bluuebunny/crossref_metadata_2025 huggingface dataset:
Diminished cardiovascular responsiveness to vagal stimulation in obese rats
Authors: Bunag R. D. , Krizsan D. , Itoh H.
Published: December 2017

Obese rats maintained on a high-fat diet since weaning were studied to determine whether parasympathetic deficiencies contribute to the cardiovascular malfunction in obesity. Elevations in tail-cuff systolic pressures and plasma insulin indicated that obese rats had borderline hypertension and hyperinsulinemia. Reflex bradycardia produced by angiotensin or phenylephrine in conscious obese rats was less than that in age-matched controls. However, reflex responses elicited by phenylephrine or sodium nitroprusside when the same rats were later anesthetized did not differ between groups. Impairment of afferent or central components of the baroreflex arc was considered unlikely, because depressor, bradycardic, and sympathoinhibitory responses to electrical stimulation of aortic depressor afferents were similar in both rat groups. By contrast, efferent parasympathetic mediation was probably reduced, since depressor and bradycardic responses to electrical stimulation of vagal nerve efferents were significantly smaller in obese than in control rats. Collectively our findings suggest that cardiovascular and baroreflex malfunction in obese rats may result from an autonomic imbalance involving diminished parasympathetic activity.
Relationships between plasma ketones and fasting duration in neonatal elephant seals
Authors: Castellini M. A. , Costa D. P.
Published: December 2017

Long-duration fasting in mammals can ultimately lead to stage three terminal starvation, which is characterized by depleted fat stores, a metabolic shift away from fat metabolism toward lean tissue catabolism, and a sharp decline in circulating levels of plasma fatty acids and ketone bodies. However, this biochemical shift has never been observed outside of the laboratory in a naturally fasting, nonhibernating mammal. In the current study, plasma levels of the ketone body D-beta-hydroxybutyrate (beta-HBA) were assayed in 10 Northern elephant seal pups during suckling and the postweaning fast and in 12 fasting adult seals. Plasma beta-HBA concentration in the pups was minimal during suckling (0.09 +/- 0.06 mM; n = 10) and began to increase immediately after weaning. The concentration rose until about 55 days into the fast (1.34 +/- 0.36 mM; n = 10) and then declined sharply. Within 10 days of this deflection point, the seal pups left for sea. By contrast, adult elephant seals showed consistently low levels of beta-HBA after several months of fasting (0.06 +/- 0.07 mM; n = 12). The data suggest that the duration of fasting in elephant seal pups may be determined, in part, by biochemical shifts that occur near the end of the fast and that the regulation of ketone concentration is different in fasting neonatal and adult elephant seals.
Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models
Authors: Guyton A. C.
Published: December 2017

Long-term arterial pressure control is very different from acute control, because many of the acute control systems are overridden by a single long-term mechanism that has little to do with short-term control. This is the renal fluid volume mechanism for pressure control. It is based on a simple functional property of the kidney: as the arterial pressure rises, the kidney output of water and electrolytes increases dramatically. When the output rises above the net intake of water and electrolytes, negative body fluid balance occurs, causing both the body fluid volume and the pressure to decrease. This decrease continues until the kidney fluid output exactly balances the net fluid intake. Conversely, if the pressure falls below the exact level for balance, intake becomes greater than output; then fluid builds up in the body and the pressure rises until intake and output again exactly balance each other. This fluid mechanism for pressure control has been known from the beginning of blood pressure research. However, its overpowering importance was not appreciated until a mathematical computer analysis in 1966 demonstrated the renal-fluid feedback mechanism to have infinite feedback gain for long-term pressure control. This is the principal topic of the present review.
Chemoreceptor modulation of endogenous respiratory rhythms in vertebrates
Authors: Smatresk N. J.
Published: December 2017

