bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization of vagal preganglionics that stimulate insulin and glucagon secretion
Authors: Berthoud H. R. , Fox E. A. , Powley T. L.
Published: December 2017

Although it is generally acknowledged that pancreatic islets are under powerful vagal control, specifics of vagal pathways and their central representation in the brain stem are unclear. To define this circuitry, we combined a protocol measuring electrical vagal stimulation-induced insulin and glucagon secretion with a retrograde tracer strategy that delineated the pool of spared motoneurons in the dorsal motor nucleus of the vagus (dmnX) following selective abdominal branch vagotomies. Three of the five branches mediated both insulin and glucagon release: posterior gastric (+198 and +117% increase from basal for insulin and glucagon, respectively), anterior gastric (+177 and +104%), and hepatic branch (+103 and +60%). In contrast, unreliable and nonsignificant hormonal responses were produced by stimulation of fibers projecting through either the posterior celiac (+12% insulin and +12% glucagon) or accessory celiac (+15% insulin and +31% glucagon) branches. Since hexamethonium almost completely blocked both insulin and glucagon responses to stimulation, the effects are not likely to have resulted from inadvertent antidromic excitation of vagal afferents. Cell bodies of stimulated motoneurons, which were responsible for insulin and glucagon secretion, were found to occupy the medial two-thirds of the right (projecting through the posterior gastric branch) and left (projecting through the anterior gastric and hepatic branches) dmnX. These medial, longitudinal dmnX columns and their associated abdominal vagal branches are likely to play the predominant role in vagal control of the endocrine pancreas.
Fuel partitioning and food intake: role for mitochondrial fatty acid transport
Authors: Friedman M. I. , Ramirez I. , Bowden C. R. , Tordoff M. G.
Published: December 2017

Administration of methyl palmoxirate (MP; 10 mg/kg po), an inhibitor of carnitine palmitoyltransferase I (CPT I), increased the food intake of rats maintained on a diet high in triglycerides comprised of long-chain fatty acids, which require CPT I for mitochondrial uptake and oxidation. MP did not affect food intake in rats fed a comparable diet high in medium-chain fatty acids, which do not require CPT I for mitochondrial uptake and oxidation. The feeding response to MP was reduced more effectively by an intragastric preload of medium-chain triglyceride (MCT) oil than a preload of a long-chain triglyceride (LCT) oil. Food intake of MCT- and LCT-fed rats differed under control conditions (no MP), and this appeared to reflect differences in the diurnal distribution of feeding. Measurement of plasma ketone body concentrations indicated that the dietary manipulations and MP had their intended metabolic effects. The results strongly suggest that mitochondrial transport of fatty acids plays a role in the control of food intake. CPT I participates in that control by regulating the partitioning of long-chain fatty acids between pathways of storage and intramitochondrial oxidation.
Subcortical sites mediating sympathetic responses from insular cortex in rats
Authors: Cechetto D. F. , Chen S. J.
Published: December 2017

Stimulation of the insular cortex elicits a number of autonomic responses. The insular cortex projects directly to the lateral hypothalamic area, the parabrachial nucleus, and the nucleus of the solitary tract, which in turn project directly to sympathetic preganglionic areas. To determine which of these subcortical sites mediates sympathetic responses evoked from the insular cortex, changes in renal nerve activity were recorded before and after injection of the synaptic blocking agent cobalt into each of these regions. Blood pressure, heart rate, and renal nerve activity were continuously monitored in chloralose or urethan-anesthetized rats. Single-pulse electrical stimulation (200 microA, 1 ms) elicited either an early increase or decrease in renal nerve activity from pressor and depressor sites, respectively, in the insular cortex. Cobalt injections (500 nl) into the lateral hypothalamic area attenuated the nerve response 10-100%. Cobalt injections into the nucleus of the solitary tract significantly enhanced the initial increase in the nerve response obtained from pressor sites in the insular cortex. Injections into the parabrachial nucleus did not affect the nerve responses. These results suggest that there is a mandatory synapse in the lateral hypothalamic area in the pathway from the insular cortex to the sympathetic nervous system.
Role of prolactin in lactation-induced changes in brown adipose tissue
Authors: Chan E. , Swaminathan R.
Published: December 2017

During lactation the efficiency of energy utilization is increased and brown adipose tissue (BAT) thermogenesis is suppressed. We have examined the role of prolactin in the suppression of BAT during lactation in the rat. Changes in BAT were studied using an enzyme-linked immunosorbent assay for the uncoupling protein (UCP). In the first experiment BAT from pregnant and lactating rats was examined at various times. Total UPC content of BAT decreased from 364 +/- 34 to 32 +/- 9 micrograms during late lactation (20 days). Serum prolactin (PRL) concentration was elevated during lactation and was highest at 10 days. When endogenous PRL was stimulated by injection of metoclopramide (1.67 mg/kg) for 5 days, UCP content of BAT decreased by 50%. This action of metoclopramide could be blocked by simultaneous administration of bromocriptine, an inhibitor of PRL secretion. Serum PRL concentration was elevated during metoclopramide administration but not when metoclopramide and bromocriptine were given together. We conclude that PRL is a possible mediator of the suppression of BAT during lactation.
Effect of vasopressin on production of cerebrospinal fluid: possible role of vasopressin (V1)-receptors
Authors: Faraci F. M. , Mayhan W. G. , Heistad D. D.
Published: December 2017

