bluuebunny/crossref_metadata_2025 huggingface dataset:
Baroreflex attenuation after hypotension induced by vena caval occlusion in anesthetized dogs
Authors: Sawano F. , Shibamoto T. , Hayashi T. , Saeki Y.
Published: December 2017

We determined effects of vena caval occlusion-induced systemic hypotension of 50 mmHg lasting 10 min (VCO) on efferent sympathetic nerve activity (SNA) and sympathetic baroreflex responsiveness. We recorded simultaneously SNA to the kidney (RNA), heart (CNA), spleen (SpNA), and liver (HNA) in anesthetized dogs. Baroreflex sensitivity was assessed using the ratio of a reflex SNA increase to a mean arterial pressure fall, which was also induced by caval occlusion. During VCO, SNA initially and equivocally increased, followed by recovery toward baseline. Cervical vagotomy attenuated the VCO-induced initial sympathoexcitation and subsequently maintained SNA at higher levels than those of intact animals, a finding basically similar to hemorrhagic hypotension [S. Koyama, F. Sawano, Y. Matsuda, Y. Saeki, T. Shibamoto, T. Hayashi, Jr., Y. Matsubayashi, and M. Kawamoto. Am. J. Physiol. 262 (Regulatory Integrative Comp. Physiol. 31): R579-R585, 1992]. At 5 min after releasing VCO, the baroreflex responsiveness was significantly attenuated: RNA, 79 +/- 11%; CNA, 78 +/- 8%; HNA, 60 +/- 16%; SpNA, 81 +/- 13% of the corresponding baseline. Fifteen minutes after VCO, this attenuation disappeared. Either vagotomy or pretreatment with intravenous vasopressin V1 receptor antagonist abolished this baroreflex attenuation. In conclusion, systemic hypotension to 50 mmHg for 10 min causes transient attenuation of sympathetic baroreflex sensitivity due to circulating vasopressin released by unloading of cardiopulmonary receptors during hypotension.
Dissociation between food intake, diet composition, and metabolism in parabiotic partners of obese rats
Authors: Harris R. B. , Martin R. J. , Bruch R. C.
Published: December 2017

When one member of a parabiosed pair of rats is overfed, its ad libitum-fed partner loses body fat in the absence of a statistically significant decrease in food intake. Three experiments investigated the relationships between food intake, metabolism, and body composition in this model. In vivo measurement of lipogenesis confirmed that loss of fat is associated with decreased fat deposition. When partners of overfed rats were compared with food-restricted single rats, proportional changes in body composition and metabolism were similar for the two treatments, although there was no significant change in the food intake of parabiotic rats, whereas restricted rats received only 60% of the intake of their controls. The final experiment demonstrated that changes in body composition of partners of overfed rats were independent of dietary composition. These results suggest that, when a rat is made obese by overfeeding, a circulatory factor is released that inhibits fat deposition and disrupts regulatory mechanisms that normally stimulate food intake during a period of negative energy balance.
Interleukin-1 increases splenic blood flow by affecting the sympathetic vasoconstrictor tonus
Authors: Rogausch H. , Del Rey A. , Kabiersch A. , Besedovsky H. O.
Published: December 2017

The possibility that interleukin-1 (IL-1), a cytokine involved in immune and inflammatory mechanisms, can affect the blood flow of the spleen was considered because changes in spleen perfusion can affect immune cell recirculation, traffic, and homing. The results indicate that administration of a subpyrogenic dose of IL-1 induced a pronounced increase in splenic blood flow. This was not a general effect, because no change in blood flow of skeletal muscle was noticed. The studies also show that 1) the increase in splenic perfusion induced by IL-1 is to a large extent independent from the secondary induction of nitric oxide (NO), 2) the splenic blood flow in the rat is under sympathetic control, and 3) the effect of IL-1 on splenic blood flow is completely abrogated after surgical interruption of the splenic nerve, which is predominantly composed of sympathetic fibers. It is concluded that the IL-1-mediated increase in splenic blood flow is most likely based on the inhibition of the sympathetic vasoconstrictor tonus in the rat spleen. These results show that a cytokine released by activated immune cells can regulate the blood flow of a main lymphoid organ, the spleen, by affecting mechanisms under neural control.
Effects of Ca2+ ionophore ionomycin on insulin-stimulated and basal glucose transport in muscle
Authors: Lee A. D. , Gulve E. A. , Chen M. , Schluter J. , Holloszy J. O.
Published: December 2017

There is evidence that an increase in sarcoplasmic Ca2+ stimulates glucose transport in muscle. Recent studies have provided the apparently conflicting finding that a sustained increase in cytosolic Ca2+ has little effect on basal glucose transport but inhibits insulin-stimulated transport. This study was done to try to explain this discrepancy. Continuous exposure of rat epitrochlearis and soleus muscles to the Ca2+ ionophore ionomycin (2 microM) had no effect on basal 2-deoxyglucose (2-DG) transport but blunted, by approximately 40%, stimulation of 2-DG transport by insulin. Decreasing Ca2+ in the medium to a very low level prevented this inhibition. Ionomycin induced a small increase in adenosine 3',5'-cyclic monophosphate (cAMP); however, studies with the protein kinase A (PKA) inhibitor HA-1004 provided evidence that activation of PKA by cAMP does not mediate the inhibition of glucose transport. When muscles were allowed to recover in the absence of ionomycin for 15 min, basal 2-DG transport was significantly increased. Our results agree with previous studies showing that a sustained influx of Ca2+ into the cytoplasm can inhibit insulin-stimulated glucose transport. They further show that stimulation of glucose transport by Ca2+ is also inhibited. A recovery period that allows this inhibition to wear off unmasks the stimulation of glucose transport by an increase in sarcoplasmic Ca2+.
Sympathoexcitatory influence of a fast conducting raphe-spinal pathway in the rat
Authors: Zhou S. Y. , Gilbey M. P.
Published: December 2017

