bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic and pulmonary hemodynamic effects of big endothelin-1 and phosphoramidon in the ovine fetus
Authors: Jones O. W. , Abman S. H.
Published: December 2017

To investigate the potential role of endothelin-1 (ET-1) in fetal vasoregulation, we examined in sheep the hemodynamic effects of infusion of big ET-1 (bET-1; precursor of ET-1) on the systemic and pulmonary circulations in chronically catheterized late-gestation fetuses. Thirteen animals [134 +/- 0.5 (SE) days gestation] received systemic infusions of bET-1 (1.5 or 3.0 micrograms/min for 10 min via the superior vena cava), which increased systemic arterial pressure by 5.0 +/- 1.9 (P < 0.01) and 13.9 +/- 1.8 mmHg (P < 0.01), respectively. Pretreatment with 10 mg of phosphoramidon, an ET-1-converting enzyme inhibitor, blocked the hypertensive response to bET-1. Six animals (136 +/- 1.5 days gestation) received intrapulmonary infusion of bET-1 (3.0 micrograms/min for 10 min via the left pulmonary artery), which increased pulmonary arterial pressure by 18.1 +/- 1.5 mmHg (P < 0.01). Three animals (130 +/- 1.5 days gestation) received phosphoramidon (1 mg/min for 10 min via the left pulmonary artery), which had no observed effect on baseline pulmonary vascular tone. We conclude that bET-1 produces systemic and pulmonary hypertension in the late-gestation fetus. Phosphoramidon inhibits bET-1-induced hypertension, suggesting that the fetus possesses ET-1-converting enzyme activity.
Doubly labeled water measurement of human energy expenditure during exercise at high altitude
Authors: Hoyt R. W. , Jones T. E. , Baker-Fulco C. J. , Schoeller D. A. , Schoene R. B. , Schwartz R. S. , Askew E. W. , Cymerman A.
Published: December 2017

Estimates of total daily energy expenditure (TDEE) by the doubly labeled water (DLW, 2H(2)18O) and intake balance (I-B) methods were compared in six male soldiers studied over 6 days that included 5 days of strenuous winter exercise at 2,500- to 3,100-m elevation. Use of body energy stores [-9.54 +/- 1.54 (SD) MJ/day or -2,280 +/- 368 kcal/day] was estimated from changes in body weight, body density (hydrodensitometry), and total body water (H(2)18O dilution). The subjects wore computerized activity monitors and kept daily records of ration consumption (9.87 +/- 3.60 MJ/day or 2,359 +/- 860 kcal/day). Accuracy of individual DLW and I-B TDEE values was estimated from the correlations of TDEE with fat-free mass (FFM) or total weight (body wt + load). The DLW and I-B estimates of TDEE differed by -12.0 to 15.2% but provided comparable estimates of group mean TDEE (DLW = 19.07 +/- 2.37 MJ/day or 4,558 +/- 566 kcal/day; I-B = 19.41 +/- 3.72 MJ/day or 4,639 +/- 889 kcal/day; P > 0.05). The DLW TDEE was correlated with both FFM (r2 = 0.89, P < 0.01, power = 0.95) and total weight (r2 = 0.95, P < 0.01, power = 0.99), whereas I-B TDEE was correlated only with total weight (r2 = 0.75, P < 0.03, power = 0.81). Under adverse field conditions the DLW method provided individual TDEE estimates that were probably more accurate than those provided by the I-B method.
Ovine fetal swallowing and renal responses to oligohydramnios
Authors: Kullama L. K. , Agnew C. L. , Day L. , Ervin M. G. , Ross M. G.
Published: December 2017

Amniotic fluid (AF) volume regulation is dependent on a balance between fluid production and fluid resorption. We examined the effects of reduced AF volume on AF production by fetal urine and resorption by fetal swallowing and the response of these parameters to AF volume replacement. Eight time-dated pregnant ewes (125 +/- 1 days gestation) were studied before (day 1) and after (day 3) AF and fetal urine drainage. Drainage resulted in a significant decrease in AF volume (415 +/- 89 to 157 +/- 36 ml). Fetal urine osmolality increased (139 +/- 10 to 286 +/- 33 mosmol/kgH2O), while urine flow did not change significantly (0.31 +/- 0.04 to 0.23 +/- 0.06 ml/min), resulting in nonsignificant increases in osmolar, sodium, and chloride excretions. Fetal electromyographic swallowing activity decreased 30% (1.0 +/- 0.1 to 0.7 +/- 0.1 swallows/min; P < 0.05), while net esophageal flow decreased 74% (0.31 +/- 0.12 to 0.07 +/- 0.04 ml/min; P < 0.05). On day 4, 0.15 M NaCl (500 ml; 37 degrees C) was administered into the AF over 30 min. During the 2 h after reinfusion, urine flow (0.29 +/- 0.07 to 0.40 +/- 0.09 ml/min) and osmolar sodium and chloride excretion significantly increased, though fetal swallowing activity and esophageal flow did not change. Thus the ovine fetus responded to reduced AF volume by maintaining AF production and decreasing AF resorption. In response to AF replacement, urine flow increased while fetal swallowing activity did not change, consistent with an intramembranous pathway for fetal AF resorption.
From damselflies to pterosaurs: how burst and sustainable flight performance scale with size
Authors: Marden J. H.
Published: December 2017