The goal of this study was to examine the role of arginine vasopressin in humoral regulation of choroid plexus function. Production of cerebrospinal fluid (CSF) was measured in anesthetized rabbits with an indicator dilution method, by using ventriculocisternal perfusion of artificial CSF containing blue dextran. Rabbits received either vehicle, vasopressin or vasopressin in the presence of the V1-antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]arginine vasopressin ([d(CH2)5Tyr(Me)]-AVP). Under control conditions, blood flow to the choroid plexus (measured with microspheres) averaged 369 +/- 26 (mean +/- SE) ml.min-1.100 g-1 and CSF production averaged 9.9 +/- 0.9 microliters/min. Intravenous infusion of vasopressin (2 mU.kg-1.min-1 for 90 min) decreased blood flow to the choroid plexus by 50-60% for the entire period of infusion. Vasopressin decreased production of CSF by 35 +/- 8%. Blood flow to the choroid plexus and production of CSF did not change significantly from control values in animals that received vehicle. In the presence of the V1-antagonist (10 micrograms/kg), infusion of vasopressin had no effect on blood flow to the choroid plexus or production of CSF. Thus circulating vasopressin, at plasma levels that are observed under physiological and pathophysiological conditions, has important effects on formation of CSF, as well as on blood flow to the choroid plexus. These findings are consistent with the hypothesis that effects of vasopressin on both variables are mediated through vasopressin (V1)-receptors.
Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus
Authors: Schreiber G. , Aldred A. R. , Jaworowski A. , Nilsson C. , Achen M. G. , Segal M. B.
Published: December 2017

The transport of thyroxine from the bloodstream to the brain and the synthesis and secretion of transthyretin (formerly called prealbumin) were studied in rats and in sheep choroid plexus perfused in vitro. Rat choroid plexus contained 4.4 micrograms and rat liver 0.39 micrograms transthyretin mRNA per gram wet tissue. The specific radioactivity of transthyretin isolated from cerebrospinal fluid of rats 60 min after intravenous injection of [14C]leucine was greater than 50 times that of transthyretin from serum. After adding [14C]leucine to the perfusion medium of an in vitro perfused sheep choroid plexus, highly radioactive transthyretin was isolated from freshly secreted cerebrospinal fluid collected from the exposed choroid plexus surface. Secretion of newly synthesized transthyretin into the perfusion medium could not be demonstrated. After intravenous injection of [125I]-thyroxine into rats, a maximum in the curve of radioactivity in tissue plotted against time after injection was observed first for choroid plexus, thereafter for cerebrospinal fluid, and still later for cortex and striatum. Based on the obtained data, a hypothesis is derived for the mechanism of the transport of thyroid hormones from the bloodstream to the brain involving transthyretin synthesized in choroid plexus and secreted into the cerebrospinal fluid.
Centrally acting vasopressin contributes to endotoxin tolerance
Authors: Wilkinson M. F. , Kasting N. W.
Published: December 2017

Repeated daily intravenous injections of bacterial endotoxin induce a refractory state to their usual pyrogenic effects. The neuropeptide arginine vasopressin (AVP) has been implicated in natural fever suppression and may be involved in the process of pyrogenic tolerance to intravenous endotoxin. This study was conducted to test this hypothesis. Tolerance was induced by two successive daily intravenous injections of Escherichia coli endotoxin (50 micrograms/kg) into conscious unrestrained rats. This tolerance was maintained, unaltered, after a third or fourth subsequent injection. However, bilateral administration of an AVP V1-receptor antagonist (0.43-4.3 nmol) into the ventral septal area (VSA) of the rat brain markedly enhanced the thermoregulatory response to a third or fourth endotoxin challenge compared with saline controls. The effect of the V1 antagonist was dose related. In contrast, an AVP V2 antagonist (0.43 nmol) bilaterally injected into the VSA did not affect the tolerant reaction to endotoxin. Furthermore, neither saline nor the V1 antagonist significantly affected core temperature when administered within the VSA without subsequent endotoxin. These results are consistent with the hypothesis that AVP acts as an endogenous antipyretic within the VSA during fever. Moreover, the data suggest a possible role for centrally acting vasopressin during pyrogenic tolerance to E. coli endotoxin.
Antiserum against tumor necrosis factor increases stress hyperthermia in rats
Authors: Long N. C. , Vander A. J. , Kunkel S. L. , Kluger M. J.
Published: December 2017

Psychological stress (e.g., exposure to a novel environment) causes a rapid rise in body temperature in rats. In this study, we examined the roles of physical activity and the immune cytokine tumor necrosis factor or cachectin (TNF) in this temperature change. The elevation in temperature of rats exposed to cage-switch stress during the day correlated poorly with the increase in activity (r = 0.07; P = 0.84) and, during cage switch at night, correlated negatively (r = 0.64; P = 0.04). TNF was not detected in the plasma or cerebrospinal fluid of rats after exposure to open-field stress. However, the injection of antiserum against TNF 3.5 h before exposure to the stress of being in an open field resulted in a significantly greater hyperthermia than was seen in the control serum-injected rats (1.38 +/- 0.11 vs. 0.79 +/- 0.14 degrees C; P = 0.002). The peak temperature change after cage-switch stress was similarly increased in rats that had been injected with anti-TNF (0.82 +/- 0.08 vs. 0.50 +/- 0.08 degrees C; P = 0.016). This enhanced hyperthermia is similar to the excessively high fever that occurs during the later phase of lipopolysaccharide fever in animals that have been injected with antiserum against TNF. These data support the hypotheses that stress hyperthermia is a true fever and that TNF is an endogenous antipyretic, limiting the magnitude of this fever.
Time course of EEG power density during long sleep in humans
Authors: Dijk D. J. , Brunner D. P. , Borbely A. A.
Published: December 2017