Experiments were carried out on 20 pentobarbitone sodium (alpha-chloralose supplemented)-anesthetized, artificially ventilated, and paralyzed rats. The possibility was explored that raphe-spinal neurons with myelinated axons arising in the rostral part of raphe obscurus provide excitatory drive to sympathetic neurons. Electrical stimulation within obscurus was observed to evoke an “early” sympathoexcitatory response compatible with its conduction over such a pathway. The effect of the microinjection of excitatory and inhibitory amino acids [DL-homocysteic acid (DLH) and gamma-aminobutyric acid (GABA), respectively] on the evoked response was studied at the sites of electrical stimulation. The size of the early response was increased by 91.7 +/- 24.4% (n = 7) and depressed by -48 +/- 4.8% (n = 7) by DLH and GABA, respectively. Saline was without effect (-14.5 +/- 12.2%, n = 6). The evoked responses were decreased when blood pressure was raised by administration of phenylephrine (2-6 micrograms/kg iv) and totally suppressed by an increase in blood pressure of 19.3 +/- 4.3 mmHg (baseline 89.1 +/- 2.5 mmHg, n = 7). It is concluded that some cell bodies located in rostral raphe obscurus that project to the spinal cord relay excitatory drive to sympathetic neurons.
Powerful depressor and sympathoinhibitory effects evoked from neurons in the caudal raphe pallidus and obscurus
Authors: Coleman M. J. , Dampney R. A.
Published: December 2017

Microinjection of glutamate into sites within the medullary raphe nuclei (pallidus and obscurus) at levels caudal to the obex resulted in a dose-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate in anesthetized rabbits. The depressor and sympathoinhibitory responses were similar in magnitude to those elicited from the previously described depressor region in the caudal ventrolateral medulla (CVLM) but had a shorter duration, in both intact and barodenervated animals. The bradycardia was not altered by barodenervation but was reduced after administration of propranolol or atropine and abolished after administration of both drugs. The neuroinhibitory compounds gamma-aminobutyric acid or muscimol had no effect on MAP or RSNA when injected into the caudal medullary raphe nuclei but evoked a pressor and sympathoexcitatory response when injected into the CVLM. The results indicate that neurons within the caudal raphe pallidus and obscurus can powerfully inhibit sympathetic activity, but unlike sympathoinhibitory neurons in the CVLM, they are not tonically active and are not capable of producing sustained changes in arterial pressure and sympathetic activity.
Antioxidant defenses and metabolic depression in a pulmonate land snail
Authors: Hermes-Lima M. , Storey K. B.
Published: December 2017

During arousal from estivation oxygen consumption by land snails (Otala lactea) increases severalfold. To determine whether snails prepared for an accompanying rise in the rates of oxyradical generation by altering their antioxidant defense mechanisms, changes in the activities of antioxidant enzymes and lipid peroxidation products were quantified in foot and hepatopancreas of control, 30-day estivating, and aroused snails. Compared with controls, estivating O. lactea showed significant increases in the activities of foot muscle superoxide dismutase (SOD) (increasing by 56-67%), catalase (51-72%), and glutathione S-transferase (79-108%), whereas, in hepatopancreas, SOD (57-78%) and glutathione peroxidase (93-144%) increased. Within 40 min after arousal began, hepatopancreas glutathione peroxidase activity had returned to control values, but SOD showed a further 70% increase in activity but then returned to control levels by 80 min. Estivation had no effect on total glutathione (GSH + 2 GSSG) concentrations in tissues, but GSSG content had increased about twofold in both organs of 30-day dormant snails. Lipid peoxidation (quantified as thiobarbituric acid reactive substances) was significantly enhanced at the onset of arousal from dormancy, indicating that oxidative stress and tissue damage occurred at this time. The data suggest that antioxidant defenses in snail organs are increased while snails are in the hypometabolic state as a preparation for oxidative stress during arousal.
Effect of chronic ANG I-converting enzyme inhibition on aging processes. V. Intracellular calcium-vasoreactivity coupling
Authors: Capdeville-Atkinson C. , Oster L. , Thorin-Trescases N. , Robert A. , Corman B. , Atkinson J.
Published: December 2017

Age-related changes in intracellular calcium ([Ca2+]i)-vasoreactivity coupling efficiency (i.e., perfusion pressure divided by [Ca2+]i) were studied in vitro in tail arteries of male, normotensive, WAG/Rij rats aged 6, 12, 24, or 30 mo; one-half of these were chronically treated with the angiotensin I-converting enzyme inhibitor (ACEI) perindopril (1 mg.kg-1.day-1 orally) from 6 mo onward. Arterial segments were perfused at a constant flow rate (perfusion pressure taken as an index of arterial tone) and loaded with the acetoxymethyl ester of fluorescent dye fura 2 (fura 2-AM). Increases in [Ca2+]i were measured simultaneously with vasoconstriction after stimulation with a depolarizing hyperkalemic solution or the agonists norepinephrine or serotonin. Age had no effect on increases in [Ca2+]i vasoconstrictor responses, or electromechanical coupling efficiency (hyperkalemic solution). Increases in [Ca2+]i after agonists were similar in all groups, but vasoconstrictor responses and pharmacomechanical coupling efficiency decreased with age. ACEI had no effect on vasoconstriction or [Ca2+]i signals. In conclusion, coupling efficiency after agonist stimulation decreased with age; ACEI had no effect on coupling efficiency.
Angiotensin II-induced thirst, but not sodium appetite, via AT1 receptors in organum cavum prelamina terminalis
Authors: el Ghissassi M. , Thornton S. N. , Nicolaidis S.
Published: December 2017