The relative contributions of O2- and CO2-sensitive chemoreceptor information to centrally generated respiratory patterns have changed dramatically during vertebrate evolution. Chemoafferent input from branchial O2 chemoreceptors modulates centrally generated respiratory patterns but is not critical for respiratory rhythmogenesis in fishes. In air-breathing fishes, branchial O2 chemoreceptors monitoring internal and external stimuli control the relative contributions of the gills and air-breathing organ to net ventilation, and chemoafferent input is necessary for initiating air breathing. In the transition from water to air breathing by amphibious vertebrates, rhythmic patterns of branchial ventilation are completely replaced by arrhythmic and intermittent patterns of air breathing, and there is progressive dependence on CO2 as a source of respiratory drive. Periodic initiation of air breathing in resting animals appears to depend on attaining a threshold level of afferent activity from O2- and CO2/pH-sensitive chemoreceptors, since hyperoxia and/or hypocapnia can abolish air breathing in all air-breathing vertebrates. Conversely, chemoreceptor stimulation in amphibians and reptiles converts intermittent to more continuous air breathing patterns, suggesting that adequate biasing input from chemoreceptors activates a central rhythm generator. Chemoafferent input in homeotherms serves as one of several sources of drive for rhythmic breathing and supplies feedback for blood gas homeostasis in the face of metabolic or environmental change.
Reduced renal perfusion pressure causes prostaglandin-dependent excitation of R2 chemoreceptors in rats
Authors: Barber J. D. , Moss N. G.
Published: December 2017

The activity of multiunit preparations of afferent renal nerve activity (ARNA) and single R2 chemoreceptors was recorded during graded reductions in renal perfusion pressure (RPP) produced by tightening an aortic snare in anesthetized rats. In 13 multiunit preparations an initial RPP reduction from 117 +/- 2 to 101 +/- 2 mmHg caused ARNA to increase 29 +/- 5% above control. Further reductions in RPP produced a 65 +/- 11% increase in ARNA at 80 +/- 1 mmHg, 87 +/- 24% at 59 +/- 1 mmHg, and 127 +/- 38% at 37 +/- 1 mmHg (P less than 0.01 ARNA vs. RPP). Renal blood flow was measured by pulsed Doppler flowmeter in these rats and showed good autoregulation and minimal reduction (-4 +/- 2%) during the initial pressure drop. Ten single R2 chemoreceptors increased their firing rate by 129 +/- 4% when RPP was reduced from 109 +/- 2 to 85 +/- 2 mmHg and showed a peak response of 494 +/- 105% at 27 +/- 2 mmHg. The activity of 11 R2 receptors increased from 3.7 +/- 1.0 to 6.8 +/- 0.8 impulses/10 s when RPP was reduced from 112 +/- 4 to 79 +/- 2 mmHg. Prostaglandin blockade with indomethacin (6 rats) or meclofenamate (7 rats) caused a decrease in basal activity in the same units to 1.8 +/- 0.5 impulses/10 s and eliminated their excitatory response to a similar reduction in RPP (108 +/- 4 to 75 +/- 3 mmHg). These data support a role for R2 chemoreceptors in neurocirculatory reflexes elicited by reductions in RPP.
Novel determination of filtration coefficient of ovine placenta and intramembranous pathway
Authors: Gilbert W. M. , Brace R. A.
Published: December 2017