In nine subjects sleep was recorded under base-line conditions with a habitual bedtime (prior wakefulness 16 h; lights off at 2300 h) and during recovery from sleep deprivation with a phase-advanced bedtime (prior wakefulness 36 h; lights off at 1900 h). The duration of phase-advanced recovery sleep was greater than 12 h in all subjects. Spectral analysis of the sleep electroencephalogram (EEG) revealed that slow-wave activity (SWA; 0.75-4.5 Hz) in non-rapid-eye-movement (NREM) sleep was significantly enhanced during the first two NREM-REM sleep cycles of displaced recovery sleep. The sleep stages 3 and 4 (slow-wave sleep) and SWA decreased monotonically over the first three and four NREM-REM cycles of, respectively, base-line and recovery sleep. The time course of SWA in base-line and recovery sleep could be adequately described by an exponentially declining function with a horizontal asymptote. The results are in accordance with the two-process model of sleep regulation in which it is assumed that SWA rises as a function of the duration of prior wakefulness and decreases exponentially as a function of prior sleep. We conclude that the present data do not provide evidence for a 12.5-h sleep-dependent rhythm of deep NREM sleep.
Role of interleukin 6 in fever in rats
Authors: LeMay L. G. , Vander A. J. , Kluger M. J.
Published: December 2017

The purpose of these studies was to assess whether interleukin 6 (IL-6) is an endogenous pyrogen, responsible for all or part of the fever caused by lipopolysaccharide (LPS) in rats. We have found that the core temperature (as measured by biotelemetry) rose significantly after intracerebroventricular (icv) injection of recombinant human IL-6. The same doses of IL-6, when administered intravenously or intraperitoneally, had no effect on body temperature. The fever caused by icv administration of IL-6 was completely blocked by indomethacin. After injection of fever-inducing doses of LPS, the plasma and cerebrospinal fluid (CSF) IL-6 activities rose, the former much more than the latter. The correlation between fever and plasma IL-6 activity was r = 0.84 (P less than 0.0025); the correlation between fever and CSF IL-6 activity was r = 0.77 (P less than 0.015). The results of this study are consistent with the hypothesis that IL-6 is a mediator of LPS-induced fever in the rat.
Metabolic control in exercising skeletal muscle
Authors: Connett R. J. , Honig C. R.
Published: December 2017

Pages R288–R290: Letters to the Editor, Reply, R. J. Connett and C. R. Honig. “Metabolic control in exercising skeletal muscle.“ The sentence beginning at the very bottom of page R289 and continuing at the top of page R290 should read: ”The salient feature of the system is that the concentrations of ADP, ATP, PCr, Cr, and Pi are so interdependent through the actions of creatine kinase and adenylate kinase that the system has only one degree of freedom: measurement of change in any one of the above compounds completely defines the change in any of the others (1).”
Central nervous system injection of dynorphin-(1-13) overrides gastric satiety factors in sheep
Authors: Della-Fera M. A. , Baile C. A. , Coleman B. D. , Miner J. L. , Paterson J. A.
Published: December 2017

Signals from the gastrointestinal (GI) tract, arising during ingestion and digestion of food, are important in the termination of feeding. This study was carried out to determine whether the satiety triggered by specific GI stimuli in sheep could be reversed by central nervous system (CNS) administration of dynorphin, a putative endogenous kappa-opiate receptor ligand, which has been shown to be a potent feed-intake stimulant in many species. Rumen distension and increased intraruminal concentration of propionic acid (an energy substrate produced during fermentation in the rumen) both significantly decreased feed intake in fasted sheep. When either of these stimuli were combined with continuous 60-min lateral cerebroventricular injection of [D-Ala2]dynorphin A-(1-13) (0.32 nmol/min), feed intake returned to control levels. Increasing feed intake in food-producing animals is an important way of improving production efficiency. The findings of these experiments illustrate how manipulation of a CNS opioid system can modify the effects of feed intake-limiting factors generated by ingestion of a meal, thereby promoting greater feed intake.
Role of catecholamines in regulating ovine median eminence blood flow
Authors: Page R. B. , Gropper M. , Woodard E. , Townsend J. , Davis S. , Bryan R. M.
Published: December 2017