Recent empirical data for short-burst lift and power production of flying animals indicate that mass-specific lift and power output scale independently (lift) or slightly positively (power) with increasing size. These results contradict previous theory, as well as simple observation, which argues for degradation of flight performance with increasing size. Here, empirical measures of lift and power during short-burst exertion are combined with empirically based estimates of maximum muscle power output in order to predict how burst and sustainable performance scale with body size. The resulting model is used to estimate performance of the largest extant flying birds and insects, along with the largest flying animals known from fossils. These estimates indicate that burst flight performance capacities of even the largest extinct fliers (estimated mass 250 kg) would allow takeoff from the ground; however, limitations on sustainable power output should constrain capacity for continuous flight at body sizes exceeding 0.003-1.0 kg, depending on relative wing length and flight muscle mass.
Does the spinal cord generate functionally significant sympathetic activity in the awake rat?
Authors: Trostel K. A. , Osborn J. W.
Published: December 2017

Previous studies reach conflicting conclusions regarding the presence of physiologically significant sympathetic nerve activity (SNA) in conscious rats with transection of the cervical spinal cord (CST). The objective of the current study was to determine whether either spinally generated SNA or nonspecific effects of antagonists are responsible for the natriuresis and decreased heart rate that accompany adrenergic blockade in CST rats. To test the first possibility, adrenergic antagonists (phentolamine and propranolol) were administered to three groups of CST rats: 1) renal denervated, 2) adrenalectomized or sham-adrenalectomized, and 3) rats who received the ganglionic blocker hexamethonium. Neither renal denervation, adrenalectomy, nor ganglionic blockade prevented either the three- to fivefold increase in sodium excretion or the 25-50 beats/min decrease in heart rate previously reported. We then administered combinations of different adrenergic antagonists to CST rats to test for nonspecific effects of the drugs. Whereas idazoxan+propranolol reproduced the natriuresis seen with phentolamine+propranolol, prazosin+yohimbine+propranolol did not. We conclude that there is no evidence for functionally significant spinally generated SNA in conscious CST rats and that the natriuresis observed with phentolamine administration is due to imidazoline binding.
Effects of food deprivation and restriction, and metabolic blockers on food hoarding in Siberian hamsters
Authors: Bartness T. J. , Clein M. R.
Published: December 2017

Syrian hamsters do not increase their food intake following several metabolic challenges, including food deprivation and blockade of metabolic fuel utilization, in contrast to the response of other small rodents to these challenges. Perhaps hamsters respond to such challenges differently, for example by altering hoarding. In the present experiments, we have begun to question the role of food hoarding in the total energy balance of Siberian hamsters. Therefore, we developed a simulated burrow system, where food was available outside the burrow for consumption and/or hoarding during a 15-h period surrounding the 8-h dark portion of the photocycle. Food hoarding, but not food intake, increased dramatically after 32- and 56-h fasts and was greater following the longer fast. Food-restricted weight-reduced hamsters (80% of ad libitum-fed controls) were refed and given the opportunity to hoard. Initially, when body weights were low, food hoarding was maximal and then decreased gradually to control levels as body weights reached those of the ad libitum-fed controls. Food intake was not affected. Neither hoarding nor food intake was affected by treatment with long-acting protamine zinc insulin, given to enhance the storage of metabolic fuels, at any dose tested. Finally, neither food intake nor hoarding was affected by treatment with the glucose utilization blocker 2-deoxy-D-glucose, the fatty acid utilization blocker methyl palmoxirate, or a combination of the two treatments, all at doses that stimulate food intake in laboratory rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Spreading depression reversibly impairs autoregulation of cortical blood flow
Authors: Florence G. , Bonvento G. , Charbonne R. , Seylaz J.
Published: December 2017

The experiment examines whether the mechanisms responsible for the autoregulation of cerebral blood flow (CBF) in response to hypotension were affected during the initial phase of cortical spreading depression (CSD). CSD was induced by a cortical pinprick in anesthetized rabbits, and CBF was measured by laser-Doppler flowmetry through a chronically implanted Plexiglas window. The reactivity to CO2 and papaverine was also studied before and after CSD. Fifteen minutes after CSD, autoregulatory vasodilation was reduced (P < 0.01). This impairment was reversible, since the autoregulatory response was restored 35 min after CSD. The time course of the reactivity to papaverine after CSD paralleled the autoregulatory response, with a significant correlation between the two reactivities (r = 0.47; P < 0.01). Conversely, the reactivity to CO2 was significantly reduced after CSD (P < 0.001) and remained affected for at least 95 min. We conclude that the mechanisms underlying autoregulation are transiently disturbed by CSD and that these mechanisms are not mediated by an accumulation of CO2 but seem instead to be related to an increase in adenosine 3',5'-cyclic monophosphate concentration.
Antilipolytic effects of alpha 2-adrenergic agonists, neuropeptide Y, adenosine, and PGE1 in mammal adipocytes
Authors: Castan I. , Valet P. , Quideau N. , Voisin T. , Ambid L. , Laburthe M. , Lafontan M. , Carpene C.
Published: December 2017