We recently reported that distilled water injected into the amniotic compartment is rapidly absorbed by the fetal blood, which perfuses the fetal membranes and the fetal surface of the placenta, i.e., by the “intramembranous pathway.” In the present study, we infused warmed distilled water at 2 ml.min-1.kg estimated fetal wt-1 into the amniotic compartment for 6-8 h in 12 chronically catheterized sheep. A steady state was achieved in amniotic fluid, fetal blood, and maternal blood osmolalities in 5.1 +/- 0.3 (SE) h. During the steady state, all of the infused water must pass to the ewe. Because the amount of water directly crossing the fetal membranes into the maternal circulation was not significantly different from zero (3.3 +/- 5.8% of total), we assumed all water crossed the placenta. The placental filtration coefficient was then calculated during the steady state as the infusion rate divided by the changes in the transplacental osmotic gradient and averaged 0.0260 +/- 0.0055 ml.min-1.mmHg-1.kg fetal wt-1. Attempts to correct this value for placental reflection coefficients less than 1 were unsatisfactory; thus the uncorrected value appears to provide the best estimate of the placental filtration coefficient. Similar calculations yielded a value of 0.00137 +/- 0.00025 ml.min-1.mmHg-1.kg-1 for the filtration coefficient of the intramembranous pathway. Thus this method provides a relatively simple new technique for estimating the filtration coefficient of the ovine placenta and intramembranous pathway under steady-state conditions.
Relationship between carbohydrate oxidation and G-1,6-P2 in human skeletal muscle during euglycemic hyperinsulinemia
Authors: Katz A. , Bogardus C.
Published: December 2017

Euglycemic (approximately 5.5 mM) hyperinsulinemic clamps were performed on normoglycemic insulin-sensitive (NIS) men and men who were normoglycemic but insulin resistant (NIR) and hyperglycemic and insulin resistant (HIR) (i.e., noninsulin-dependent diabetes mellitus). Insulin was infused at successive rates of 40 and 400 mU.m-2.min-1, and biopsies were obtained from the quadriceps femoris muscles before and after insulin and analyzed for regulators of phosphofructokinase, a rate-limiting enzyme for glycolysis. Glucose disposal and whole body carbohydrate oxidation were markedly lower in NIR and HIR vs. NIS (P less than 0.001 for disposal and oxidation). The alpha-D-glucose 1,6-bisphosphate (G-1,6-P2) content increased almost twofold during the 40-mU insulin infusion (P less than 0.001) without any further change during the 400-mU infusion in NIS men. The increase in G-1,6-P2 in NIR and HIR was only approximately 25 and 50% of the increase observed in NIS during the 40- and 400-mU infusions, respectively. The mean content of G-1,6-P2 was strongly related to the mean rate of carbohydrate oxidation (r = 0.99; P less than 0.001). Because during euglycemic hyperinsulinemia approximately 90% of the glucose utilization is accounted for by skeletal muscle (J. Clin. Invest. 76: 149, 1985), it is likely that whole body carbohydrate oxidation is proportional to carbohydrate oxidation and glycolysis in muscle. The different rates of carbohydrate oxidation between NIS and insulin-resistant men could not be associated with differences in fructose 6-phosphate, fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, Pi, free ADP and free AMP (activators of phosphofructokinase), or ATP and citrate (inhibitors of phosphofructokinase).
GABAA and excitatory amino acid receptors in dorsomedial hypothalamus and heart rate in rats
Authors: Soltis R. P. , DiMicco J. A.
Published: December 2017

We have previously shown that microinjection of drugs that interfere with the function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into the hypothalamus produces cardiorespiratory and behavioral changes resembling those seen in emotional stress. The purpose of this study was to determine whether excitatory amino acids (EAAs) can produce a cardiovascular response similar to that caused by the GABAA receptor antagonist bicuculline methiodide (BMI) when microinjected at the same hypothalamic site in urethan-anesthetized rats and to clarify the precise locus of action of these agents. N-methyl-D-aspartic acid (NMDA, 0.68-6.8 pmol/50 nl) and kainic acid (KA, 0.47-4.7 pmol/50 nl) produced dose-related increases in heart rate and blood pressure when injected at sites in the dorsomedial hypothalamus reactive to BMI (20 pmol/50 nl). Higher doses of NMDA (68 pmol), however, failed to elicit consistent increases in heart rate and blood pressure when injected at these same sites. The effects of NMDA were selectively blocked by the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid, whereas the effects of KA were selectively blocked by the non-NMDA EAA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. These results demonstrate that 1) blockade of inhibitory amino acid receptors or stimulation of EAA receptors in the dorsomedial nucleus of the hypothalamus produces tachycardic and pressor responses in urethan-anesthetized rats and 2) use of high doses of EAAs may be an unreliable method of evoking local neuronal excitation in certain regions of the central nervous system.
Cholecystokinin conditions flavor preferences in rats
Authors: Perez C. , Sclafani A.
Published: December 2017