Blood flow was measured in the ovine median eminence and neural lobe before and after the intravenous infusion of dopamine (n = 7), the D1 agonist SKF 38393 (n = 4), the D2 agonist bromocriptine (n = 4), and the dopamine antagonist haloperidol (n = 5). It was also measured before and after the intracarotid infusion of dopamine into eight naive sheep and seven sheep pretreated with phenoxybenzamine. Radiolabeled microspheres were used to determine regional cerebral and regional neurohypophysial blood flows (RNHBF) in these 35 adult female sheep anesthetized with pentobarbital sodium. Samples for serum prolactin measurement by radioimmunoassay were obtained before and after drug infusion. Intravenous dopamine infusion did not change median eminence or neural lobe blood flow (RNHBF) but increased renal and choroid plexus blood flow. Intravenous haloperidol caused a significant fall in RNHBF and blood flow in choroid plexus, caudate nucleus, and kidneys. Intracarotid dopamine infusion decreased RNHBF but increased choroid plexus blood flow. RNHBF was significantly greater in the seven sheep pretreated with phenoxybenzamine than in the eight naive sheep. These findings do not support a role for dopamine in the regulation of median eminence blood flow. The last observation does add support to the hypothesis that norepinephrine or epinephrine interaction with alpha-receptors plays a role in the control of ovine median eminence blood flow and hence in the regulation of delivery of humoral messages from the brain to the anterior pituitary gland.
Cardiovascular changes after closure of uterine circulation during pregnancy
Authors: Valenzuela G. J. , Kim S. , Rauld H. F.
Published: December 2017

To assess the effects of the presence of the uteroplacental circulation on the systemic arterial pressure, blood volume, and cardiac output during pregnancy, we measured those variables and plasma renin activity (PRA) during a 30-min period before and after occlusion of the uterine circulation. After uterine vascular occlusion, pregnant rabbits (n = 7) experienced a drop in mean arterial pressure of 8.7%, heart rate of 9.5%, cardiac output of 30.2%, and hematocrit of 18.2% (each with P less than 0.05). Stroke volume decreased an average of 29.7%; however, it did not reach significance. PRA and venous pressure did not change significantly from the control period (P greater than 0.1). Nonpregnant rabbits did not experience changes in arterial or venous pressures, hematocrit, heart rate, cardiac output, or PRA after closure of the uterine circulation. To exclude the possibility that the findings were secondary to the release of toxic products to the peritoneal cavity by the ischemic pregnant uterus, we also studied the effect of closure of the uterine circulation in five anesthetized pregnant guinea pigs. These animals' uteri were exteriorized and maintained in a sealed plastic container during the experiment. In these animals, arterial pressure decreased 15.6% by 10 min (P less than 0.05). The finding of a significant decrease in arterial pressure and heart rate is compatible with the idea that the uterine circulation produces a substance with a short half-life that has a significant direct effect on the heart and/or systemic vascular tone.
A feverlike response inhibits expression of delayed-type hypersensitivity in rats
Authors: Banet M.
Published: December 2017

To determine the effect of fever on cell-mediated immunity, the preoptic area of male rats was cooled after either a sensitizing or a challenge injection of keyhole-limpet hemocyanin, and the delayed-type hypersensitivity inflammatory response was measured. Cooling the preoptic area for 5 days, starting shortly after the sensitizing injection of antigen, did not speed up the development of the capacity to respond to a challenge injection of antigen nor did it influence the magnitude of the resulting inflammatory response. In sensitized animals, however, cooling the preoptic area for 24 h, starting shortly after the challenge injection of antigen, raised core temperature to an average of 40 degrees C and decreased the magnitude of the inflammatory response by 25%, whereas heating the preoptic area caused a fall in core temperature to an average of 35 degrees C and increased the response by about 25%. There was, in fact, a moderate negative correlation (r = 0.85) between core temperature and the size of the inflammation. Furthermore, the inhibitory effect of cooling the preoptic area could be blocked neither by adrenalectomy nor by diazepam (0.5 mg/kg body wt), a drug that suppresses most endocrine responses to stress. It is therefore suggested that the expression of delayed-type hypersensitivity is inhibited at elevated body temperatures and that fever may thus weaken the defenses of the host against infection.
Functional significance of metabolic responses to thermal acclimation in fish muscle
Authors: Guderley H.
Published: December 2017

Compensatory increases of the aerobic capacity of fish swimming muscle are frequently observed in response to cold acclimation. Such thermal compensation occurs both in fish that remain active in the cold and in fish that become dormant at cold temperatures. For cold-active fish, positive thermal compensation is best explained by conservation of the capacity for aerobic metabolic flux at low temperatures. The compensatory responses of cold-active species can be used to suggest the temperature range over which the activities of glycolytic and tricarboxylic acid cycle enzymes in a muscle, i.e., the muscle's "metabolic profile," can suffice. Analysis of the available data suggests that a 16 degrees C range of temperatures cannot be covered by one metabolic profile, even when the preferred temperatures are centered between the acclimation temperatures. For cold-inactive species that remain normoxic during winter dormancy, the compensatory metabolic modifications may facilitate lipid catabolism. Alternately, an increased aerobic capacity may be adaptive during the relatively cold periods that precede and follow winter dormancy. For goldfish and carp that encounter hypoxia and anoxia during winter dormancy, increased mitochondrial abundance could facilitate ethanol production during anoxia and the diffusion of oxygen to mitochondria during hypoxia. Finally, metabolic modifications during natural acclimatization indicate both thermal compensation and direct thermal effects and suggest that thermal compensation may be masked by reproductive and feeding activities.
Large synergism between monosodium glutamate and 5'-nucleotides in canine taste nerve responses
Authors: Kumazawa T. , Kurihara K.
Published: December 2017