Lipolysis is stimulated by different hormones, depending on the species, but is also regulated by antilipolytic modulators, such as catecholamines (alpha 2-agonists), neuropeptide Y (NPY), adenosine, and prostaglandin E1 (PGE1), for which species-specific variations are poorly described. Comparison of the efficiency of these antilipolytic systems showed that PGE1 or phenylisopropyladenosine was able to totally inhibit lipolysis activation in nine mammalian species. However, the antilipolytic responses to clonidine or UK-14304 were fully developed in hamster and rabbit but blunted in the adipocytes of jerboa, rat, guinea pig, garden dormouse, and dormouse. A powerful antilipolytic effect of NPY was found only in the garden dormouse. Only human and dog adipocytes exhibited antilipolytic responses to alpha 2-adrenergic and NPY stimulation. These observations were explained by differences in alpha 2-adrenergic and NPY/peptide YY receptor number. Thus, inhibitory regulation of lipolysis in white adipocytes seems to be composed of two systems: a constitutive one that is related to paracrine mediators (adenosine, prostaglandins) and a regulatory one including neuroendocrine messengers such as catecholamines and NPY.
Regional cerebral blood flow during submergence asphyxia in Pekin duck
Authors: Stephenson R. , Jones D. R. , Bryan R. M.
Published: December 2017

The cerebrovascular response to submergence asphyxia was studied in the Pekin duck (Anas platyrhynchos var.) by use of the cerebral blood flow (CBF) tracer [14C]isopropyliodoamphetamine and quantitative autoradiography. Blood flow of the whole brain was 158 +/- 14 (SE) ml.min-1 x 100 g-1 (n = 7) in control animals. There was a doubling of flow to 320 +/- 61 ml.min-1 x 100 g-1 (n = 6) during submergence asphyxia. The hypothesis that CBF is redistributed within the brain during asphyxia was not supported. There were no regional reductions in CBF during submergence asphyxia. Mean arterial blood pressure was similar (approximately 140 mmHg), but heart rate, arterial blood gas tensions, and arterial pH were significantly different in control and submerged ducks at the time CBF was measured. The differences in CBF among submerged animals correlated strongly with arterial PCO2 and mean arterial blood pressure. The smallest proportional difference in regional CBF between control and submerged ducks occurred in the ectostriatum (+141%) and the largest in the locus ceruleus (+241%). The largest absolute difference in regional CBF was in the nucleus ruber (+322 ml.min-1 x 100 g-1). These are the first measurements of blood flow in discrete nuclei and regions of the avian brain.
Thermal effects on neuronal activity in suprachiasmatic nuclei of hibernators and nonhibernators
Authors: Miller J. D. , Cao V. H. , Heller H. C.
Published: December 2017

The temperature sensitivity of neuronal firing rates in the suprachiasmatic nuclei (SCN) of the hypothalami of rats and ground squirrels was studied in vitro. SCN from euthermic squirrels were studied during the hibernation season (winter) and during the summer. SCN from hibernating squirrels were also studied. Most properties of SCN cells from hibernators and nonhibernators were similar. Warm- and cold-sensitive neurons were observed in all groups, but cold-sensitive neurons were more common in SCN from hibernating squirrels. No evidence for temperature compensation of firing rate was accumulated; no cell was observed to fire below 16.6 degrees C. If the persistence of circadian rhythmicity is a function of action potential-dependent neurotransmission from the SCN, these results suggest that deep hibernation (5-17 degrees C) should be characterized by an absence of circadian fluctuation in temperature. Two possible adaptations for the shallow torpor seen at somewhat higher temperatures were observed in the SCN: 1) a relatively large population of cold-sensitive neurons and 2) a population of neurons with very high activation energies. Activation energy analysis suggested that most of the temperature-sensitive properties of these cells could be explained in terms of the thermal sensitivity of the sodium channel.
Dynamics of intake suppression after a preload: role of calories, volume, and macronutrients
Authors: Warwick Z. S. , Weingarten H. P.
Published: December 2017

Twenty-four-hour cumulative food intake is the summation of repeated bouts of feeding, separated by intermeal intervals. Intake in a given meal influences subsequent feeding by modulating the duration of the intermeal interval, meal size, or both. Analysis of the time course of the effect of an individual meal on subsequent feeding may therefore clarify the controls of meal patterning and 24-h intake. In the present experiments, rats consumed a preload and then ate a test meal ad libitum. With the length of the preload-to-test meal interval varied from 10 to 180 min, the time course of the impact of various preloads on meal size was revealed. The main findings were the following: 1) caloric content, rather than volume, was the primary determinant of the intake-reducing effect of a glucose preload; 2) no differences in the time course of intake reduction were found after isocaloric preloads of fructose, glucose, and sucrose; 3) a fat preload attenuated subsequent intake less than an isocaloric sucrose preload; and 4) a short-lived (< 20 min) effect of sensory-specific satiety was evident. These findings are consistent with what is known about long-term effects of dietary manipulations on 24-h intake. Because daily intake reflects multiple iterations of feeding followed by an intermeal interval, a focused study of the duration of the impact of meals on subsequent ingestion may clarify the relationship between controls of individual meals and 24-h food intake.
Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats
Authors: Himms-Hagen J. , Cui J. , Danforth E. , Taatjes D. J. , Lang S. S. , Waters B. L. , Claus T. H.
Published: December 2017