The present study investigated whether cholecystokinin (CCK), an intestinal hormone that is a putative satiety agent, can condition flavor preference in rats. In experiment 1 food-deprived rats were trained to consume two different-flavored saccharin solutions in separate one-bottle tests. One flavor (the CS+) was paired with intraperitoneal injections of CCK octapeptide (0.125-4 micrograms/kg); the other flavor was paired with intraperitoneal injections of saline. Flavor preferences were then assessed in subsequent two-bottle choice tests. The 0.125 and 0.25 micrograms/kg doses failed to suppress CS+ intake or produce flavor preferences. CCK at 0.5 micrograms/kg did not reliably suppress CS+ intake in the one-bottle tests but produced a reliable preference for the CS+ in the two-bottle tests; percent CS+ intakes ranged from 50 to 62% in the four preference tests. At 1 microgram/kg, CCK suppressed CS+ intake and produced a marginal preference for the CS+. The 2 micrograms/kg dose suppressed CS+ intake but failed to condition a CS+ preference. The 4 micrograms/kg dose of CCK produced a potent suppression of CS+ intake and a strong aversion to that flavor. The preference conditioning effect of CCK at 0.5 microgram/kg was replicated in a second experiment using flavored Polycose solutions. The finding that low doses of CCK condition flavor preferences in rats is compatible with the hypothesis that endogenous CCK can mediate satiety and further suggests a role for CCK in learned food preferences. The aversion conditioned by the highest dose of CCK does not detract from this interpretation, since food, if consumed in excess, can also have aversive consequences.
Role of sympathetic nerves in effects of estradiol on rat white adipose tissue
Authors: Lazzarini S. J. , Wade G. N.
Published: December 2017

Two experiments examined the role of the sympathetic nerves in estradiol-induced fat pad weight losses in ovariectomized (OVX) rats. Rats were OVX, and the retroperitoneal white adipose tissue (RWAT) was unilaterally denervated 4 wk later. After 14 days of treatment with estradiol benzoate (EB, 2 micrograms/day), the intact pads lost 23% more weight than the denervated pads. There was no effect of denervation on fat pad weight or on cytosol estrogen receptor concentration in RWAT in the animals treated with sesame oil vehicle. These data suggest that the sympathetic nerves play a role in estrogen-induced reductions in fat pad weight but not via changes in adipose tissue cytosol estrogen receptors. A second experiment examined whether estradiol-induced fat pad weight losses are accompanied by increased norepinephrine (NE) turnover, an index of sympathetic activity, in adipose tissue. Rats were OVX and treated with EB or sesame oil vehicle. NE turnover was assessed by measuring the decline of tissue NE over time after injection of alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase activity and thus NE biosynthesis. NE turnover in RWAT, but not heart, was significantly greater in animals treated with EB, suggesting that estradiol decreases fat pad weight in part by increasing sympathetic nervous system activity. It is possible that estradiol acts in the brain to regulate the activity of the sympathetic nerves to white adipose tissue and peripherally to alter adipose tissue responsiveness to catecholamines.
Interleukin 1 alters rat sleep: temporal and dose-related effects
Authors: Opp M. R. , Obal F. , Krueger J. M.
Published: December 2017