The angiotensin receptor specificity, with respect to fluid intake, of the organum cavum prelamina terminalis (OCPLT), a recently discovered discrete forebrain structure with high sensitivity to angiotensin II (ANG II), was investigated. ANG II (10 ng) microinjected into the OCPLT significantly increased water consumption but did not induce intake of a hypertonic (3%) NaCl solution. Losartan, an ANG II type 1 (AT1) receptor-specific antagonist, produced dose-related (1-100 ng) inhibition of ANG II-induced drinking. The ANG II type 2 receptor-specific antagonist CGP-42112A was ineffective. Intake of the 3% NaCl solution in response to microinjection of either of the antagonists into the OCPLT was never observed. These findings suggest that water intake produced by microinjection of ANG II into the OCPLT is mediated by AT1 receptors uniquely and that, in contrast to other regions of the brain, these receptors do not induce salt intake when stimulated by ANG II.
Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep
Authors: Porkka-Heiskanen T. , Smith S. E. , Taira T. , Urban J. H. , Levine J. E. , Turek F. W. , Stenberg D.
Published: December 2017

Noradrenergic locus ceruleus neurons are most active during waking and least active during rapid eye movement (REM) sleep. We expected REM sleep deprivation (REMSD) to increase norepinephrine utilization and activate the tyrosine hydroxylase (TH) gene critical for norepinephrine production. Male Wistar rats were deprived of REM sleep with the platform method. Rats were decapitated after 8, 24, or 72 h on small (REMSD) or large (control) platforms or after 8 or 24 h of rebound sleep after 72 h of the platform treatment. During the first 24 h, norepinephrine concentration, measured by high-performance liquid chromatography/electrochemical detection, was lower in the neocortex, hippocampus, and posterior hypothalamus in REMSD rats than in large-platform controls. After 72 h of REMSD, TH mRNA, measured by in situ hybridization, was increased in the locus ceruleus and norepinephrine concentrations were increased. Polygraphy showed that small-platform treatment caused effective and selective REMSD. Serum corticosterone measurement by radioimmunoassay indicated that the differences found in norepinephrine and TH mRNA were not due to differences in stress between the treatments. The novel finding of sleep deprivation-specific increase in TH gene expression indicates an important mechanism of adjusting to sleep deprivation.
Synchronization of cardiac-related discharges of sympathetic nerves with inputs from widely separated spinal segments
Authors: Gebber G. L. , Zhong S. , Barman S. M.
Published: December 2017

We used phase spectral analysis to study the relationships between the cardiac-related discharges of pairs of postganglionic sympathetic nerves in urethan-anesthetized or decerebrate cats. Phase angle when converted to a time interval should equal the difference in conduction times from the brain to the nerves (i.e., transportation lag) if their cardiac-related discharges have a common central source. Transportation lag was estimated as the difference in the onset latencies of activation of the nerves by electrical stimulation of the medulla or cervical spinal cord. The phase angle for the cardiac-related discharges of two nerves was not always equivalent in time to the transportation lag. For example, in some cases the cardiac-related discharges of the renal nerve were coincident with or led those of the inferior cardiac nerve. In contrast, the electrically evoked responses of the renal nerve lagged those of the inferior cardiac nerve by > or = 32 ms. These observations are consistent with a model of multiple and dynamically coupled brain stem generators of the cardiac-related rhythm, each controlling a different sympathetic nerve or exerting nonuniform influences on different portions of the spinal sympathetic outflow.
alpha 2-Macroglobulin gene expression during hibernation in ground squirrels is independent of acute phase response
Authors: Srere H. K. , Belke D. , Wang L. C. , Martin S. L.
Published: December 2017

alpha 2-Macroglobulin, a major acute phase reactant in many species, increases in the Richardson's ground squirrel (Spermophilus richarsonii) during hibernation at the level of both mRNA and protein. To determine if the pattern of liver gene expression known as the acute phase response is elicited as a normal part of the physiological adaptation of hibernation, acute phase reactants were identified in the Richardson's ground squirrel and were then assayed for changes in mRNA expression in the livers of active and hibernating ground squirrels. Our data demonstrate that alpha 1-antitrypsin, alpha 2-macroglobulin, ceruloplasmin, C-reactive protein, and serum amyloid A are acute phase reactants in the Richardson's ground squirrel. Of these, only alpha 2-macroglobulin (alpha 2M) mRNA increases during hibernation, demonstrating that the entire acute phase response is not elicited as a part of the adaptation for hibernation. Alternatively, data from blood clotting assays of serum from active and hibernating animals support a role for the increase in alpha 2M protein during hibernation in decreasing the coagulative properties of the blood.
Determinants of high-fat diet hyperphagia: experimental dissection of orosensory and postingestive effects
Authors: Warwick Z. S. , Weingarten H. P.
Published: December 2017