The objective was to assess the effect of a new, highly selective beta 3-adrenergic agonist, CL-316,243 (CL) (J. D. Bloom, M. D. Dutia, B. D. Johnson, A. Wissner, M. G. Burns, E. E. Largis, J. A. Dolan, and T. H. Claus., J. Med. Chem. 35: 3081, 1992), on energy balance and brown and white adipose tissues (BAT and WAT, respectively) in young rats eating a high-fat diet to induce obesity. Chronic treatment with CL increased body temperature and 24-h energy expenditure, mainly by increasing resting metabolic rate. Food intake was not altered but carcass fat was reduced. Interscapular BAT was markedly hypertrophied, with three- to fourfold increases in the content of uncoupling protein (UCP) and cytochrome oxidase. Quantitative immunoelectron microscopy of interscapular BAT of CL-treated rats showed smaller mitochondria with an unchanged total amount of UCP per mitochondrion. The relative frequency of the four major cell types in BAT (mature brown adipocytes, preadipocytes, interstitial cells, endothelial cells) was not altered. The CL-induced hypertrophy differed from that induced by chronic stimulation by endogenous norepinephrine (as in cold-adaptation) in absence of hyperplasia (there was a slightly reduced DNA content), absence of an increase in the thyroxine (T4) 5'-deiodinase activity, and absence of a selective increase in UCP concentration. WAT depots weighed less and had fewer cells (lower DNA content) in the CL-treated rats. Some multilocular adipocytes appeared in these normally almost exclusively unilocular WAT depots (mesenteric, inguinal, epididymal, retroperitoneal). We conclude that CL not only promotes BAT mitochondrial proliferation and thermogenesis and overall energy expenditure and leanness, but also retards the development of WAT hyperplasia during the early stage of diet-induced obesity.
The parasympathetic vasodilator fibers in the trigeminal portion of the distal lingual nerve in the cat tongue
Authors: Izumi H. , Karita K.
Published: December 2017

Electrical stimulation of the peripheral and central cut ends of the chorda tympani nerve (CTN) caused an increase in ipsilateral tongue blood flow in anesthetized cats. Both blood flow increases were markedly reduced by pretreatment with the autonomic ganglionic blocker hexamethonium (1.0 mg/kg). Electrical stimulation of the central cut ends of the CTN, inferior alveolar nerve, and vagus nerve as well as of the upper buccal gingiva also caused the vasodilator responses in the sympathectomized cat tongue. These vasodilatations were notably reduced by hexamethonium pretreatment, and were almost completely abolished by the section of the distal lingual nerve (DLN) and the lingual nerve proper but not by section of the CTN. The present data suggest that the parasympathetic vasodilator fibers in the CTN are not involved in somatoautonomic reflex vasodilatation in the cat tongue and that the major part of the somatoautonomic reflex vasodilator response is mediated by parasympathetic fibers running together with the trigeminal portion of the DLN as vasodilator fibers in the cat tongue. This also implies that there are two groups of parasympathetic vasodilator fibers, that is, one originates from the CTN (the facial nerve) and other from the trigeminal portion of the DLN (probably via the glossopharyngeal nerve).
Potential adaptations to acute hypoxia: Hct, stress proteins, and set point for temperature regulation
Authors: Mayfield K. P. , Hong E. J. , Carney K. M. , D'Alecy L. G.
Published: December 2017

Severe, intermittent hypoxia (hypoxic conditioning, HC) increases survival time during subsequent lethal hypoxia in mice. This protective effect was blocked by naloxone, suggesting an opioid-dependent mechanism. We proposed and evaluated three potential mechanisms of this acute adaptation: 1) increased hematocrit (Hct), 2) protein synthesis, and 3) decreased set point for temperature regulation (set point). Increased hematocrit is a well-studied adaptation to chronic hypoxia and could be acutely initiated by sympathetically mediated splenic contraction. Survival during stress can be prolonged by synthesis of stress proteins. We tested this hypothesis using two protein synthesis inhibitors, anisomycin and cycloheximide. Our third hypothesis is that set point is decreased after HC. A regulated decrease in body temperature would lower oxygen demand during hypoxia. Our studies indicate that hematocrit and protein synthesis are not dominant mechanisms of acute adaptation to hypoxia. However, we have observed a naloxone blockable decrease in set point after HC, supporting a mechanism in which acute adaptation involves an endogenous opioid-dependent decrease in set point. These studies also demonstrate that set point could be a more dominant contributor than body temperature to hypoxic tolerance.
Involvement of 5-HT3 receptors in the initiation of pharyngeal reflex
Authors: Yoshioka M. , Goda Y. , Ikeda T. , Togashi H. , Ushiki T. , Saito H.
Published: December 2017

Activation of peripheral serotonin (5-HT) receptors, classified as 5-HT3, was shown to elicit the pharyngeal reflex in anesthetized rats. Intravenous bolus injection of 5-HT (6.25-50 micrograms/kg) evoked rhythmic bursts in the efferent pharyngeal branch of the vagus nerve in a dose-related manner, whereas afferent superior laryngeal nerve activity was not altered by even a high dose of 5-HT. The pharyngeal branch response was blocked by pretreatment with a selective 5-HT3-receptor antagonist YM060 (1 and 10 micrograms/kg). A 5-HT3-receptor agonist, 2-methyl-5-HT, also produced a rhythmic burst in the pharyngeal branch, and this effect was blocked by YM060. Intrapharyngeal pressure was rhythmically increased by both 5-HT (12.5-50 micrograms/kg) and 2-methyl-5-HT (6.25-50 micrograms/kg) in a dose-related manner. Both of these effects were antagonized by YM060 (10 micrograms/kg). In addition, a neuromuscular blocking agent vecuronium (1 mg/kg iv) completely inhibited the 5-HT-induced increase in pharyngeal pressure. After a bilateral vagotomy was performed below the nodose ganglia, the 5-HT-induced increase in pharyngeal branch activity was abolished, whereas a bilateral sectioning of the superior laryngeal nerve did not alter the 5-HT-induced increase in pharyngeal branch activity. Retrograde tracing with fluorescent dye (fast blue) was used to identify the cell bodies of the pharyngeal branch. Pharyngeal motoneuron cell bodies were distributed along the entire length of the nucleus ambiguus. Our results suggest that exogenous 5-HT-induced increases in pharyngeal branch activity and intrapharyngeal pressure may be initiated by the peripheral 5-HT3-receptors of the vagal nervous system and that this may be a viscerosomatic reflex.
Interleukin-8 induces fever by a prostaglandin-independent mechanism
Authors: Zampronio A. R. , Souza G. E. , Silva C. A. , Cunha F. Q. , Ferreira S. H.
Published: December 2017