Rats received various doses of interleukin 1 (IL-1) (range, 0.5-25.0 ng) or pyrogen-free saline intracerebroventricularly during the rest (light) and the active (dark) cycles of the day, and sleep-wake activity and brain temperature were determined for 6 h. Low doses of IL-1 (0.5 ng at night, 2.5 ng during the day) increased both the duration of non-rapid-eye-movement sleep (NREMS) and electroencephalogram (EEG) slow-wave activity during NREMS episodes. Increasing doses of IL-1 had divergent effects on NREMS duration and EEG slow-wave activity, and the direction of the changes depended on the diurnal cycle. Thus NREMS duration was promoted at night and EEG slow-wave amplitudes during the day, whereas NREMS duration during the day and EEG slow-wave amplitudes at night were suppressed after higher doses of IL-1. High doses of IL-1 also induced decreases in rapid-eye-movement sleep during both phases of the day. Each dose of IL-1 that promoted NREMS also tended to increase brain temperature. These results demonstrate that IL-1 promotes NREMS in the rat. However, unlike previously reported findings in rabbits, the circadian rhythm of sleep regulation strongly interferes with the sleep-promoting activity of IL-1 in rats.
Capsaicin attenuates bombesin-induced suppression of food intake
Authors: Ladenheim E. E. , Ritter R. C.
Published: December 2017

This study was conducted to evaluate the extent to which bombesin (BBS)-induced suppression of food intake relies on small, unmyelinated sensory neurons. Rats were pretreated intraperitoneally with capsaicin, a neurotoxin that destroys a subpopulation of small-diameter sensory neurons, and tested for suppression of food intake after intraperitoneal administration of 2, 4, 8, 16, and 32 micrograms/kg BBS. Capsaicin pretreatment attenuated suppression of food intake by BBS over a wide range of doses. The site of capsaicin action was not determined in this study. However, work by others indicates that vagal and nonvagal neural substrates participate in suppression of food intake by BBS. Afferents of both of these substrates are predominantly small and unmyelinated. Therefore, the deficits in BBS-induced suppression of food intake that we observed may reflect damage to both vagal and/or nonvagal neurons that participate in BBS-induced suppression of food intake.
Adaptations to prolonged fasting in free-living weaned gray seal pups
Authors: Reilly J. J.
Published: December 2017

The water and energy metabolism of 12 free-living gray seal pups during their postweaning fast was investigated using tritiated water for determination of rates of energy expenditure and water turnover and changes in body composition. Changes in serum composition and urinary output were also measured. The duration of the postweaning fast ranged from 10 to greater than 28 days. The mean daily energy expenditure of pups was 12.0 +/- 1.0 (SE) MJ, equivalent to 2.7 times the basal metabolic rate predicted from M. Kleiber (The Fire of Life. Huntington, NY: Krieger, 1975). On average, lipid catabolism provided 94% of the energy used. Water-turnover rates were lower than predicted from C. R. Richmond, W. H. Langham, and T. T. Trujillo (J. Cell. Comp. Physiol. 59: 45-55, 1962). Urinary output of water and solute were also low, and these declined as the fast progressed. Although pups were in negative water balance, there was no evidence that they experience dehydration during the post-weaning fast. The principal adaptations to prolonged fasting in weaned gray seals are, therefore, lowering of field metabolic and water-turnover rate and reliance on stored lipid as fuel.
Vagotomy attenuates suppression of sham feeding induced by intestinal nutrients
Authors: Yox D. P. , Stokesberry H. , Ritter R. C.
Published: December 2017

The ability of intraintestinal nutrient infusions to suppress sham feeding was examined in intact rats and in rats with total subdiaphragmatic vagal transections. Vagotomy abolished the suppression of sham feeding by intraintestinal infusion of maltose or oleate. Suppression of sham feeding by intraintestinal L-phenylalanine was reduced but not abolished by vagotomy. The results of this examination indicate that the vagus nerve mediates suppression of the sham feeding by intraintestinal maltose and oleate but is only partially responsible for suppression of food intake produced by L-phenylalanine. Taken together with previously published data these results suggest that effects on feeding by specific nutrients may be mediated by anatomically distinct populations of visceral afferent neurons.
Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men
Authors: Thompson C. J. , Selby P. , Baylis P. H.
Published: December 2017