High-fat diets often promote greater caloric intake and/or weight gain than high-carbohydrate diets in both laboratory animals and humans. Because altering the fat content of a diet simultaneously changes both its sensory properties and postingestive effects, it is unclear whether high-fat hyperphagia is due to the diet's palatability, its postingestive effects, or both. The present studies isolated the independent capacity of the orosensory and postingestive effects of a liquid high-fat diet (High-Fat) to produce overeating relative to an isocaloric liquid high-carbohydrate (High-CHO) diet. Rats fed High-Fat orally ate more calories and gained more weight over 16 days than rats fed High-CHO orally. One-bottle sham-feeding intake of High-Fat and High-CHO did not differ, but in two-bottle sham-feeding tests High-Fat was clearly preferred. When orosensory influences on intake were equated via chronic self-regulated intragastric feeding, High-Fat still promoted greater intake than High-CHO, although absolute intake across both diets was lower during intragastric feeding relative to oral feeding. An analysis of short-term intake revealed that rats accustomed to infusion of High-CHO increased meal size immediately when switched to High-Fat. The present results, coupled with previous findings, suggest that the postingestive effects of fat enhance daily caloric intake in two ways: 1) during a meal, fat produces less suppression of intake per calorie than carbohydrate; and 2) after a meal, fat produces less suppression of intake per calorie during the intermeal interval than carbohydrate.
Development of metabolic enzyme activity in locomotor and cardiac muscles of the migratory barnacle goose
Authors: Bishop C. M. , Butler P. J. , Egginton S. , el Haj A. J. , Gabrielsen G. W.
Published: December 2017

Preflight development of the goslings was typified by rapid increases in the mitochondrial enzymes of the semimembranosus and heart ventricular muscles resulting in near-adult values by 3 wk of age. In contrast, aerobic capacity of the pectoralis muscle initially developed slowly but showed a rapid increase between 5 and 7 wk of age, in preparation for becoming airborne. Activities of glycolytic enzymes in the pectoralis muscle showed similar patterns of development as those found for the aerobic enzymes, except for hexokinase, which was low at all ages, indicating an adaptation for catabolism of both intracellular glycogen and plasma fatty acids in preference to plasma glucose. Muscle mass specific activity of citrate synthase in the pectoralis increased by only 33% from goslings during the first few days of flight, compared with premigratory geese. Activities of anaerobic glycolytic enzymes in the ventricles were low, but values for hexokinase, which is involved in the phosphorylation of plasma glucose, developed rapidly. Values for lactate dehydrogenase were also high, reflecting the capacity of the heart to catabolize plasma lactate. Substrate flux supplied by carnitine palmitoyltransferase and oxoglutarate dehydrogenase (OGD), in the pectoralis muscles of the premigratory geese, appears to have the smallest excess capacities to meet the requirements of sustained aerobic flight. The average maximum oxygen uptake for premigratory geese during flight, as indicated by values for OGD, is calculated to be 484 ml O2/min (or 208 ml O2.min-1.kg-1).
Linoleic and linolenic acids are selectively secreted in triacylglycerol by hepatocytes from neonatal rats
Authors: Emmison N. , Gallagher P. A. , Coleman R. A.
Published: December 2017

To determine whether specific fatty acids are metabolized differently by neonatal liver, hepatocyte cultures from neonatal (age: 5, 11, and 21 days) and adult rats were incubated with radiolabeled 18:1, 18:2, or 18:3. At each age, the rate of oxidation was highest for 18:3 and lowest for 18:1. Conversely, esterification was highest for 18:1 and lowest for 18:3. Fatty acid esterification was of the order: day 5 > day 11 > adult > day 21. When incubations contained each of two of the above fatty acids, one radiolabeled and the other not, 18:1 inhibited oxidation of radiolabeled 18:2 by up to 45% in neonatal hepatocytes. In addition, added 18:1 increased glycerolipid accumulation from 18:2 and 18:3. Under these conditions, the relative proportion of triacylglycerol secreted in the medium, compared with that accumulated in the cells, was two- to fourfold higher for day 11 and 21 rat hepatocytes. The results suggest that a specific mechanism exists in the livers of neonatal rats to spare n-3 and n-6 fatty acids from oxidation and instead secrete them in triacylglycerol.
Acidic fibroblast growth factor (FGF) but not basic FGF induces sleep and fever in rabbits
Authors: Knefati M. , Somogyi C. , Kapas L. , Bourcier T. , Krueger J. M.
Published: December 2017

Acidic fibroblast growth factor (FGF) and basic FGF belong to a growth factor family. Interleukin-1, another member of that family, is involved in sleep regulation. FGFs and interleukin-1 share structural and functional features. We therefore determined whether acidic FGF and basic FGF were somnogenic. Male New Zealand White rabbits were provided with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular (icv) cannula. The animals were injected icv with isotonic NaCl (control) and on separate days with one of three doses of acidic or basic FGF (0.01, 0.1, or 1.0 micrograms) or with heat-treated acidic FGF (1.0 micrograms). The EEG, brain temperature, and motor activity were recorded for 23 h. The biological activity of basic FGF was determined in vitro by its ability to induce DNA synthesis in rat aortic smooth muscle cells. Acidic FGF induced prolonged dose-related increases in non-rapid eye movement sleep beginning in the 1st postinjection h and continuing for 12-23 h after the treatment. Acidic FGF also induced fevers of approximately 1 degree C after the 1.0 micrograms dose. Both activities of acidic FGF were lost after heat treatment. In contrast, basic FGF lacked somnogenic and pyrogenic activity, although it did induce DNA synthesis. Current results suggest that acidic FGF is part of the complex cytokine network in brain involved in sleep regulation.
Central administration of prostaglandin E2 suppresses in vitro cellular immune responses
Authors: Rassnick S. , Zhou D. , Rabin B. S.
Published: December 2017

