bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure
Authors: Iwasaki Ken-Ichi , Zhang Rong , Zuckerman Julie H. , Pawelczyk James A. , Levine Benjamin D.
Published: December 2017

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this “deconditioning response” could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of −6° head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15–0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate × stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05–0.15 Hz) power of systolic BP variability decreased after bed rest (−22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.
Mechanisms of salt-sensitive hypertension: role of inducible nitric oxide synthase
Authors: Tan Dunyong Y. , Meng Shumei , Cason Garrick W. , Manning R. Davis
Published: December 2017

The goal of this study was to determine the role of inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, renal excretory, and hormonal changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during changes in Na intake. Thirty-two R and S rats, equipped with indwelling arterial and venous catheters, were subjected to low (0.87 mmol/day) or high (20.6 mmol/day) Na intake, and selective iNOS inhibition was achieved with intravenous aminoguanidine (AG, 12.3 mg · kg−1· h−1). After 5 days of AG, mean arterial pressure increased to 121 ± 3% control in the R-high Na AG rats compared with 98 ± 1% control ( P < 0.05) in the R-high Na alone rats, and S-high Na rats increased their arterial pressure to 123 ± 3% control compared with 110 ± 2% control ( P < 0.05) in S-high Na alone rats. AG caused no significant changes in renal hemodynamics, urinary Na or H2O excretion, plasma renin activity, or cerebellar Ca-dependent NOS activity. The data suggest that nitric oxide produced by iNOS normally helps to prevent salt-sensitive hypertension in the Dahl R rat and decreases salt sensitivity in the Dahl S rat.
Inferences on force transmission from muscle fiber architecture of the canine diaphragm
Authors: Boriek Aladin M. , Zhu Deshen , Zeller Mark , Rodarte Joseph R.
Published: December 2017

Functional properties of the diaphragm are mediated by muscle structure. Modeling of force transmission necessitates a precise knowledge of muscle fiber architecture. Because the diaphragm experiences loads both along and transverse to the long axes of its muscle fibers in vivo, the mechanism of force transmission may be more complex than in other skeletal muscles that are loaded uniaxially along the muscle fibers. Using a combination of fiber microdissections and histological and morphological methods, we determined regional muscle fiber architecture and measured the shape of the cell membrane of single fibers isolated from diaphragm muscles from 11 mongrel dogs. We found that muscle fibers were either spanning fibers (SPF), running uninterrupted between central tendon (CT) and chest wall (CW), or were non-spanning fibers (NSF) that ended within the muscle fascicle. NSF accounted for the majority of fibers in the midcostal, dorsal costal, and lateral crural regions but were only 25–41% of fibers in the sternal region. In the midcostal and dorsal costal regions, only ∼1% of the NSF terminated within the fascicle at both ends; the lateral crural region contained no such fibers. We measured fiber length, tapered length, fiber diameters along fiber length, and the taper angle for 271 fibers. The lateral crural region had the longest mean length of SPF, which is equivalent to the mean muscle length, followed by the costal and sternal regions. For the midcostal and crural regions, the percentage of tapered length of NSF was 45.9 ± 5.3 and 40.6 ± 7.5, respectively. The taper angle was ∼0.15° for both, and, therefore, the shear component of force was ∼380 times greater than the tensile component. When the diaphragm is submaximally activated, as during normal breathing and maximal inspiratory efforts, muscle forces could be transmitted to the cell membrane and to the extracellular intramuscular connective tissue by shear linkage, presumably via structural transmembrane proteins.
Active urea transport and an unusual basolateral membrane composition in the gills of a marine elasmobranch
Authors: Fines Glenn A. , Ballantyne James S. , Wright Patricia A.
Published: December 2017

In elasmobranch fishes, urea occurs at high concentrations (350–600 mM) in the body fluids and tissues, where it plays an important role in osmoregulation. Retention of urea by the gill against this huge blood-to-water diffusion gradient requires specialized adaptations to the epithelial cell membranes. Experiments were performed to determine the mechanisms and structural features that facilitate urea retention by the gill of the spiny dogfish Squalus acanthias. Analysis of urea uptake by gill basolateral membrane vesicles revealed the presence of a phloretin-sensitive (half inhibition 0.09 mM), sodium-coupled, secondary active urea transporter (Michaelis constant = 10.1 mM, maximal velocity = 0.34 μmol · h−1· mg protein−1). We propose that this system actively transports urea out of the gill epithelial cells back into the blood against the urea concentration gradient. Lipid analyses of the basolateral membrane revealed high levels of cholesterol contributing to the highest reported cholesterol-to-phospholipid molar ratio (3.68). This unique combination of active urea transport and modification of the phospholipid bilayer membrane is responsible for decreasing the gill permeability to urea and facilitating urea retention by the gill of Squalus acanthias.
Shape and tension distribution of the passive rat diaphragm
Authors: Boriek Aladin M. , Rodarte Joseph R. , Reid Michael B.
Published: December 2017