We have studied the mechanism by which interleukin-8 (IL-8) induces fever in rats. Intracerebroventricular injections of IL-8 (5.5-50 ng) evoked dose-dependent increases in body temperature, which reached a plateau 5 h after injection, i.e., later than intracerebroventricular interleukin-1 beta (IL-1 beta; 2 h). The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS) because preincubation of IL-8 with a specific antibody or boiling the IL-8 for 30 min abolished its activity but not that of LPS; also, IL-8 but not LPS induced fever in LPS-tolerant rats. Indomethacin significantly reduced the pyrogenic effects of intracerebroventricular injections of LPS and IL-1 beta but not responses to IL-8, suggesting that pyrogenic responses to IL-8 were mediated independently of prostaglandins. In contrast, dexamethasone markedly attenuated pyrogenic responses to IL-8 and IL-1 beta. These data suggest that inhibition of IL-8 by glucocorticoids contributes to the antipyretic effects of these drugs in fevers resistant to cyclooxygenase inhibitors.
Physiological increases in cortisol inhibit basal vasopressin release in conscious dogs
Authors: Papanek P. E. , Raff H.
Published: December 2017

Glucocorticoid deficiency leads to elevated plasma vasopressin (AVP), while chronic endogenous hypercortisolism may inhibit osmotically stimulated AVP, suggesting that glucocorticoids may be feedback inhibitors of AVP secretion. We evaluated the effect of physiological increases in cortisol (65 mg/day iv) for 7 days on basal AVP and oxytocin (OT) in five conscious, male dogs. Cortisol increased from 1.3 +/- 0.1 to 5.0 +/- 0.8 micrograms/dl during infusion. Basal plasma AVP significantly decreased from 3.5 +/- 0.2 to 2.6 +/- 0.3 pg/ml during cortisol infusion. Plasma OT, osmolality, and sodium did not change while arterial pressure decreased (from 107 +/- 3 to 102 +/- 2 mmHg) on days 4 and 6. Increases in cortisol led to a physiologically significant, nonosmotic decrease in AVP. The effect was specific to AVP and independent of changes in arterial pressure. Glucocorticoid administration significantly decreased basal AVP within 24 h, which is comparable to the negative feedback control of adrenocorticotropic hormone. The inverse relationship between cortisol and AVP may account for the nonosmotic change in AVP in patients with disorders of glucocorticoid secretion.
Renal function during chronic anemia in the ovine fetus
Authors: Davis L. E. , Hohimer A. R. , Woods L. L.
Published: December 2017

Our purpose was to determine how prolonged anemia alters fetal renal function and acid-base balance. In seven ovine fetuses made progressively anemic over 1 wk by serial isovolemic hemorrhage, hematocrit was reduced from 33.3 +/- 4.5 to 14.0 +/- 1.0%. Femoral arterial oxygen content was less and renal plasma flow was greater in anemic fetuses (1.5 +/- 0.1 ml/dl and 339 +/- 58 ml.min-1.100 g kidney-1) than in 6 control fetuses (7.0 +/- 1.3 ml/dl and 160 +/- 34 ml.min-1.100 g kidney-1). Urine flow and sodium excretion were also greater in anemic fetuses (1.2 +/- 0.6 ml/min and 79 +/- 49.5 mumol/min) than in controls (0.5 +/- 0.2 ml/min and 16 +/- 9.8 mumol/min). This higher sodium excretion was apparently due to a lower fractional sodium reabsorption in anemic fetuses compared with controls (84.1 +/- 5.8 vs. 96.5 +/- 1.7%), rather than to differences in either glomerular filtration rate or amount of filtered sodium. In addition, the higher sodium excretion in anemic fetuses was associated with greater urinary lactate and inorganic phosphate excretions and larger amniotic fluid volumes than in controls. From these data we conclude that when fetal renal oxygen delivery is limited by a prolonged reduction in hematocrit, excretions of sodium and water, as well as other osmotically active solutes, increase, and this results in an increase in amniotic fluid volume.
Downregulation of hepatocyte P2-purinoceptor binding capacity after trauma-hemorrhage/resuscitation
Authors: Mahmoud M. S. , Wang P. , Hootman S. R. , Reich S. S. , Chaudry I. H.
Published: December 2017

Although P2-purinoceptors play an important role in the regulation of liver metabolism under normal conditions, it is not known if trauma-hemorrhage and resuscitation have any effects on such receptors. To study this, we performed a 5-cm midline laparotomy (i.e., trauma induced) on rats and then bled them to and maintained them at a mean arterial pressure of 40 mmHg until 40% of maximum bleedout volume was returned in the form of Ringer lactate (RL). The animals were then resuscitated with 3x the volume of shed blood with RL over 45 min followed by 2x RL over 95 min. Hepatocytes were isolated at the time of maximum bleedout or at 0, 4, 17, and 27 h after the completion of crystalloid resuscitation. P2-purinoceptor binding characteristics were determined in the isolated hepatocytes by using [alpha-35S]ATP. Scatchard analysis revealed high- and low-affinity components of P2-purinoceptors in hepatocytes from sham-operated as well as hemorrhaged and resuscitated animals. The maximum binding capacity (Bmax) of the high-affinity receptor component decreased at the time of maximum bleedout and at 4, 17, and 27 h after resuscitation. In addition to this, the Bmax of low-affinity receptor components also decreased at 4-27 h after resuscitation. In contrast, the dissociation constants of both receptor components were not altered. Because hemorrhagic shock produces abnormalities in glucose metabolism, the downregulation of hepatocyte P2-purinoceptor Bmax may be responsible for the altered glucose homeostasis under such conditions.
Interleukin-6 activity in wounds
Authors: Mateo R. B. , Reichner J. S. , Albina J. E.
Published: December 2017