Research suggests that the regulation of the function of the immune system by the central nervous system (CNS) involves the integrative responses of multiple neural systems that affect neuroendocrine and sympathetic nervous systems. To determine whether prostaglandin E2 (PGE2) is involved in the modulatory mechanisms of immune system function, it was administered intracerebroventricularly (ICV) to conscious male rats. One hour later, spleen and peripheral blood lymphocytes were collected for culture with nonspecific mitogens. ICV administration of PGE2 decreased blood lymphocyte proliferative responses to the T-cell mitogens phytohemagglutinin and concanavalin A and decreased spleen lymphocyte proliferative responses to phytohemagglutinin and lipopolysaccharide (a B-lymphocyte mitogen). ICV administered PGE2 also stimulated the activity of the hypothalamic-pituitary-adrenal axis, as reflected by increased plasma concentrations of adrenocorticotropic hormone and corticosterone. Thus PGE2 may act in the CNS as a hormonal modulator of immune system function.
A comparative study of voiding in rat and guinea pig: simultaneous measurement of flow rate and pressure
Authors: Van Asselt E. , Groen J. , Van Mastrigt R.
Published: December 2017

In this study, the voiding phase of the micturition cycle in the anesthetized rat and guinea pig is analyzed. In both animals, voiding is characterized by an increase in intravesical pressure and then a decrease, which is accompanied by flow through the urethra and emission of urine. An ultrasonic flow probe was used in both species to measure the flow rate in relation to the intravesical pressure. In the (male) rat, so-called high-frequency oscillations are superimposed on the decreasing bladder pressure. These oscillations do not occur in the guinea pig. It is concluded that the high-frequency oscillations are caused by intermittent flow and not by variations in the bladder contraction. The intermittent flow most likely is caused by the relaxation and contraction of the external urethral sphincter and may have a function in territory marking. In our view, it is not likely that the oscillations enhance bladder emptying, as has been suggested in the literature.
Continuous measurement of blood flow in the superior sagittal sinus of the lamb
Authors: Grant D. A. , Franzini C. , Wild J. , Walker A. M.
Published: December 2017

We assessed the validity of recording blood flow in the superior sagittal sinus (Qss) as a measure of cerebral blood flow (CBF). While anesthetized, 10 lambs were instrumented with a transit-time ultrasonic flow probe around the superior sagittal sinus to measure Qss, electrodes to assess sleep state, catheters to measure cerebral perfusion pressure (Pcp), and an occlusive cuff around the common brachiocephalic artery to vary blood pressure. After 72 h recovery, lambs were studied during spontaneous sleep-wake cycles to establish 1) the normal range of Qss and 2) the response rate of Qss to rapid alterations of Pcp. Subsequently, the lambs were reanesthetized, and the measurement of Qss was calibrated and validated. Qss was linearly related to the arterial inflow of 35% of the brain mass (y = 0.5 x + 1.6, r = 0.93, n = 4). Qss was greater in active sleep (154.1 +/- 45.7 ml.min-1 x 100 g-1, mean +/- SD, n = 5) than in quiet sleep (97.1 +/- 40.8 ml.min-1 x 100 g-1) and quiet wakefulness (107 +/- 44.3 ml.min-1 x 100 g-1, P < 0.05). Qss responded rapidly (within one beat) to spontaneous and to induced transient changes in Pcp. We conclude that recording blood flow in the superior sagittal sinus provides a simple, continuous, and quantitative measure of CBF from a defined area of the brain and is appropriate for studying transient changes in the cerebral circulation.
Pertussis toxin-sensitive G proteins mediate carbachol-induced REM sleep and respiratory depression
Authors: Shuman S. L. , Capece M. L. , Baghdoyan H. A. , Lydic R.
Published: December 2017

Microinjecting cholinomimetics into the medial pontine reticular formation (mPRF) of conscious cats causes a rapid eye movement (REM) sleep-like state and state-dependent respiratory depression. Muscarinic receptors within the mPRF have been shown to mediate this state-dependent respiratory depression, but the specific signal transduction mechanisms remain poorly understood. This study tested the hypothesis that the cholinergically induced REM sleep-like state and state-dependent respiratory depression are mediated by guanine nucleotide binding proteins (G proteins). Cholera toxin, pertussis toxin, 5'-guanylylimidodiphosphate, and forskolin were microinjected alone and in combination with carbachol into the mPRF of intact unanesthetized cats. All of the G protein-altering compounds significantly reduced the ability of carbachol to produce the REM sleep-like state. Pertussis toxin caused the greatest decrease in the percent of time spent in the carbachol-evoked REM sleep-like state, showing for the first time mediation by a pertussis toxin-sensitive (Gi- or G(o)-like) G protein. Cholera toxin blocked the carbachol-induced respiratory depression, indicating mediation by a Gs-like G protein. Forskolin significantly decreased carbachol-evoked REM sleep. These data provide the first demonstration that adenylyl cyclase within the mPRF contributes to the carbachol induction of REM sleep and respiratory depression.
Cold-induced alterations in uncoupling protein and its mRNA are seasonally dependent in ground squirrels
Authors: Nizielski S. E. , Billington C. J. , Levine A. S.
Published: December 2017