We developed an in vitro preparation to investigate shape and stress distribution in the intact rat diaphragm. Our hypothesis was that the diaphragm is anisotropic with smaller compliance in transverse fiber direction than along fibers, and therefore shape change may be small. After the animals were killed (8 rats), the entire diaphragm was excised and fixed into a mold at the insertions. Oxygenated Krebs-Ringer solution was circulated under the diaphragm and perfused over its surface. A total of 20–23 small markers were sutured on the diaphragm surface. At transdiaphragmatic pressure (Pdi) of 3–15 cmH2O, curvature was smaller in transverse direction than along fibers. Using finite element analysis we computed membrane tension. At Pdi of 15 cmH2O, tension in central tendon was larger than muscle. In costal region maximum principal tension (ς1) is essentially along the fibers and ranged from 6–10 g/cm. Minimum principal tension (ς2) was 0.3–4 g/cm. In central tendon, ς1 was 10–15 g/cm, compared with 4–10 g/cm for ς2. The diaphragm was considerably stiffer in transverse fiber direction than along the fibers.
Activity-induced recovery of excitability in K+-depressed rat soleus muscle
Authors: Overgaard Kristian , Nielsen Ole Bækgaard
Published: December 2017

Increased extracellular K+concentration ([K+]o) can reduce excitability and force in skeletal muscle. Here we examine the effects of muscle activation on compound muscle action potentials (M waves), resting membrane potential, and contractility in isolated rat soleus muscles. In muscles incubated for 60 min at 10 mM K+, tetanic force and M wave area decreased to 23 and 24%, respectively, of the control value. Subsequently, short (1.5 s) tetanic stimulations given at 1-min intervals induced recovery of force and M wave area to 81 and 90% of control levels, respectively, within 15 min ( P < 0.001). The recovery of force and M wave was associated with a partial repolarization of the muscle fibers. Experiments with tubocurarine suggest that the force recovery was related to activation of muscle Na+-K+ pumps caused by the release of some compound from sensory nerves in response to muscle activity. In conclusion, activity produces marked recovery of excitability in K+-depressed muscle, and this may protect muscles against fatigue caused by increased [K+]o during exercise.
Free fatty acids/triglycerides increase ocular and subcutaneous blood flow
Authors: Polak Kaija , Schmetterer Leopold , Luksch Alexandra , Gruber Susanna , Polska Elzbieta , Peternell Vanessa , Bayerle-Eder Michaela , Wolzt Michael , Krebs Michael , Roden Michael
Published: December 2017

Elevated plasma free fatty acids (FFA) induce skeletal muscle insulin resistance and impair endothelial function. The aim of this study was to characterize the acute hemodynamic effects of FFA in the eye and skin. A triglyceride (Intralipid 20%, 1.5 ml/min)/heparin (bolus: 200 IU; constant infusion rate: 0.2 IU · kg−1· min−1) emulsion or placebo was administered to 10 healthy subjects. Measurements of pulsatile choroidal blood flow with laser interferometry, retinal blood flow with the blue field entoptic technique, peak systolic and end diastolic blood velocity (PSV, EDV) in the ophthalmic artery with Doppler sonography, and subcutaneous blood flow with laser Doppler flowmetry were performed during an euglycemic somatostatin-insulin clamp over 405 min. Plasma FFA/triglyceride elevation induced a rise in pulsatile choroidal blood flow by 25 ± 3% ( P < 0.001) and in retinal blood flow by 60 ± 23% ( P= 0.0125). PSV increased by 27 ± 8% ( P = 0.001), whereas EDV was not affected. Skin blood flow increased by 149 ± 38% ( P = 0.001). Mean blood pressure and pulse rate remained unchanged, whereas pulse pressure amplitude increased by 17 ± 5% ( P = 0.019). Infusion of heparin alone had no hemodynamic effect in the eye or skin. In conclusion, FFA/triglyceride elevation increases subcutaneous and ocular blood flow with a more pronounced effect in the retina than in the choroid, which may play a role for early changes of ocular perfusion in the insulin resistance syndrome.
Effect of heat stress on LPS-induced febrile response ind-galactosamine-sensitized rats
Authors: Dokladny Karol , Kozak Anna , Wachulec Maciej , Wallen Erik S. , Menache Margaret G. , Kozak Wieslaw , Kluger Matthew J. , Moseley Pope L.
Published: December 2017