Interleukin-6 (IL-6) is a multifunctional cytokine with local and systemic effects during immunological and inflammatory reactions. The IL-6 activity in wound fluids and serum from wounded animals, its release by wound cells in culture, and its role in the regulation of wound fibroblast proliferation were determined. IL-6 activity in wound fluid and serum peaked within 12 h after wounding. Wound-derived polymorphonuclear leukocytes, macrophages, and fibroblasts released IL-6 in culture. Wound macrophages harvested 5 days after injury produced more IL-6 than those taken at 3 or 10 days. An anti-IL-6 antibody partially reversed the suppression of wound fibroblast proliferation by wound fluid and wound macrophage culture supernatants. Finally, human wound fluids exhibited a temporal pattern of IL-6 activity similar to that found in rat wounds. The early wound, then, and more specifically the polymorphonuclear leukocytes of the immediate inflammatory response appear to be the source of circulating IL-6 after injury. In the later wound, IL-6 may provide signals to suppress fibroblast proliferation.
Angiotensin II relaxation of rainbow trout vessels in vitro
Authors: Conklin D. J. , Olson K. R.
Published: December 2017

The effects of salmonid angiotensin II ([Asn1,Val5]ANG II) were examined in isolated trout arteries [celiacomesenteric (CMA), coronary (COA), 3rd or 4th gill arch epibranchial (EBA), ventral aorta (VA)] and veins [anterior cardinal (ACV) and ductus Cuvier strips (DOC)]. ANG II (10(-10)-10(-6) M) produced modest (< 50% other agonists) transient contractions in otherwise unstimulated COA but was a poor agonist in other vessels. In precontracted vessels, ANG II responses were triphasic; transient contraction (P1), relaxation (P2), and partial recovery (P3) and vessel specific. P1 was similar to uncontracted vessels. With 10(-6) MANG II, %P2 was: EBA, 60.3 +/- 8.3% (n = 22); CMA, 48.8 +/- 8.8% (n = 4); ACV, 38.8 +/- 5.3% (n = 29); VA, 29.4 +/- 4.9% (n = 8); DOC, 25.5 +/- 2.4% (n = 14); COA, 13.2 +/- 6.7% (n = 4). P2 in EBA and ACV was dose dependent [EBA vs. ACV: mean effective concentration (EC50) = 3.6 x 10(-9) +/- 8.1 x 10(-10) M, n = 7 vs. 6.2 x 10(-8) +/- 2.3 x 10(-8) M, n = 8, respectively; P < or = 0.05] and inhibited by indomethacin but unaffected by propranolol, NG-monomethyl-L-arginine, saralasin, PD-123177, or DuP-753. Removal of EBA endothelium also inhibited relaxation. By comparison, ANG II did not relax bullfrog arteries (dorsal aorta, systemic arch, CMA) or femoral veins. These results show that, in large vessels of trout, the predominant effect of ANG II is an endothelium-dependent, prostanoid-mediated relaxation that is unaffected by classical ANG II-receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Intrapericardial blocking agents have extracardiac effects in dogs
Authors: Mittelstadt S. W. , O'Hagan K. P. , Bell L. B. , Clifford P. S.
Published: December 2017

The purpose of this study was to determine if intrapericardial infusion of hexamethonium, propranolol, or atropine affected extracardiac receptors in anesthetized dogs. Intrapericardial hexamethonium (> or = 25 mg) decreased renal sympathetic nerve activity (RSNA) in a dose-dependent fashion. After 250 mg, RSNA began to decrease in 65 +/- 7 s. Whereas vagal stimulation caused a muscarinic receptor-mediated increase in tracheal smooth muscle tone (as indicated by a 9.6 +/- 1.1 mmHg increase in endotracheal cuff pressure), the increase in cuff pressure (1.8 +/- 0.4 mmHg) was attenuated after intrapericardial tropine (4 mg). When the ansa and vagus were stimulated simultaneously, beta-adrenergic receptor-mediated smooth muscle relaxation opposed the muscarinic receptor-mediated constriction resulting in an increase in cuff pressure of only 3.6 +/- 0.9 mmHg. After intrapericardial propranolol (8 mg), simultaneous ansa and vagal stimulation caused a 7.0 +/- 1.6 mmHg increase in cuff pressure, demonstrating that intrapericardial propranolol blocked beta-adrenergic receptor-mediated relaxation of tracheal smooth muscle. These results show that hexamethonium, atropine, and propranolol infused intrapericardially have extracardiac effects.
Confocal microscopic analysis of fluorescein compartmentation within crab urinary bladder cells
Authors: Miller D. S. , Barnes D. M. , Pritchard J. B.
Published: December 2017