We were interested in determining whether season affects the ability of cold exposure to increase brown adipose tissue (BAT) thermogenic function in 13-lined ground squirrels after acute and chronic cold (4 degrees C) exposure. Tissues were collected from animals in April and September after cold exposure for 12, 24, or 48 h. Animals chronically exposed to the cold (10 days) were killed in early May and mid-August. We found that mitochondrial uncoupling protein (UCP) concentrations varied seasonally, with concentrations in control animals (at 23 degrees C) higher in late summer (mid-August and September) than in the spring (April and early May). Cold exposure in late summer did not induce further increases in UCP concentrations. In contrast, when animals were cold exposed in the spring, UCP concentrations and total UCP increased. Surprisingly, 10 days at 4 degrees C did not cause a greater increase in UCP concentrations than did 24 h at 4 degrees C. Chronic cold exposure increased the UCP mRNA-to-beta-actin mRNA ratio 48% in May, whereas a fivefold increase occurred in August. GDP binding was increased after 12 h at 4 degrees C in April; in contrast, animals attempted to hibernate when placed in the cold in September, and no increase in GDP binding was observed. Chronic cold exposure caused GDP binding to increase at both times. These results indicate that mitochondrial UCP concentrations are seasonally regulated in the 13-lined ground squirrel.
Dietary modulation of intestinal hydrolytic enzymes in yellow-rumped warblers
Authors: Afik D. , Vidal E. C. , Martinez del Rio C. , Karasov W. H.
Published: December 2017

Many birds exhibit seasonal switches in diet and thus alter the nutrients predominating their food intake. We tested for dietary modulation of small intestine (SI) enzymes in yellow-rumped warblers, a species for which such diet changes are well documented. Birds were fed three diets formulated from either fruit, insect, or seed. We predicted that SI carbohydrases and peptidases would be modulated in direct correlation with relative levels of dietary carbohydrate and protein, respectively. Aminopeptidase N activity was about twice as high in birds eating the highest protein content diet. In contrast, there was no significant dietary effect on any of the carbohydrase activities. There was a proximal-to-distal decrease in activities of all the carbohydrases but not aminopeptidase N. The carbohydrase levels of yellow-rumps are relatively low when compared with other species in the same family and most similar to lower levels found in primarily insectivorous birds rather than in primarily granivorous or nectarivorous species. Considering this and the fact that they do not exhibit dietary modulation of carbohydrase levels, we conclude that yellow-rumps are not highly adapted for handling dietary carbohydrates, especially starch, although they might still efficiently break down and absorb sucrose and maltose if retention time were sufficiently long.
Determination of local rates of 45Ca influx into rat brain by quantitative autoradiography: studies of aging
Authors: Dienel G. A. , Tofel-Grehl B. , Cruz C. C. , Luludis K. , Pettigrew K. , Sokoloff L. , Gibson G. E.
Published: December 2017

Calcium homeostasis in brain is altered in many conditions, but there is no method to assay quantitatively local calcium flux into brain in vivo. 45Ca uptake into gross-dissected brain regions was measured and compared with results obtained with a quantitative autoradiographic procedure developed to assay influx of 45Ca into brain. Regional calcium contents, brain-to-plasma distribution ratios for calcium and 45Ca, apparent plasma-to-brain transfer coefficients, and net uptake of 45Ca into gross-dissected regions varied by as much as 80%. Local rates of net uptake of 45Ca into 34 structures determined by autoradiography varied by 12- to 14-fold, and rates of movement of 45Ca down concentrations gradients varied by a factor of 7. Previous studies with gross-dissected brain regions suggested changes in calcium uptake into brain during aging, but the values of all the variables assayed in the present study were similar in young adult, middle-aged, and old male rats. A quantitative autoradiographic procedure to assay levels of 45Ca in brain provides the anatomical resolution required to investigate local calcium flux in a variety of physiological and pathological conditions.
Actions of endogenous endothelin on glomerular hemodynamics in the rat
Authors: Qiu C. , Samsell L. , Baylis C.
Published: December 2017

Both endothelin (ET) ETA/ETB receptors are distributed in the glomerular microcirculation, but their physiological functions, if any, are unknown. We used a nonpeptide mixed ETA/ETB receptor antagonist (Bosentan) and a selective ETA receptor antagonist (BQ-123) to investigate the glomerular hemodynamic actions of endogenous ET in the anesthetized euvolemic rat. Blockade of ETA and ETB receptors with Bosentan produced a small fall in systemic blood pressure and a large fall in glomerular blood pressure due to a significant increase in preglomerular (afferent) arteriolar resistance. Single-nephron glomerular filtration rate was not reduced because of an offsetting rise in the glomerular capillary ultrafiltration coefficient. Blockade of the selective ETA receptor with BQ-123 had no effect on blood pressure or glomerular hemodynamics. These observations indicate that endogenous ET is of physiological importance in control of glomerular hemodynamics. Surprisingly, endogenous ET tonically dilates rather than contracts the preglomerular arteriole, and it also tonically lowers the glomerular capillary ultrafiltration coefficient, probably by contracting the mesangial cell. All physiological glomerular actions of ET are mediated via the ETB receptor.
Interactions between angiotensin and nitric oxide in the renal response to volume expansion
Authors: Llinas M. T. , Gonzalez J. D. , Salazar F. J.
Published: December 2017

This study examined, in anesthetized dogs, the possible interactions between nitric oxide (NO) and angiotensin II (ANG II) in mediating the renal response to an extracellular volume expansion (ECVE). It was found that the intrarenal maintenance of ANG II levels (group 1) or the intrarenal NO synthesis inhibition (group 2) did not induce changes in renal hemodynamics but reduced (P < 0.05) the ECVE-induced increments in sodium excretion and fractional lithium excretion (FeLi). In the third group, ANG II synthesis was inhibited during NO synthesis blockade. It was found in this group that the NO synthesis inhibition reduced the ECVE-induced increment in sodium excretion (P < 0.05) but did not modify the ECVE-induced increment in FeLi. These results suggest that the increase of proximal sodium reabsorption induced by the No synthesis inhibition is mediated by endogenous ANG II levels. In the fourth group, it was observed that NO synthesis inhibition, during the intrarenal maintenance of ANG II levels, induced a decrease of renal blood flow (P < 0.05) and reduced the natriuretic response to ECVE to a lower level (P < 0.05) than that observed in groups 1 and 2. The results of this group suggest that endogenous NO modulates the vasoconstrictor and antinatriuretic effects of ANG II during an ECVE. In summary, the results of this study suggest that there is an important interaction between NO and ANG II in mediating the renal response to an ECVE.
Effect of diet on insulin- and contraction-mediated glucose transport and uptake in rat muscle
Authors: Han X. , Ploug T. , Galbo H.
Published: December 2017