We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-α) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858–R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat.d-galactosamine (d-gal) was used to selectively inhibit liver protein synthesis. d-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 μg/kg ip) was injected 24 h post-heat exposure. Treatment with d-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with d-gal and subsequently with LPS demonstrated a profound fall in core temperature 10–18 h post-LPS. A significant increase of serum TNF-α accompanied this effect of d-gal on fever. Heat-conditioned animals receiving d-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS.
Expression of carbonic anhydrase IV in mouse placenta
Authors: Rosen Orna , Suarez Carlos , Schuster Victor L. , Brion Luc P.
Published: December 2017

Carbonic anhydrase (CA) facilitates acid-base transport in several tissues. Acidosis upregulates membrane-bound SDS-resistant hydratase activity in various tissues and CA IV mRNA in rabbit kidney. This study was designed to assess whether the expression of membrane-bound CA IV isozyme in mouse placenta is regulated developmentally and by maternal ammonium chloride loading at the end of pregnancy. For this purpose we used Northern blot analysis, Western blots of microsomal membranes, and immunocytochemistry. The expression of CA IV mRNA on Northern blots tripled from day 11 to day 15 and then remained stable until the end of pregnancy. Expression of CA IV immunoreactive protein on Western blot tripled from day 11 to day 15 and decreased almost to baseline by day 19. Strong staining for CA IV was detected by immunocytochemistry in labyrinthine trophoblast, in the endodermal layer of the yolk sac (both intra- and extraplacental) and in the uterine epithelium. Weak staining was observed in most fetal endothelial cells at 11 days but not later in gestation. Maternal acidosis did not upregulate the expression of CA IV mRNA or CA IV immunoreactive protein. Thus CA IV expression in mouse placenta is developmentally regulated. Maternal acidosis during the last quarter of pregnancy does not upregulate CA IV mRNA or CA IV immunoreactive protein.
Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen
Authors: Baltatu Ovidiu , Fontes Marco A. P. , Campagnole-Santos Maria J. , Caligiorni Sordaine , Ganten Detlev , Santos Robson A. S. , Bader Michael
Published: December 2017

The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT1) antagonists [CV-11974, AT1 specific; A-779, ANG-(1–7) selective; sarthran, nonspecific] into the rostral ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of ANG II receptors in TGR. CV-11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups. The pressor effect of the AT1 antagonist may indicate an inhibitory role of AT1 receptors in the RVLM. On the other hand, ANG-(1–7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis.
Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle
Authors: Leek Bryan T. , Mudaliar Sundar R. D. , Henry Robert , Mathieu-Costello Odile , Richardson Russell S.
Published: December 2017

Maximal citrate synthase activity (CS) is routinely used as a marker of aerobic capacity and mitochondrial density in skeletal muscle. However, reported CS has been notoriously variable, even with similar experimental protocols and sampling from the same muscles. Exercise training has resulted in increases in CS ranging from 0 to 100%. Previously, it has been reported that acute exercise may significantly affect CS. To investigate the hypothesis that the large variation in CS that occurs with training is influenced by alterations during the exercise itself, we studied CS in human vastus lateralis both in the rested and acutely exercised state while trained and untrained ( n = 6). Tissues obtained from four biopsies (untrained rested, untrained acutely exercised, trained rested, and trained acutely exercised) were analyzed spectrophotometrically for maximal CS. Exercise training measured in a rested state resulted in an 18.2% increase in CS (12.3 ± 0.3 to 14.5 ± 0.3 μmol · min−1· g tissue−1, P ≤ 0.05). However, even greater increases were recorded 1 h after acute exercise: 49.4% in the untrained state (12.3 ± 0.3 to 18.3 ± 0.5 μmol · min−1· g tissue−1, P ≤ 0.05) and 50.8% in the trained state (14.5 ± 0.3 to 21.8 ± 0.4 μmol · min−1· g tissue−1, P ≤ 0.05). Ultrastructural analysis, by electron microscopy, supported an effect of acute exercise with the finding of numerous swollen mitochondria 1 h after exercise that may result in greater access to the CS itself in the CS assay. In conclusion, although unexplained, the increased CS with acute exercise can clearly confound training responses and artificially elevate CS values. Therefore, the timing of muscle sampling relative to the last exercise session is critical when measuring CS and offers an explanation for the large variation in CS previously reported.
Relationship of ovarian hormones to hypoxemia in women residents of 4,300 m
Authors: León-Velarde F. , Rivera-Chira M. , Tapia R. , Huicho L. , Monge-C C.
Published: December 2017