We have studied the reproducibility of the thirst and arginine vasopressin (AVP) responses to osmotic and hypoglycemic stimulation in healthy volunteers undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined close relationships between the slopes (r = +0.72, P less than 0.05) and the abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group intraindividual component of the variance for the slopes and intercepts was 7 and 0.6%, respectively. There were close correlations between the slopes (r = +0.79, P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the regression lines relating Posmol and thirst, and group intraindividual component of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was infused on four occasions in four subjects, and the results showed that the linear regression lines relating PAVP and Posmol and thirst and Posmol were reproducible within an individual. There were similar falls in blood glucose and elevations in PAVP in both ITTs. No relationship was defined between the fall in blood glucose and either the rise in PAVP or the area under the AVP curve (AUC). The intraindividual component of the variance for the rise in AVP and the AUC was 77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation are highly reproducible, but there is considerable intraindividual variation in the AVP response to hypoglycemia.
Nicotinic- and muscarinic-evoked release of canine adrenal catecholamines and peptides
Authors: Chritton S. L. , Dousa M. K. , Yaksh T. L. , Tyce G. M.
Published: December 2017

The tissue content and overflow of norepinephrine (NE), epinephrine (Epi), dopamine (DA), Met-enkephalin (Met-Enk), and neuropeptide Y (NPY) from isolated, retrogradely perfused dog adrenal glands were studied. Under resting conditions, approximately 25% of the overflow of autocoids from the glands was Ca2+ dependent; the cholinergic antagonists hexamethonium and atropine had no effects on basal efflux. Stimulation with the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; 3 or 50 microM) or with the muscarinic agonist pilocarpine (50 microM or 1 mM) evoked releases of autocoids. These releases were blocked or dramatically reduced by appropriate antagonists or by the removal of Ca2+ from the perfusate. Expressed as percentages of tissue stores, the rank order of overflow of autocoids was E approximately DA much greater than NE during resting conditions, DA much greater than E approximately NE during stimulation with 50 microM DMPP, and DA greater than Epi greater than NE during stimulation with 1 mM pilocarpine. These data are consistent with different mechanisms of release for the catecholamines, perhaps from different cell populations. The data support corelease of peptides and catecholamines, although clear pairing of autocoids could not be confirmed.
Sustained hyperinsulinemia increases arterial pressure in conscious rats
Authors: Brands M. W. , Hildebrandt D. A. , Mizelle H. L. , Hall J. E.
Published: December 2017

A large body of correlational evidence relating plasma insulin levels and arterial pressure in obese hypertensives suggests that hyperinsulinemia may play a causal role in the development of hypertension in these subjects. However, experimental evidence supporting the ability of increased plasma insulin per se to increase blood pressure is lacking. The goal of this study was to determine the effect of hyperinsulinemia on mean arterial pressure and renal electrolyte excretion in eight conscious rats. Arterial pressure was determined by sampling the signal from an abdominal aortic catheter once per minute, 19 h/day by computer. A 5-day intravenous insulin and glucose infusion that increased plasma insulin concentration 43% significantly increased mean arterial pressure from 93 +/- 1 mmHg to an average of 101 +/- 2 mmHg for the 5-day experimental period. Heart rate increased from 369 +/- 8 to 406 +/- 3 beats/min. Urinary sodium excretion transiently decreased on day 1 of insulin, but no significant sodium retention was measured after 5 days of insulin infusion, suggesting that the blood pressure increase was not volume mediated. There were no changes in any of these variables in eight vehicle-infused rats. These results suggest that hyperinsulinemia can increase mean arterial pressure in conscious rats, but the underlying mechanism remains to be elucidated.
Metabolism of arachidonic acid in nervous system of marine mollusk Aplysia californica
Authors: Piomelli D.
Published: December 2017