A diet rich in fat diminishes insulin-mediated glucose uptake in muscle. This study explored whether contraction-mediated glucose uptake is also affected. Rats were fed a diet rich in fat (FAT, 73% of energy) or carbohydrate (CHO, 66%) for 5 wk. Hindquarters were perfused, and either glucose uptake or glucose transport capacity (uptake of 3-O-[14C]-methyl-D-glucose (40 mM)) was measured. Amounts of glucose transporter isoform GLUT-1 and GLUT-4 glucose-transporting proteins were determined by Western blot. Glucose uptake was lower (P < 0.05) in hindlegs from FAT than from CHO rats at submaximum and maximum insulin [4 +/- 0.4 vs. 5 +/- 0.3 (SE) mumol.min-1.leg-1 at 150 microU/ml insulin] as well as during prolonged stimulation of the sciatic nerve (4.4 +/- 0.4 vs. 5.6 +/- 0.6 mumol.min-1.leg-1). Maximum glucose transport elicited by insulin (soleus: 1.7 +/- 0.2 vs. 2.6 +/- 0.2 mumol.g-1.5 min-1, P < 0.05) or contractions (soleus: 1.8 +/- 0.2 vs. 2.6 +/- 0.3, P < 0.05) in red muscle was decreased in parallel in FAT compared with CHO rats. GLUT-4 content was decreased by 13-29% (P < 0.05) in the various fiber types, whereas GLUT-1 content was identical in FAT compared with CHO rats. It is concluded that a FAT diet reduces both insulin and contraction stimulation of glucose uptake in muscle and that these effects are associated with diminished skeletal muscle glucose transport capacities and GLUT-4 contents.
Isolation, localization, and cardiovascular activity of tachykinins from the stomach of the bowfin Amia calva
Authors: Waugh D. , Groff K. E. , Platzack B. , Youson J. H. , Olson K. R. , Conlon J. M.
Published: December 2017

The bowfin is an extant representative of an ancient group of ray-finned fish with evolutionary connections to modern teleosts. A peptide with substance P-like immunoreactivity was isolated from an extract of bowfin stomach and its primary structure was established as Ser-Lys-Ser-His-Gln-Phe-Tyr-Gly-Leu-Met-NH2. This amino acid sequence resembles mammalian substance P only in the COOH-terminal region of the peptide. A second tachykinin with neurokinin A-like immunoreactivity isolated from the extract comprises 23 amino acid residues and shows limited structural similarity to mammalian neuropeptide-gamma. A randomly distributed population of cells in the gastric glands of the bowfin were immunostained with an antiserum raised against substance P, but no immunopositive structures were identified in the surface epithelium, lamina propria, or the nerve plexuses of the submucosa. Bolus injections of synthetic bowfin substance P (0.1-10 nmol/kg) into the bulbus arteriosus of unanesthetized bowfin resulted in a significant and dose-dependent rise in vascular resistance and arterial blood pressure (P < 0.01) and a fall in cardiac output (P < 0.05) without change in heart rate. After 5-10 min, arterial pressure and vascular resistance returned to preinjection levels, but cardiac output significantly (P < 0.05) increased over baseline values. The response to the peptide was unaffected by pretreatment of the animals with phentolamine. The study has shown that the stomach of the bowfin synthesizes tachykinins with novel structural features that display cardiovascular activity in this species.
Sulfate/oxalate exchange by lobster hepatopancreatic basolateral membrane vesicles
Authors: Gerencser G. A. , Cattey M. A. , Ahearn G. A.
Published: December 2017

Purified basolateral membrane vesicles (BLMV) were prepared from lobster hepatopancreas by osmotic disruption and discontinuous sucrose gradient centrifugation. Radiolabeled sulfate uptake was stimulated by 10 mM intravesicular oxalate compared with gluconate-loaded vesicles. Sulfate/oxalate exchange was not affected by transmembrane valinomycin-induced potassium diffusion potentials (inside negative or inside positive), suggesting electroneutral anion transport. Sulfate uptake was not stimulated by the similar carboxylic anions formate, succinate, oxaloacetate, or ketoglutarate. Sulfate influx occurred by at least one saturable Michaelis-Menten carrier system [apparent Km = 6.0 +/- 1.7 mM; maximum flux (Jmax) = 382.3 +/- 37.0 pmol.mg protein-1 x 7 s-1]. Sulfate/oxalate exchange was significantly reduced by the anion antiport inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid but was not affected by bumetanide or furosemide. The possible physiological role of this exchange mechanism in anion/sulfate transport across the crustacean hepatopancreas is discussed.
Dietary medium-chain triglycerides can prevent changes in myosin and SR due to CPT-1 inhibition by etomoxir
Authors: Rupp H. , Schulze W. , Vetter R.
Published: December 2017