Prevalence of excessive erythrocytosis, the main sign of chronic mountain sickness (CMS), is greater in postmenopausal Andean women than in premenopausal women. It is uncertain whether this greater prevalence is related to the decline in female hormones and ventilatory function after the occurrence of the menopause. To study this, we compared the physiological variables involved in the physiopathology of CMS [end-tidal CO2 (Pet CO2 , Torr) and end-tidal O2 (Pet O2 , Torr), arterial oxygen saturation (SaO2 , %), and Hb concentration (g/dl)] and progesterone and estradiol levels between postmenopausal and premenopausal women, both in the luteal and follicular phases. Women residing in Cerro de Pasco ( n= 33; 4,300 m) aged 26–62 yr were studied. Postmenopausal women compared with premenopausal women in the luteal phase had lower Pet O2 (48 ± 4 vs. 53 ± 2 Torr, P = 0.005) and SaO2 levels (82 ± 12 vs. 88 ± 12%, P < 0.005) and higher Pet CO2 (34 ± 2 vs. 29 ± 3 Torr, P = 0.005) and Hb concentration (19 ± 1 vs. 14 ± 2 g/dl, P < 0.005). In addition, plasma progesterone was negatively correlated with Pet CO2 and positively correlated with Pet O2 and SaO2 . No clear relationship was found among the cycle phases between estradiol and the variables studied. In conclusion, our results reveal that, before menopause, there is better oxygenation and lower Hb levels in women long residing at altitude, and this is associated with higher levels of progesterone in the luteal phase of the cycle.
Effects of glucose supplementation on gastric emptying, blood glucose homeostasis, and appetite in the elderly
Authors: Beckoff Katherine , MacIntosh Caroline G. , Chapman Ian M. , Wishart Judith M. , Morris Howard A. , Horowitz Michael , Jones Karen L.
Published: December 2017

The aims of this study were to evaluate the effects of dietary glucose supplementation on gastric emptying (GE) of both glucose and fat, postprandial blood glucose homeostasis, and appetite in eight older subjects (4 males, 4 females, aged 65–84 yr). GE of a drink (15 ml olive oil and 33 g glucose dissolved in 185 ml water), blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and appetite (diet diaries, visual analog scales, and food intake at a buffet meal consumed after the GE study) were evaluated twice, after 10 days on a standard or a glucose-supplemented diet (70 g glucose 3 times a day). Glucose supplementation accelerated GE of glucose ( P < 0.05), but not oil; there was a trend for an increase in GIP (at 15 min, P = 0.06), no change in GLP-1, an earlier insulin peak ( P < 0.01), and a subsequent reduction in blood glucose (at 75 min, P < 0.01). Glucose supplementation had no effect on food intake during each diet so that energy intake was greater ( P < 0.001) during the glucose-supplemented diet. Appetite ratings and energy intake at the buffet meal were not different. We conclude that, in older subjects, glucose supplementation 1) accelerates GE of glucose, but not fat; 2) modifies postprandial blood glucose homeostasis; and 3) increases energy intake.
Modeling the kinematics of the canine midcostal diaphragm
Authors: Amancharla Maneesh R. , Rodarte Joseph R. , Boriek Aladin M.
Published: December 2017

The hypotheses that the chest wall insertion (CW) is displaced laterally during inspiration and that this displacement is essential in maintaining muscle curvature of the costal diaphragmatic muscle fibers were tested. With the use of data from three dogs, caudal, lateral, and ventral displacements of CW during both quiet, spontaneous inspiration and during inspiratory efforts against an occluded airway were observed and recorded. We have developed a kinematic model of the diaphragm that incorporates these displacements. This model describes the motions of the muscle fibers and central tendon; the displacements of the midplane, muscle-tendon junction (MTJ), CW, and center of the muscle fiber-central tendon arcs are modeled as functions of muscle fiber length. In the model, the center of the fiber arcs and MTJ both move caudally parallel to the midplane during inspiration, whereas CW moves both caudally and laterally. The observed lateral displacement of CW and the observed caudal displacement of MTJ, as functions of muscle fiber length, both approximate well the theoretical displacements that would be necessary to maintain curvature of the fiber arcs. In confirming our hypotheses, we have found that lateral displacement of CW is a mechanism by which changes in the shape of the costal diaphragm, as described by its curvature, are limited.
Relationship of osmotic inhibition in thermoregulatory responses and sweat sodium concentration in humans
Authors: Takamata Akira , Yoshida Tetsuya , Nishida Naoko , Morimoto Taketoshi
Published: December 2017