The taste responses to the "umami" substances such as monosodium glutamate (MSG), GMP, and IMP were recorded from the chorda tympani nerve of mongrel dogs and beagles. A large synergism was observed between MSG and two species of nucleotides (GMP and IMP) in most mongrel dogs and between MSG and three species of nucleotides (GMP, IMP, and AMP) in beagles. The extent of the synergism between MSG and the nucleotides was much larger than that observed in any other animals examined except for humans. In the presence of GMP, the response magnitude of the chorda tympani nerve to MSG was increased but that to NaCl, HCl, sucrose, quinine, and glycine was unchanged. It was concluded that the canine taste responses to the umami substances closely resemble those in humans, and the dog is a suitable animal model for studies on the responses to the umami substances.
Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats
Authors: Shapira S. , Adeyemo O. M. , Feuerstein G.
Published: December 2017

omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.
Beta-cell hyperresponsiveness: earliest event in development of diabetes in monkeys
Authors: Hansen B. C. , Bodkin N. L.
Published: December 2017

Diabetes develops spontaneously in some, but not all, obese middle-aged monkeys. Longitudinal study of spontaneously obese rhesus monkeys has now shown the separation in time of the onset of various abnormalities associated with non-insulin-dependent diabetes mellitus (NIDDM). Glucose tolerance and acute and late insulin release were assessed at 6-mo to 1-yr intervals over a period of 7 yr in six young, lean, normal animals and 14 middle-aged obese, initially normoglycemic monkeys. Over 2-5 yr, while under study, five of the obese subjects developed overt diabetes [fasting plasma glucose greater than 140 mg/dl and decreased glucose disappearance rates (KG) less than 1.5]. Progressively increasing hyperinsulinemia leading to a 10-fold increase in basal plasma insulin levels (mean +/- SE = 443 +/- 69 microU/ml) and a fivefold increase in insulin response to glucose occurred independent of degree of obesity and before hyperglycemia. Later, basal and stimulated insulin levels declined before significant hyperglycemia. We conclude that in the monkey beta-cell function is clearly enhanced, not reduced, in the earliest stages of the progression to NIDDM but is reduced just before overt diabetes.
Norepinephrine sensitivity of mesenteric veins in pregnant rats
Authors: Hohmann M. , Keve T. M. , Osol G. , McLaughlin M. K.
Published: December 2017

This study was designed to test the hypothesis that during the course of pregnancy there is a decrease in the venous response to adrenergic stimulation that is characterized by a decrease in venoconstriction to both exogenous norepinephrine (NE) and to transmural electric stimulation of endogenous sympathetic nerves. Capacitance-size mesenteric veins were removed from nonpregnant and early- (7/8 day) and late-pregnant (18/19 and 20/21 day) Sprague-Dawley rats and studied in vitro under pressurized conditions. Lumen diameter was measured continuously by a video-electronic method. There was a marked increase in the sensitivity of the veins to exogenous NE stimulation at the end of pregnancy, which was most dramatic at a transmural pressure of 6 compared with 2 mmHg. The increase in exogenous NE sensitivity was associated with a progressive decline in the response to transmural nerve stimulation during pregnancy. Cocaine, an inhibitor of neuronal uptake, resulted in a greater potentiation of the response to transmural nerve stimulation in the pregnant rats compared to controls, suggesting an increased reuptake mechanism during pregnancy. Additional studies in the pseudopregnant, lactating, and nonlactating rat suggested that the conceptus was necessary for the alterations in neural response but not for the increase in exogenous NE sensitivity. In conclusion there is a dramatic change in venous function during pregnancy in the rat that is characterized by a difference between endogenous and exogenous NE sensitivity. The fact that transmural pressure can profoundly affect exogenous NE sensitivity suggests that pregnancy-induced changes in venous volume could contribute to changes in venous reactivity.
Light-dark cycle modulates drinking to homeostatic challenges
Authors: Johnson R. F. , Johnson A. K.
Published: December 2017

Both homeostatic and rhythmic variables are empirically and theoretically important controls of behavior. Yet, drinking behavior has been studied largely from one point of view or the other. The present study examined both homeostatic and rhythmic variables and found evidence for an important interaction of these two types of control of drinking behavior. The drinking rhythm of rats on a light-dark cycle was established. Water intake after cellular- or extracellular-related challenges was then measured both at a time of a peak and at a time of a trough of the drinking rhythm. The results indicate that rats drink more water after challenges in their early active phase than in their early inactive phase. The results demonstrate that rhythmic variables modulate the homeostatic controls of drinking behavior. The importance of the interaction of homeostatic and rhythmic variables in models of integrative control of behavior is discussed.
Metabolic differences between obesity-prone and obesity-resistant rats
Authors: Chang S. , Graham B. , Yakubu F. , Lin D. , Peters J. C. , Hill J. O.
Published: December 2017

