakes of primarily the essential AA and decreases fetal branched-chain [AA]. These changes are reversed with correction of maternal [AA], which also increases fetal [I].
Cerebral artery sarcoplasmic reticulum Ca2+stores and contractility: changes with development
Authors: Long Wen , Zhang Lubo , Longo Lawrence D.
Published: December 2017

To test the hypothesis that sarcoplasmic reticulum (SR) Ca2+stores play a key role in norepinephrine (NE)-induced contraction of fetal and adult cerebral arteries and that Ca2+stores change with development, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal (∼140 days) and nonpregnant adult sheep, we measured NE-induced contraction and intracellular Ca2+concentration ([Ca2+]i) in the absence and presence of different blockers. In adult MCA, after thapsigargin (10−6M), the NE-induced responses of tension and [Ca2+]iwere 37 ± 5 and 47 ± 7%, respectively, of control values ( P < 0.01 for each). In the fetal artery, in contrast, this treatment resulted in no significant changes from control. When this was repeated in the absence of extracellular Ca2+, adult MCA increases in tension and [Ca2+]iwere 32 ± 5 and 13 ± 3%, respectively, of control. Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN, 3 × 10−6to 10−5M) resulted in increases in tension and [Ca2+]iin both fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA, the increased tension and [Ca2+]iresponses to RYN were essentially eliminated in the presence of zero extracellular Ca2+. These findings provide evidence that in fetal MCA, in contrast to those in the adult, SR Ca2+stores are of less importance in NE-induced contraction, with such contraction being almost wholly dependent on Ca2+flux via plasma membrane L-type Ca2+channels. In addition, they suggest that in both adult and fetal MCA, the RYN receptor is coupled to the plasma membrane Ca2+-activated K+channel and/or L-type Ca2+channel.
NF-κB mediates the protein loss induced by TNF-α in differentiated skeletal muscle myotubes
Authors: Li Yi-Ping , Reid Micheal B.
Published: December 2017

Nuclear factor-κB (NF-κB) regulates the transcription of a variety of genes involved in immune responses, cell growth, and cell death. However, the role of NF-κB in muscle biology is poorly understood. We recently reported that tumor necrosis factor-α (TNF-α) rapidly activates NF-κB in differentiated skeletal muscle myotubes and that TNF-α acts directly on the muscle cell to induce protein degradation. In the present study, we ask whether NF-κB mediates the protein loss induced by TNF-α. We addressed this problem by creating stable, transdominant negative muscle cell lines. C2C12 myoblasts were transfected with viral plasmid constructs that induce overexpression of mutant I-κBα proteins that are insensitive to degradation via the ubiquitin-proteasome pathway. These mutant proteins selectively inhibit NF-κB activation. We found that differentiated myotubes transfected with the empty viral vector (controls) underwent a drop in total protein content and in fast-type myosin heavy-chain content during 72 h of exposure to TNF-α. In contrast, total protein and fast-type myosin heavy-chain levels were unaltered by TNF-α in the transdominant negative cell lines. TNF-α did not induce apoptosis in any cell line, as assessed by DNA ladder and annexin V assays. These data indicate that NF-κB is an essential mediator of TNF-α-induced catabolism in differentiated muscle cells.
Blunted arterial baroreflex causes “pathological” heart rate turbulence
Authors: Mrowka Ralf , Persson Pontus B. , Theres Heinz , Patzak Andreas
Published: December 2017

Sudden cardiac death is the leading cause of cardiovascular mortality in developed countries. Recently, two post-myocardial-infarction risk predictors were introduced that are superior to all other presently available indicators: turbulence onset (TO) and turbulence slope (TS). These parameters characterize the behavior of instantaneous heart rate after a ventricular premature beat, i.e., they describe the reestablishing of heart rate control after an acute perturbation. We propose that the dysfunction of an important cardiovascular control mechanism, the arterial baroreflex, is the mechanism behind these new potent markers. The hypothesis is tested by means of a physiological model involving the excitation generation in the heart, the hemodynamic situation in the aorta, and baroreceptor feedback mechanisms. The data show that a blunted baroreceptor response of the heart resembles patterns of heart rate turbulence that correspond to pathological values of TO and TS. The results of the model suggest that the recently established risk parameters TO and TS characterize baroreflex function, a known risk stratifier in patients.
Testicular development in Siberian hamsters depends on frequency and pattern of melatonin signals
Authors: Flynn Alison K. , Freeman David A. , Zucker Irving , Prendergast Brian J.
Published: December 2017