Heat acclimatization improves thermoregulatory responses to heat stress and decreases sweat sodium concentration ([Na+]sweat). The reduced [Na+]sweat results in a larger increase in plasma osmolality (Posmol) at a given amount of sweat output. The increase in Posmol inhibits thermoregulatory responses to increased body core temperature. Therefore, we hypothesized that the inhibitory effect of plasma hyperosmolality on the thermoregulatory responses to heat stress should be attenuated with the reduction of [Na+]sweat due to heat acclimatization. Eleven subjects (9 male and 2 female) were passively heated by immersing their lower legs into water at 42°C (room temperature 28°C and relative humidity 30%) for 50 min following isotonic or hypertonic saline infusion. We determined the increase in the esophageal temperature (Tes) required to elicit sweating and cutaneous vasodilation (CVD) (ΔTes thresholds for sweating and CVD, respectively) in each condition and calculated the elevation of the Tes thresholds per unit increase in Posmol as the osmotic inhibition of sweating and CVD. The osmotic shift in the ΔTes thresholds for both sweating and CVD correlated linearly with [Na+]sweat( r = 0.858 and r = 0.628, respectively). Thus subjects with a lower [Na+]sweat showed a smaller osmotic elevation of the ΔTes thresholds for sweating and CVD. These results suggest the possibility that heat acclimatization attenuates osmotic inhibition of thermoregulatory responses as well as reducing [Na+]sweat.
Adenosine induces initial hypoxic-ischemic depression of synaptic transmission in the rat hippocampus in vivo
Authors: Gervitz L. M. , Lutherer L. O. , Davies D. G. , Pirch J. H. , Fowler J. C.
Published: December 2017

The present study was designed to investigate the role of adenosine in the hypoxic depression of synaptic transmission in rat hippocampus. An in vivo model of hypoxic synaptic depression was developed in which the common carotid artery was occluded on one side in the urethane-anesthetized rat. Inspired oxygen levels were controlled through a tracheal cannula. Rats were placed in a stereotaxic apparatus for stimulation and recording of bilateral hippocampal field excitatory postsynaptic potentials. The percent inspired oxygen could be reduced to levels that produced a reversible and repeatable depression of evoked synaptic transmission restricted to the hippocampus ipsilateral to the occlusion. Further reduction in the level of inspired oxygen depressed synaptic transmission recorded from both hippocampi. The adenosine nonselective antagonist caffeine and the A1selective antagonist 8-cyclopentyltheophylline prevented the initial depression in synaptic transmission. We conclude that the initial depression of synaptic transmission observed in the rat hippocampus in vivo is due to endogenous adenosine acting at neuronal adenosine A1 receptors.
Influence of the subfornical organ on meal-associated drinking in rats
Authors: Starbuck Elizabeth M. , Fitts Douglas A.
Published: December 2017

A lesion of the subfornical organ (SFO) may disrupt drinking after a meal of dry chow as it does drinking after intragastric administration of hypertonic saline. Food and water intakes of SFO-lesioned (SFOX) and sham-lesioned rats were measured during 90-min tests following various lengths of food deprivation. During the tests, all rats began eating before they began drinking. After 20–24 h of food deprivation, latency to begin drinking after eating had started was longer for SFOX than for sham-lesioned rats. Plasma osmolality was elevated by 2–3% in both lesion groups at 12 min, the latency for sham-lesioned rats to drink, but SFOX rats nevertheless continued eating and delayed drinking. Eating after shorter 4-h food deprivations and ad libitum feeding produced more variable drinking latencies and less consistent effects of SFO lesion. During 24 h of water deprivation, SFO lesion had no effect on the suppression of food intake and did not affect food or water intakes during the first 2 h of subsequent rehydration. These findings indicate that the SFO is involved in initiating water intake during eating and in determining drinking patterns and the amount of water ingested during a meal.
Secretory process regularity monitors neuroendocrine feedback and feedforward signaling strength in humans
Authors: Veldhuis J. D. , Straume M. , Iranmanesh A. , Mulligan T. , Jaffe C. , Barkan A. , Johnson M. L. , Pincus S.
Published: December 2017

The present experiments examine the neuroregulatory hypothesis that the degree of sample-by-sample regularity of hormone output by an interlinked hypothalamopituitary target-organ system monitors the strength of feedback and/or feedforward signaling. To test this postulate and assess its generality, we implemented a total of nine thematically complementary perturbation experiments. In particular, we altered feedback or feedforward signaling selectively in two distinct neuroendocrine systems; namely, the growth hormone (GH) insulin-like growth factor type I (IGF-I) and the luteinizing hormone-testosterone axes. Four experimental paradigms comprised preferential reduction vs. enhancement of IGF-I or testosterone feedback signal strength; and, conversely, five others entailed selective attenuation vs. augmentation of GH-releasing hormone and gonadotropin-releasing hormone feedforward signal intensity. In these independent interventions, quantitation of subordinate (nonpulsatile) secretory pattern reproducibility via the approximate entropy statistic unmasked salient changes ( Pvalues typically <10−3) in the conditional regularity of serial hormone output with high consistency (96–100%). In particular, approximate entropy quantified degradation of secretory subpattern orderliness under either muted feedback restraint or heightened feedforward drive. Assuming valid interpretation of the biological constraints imposed, these experimental observations coincide with earlier reductionist mathematical predictions, wherein increased irregularity of coupled parameter output mirrors attenuated feedback and/or augmented feedforward coupling within an integrative system.
Renal ischemia in the rat stimulates glomerular nitric oxide synthesis
Authors: Valdivielso José M. , Crespo Carlos , Alonso José R. , Martı́nez-Salgado Carlos , Eleno Nelida , Arévalo Miguel , Pérez-Barriocanal Fernando , López-Novoa José M.
Published: December 2017