To define determinants of subcellular structures of heart, Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated for 5 wk with 15 mg.kg-1.day-1 etomoxir [reduces mitochondrial carnitine palmitoyltransferase-1 (CPT-1) activity and fatty acid synthesis]. To bypass CPT-1 inhibition, etomoxir-treated rats were fed a medium-chain fatty acid (MCFA) diet. Etomoxir induced a proportionate growth of heart, which could partially (WKY, P < 0.05) or completely (SHR, P < 0.05) be prevented by the MCFA diet. Also the etomoxir-induced increase in myosin V1 was partially prevented (P < 0.05). Etomoxir increased (P < 0.05) rate of sarcoplasmic reticulum (SR) Ca2+ uptake of WKY and SHR ventricular homogenates in the presence or absence of the SR Ca2+ release inhibitor ruthenium red. The MCFA diet resulted in SR Ca2+ uptake rates that were in between those of etomoxir-treated and untreated rats. The in vitro 32P incorporation into phospholamban and troponin I did not differ significantly in WKY. Etomoxir induced, however, an increase (P < 0.05) in the phosphorylated intermediate of the Ca2+ adenosinetriphosphatase in WKY that was prevented by the MCFA diet. In SHR, etomoxir increased the in vitro phospholamban phosphorylation, which was reduced compared with WKY. The data show that myosin and SR are affected by a chronically altered substrate utilization of heart.
An intact glutamatergic trigeminal pathway is essential for the cardiac response to simulated diving
Authors: McCulloch P. F. , Paterson I. A. , West N. H.
Published: December 2017

Nasal water flow plus concomitant expiratory apnea in anesthetized (Innovar-Vet), paralyzed, and artificially ventilated rats produces immediate bradycardia. To investigate the origin of this response, four procedures were used to block the trigeminal pathway. 1) Trigeminal receptors within the nasal passages were anesthetized by infusing local anesthetic through the external nares. 2) Trigeminal nerves that innervate the nasal passages were sectioned bilaterally as they passed through the orbit. 3) The trigeminal neural pathway was blocked within the brain stem by either electrolytically lesioning or infusing local anesthetic into the spinal trigeminal nucleus interpolaris (Sp5I). 4) Synaptic transmission within Sp5I was prevented by infusing glutamate receptor antagonists D-2-amino-7-phosphonoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione. After each of the procedures was completed, the cardiovascular responses to nasal water flow plus apnea were either attenuated or eliminated. The major conclusion of this study is that an intact glutamatergic trigeminal pathway is required for manifestation of the cardiovascular responses to nasal stimulation. Evidence also suggests that N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors are both required for synaptic neurotransmission within Sp5I.
Influence of the renal nerves on sodium excretion during progressive reductions in cardiac output
Authors: Lohmeier T. E. , Reinhart G. A. , Mizelle H. L. , Montani J. P. , Hester R. , Hord C. E. , Hildebrandt D. A.
Published: December 2017

The purpose of this study was to elucidate the role of the renal nerves in promoting sodium retention during chronic reductions in cardiac output. In five dogs, the left kidney was denervated and the urinary bladder was surgically divided to allow separate 24-h urine collection from the innervated and denervated kidneys. Additionally, progressive reductions in cardiac output were achieved by employing an externally adjustable occluder around the pulmonary artery and by servo-controlling right atrial pressure (control = 0.9 +/- 0.2 mmHg) at 4.7 +/- 0.1, 7.5 +/- 0.1, and 9.8 +/- 0.2 mmHg for 3 days at each level. At the highest level of right atrial pressure, the 24-h values for mean arterial pressure (control = 97 +/- 3 mmHg) and cardiac output (control = 2,434 +/- 177 ml/min) were reduced approximately 25 and 55%, respectively; glomerular filtration rate fell by approximately 35% and renal plasma flow by approximately 65%. However, despite the sodium retention induced by these hemodynamic changes, there were no significant differences in renal hemodynamics or sodium excretion between the two kidneys during pulmonary artery constriction. In contrast, after release of the pulmonary artery occluder on day 9, sodium excretion increased more (approximately 28% during the initial 24 h) in innervated than in denervated kidneys. These results suggest that the renal nerves are relatively unimportant in promoting sodium retention in this model of low cardiac output but contribute significantly to the short-term elimination of sodium after partial restoration of cardiac output and mean arterial pressure.
Central inhibitory action of peptide YY on gastric motility in rats
Authors: Chen C. H. , Rogers R. C.
Published: December 2017

Specific peptide YY (PYY) binding sites have recently been identified autoradiographically in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus regions [collectively referred to as the dorsal vagal complex (DVC)] in rats. These medullary brain stem regions are responsible for vagovagal reflex control of gastric function, including gastric motility. We propose that PYY can modulate gastrointestinal functions, such as gastric motility, by interacting with PYY binding sites found in DVC. Furthermore, we predict that central PYY effects on gastric function are mediated by the vagus nerve. In the present study, urethan-anesthetized rats were used. PYY (20.0 and 2.0 fmol) injected directly into DVCs of the animals produced significant inhibition of gastric motility that was stimulated by centrally applied thyrotropin-releasing hormone (TRH). TRH is a well-accepted central stimulator of vagal efferent pathway to the stomach. Otherwise, an excitatory effect of PYY (2 pmol) on basal gastric motility was observed and considered as being pharmacological. The inhibitory effect of PYY was abolished completely by unilateral (the injection side) cervical vagotomy, suggesting that the inhibition was vagally dependent. These results support the view that physiological concentrations of PYY may inhibit proximal gut function as part of the “ileal brake” mechanism by acting directly on vagovagal control circuits in the dorsal medulla. However, extremely high doses of PYY may activate gastric function through pharmacological action at pancreatic polypeptide receptors in the DVC.