We investigated the impact of frequency and pattern of melatonin signals on reproductive development in Siberian hamsters. Juvenile males gestated in short day lengths and housed in constant illumination to suppress melatonin secretion were infused with melatonin for 5 h either once or twice per day for 20 days. Melatonin infusions at either frequency produced equivalent increases in testes and body weights that exceeded those of animals infused with saline but were indistinguishable from those of hamsters transferred to long day lengths. The reproductive system appears to be maximally stimulated by a single short melatonin signal each day. Other animals kept from birth in a short photoperiod were treated 6 h after onset of darkness with the β-adrenergic receptor antagonistdl-propranolol to shorten melatonin secretion on the night of injection but not on subsequent nights. This permitted interpolation of short nightly melatonin signals of 4–5 h duration against a background of long melatonin signals of 10–12 h duration on other nights. Treatment regimes that maintained a 1:1 ratio of short to long melatonin signals for 8 wk stimulated reproductive development; a 1:2 signal ratio, in each of three different patterns, was uniformly ineffective. The number of successive short melatonin signals had little influence on the interval across which successive melatonin signals were summated to influence photoperiodic traits. The neuroendocrine axis appears more responsive to short melatonin signal frequency than pattern for development of the summer phenotype.
Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output
Authors: Mutoh T. , Bonham A. C. , Joad J. P.
Published: December 2017

Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by a central nervous system reflex consisting of apnea, cough, bronchoconstriction, hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the first central synapses in the nucleus of the solitary tract (NTS), but substance P, also released in the NTS, may modulate the transmission. To test the hypothesis that substance P in the NTS augments bronchopulmonary C fiber input and hence reflex output, we stimulated the C fibers with left atrial capsaicin (LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs before and after substance P injections (200 μM, 25 nl) in the NTS. Substance P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold and increases in TP and decreases in ABP and HR by threefold, effects prevented by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1 receptors can exaggerate bronchopulmonary C fiber reflex output. Because substance P synthesis in vagal airway C fibers may be enhanced in pathological conditions such as allergic asthma, the findings may help explain some of the associated respiratory symptoms including cough and bronchoconstriction.
Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality versus hyposmolality
Authors: Glasgow Eric , Murase Takashi , Zhang Bingjun , Verbalis Joseph G. , Gainer Harold
Published: December 2017

Magnocellular neurons of the hypothalamo-neurohypophysial system play a fundamental role in the maintenance of body homeostasis by secreting vasopressin and oxytocin in response to systemic osmotic perturbations. During chronic hyperosmolality, vasopressin and oxytocin mRNA levels increase twofold, whereas, during chronic hyposmolality, these mRNA levels decrease to 10–20% of that of normoosmolar control animals. To determine what other genes respond to these osmotic perturbations, we have analyzed gene expression during chronic hyper- versus hyponatremia. Thirty-seven cDNA clones were isolated by differentially screening cDNA libraries that were generated from supraoptic nucleus tissue punches from hyper- or hyponatremic rats. Further analysis of 12 of these cDNAs by in situ hybridization histochemistry confirmed that they are osmotically regulated. These cDNAs represent a variety of functional classes and include cytochrome oxidase, tubulin, Na+-K+-ATPase, spectrin, PEP-19, calmodulin, GTPase, DnaJ-like, clathrin-associated, synaptic glycoprotein, regulator of GTPase stimulation, and gene for oligodendrocyte lineage-myelin basic proteins. This analysis therefore suggests that adaptation to chronic osmotic stress results in global changes in gene expression in the magnocellular neurons of the supraoptic nucleus.
Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis
Authors: Leyssac Paul P. , Holstein-Rathlou Niels-Henrik , Skøtt Ole
Published: December 2017

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (EDNaCl) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, EDNaClfell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), EDNaClincreased by 3.6 mM, ( P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 μmol NaCl in a smaller volume caused EDNaClto increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron EDNaCland PRC. We conclude that EDNadecreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.