Renal ischemia in humans and in experimental animals is associated with a complex and possibly interrelated series of events. In this study, we have investigated the glomerular nitric oxide (NO) production after renal ischemia. Unilateral or bilateral renal ischemia was induced in Wistar rats by clamping one or both renal arteries. NO production was assessed by measuring glomerular production of nitrite, a stable end product of NO catabolism, and NO-dependent glomerular cGMP production and by assessing the glomerular NADPH diaphorase (ND) activity, an enzymatic activity that colocalizes with NO-synthesis activity. Furthermore, we determined the isoform of NO synthase (NOS) implicated in NO synthesis by Western blot and immunohistochemistry. Glomeruli from rats with bilateral ischemia showed elevated glomerular nitrite and cGMP production. Besides, glomeruli from this group of rats showed an increased ND activity, whereas glomeruli from the ischemic and nonischemic rats with unilateral ischemia did not show this increase in nitrite, cGMP, and ND activity. In addition, glomeruli from ischemic kidneys showed an increased expression of endothelial NOS without changes in the inducible isoform. Addition ofl-NAME in the drinking water induced a higher increase in the severity of the functional and structural damage in rats with bilateral ischemia than in rats with unilateral ischemia and in sham-operated animals. We can conclude that after renal ischemia, there is an increased glomerular NO synthesis subsequent to an activation of endothelial NOS that plays a protective role in the renal damage induced by ischemia and reperfusion.
Effects of food texture change on metabolic parameters: short- and long-term feeding patterns and body weight
Authors: Labouré Hélène , Saux Sandrine , Nicolaidis Stylianos
Published: December 2017

A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.
Opioid receptor involvement in the effect of AgRP- (83–132) on food intake and food selection
Authors: Hagan Mary M. , Rushing Paul A. , Benoit Stephen C. , Woods Stephen C. , Seeley Randy J.
Published: December 2017

Agouti-related peptide (AgRP) is a receptor antagonist of central nervous system (CNS) melanocortin receptors and appears to have an important role in the control of food intake since exogenous CNS administration in rats and overexpression in mice result in profound hyperphagia and weight gain. Given that AgRP is heavily colocalized with neuropeptide Y (NPY) and that orexigenic effects of NPY depend on activity at opioid receptors, we hypothesized that AgRP's food-intake effects are also mediated by opioid receptors. Subthreshold doses of the opioid receptor antagonist naloxone blocked AgRP-induced intake when given simultaneously but not 24 h after AgRP injection. Opioids not only influence food intake but food selection as well. Hence, we tested AgRP's effect to alter food choice between matched diets with differing dietary fat content. AgRP selectively enhanced intake of the high-fat but not the low-fat diet. Additionally, AgRP selectively increased chow intake in rats given ad libitum access to a 20% sucrose solution and standard rat chow. The current results indicate that AgRP influences not only caloric intake but food selection as well and that the early effects of AgRP depend critically on an interaction with opioid receptors.
Increased heat-escape/cold-seeking behavior following hypertonic saline injection in rats
Authors: Nagashima Kei , Nakai Sadamu , Konishi Masahiro , Su Liu , Kanosue Kazuyuki
Published: December 2017

We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40°C heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g body wt). The rats received a 0°C air for 30 s when they entered a specific area in an experimental box. Core temperature (Tc) surpassed 40°C in both conditions when 0°C air was not available. Hypertonic saline injection produced a lower baseline Tcthan control [36.9 ± 0.2 and 37.9 ± 0.2°C (means ± SE), P < 0.05] and a greater number of 0°C air rewards during the 2-h heat with lower Tc at the end (48 ± 1 and 34 ± 2, 37.6 ± 0.1, and 37.3 ± 0.1°C in the control and hypertonic saline injection trial, respectively, P < 0.05, n = 6). However, Tc was similar (37.7 ± 0.2 and 37.6 ± 0.4°C in the control and hypertonic saline injection trial, n = 5) when 0°C air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline Tc and increasing heat-escape/cold-seeking behavior.
Fcγ-receptor signaling augments the LPS-stimulated increase in serum tumor necrosis factor-α levels
Authors: Refici Marion L. , Metzger Dennis W. , Arulanandam Bernard P. , Lennartz Michelle R. , Loegering Daniel J.
Published: December 2017