Fluorescein (FL), a fluorescent organic anion, is compartmentalized in cells of organic anion-secreting epithelia, e.g., OK cells, teleost proximal tubule, and crab (Cancer borealis) urinary bladder, a proximal tubule analogue. To further examine the processes involved, FL uptake and distribution were studied in C. borealis urinary bladder cells using epifluorescence and laser confocal microscopy combined with video-image analysis. Intracellular FL was about evenly split between diffuse and punctate compartments after in vitro or in vivo loading. Treatments that affected FL transport into cells (incubation with p-aminohippuric acid or glutarate) altered the FL content of both compartments. However, nocodazole, a microtubule inhibitor, did not affect diffuse FL but significantly reduced punctate FL. Finally, confocal analysis indicated that individual sites of punctate FL accumulation moved in the secretory direction at 0.83 micron/min. Nocodazole nearly abolished this movement and significantly reduced transepithelial organic anion secretion. Thus, in crab urinary bladder, a substantial fraction of total cellular FL is sequestered in vesicles, and these vesicles move in the secretory direction, by a microtubule-dependent process.
Hepatic vascular response to anaphylaxis in isolated canine liver
Authors: Yamaguchi Y. , Shibamoto T. , Hayashi T. , Saeki Y. , Tanaka S.
Published: December 2017

We determined the vascular response to anaphylaxis in isolated canine livers perfused with autologous blood at a constant pressure via the portal vein, with hepatic artery ligation to simplify the vascular system. We also studied the validity of the double occlusion pressure (Pdo) as a measure of the capillary pressure (Pc) in the isolated canine liver. Pdo was compared with Pc measured using the traditional isogravimetric method (Pc,i), and both parameters showed a strong correlation (Pdo = 0.34 + 0.90 Pc,i; r = 0.93; P < 0.01). This indicated that Pdo provided an accurate indication of Pc in the isolated liver. In livers with anaphylaxis induced by the intraportal injection of Ascaris suum antigen (5 mg; 1.0 +/- 0.03 mg/kg body wt), hepatic vascular resistance and Pc (assessed as Pdo) were increased transiently by 29-fold and 3.4 mmHg, respectively, along with a significant increase of liver weight. The ratio of presinusoidal to postsinusoidal vascular resistance decreased from 0.89 +/- 0.05 to 0.36 +/- 0.12, suggesting that hepatic venous constriction was predominant. In livers perfused in the antidromic direction from the hepatic vein to the portal vein, anaphylaxis caused marked presinusoidal vasoconstriction that was consistent with hepatic venoconstriction as well as a significant and sustained decrease of liver weight below the baseline. These results suggest that anaphylaxis produced hepatic weight gain because of an increase in sinusoidal pressure caused by hepatic venoconstriction. Such hepatic venoconstriction may play an important role in the development of portal hypertension and hepatic congestion associated with anaphylactic shock.
Hypothalamic network for thermoregulatory vasomotor control
Authors: Kanosue K. , Yanase-Fujiwara M. , Hosono T.
Published: December 2017

Warming one side of a rat's preoptic area and anterior hypothalamus (POAH) causes skin vasodilation on both sides of the body, and the present study evaluated the extent to which signals mediating this vasodilation cross the midline within and below the POAH. Hind paw vasomotion during unilateral POAH thermal or electrical stimulation was measured for rats in which the POAH had been midsagittally transected and for rats in which one side of the hypothalamus had been coronally transected just below the POAH. In midsagittally transected rats, unilateral POAH thermal or electrical stimulation produced bilateral paw vasodilation, but the ipsilateral dilation occurred at a hypothalamic temperature lower than that at which contralateral dilation occurred. In the unilaterally transected rats, unilateral POAH warming produced bilateral vasodilation and, regardless of which side of the POAH was warmed, the threshold stimulus temperature was always lower for vasodilation on the intact side. Unilateral transection of a part of the hypothalamus that included the medial forebrain bundle had the same effect as did unilateral transection of the whole hypothalamus. Information controlling thermoregulatory vasomotion thus crosses the midline both within and below the POAH. Although efferent signals descending through the medial forebrain bundle innervate skin blood vessels on both sides of the body, this innervation is stronger on the ipsilateral side.
Altered interleukin-1 and tumor necrosis factor production and secretion during pyrogenic tolerance to LPS in rabbits
Authors: Wakabayashi G. , Cannon J. G. , Gelfand J. A. , Clark B. D. , Aiura K. , Burke J. F. , Wolff S. M. , Dinarello C. A.
Published: December 2017

Rabbits were injected intravenously with 10 micrograms/kg of endotoxin [lipopolysaccharide (LPS)] on days 0, 1, and 7, and rectal temperatures were monitored. The febrile responses were compared with circulating levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) and in vitro synthesis of these cytokines by peripheral blood mononuclear cells (PBMC) isolated just before the injection of LPS. Fever after the first LPS injection was biphasic on day 0, attenuated and monophasic after the second LPS injection on day 1, and augmented after third injection of LPS on day 7. On day 1, circulating TNF and IL-1 beta levels were significantly (P < 0.05) decreased compared with those on days 0 and 7. Similarly, TNF and IL-1 beta synthesis by LPS-stimulated PBMC were significantly reduced on day 1. On day 7, cellular synthesis and secretion of IL-1 beta were significantly increased compared with that on day 0. A significant positive correlation was observed between fever index and total in vitro IL-1 beta synthesis by LPS-stimulated PBMC (r = 0.866, P = 0.001). These data demonstrate that pyrogenic tolerance in the rabbit after a single LPS injection is associated with decreased circulating IL-1 beta and TNF levels as well as decreased production of these cytokines in vitro. In addition, the pyrogenic hyperresponsiveness to LPS after 7 days is associated with increased synthesis and secretion of IL-1 beta from PBMC in vitro.
Temperature and pH effects on Ca2+ sensitivity of cardiac myofibrils: a comparison of trout with mammals
Authors: Churcott C. S. , Moyes C. D. , Bressler B. H. , Baldwin K. M. , Tibbits G. F.
Published: December 2017