We compared, across several physiological variables, rats most and least susceptible to develop obesity when given a high-fat diet. After 4 wk of eating a high-fat diet (60% of calories from fat), rats in the upper (obesity prone, OP) and lower (obesity resistant, OR) quartiles for weight gain were further studied. OP rats ate significantly more than OR rats, but this did not completely explain differences in their susceptibility to dietary obesity. No differences in 24-h energy expenditure were found between groups. OR rats had a significantly lower 24-h respiratory quotient, indicative of a greater relative proportion of fat oxidation and lower plasma levels of free fatty acids (FFA) than OP rats. Thus the ability to avoid dietary obesity produced by a high-fat diet may depend on an ability to increase fat oxidation in response to increased fat intake. Insulin sensitivity, measured by a euglycemic insulin clamp, was significantly higher in OR than OP rats. We cannot determine from these data whether insulin resistance developed as a consequence of elevated FFA levels or whether the ability to oxidize FFA declined as a result of development of insulin resistance. In summary, we propose that rats able to resist becoming obese on a high-fat diet have the ability to adjust the composition of fuel oxidized to the fuel composition of the diet with a minimum increase in body fat. The specific mechanisms by which this occurs are unknown but may be related to effects of diet on insulin sensitivity.
Effects of diet and body fat content on cold-induced anestrus in Syrian hamsters
Authors: Schneider J. E. , Wade G. N.
Published: December 2017

Mammalian reproduction is inhibited by food shortages, increased foraging requirements, and other factors that decrease the energy available for biological processes. Cold-induced inhibition of reproduction may result from a depletion of available metabolic energy due to the increased requirements for thermogenesis or, alternatively, from mechanisms unrelated to energy expenditure. We examined the relationship between energy availability (in the diet and the body fat stores) and cold-induced anestrus in Syrian hamsters. In experiment 1, hamsters were housed in the cold (5 degrees C) and fed diets that differed in the amount of effort required to ingest them. The number of consecutive estrous cycles was positively correlated with caloric intake and negatively correlated with body weight loss in the cold. In experiment 2, hamsters were fed these diets for several weeks, so that they differed dramatically in body weight and fat content before cold exposure. Half of each group retained the same diet during cold exposure, whereas the other half were fed a regular chow diet. The effects of body weight before cold exposure were less pronounced than the effects of caloric intake during cold exposure. In experiment 3, females were fed different diets before cold exposure, then, during cold exposure, all were fed in a manner that decreased food intake and increased the effort required to obtain food. This energetic challenge exaggerated the effect of prior body weight on the latency to cold-induced anestrus. Thus the latency to cold-induced anestrus in Syrian hamsters is primarily a function of the availability of metabolic energy.(ABSTRACT TRUNCATED AT 250 WORDS)
Basal and pentagastrin-stimulated gastric secretion in young horses
Authors: Campbell-Thompson M. L. , Merritt A. M.
Published: December 2017

Equine gastric secretion was studied using a gastric cannula model after fasting (basal) and pentagastrin infusion. Gastric secretory rate, pH, osmolality, and electrolyte concentrations and outputs were determined over a 5-h period. Dose-response tests estimated that the maximally effective intravenous dose of pentagastrin was between 3 and 6 micrograms.kg-1.h-1. Basal secretory rate was 278 +/- 29 (SE) ml/15 min, and the pH was 2.00 +/- 0.31. Pentagastrin infusion at 6 micrograms.kg-1.h-1 increased secretory rate to 533 +/- 60 ml/15 min and decreased pH to 1.41 +/- 0.11. Basal gastric acid concentration and output were 38 +/- 5 meq/l and 211 +/- 36 mu eg.kg-1.h-1, respectively. Pentagastrin increased acid concentration to 60 +/- 5 meq/l and acid output to 474 +/- 61 mu eq.kg-1.h-1. Gastric fluid osmolality remained hypotonic during both basal and pentagastrin conditions. Sodium concentration remained high in comparison with hydrogen ion concentration, and sodium output increased during pentagastrin infusion. Equine gastric secretion did not attain maximal acid concentrations nor the marked drop in pH, which has been reported for other monogastric species. These data suggest that in the horse a large nonparietal component exists that modifies parietal secretions and is increased by pentagastrin stimulation.
Axial heterogeneity of apical water permeability along rabbit kidney proximal tubule
Authors: Van Der Goot F. , Corman B.
Published: December 2017

In the rabbit nephron, the luminal membrane surface area of the proximal convoluted tubule (PCT) is more than twice that of the proximal straight tubule (PST). What seemed to be an increase in histological specialization in solute and water transport is curiously reflected by a lower transepithelial water permeability per unit of apical membrane area in PCT than in PST. To evaluate what change in luminal membrane water permeability corresponds to this morphological difference, the osmotic permeabilities (Pf) of brush-border membrane vesicles isolated from PCT and PST of rabbit kidney were compared. D-Glucose uptake rates indicated proper separation of two populations of vesicles. Vesicle size measured by quasi-elastic light scattering was 123 +/- 7 nm and 125 +/- 6 nm for vesicles isolated from PCT and PST, respectively. Pf obtained by stop-flow light scattering techniques was of 106 +/- 6 microns/s in PCT vesicles and 191 +/- 7 microns/s in PST vesicles (T = 26 degrees C). In the presence of the sulfhydryl reagent HgCl2, the water permeabilities of both types of membrane dropped to comparable values. These data, which show an 80% increase in apical water permeability along the length of the proximal tubule, suggest that the number of proteic water channels per unit of membrane area is greater in PST than in PCT.
Hypo- and hypercalcemic peptides in fish pituitary glands
Authors: Fraser R. A. , Kaneko T. , Pang P. K. , Harvey S.
Published: December 2017