The phagocytosis of IgG-coated erythrocytes (EIgG) has been shown to augment the bacterial lipopolysaccharide (LPS)-stimulated increase in serum tumor necrosis factor-α (TNF-α) levels. The present study evaluated the role of Fcγ-receptor (FcγR) signaling and complement activation in the effect of EIgG on the TNF-α response to LPS. The role of FcγR was determined using FcR γ-chain knockout mice that lack functional FcγRI and FcγRIII. In wild-type animals, EIgG caused a 16-fold augmentation of the serum TNF-α response to LPS, whereas there was no augmentation in the FcγR-deficient animals. Heat-damaged erythrocytes also augmented the TNF-α response to LPS. This effect was absent in FcγR-deficient animals. An IgG antibody against heated erythrocytes was detected in mouse serum. The complement activation caused by EIgG had little effect on the LPS-stimulated increase in serum TNF-α levels as indicated by activation of complement with cobra venom factor or IgM-coated erythrocytes as well as studies with C5-deficient mice. These results indicate that FcγR signaling primarily mediates the augmented serum TNF-α response to LPS caused by EIgG.
Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters
Authors: Corp Eric S. , Gréco Beatrice , Powers J. Bradley , Bivens Carrie L. Marín , Wade George N.
Published: December 2017

Central injections of neuropeptide Y (NPY) increase food intake in Syrian hamsters; however, the effect of NPY on sexual behavior in hamsters is not known nor are the receptor subtypes involved in feeding and sexual behaviors. We demonstrate that NPY inhibits lordosis duration in a dose-related fashion after lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters. Under the same conditions, we compared the effect of two receptor-differentiating agonists derived from peptide YY (PYY), PYY-(3–36) and [Leu31,Pro34]PYY, on lordosis duration and food intake. PYY-(3–36) produced a 91% reduction in lordosis duration at 0.24 nmol. [Leu31,Pro34]PYY was less potent, producing a reduction in lordosis duration (66%) only at 2.4 nmol. These results suggest NPY effects on estrous behavior are principally mediated by Y2 receptors. PYY-(3–36) and [Leu31,Pro34]PYY stimulated comparable dose-related increases in total food intake (2 h), suggesting Y5 receptors are involved in feeding. The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3–36) or [Leu31,Pro34]PYY at a dose of each that differentiated between the two behaviors. Some differences were seen in the distribution of Fos-IR produced by the two peptides. Overall, however, the patterns of expression were similar. Our behavioral and anatomic results suggest that NPY-containing pathways controlling estrous and feeding behavior innervate similar nuclei, with the divergence in pathways controlling the separate behaviors characterized by linkage to different NPY receptor subtypes.
Effects of dietary salt intake on plasma arginine
Authors: Kitiyakara Chagriya , Chabrashvili Tina , Jose Pedro , Welch William J. , Wilcox Christopher S.
Published: December 2017

Because l-arginine is degraded by hepatic arginase to ornithine and urea and is transported by the regulated 2A cationic amino acid y+transporter (CAT2A), hepatic transport may regulate plasma arginine concentration. Groups of rats ( n = 6) were fed a diet of either low salt (LS) or high salt (HS) for 7 days to test the hypothesis that dietary salt intake regulates plasma arginine concentration and renal nitric oxide (NO) generation by measuring plasma arginine and ornithine concentrations, renal NO excretion, and expression of hepatic CAT2A, and arginase. LS rats had lower excretion of NO metabolites and cGMP, lower plasma arginine concentration (LS: 83 ± 7 vs. HS: 165 ± 10 μmol/l, P < 0.001), but higher plasma ornithine concentration (LS: 82 ± 6 vs. HS: 66 ± 4 μmol/l, P < 0.05) and urea excretion. However, neither the in vitro hepatic arginase activity nor the mRNA for hepatic arginase I was different between groups. In contrast, LS rats had twice the abundance of mRNA for hepatic CAT2A (LS: 3.4 ± 0.4 vs. HS: 1.6 ± 0.5, P < 0.05). The reduced plasma arginine concentration with increased plasma ornithine concentration and urea excretion during LS indicates increased arginine metabolism by arginase. This cannot be ascribed to changes in hepatic arginase expression but may be a consequence of increased hepatic arginine uptake via CAT2A.
Identification of the suprachiasmatic nucleus in birds
Authors: Yoshimura Takashi , Yasuo Shinobu , Suzuki Yoshikazu , Makino Eri , Yokota Yuki , Ebihara Shizufumi
Published: December 2017