Active salmonids maintain myocardial contractility at temperatures that are cardioplegic for mammals. We postulated that myofibrillar Ca2+ sensitivity in the trout heart might 1) exhibit lower temperature dependence and/or 2) be greater over the range of physiological temperatures. Temperature-induced changes in intracellular pH may also play a role as alkalosis typically increases calcium affinity of myofibrillar adenosinetriphosphatase (ATPase). Ca2+ sensitivities of ventricular myofibrillar ATPase were determined in rats and in rainbow trout (Oncorhynchus mykiss) over a physiological range of pH and temperatures. Maximal myofibrillar ATPase activities of each species were similar and equally affected by temperature. Trout myofibrillar ATPase lost Ca2+ dependence at 37 degrees C. At constant pH, reduced temperature decreased calcium affinity more in trout (0.35 pCa/10 degrees C) than in rat (0.08-0.16 pCa/10 degrees C). Under alpha-stat conditions, the effects of temperature were reduced in both trout (0.2 pCa/10 degrees C) and rat (no significant effect). Over trout physiological temperatures, Ca2+ sensitivity was greater than rat at 37 degrees C. Qualitatively similar results were observed in studies measuring tension in skinned trout ventricular fibers. One mechanism by which the trout heart is able to maintain contractility at low temperatures is through the inherent higher Ca2+ sensitivity of the contractile element compared with mammalian species.
Glutamate metabolism in fetus and placenta of late-gestation sheep
Authors: Moores R. R. , Vaughn P. R. , Battaglia F. C. , Fennessey P. V. , Wilkening R. B. , Meschia G.
Published: December 2017

Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.
Developmental changes in plasma thiol-disulfide turnover in rats: a multicompartmental approach
Authors: Ookhtens M. , Mittur A. V.
Published: December 2017

Plasma glutathione (GSH), derived principally from the liver, has been proposed as the main endogenous source of plasma cysteine (CYSH). In an earlier study in immature (I) and mature (M) rats, with the use of tracer boluses of intravenous [35S]GSH, we found the movement of the label through plasma GSH, CYSH, and cystine (CYSS) pools to be incompatible with a series of precursor-product compartments (GSH-->CYSH-->CYSS). Thus plasma GSH did not appear to account for sole source of plasma CYSH. To delineate the quantitative interrelationships of plasma GSH, CYSH, and CYSS in I and M rats, we used tracer bolus injections of intravenous [35S]CYSH and [35S]CYSS. The data from the present and previous studies were then used to develop a comprehensive multicompartmental model that fits the data from all experiments. Our analysis indicates the following. 1) Plasma CYSH does not account for the sole intermediate, kinetically homogeneous pool for the movement of label from GSH to CYSS. 2) Only one-half of the irreversible disposal rate (IDR; nmol.min-1.ml-1) of plasma GSH in I rats, but all of it in M rats, is accounted for by hydrolysis to CYSH+CYSS. Thus I rats appear capable of taking up substantial amounts of plasma GSH intact. 3) Significant age-related declines take place in the following IDRs: GSH, from 38 to 18 (approximately 55%); CYSH, from 81 to 11 (approximately 85%); CYSS (in CYSH equivalents), from 30 to 10 (approximately 67%). 4) Hydrolysis of GSH supplies only approximately 22% of plasma IDR of CYSH in I rats vs. approximately 78% in M rats. Thus, in I rats, a sizable inflow of CYSH from other sources than GSH is required to maintain plasma CYSH. 5) In contrast, plasma CYSS appears fully supplied through circulating GSH and CYSH.
Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems
Authors: Leeuwenburgh C. , Fiebig R. , Chandwaney R. , Ji L. L.
Published: December 2017

Glutathione (GSH) content and antioxidant enzyme activities were investigated in skeletal muscle of young, adult, and old male Fischer 344 rats. Furthermore, the effect of 10 wk of exercise training on these antioxidant systems was evaluated at all ages. In the soleus muscle, GSH concentration increased markedly with age, with no significant change in glutathione disulfide (GSSG) content. Training caused a 30% decrease of GSH (P < 0.05) in the soleus of young rats and a reduction of the GSH-to-GSSG ratio at all ages. Activity of gamma-glutamyl transpeptidase (GGT), a key enzyme for GSH uptake by muscle, was also significantly decreased with training. GSH, GSSG, and the GSH-to-GSSG ratio were not altered with aging or training in the deep portion of vastus lateralis muscle (DVL). Activities of GSH peroxidase (GPX), GSSG reductase (GR), superoxide dismutase (SOD), catalase (CAT), and GSH sulfur-transferase were increased significantly with aging in both soleus and DVL. In DVL, training increased GPX and SOD activities in the young rats, whereas in soleus, training decreased GR and CAT activities in the adult rats and GGT and CAT activities in the old rats. Muscle lipid peroxidation was significantly increased with aging in both DVL and soleus but was not affected by training. These data indicate that aging may cause not only an overall elevation of antioxidant enzyme activities but also a fiber-specific adaptation of GSH system in skeletal muscle. Exercise training, although increasing selective antioxidant enzymes in the young rats, does not offer additional protection against oxidative stress in the senescent muscle.