Immunoreactive parathyroid hormone (irPTH), PTH-related peptide (PTHrp), and stanniocalcin-like peptides were detected in Coho salmon pituitary glands. The PTH, PTHrp, and stanniocalcin immunoreactivity of the salmon pituitary was separated by high-performance liquid chromatography purification into distinct peptide fractions that coeluted with pure preparations of these hormones. Stanniocalcin was localized by immunocytochemistry in the neurohypophysis and preoptic area of the platyfish brain, in areas in which irPTH has previously been detected in other teleosts. Although it is well established that the fish pituitary exerts hypercalcemic control over calcium metabolism, these results demonstrate the presence of hyper- and hypocalcemic peptides in teleost pituitary glands. The detection of PTHrp in the fish pituitary is the first report of its presence outside of mammalian species and suggests an early evolutionary divergence of PTH and PTHrp from an ancestral gene.
Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats
Authors: Blake M. J. , Fargnoli J. , Gershon D. , Holbrook N. J.
Published: December 2017

An age-related impairment in the induction of heat-shock proteins (HSPs), which are thought to comprise a protective or adaptive response to cellular stress, may contribute to a reduction in thermal tolerance with age. When 5- and 24-mo-old rats were exposed to ambient temperatures of 23, 35, 37.5, or 40 degrees C for 90 min, a graded increase in the level of HSP70 mRNA expression was observed in brain, lung, and skin of animals from both groups. However, at temperatures above 23 degrees C, HSP70 expression was less in tissues of older rats when compared with those of young animals. This relative decline of heat-induced HSP70 mRNA levels with age correlated with an attenuated increase in colonic temperature (Tc) of old rats resulting from heat exposure. In other experiments, it was determined that the duration of hyperthermia was also an important factor in determining the level of HSP70 mRNA expression in vivo. Thus age-related differences in heat-induced HSP70 mRNA expression appear to result from differences in Tc due to heat stress rather than an impairment in the regulation of HSP70 gene expression.
Hyperglycemia induces accumulation of glucose in human skeletal muscle
Authors: Katz A. , Raz I. , Spencer M. K. , Rising R. , Mott D. M.
Published: December 2017

The effect of hyperglycemia on whole body substrate utilization and the metabolic profile of skeletal muscle has been investigated. Eight glucose-tolerant men were infused with somatostatin (S) for 190 min. During the last 120 min of S infusion, glucose was infused to achieve a steady-state plasma level of 26 mmol/l. Biopsies were obtained from the quadriceps femoris muscle immediately before and 35 and 120 min after induction of hyperglycemia. Steady-state glucose disposal during hyperglycemia averaged (+/- SE) 33.8 +/- 3.2 mumol.kg fat-free mass-1.min-1, and approximately 70% of the glucose disposal was accounted for by skeletal muscle. Intracellular glucose increased from 0.9 +/- 0.2 mmol/kg dry wt during S to 9.5 +/- 2.5 during hyperglycemia (P less than 0.01). It was estimated that approximately 35% of the glucose taken up by muscle during 120 min of hyperglycemia was not phosphorylated. Muscle contents of alpha-D-glucose 1,6-diphosphate, D-glucose 6-phosphate, ATP, ADP, and AMP (both of which are based on the phosphocreatine-to-creatine ratio), which have been shown to inhibit hexokinase in vitro, did not change significantly during hyperglycemia, nor were there any significant changes in any of the other postphosphofructokinase intermediates, D-fructose 2,6-diphosphate, and citrate. Hyperglycemia did not alter the fractional activities of glycogen synthase or phosphorylase, nor total phosphorylase activity. However, hyperglycemia resulted in a 55% increase in glycogen synthase-specific activity (P less than 0.01). It is concluded that hyperglycemia results in a marked increase in muscle glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypothalamic NE release and cardiovascular response to NaCl in sinoaortic-denervated rats
Authors: Nakata T. , Berard W. , Kogosov E. , Alexander N.
Published: December 2017

We determined the activity of noradrenergic neurons in the nucleus of the posterior hypothalamus (PH) of sinoaortic-denervated (SAD) and sham-operated (SO) rats during cardiovascular responses to intravenous (iv) or local brain dialysis of NaCl. PH extracellular norepinephrine (NE) was collected by microdialysis from freely moving rats, and dialysate NE was measured by radioenzymatic assay. Three days after SAD or SO, mean arterial pressure (MAP) and heart rate (HR) were significantly higher in SAD rats than SO rats. Basal levels of PH dialysate were also significantly elevated in SAD rats. Local dialysis of PH with hypertonic NaCl produced pressor and tachycardiac responses coupled with increased NE release in PH in both groups, but the increases in MAP and dialysate NE were larger in SAD than SO rats. Ganglionic blockade with iv hexamethonium elicited significantly larger depressor and bradycardiac responses in SAD rats, whereas the percent increase of dialysate NE was smaller than that of SO rats. The iv infusion of hypertonic NaCl produced larger pressor responses in SAD than SO rats and a significant increase in dialysate NE from PH of SAD but not SO rats. These findings indicate that 1) PH is an important site of NaCl action and 2) noradrenergic input in PH receives tonic inhibitory input from baroreflex pathways and contributes to cardiovascular hyperactivity and hypertension in SAD rats.
High salt mimics effects of light pulses on circadian pacemaker in cultured chick pineal cells
Authors: Zatz M. , Wang H. M.
Published: December 2017