Circadian rhythms are generated by an internal biological clock. The suprachiasmatic nucleus (SCN) in the hypothalamus is known to be the dominant biological clock regulating circadian rhythms in mammals. In birds, two nuclei, the so-called medial SCN (mSCN) and the visual SCN (vSCN), have both been proposed to be the avian SCN. However, it remains an unsettled question which nuclei are homologous to the mammalian SCN. We have identified circadian clock genes in Japanese quail and demonstrated that these genes are expressed in known circadian oscillators, the pineal and the retina. Here, we report that these clock genes are expressed in the mSCN but not in the vSCN in Japanese quail, Java sparrow, chicken, and pigeon. In addition, mSCN lesions eliminated or disorganized circadian rhythms of locomotor activity under constant dim light, but did not eliminate entrainment under light-dark (LD) cycles in pigeon. However, the lesioned birds became completely arrhythmic even under LD after the pineal and the eye were removed. These results indicate that the mSCN is a circadian oscillator in birds.
Impaired muscle oxygen transfer in patients with chronic renal failure
Authors: Sala Ernest , Noyszewski Elizabeth A. , Campistol Josep M. , Marrades Ramon M. , Dreha Steffi , Torregrossa Josep V. , Beers Jennifer S. , Wagner Peter D. , Roca Josep
Published: December 2017

We hypothesized that impaired O2transport plays a role in limiting exercise in patients with chronic renal failure (CRF). Six CRF patients (25 ± 6 yr) and six controls (24 ± 6 yr) were examined twice during incremental single-leg isolated quadriceps exercise. Leg O2delivery (Q˙o2leg) and leg O2uptake (V˙o2leg) were obtained when subjects breathed gas of three inspired O2fractions (FiO2) (0.13, 0.21, and 1.0). On a different day, myoglobin O2saturation and muscle bioenergetics were measured by proton and phosphorus magnetic resonance spectroscopy. CRF patients, but not controls, showed O2supply dependency of peak V˙o2(V˙o2peak) by a proportional relationship between peak V˙o2legat each inspired O2fraction (0.59 ± 0.20, 0.47 ± 0.10, 0.43 ± 0.10 l/min, respectively) and 1) work rate (933 ± 372, 733 ± 163, 667 ± 207 g), 2) Q˙o2leg(0.80 ± 0.20, 0.64 ± 0.10, 0.59 ± 0.10 l/min), and 3) cell Po2(6.3 ± 5.4, 1.7 ± 1.3, 1.2 ± 0.7 mmHg). CRF patients breathing 100% O2and controls breathing 21% O2had similar peakQ˙o2leg(0.80 ± 0.20 vs. 0.79 ± 0.10 l/min) and similar peak V˙o2leg(0.59 ± 0.20 vs. 0.57 ± 0.10 l/min). However, mean capillary Po2(47.9 ± 4.0 vs. 38.2 ± 4.6 mmHg) and the capillary-to-myocite gradient (40.7 ± 6.2 vs. 34.4 ± 4.0 mmHg) were both higher in CRF patients than in controls ( P < 0.03 each). We conclude that low muscle O2conductance, but not limited mitochondrial oxidative capacity, plays a role in limiting exercise tolerance in these patients.
Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy
Authors: Spangenburg Espen E. , Williams Jay H. , Roy Roland R. , Talmadge Robert J.
Published: December 2017

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.
The contribution of the vagus nerve in interleukin-1β-induced fever is dependent on dose
Authors: Hansen Michael K. , O'Connor Kevin A. , Goehler Lisa E. , Watkins Linda R. , Maier Steven F.
Published: December 2017

It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1β (IL-1β), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1β-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1β (rh-IL-1β). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 μg/kg, only partially blocked the fever produced by 0.5 μg/kg, and had no effect at all on the fever that followed 1.0 μg/kg rh-IL-1β. Blood levels of rh-IL-1β did not become greater than normal basal levels of endogenous rat IL-β until the 0.5-μg/kg dose nor was IL-1β induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1β induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.
GRK3 mediates desensitization of CRF1receptors: a potential mechanism regulating stress adaptation
Authors: Dautzenberg Frank M. , Braun Sandra , Hauger Richard L.
Published: December 2017

Potential G protein-coupled receptor kinase (GRK) and protein kinase A (PKA) mediation of homologous desensitization of corticotropin-releasing factor type 1 (CRF1) receptors was investigated in human retinoblastoma Y-79 cells. Inhibition of PKA activity by PKI5–22or H-89 failed to attenuate homologous desensitization of CRF1receptors, and direct activation of PKA by forskolin or dibutyryl cAMP failed to desensitize CRF-induced cAMP accumulation. However, treatment of permeabilized Y-79 cells with heparin, a nonselective GRK inhibitor, reduced homologous desensitization of CRF1receptors by ∼35%. Furthermore, Y-79 cell uptake of a GRK3 antisense oligonucleotide (ODN), but not of a random or mismatched ODN, reduced GRK3 mRNA expression by ∼50% without altering GRK2 mRNA expression and inhibited homologous desensitization of CRF1receptors by ∼55%. Finally, Y-79 cells transfected with a GRK3 antisense cDNA construct exhibited an ∼50% reduction in GRK3 protein expression and an ∼65% reduction in homologous desensitization of CRF1receptors. We conclude that GRK3 contributes importantly to the homologous desensitization of CRF1receptors in Y-79 cells, a brain-derived cell line.