Chick pineal cells in static culture display a persistent photosensitive circadian rhythm of melatonin production and release. Pulses of white light or darkness, in otherwise constant red light, induce phase shifts in subsequent cycles whose magnitude and direction depend on the phase at which the pusle is given. Such "phase-dependent phase shifts" are mediated by effects on the underlying pacemaker. We reported previously that inhibiting the Na+-K+-adenosinetriphosphatase with ouabain evokes phase shifts with the same phase dependence as those induced by pulses of darkness. Two of the consequences of inhibiting the Na+ pump are membrane depolarization and cell swelling. To test the relevance of these effects and to distinguish between them, we exposed chick pineal cells to pulses of high concentrations of added KCl, which should cause both membrane depolarization and cell shrinkage. We also compared the effects of added NaCl, sodium gluconate, and mannitol, which should cause cell shrinkage without comparable depolarization. Each of these hypertonic solutions induced phase shifts in the melatonin rhythm with the same phase dependence as those caused by pulses of light rather than those caused by ouabain or darkness. These results argue strongly against a dominant role for changes in membrane potential in phase shifting the melatonin rhythm. Rather, they suggest that cell swelling may mediate the darklike effects of ouabain on the circadian pacemaker in chick pineal cells and indicate that cell shrinkage mimics the effects of light.
Delayed treatment with an LTD4/E4 antagonist limits pulmonary edema in endotoxic pigs
Authors: Fink M. P. , Kruithoff K. L. , Antonsson J. B. , Wang H. L. , Rothschild H. R.
Published: December 2017

We used a selective leukotriene (LT) D4/E4 receptor antagonist (LY 203647) to investigate the role of cysteinyl LTs as mediators of several important pathophysiological events in a porcine model of endotoxic shock. Pentobarbital-anesthetized pigs (11.8-17.5 kg) were mechanically ventilated with 100% O2. Pigs in groups I (n = 10), IIA (n = 10), and IIB (n = 5) were infused with Escherichia coli lipopolysaccharide (LPS; 250 micrograms/kg) from time (t) = 0-20 min. Pigs in group III (n = 3) were normal controls. All pigs were resuscitated from t = 0-240 min with Ringer lactate (0.8 ml.kg-1.min-1). Pigs in group I received no further treatment. At t = 30 min, groups IIA and IIB were injected with LY 203647 (30 mg/kg) and were started on an infusion of the compound at 10 (group IIA) or 30 mg.kg-1.h-1 (group IIB). Delayed treatment with LY 203647 significantly (P less than 0.05) and persistently ameliorated LPS-induced pulmonary hypertension. The compound also abrogated LPS-induced pulmonary edema, as assessed by gravimetrically determined lung extravascular wet-to-dry weight ratios. Despite its beneficial effect on pulmonary edema, delayed treatment with LY 203647 did not improve arterial oxygenation. Delayed treatment with LY 203647 transiently improved mesenteric perfusion. These data suggest that cysteinyl LTs are important mediators in porcine endotoxicosis.
Emesis, learned aversion, and chemical defense in octocorals: a central role for prostaglandins?
Authors: Gerhart D. J.
Published: December 2017

Prostaglandin A2 and its ester derivatives comprise as much as 8% of the wet tissue weight of some octocoral species such as Plexaura homomalla (phylum Cnidaria, class Anthozoa, subclass Octocorallia). These high levels of prostaglandins, although initially palatable to fish, may function as defensive toxins by inducing emesis and learned aversions in potential predators. As the fish Fundulus heteroclitus and Halichoeres garnoti gain experience through the course of experiments, they increasingly reject foods containing emetic prostaglandins, but do not alter their acceptance of untreated control foods. Emesis is also induced in fish by consumption of tissue or lipid extracts from the subtropical whip coral Leptogorgia virgulata (subclass Octocorallia, order Gorgonacea). The emetic properties of L. virgulata induce learned aversions in the fish Micropterus salmoides and Morone saxatilis. Extracts of L. virgulata do not contain high levels of prostaglandins but do, however, contain other metabolites that appear to mimic the effects of eicosanoids. Some nonprostanoid secondary metabolites may induce emesis by stimulating prostaglandin biosynthesis in the gastric mucosa of predators.
Compartmentalization of prostaglandin synthesis within the fish ovary
Authors: Goetz F. W.
Published: December 2017

Numerous studies have shown that the follicle walls surrounding mature vertebrate oocytes are capable of producing primary prostaglandins. However, very few studies have looked at the prostaglandin synthetic potential of other ovarian tissue components. In brook trout (Salvelinus fontinalis) and goldfish (Carassius auratus), mature follicle walls can produce prostaglandins E and F (PGE and PGF, respectively); however, it is apparent that several other tissues within the fish ovary also produce specific primary PGs. Incubation of stroma or connective tissue from brook trout and goldfish ovaries with [14C]-arachidonic acid resulted in a very significant production of PGE2, whereas small immature oocytes of both species produced primarily PGF2 alpha. While the function of the primary prostaglandins produced by tissues external to the mature oocytes is unknown, it is important to recognize that multiple sites for prostaglandin synthesis are present within the fish ovary.