Studies of the marine mollusk Aplysia californica indicate that products of the 12-lipoxygenase pathway may be involved in neuronal intracellular signaling. The nervous tissue of Aplysia has a 12-lipoxygenase activity that converts both exogenous and endogenous arachidonic acid to an array of products, which include 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and its metabolites hepoxilin A3, hepoxilin B3, 12-ketoeicosatetraenoic acid, and 12-oxododecatrienoic acid. These eicosanoids were identified using a combination of high-performance liquid chromatography, ultraviolet spectrometry and gas chromatography-mass spectrometry. Generation of 12-lipoxygenase products was stimulated by application of the neurotransmitters, histamine and FMRF-amide, or by stimulation of identified neural cells. In electrophysiological studies of identified L14 and sensory neurons it was found that 12-HPETE and its metabolic products exert physiological actions that resemble those of histamine and FMRF-amide. These results suggest that products of 12-HPETE metabolism may act as second messengers in Aplysia neurons.
Comparative eicosanoid physiology in invertebrate animals
Authors: Stanley-Samuelson D. W.
Published: December 2017

A comparative survey of eicosanoid physiology in invertebrate animals is presented. Topics include host skin penetration behavior in blood flukes, oocyte maturation in starfishes, prevention of polyspermic fertilizations in sea urchins, ion regulation in bivalves, egg production in snails, egg release in scallops, neurobiology of Aplysia, hatching in barnacles, and release of egg-laying behavior in some insects. Some eicosanoid actions, such as ion regulation, may be common to most vertebrate and invertebrate animals, whereas other actions, such as mediation of whole organism behavior, are not shared. Comparative physiology is revealing that the biological significance of eicosanoids extends far beyond vertebrate animals.
Hyperoxia lowers sympathetic activity at rest but not during exercise in humans
Authors: Seals D. R. , Johnson D. G. , Fregosi R. F.
Published: December 2017

The primary aim of this study was to determine the influence of systemic hyperoxia on sympathetic nervous system behavior at rest and during submaximal exercise in humans. In seven healthy subjects (aged 19-31 yr) we measured postganglionic sympathetic nerve activity to skeletal muscle (MSNA) in the leg, antecubital venous norepinephrine concentrations, heart rate, and arterial blood pressure during normoxic rest (control) followed by 3- to 4-min periods of either hyperoxic (100% O2 breathing) rest, normoxic exercise (rhythmic handgrips at 50% of maximum force), or hyperoxic exercise. During exercise, isocapnia was maintained by adding CO2 to the inspirate as necessary. At rest, hyperoxia lowered MSNA burst frequency (12-42%) and total activity (6-42%) in all subjects; the average reductions were 25 and 23%, respectively (P less than 0.05 vs. control). Heart rate also decreased during hyperoxia (6 +/- 1 beats/min, P less than 0.05), but arterial blood pressure was not affected. During hyperoxic compared with normoxic exercise, there were no differences in the magnitudes of the increases in MSNA burst frequency or total activity, plasma norepinephrine concentrations, or mean arterial blood pressure. In contrast, the increase in heart rate during hyperoxic exercise (13 +/- 2 beats/min) was less than the increase during normoxic exercise (20 +/- 2 beats/min; P less than 0.05). We conclude that, in healthy humans, systemic hyperoxia 1) lowers efferent sympathetic nerve activity to skeletal muscle under resting conditions without altering venous norepinephrine concentrations and 2) has no obvious modulatory effect on the nonactive muscle sympathetic nerve adjustments to rhythmic exercise.
Consequences of differential effects of ADH and other peptide hormones on thick ascending limb of mammalian kidney
Authors: De Rouffignac C. , Di Stefano A. , Wittner M. , Roinel N. , Elalouf J. M.
Published: December 2017

Several hormones stimulate the adenylate cyclase system of the thick ascending limb (TAL). There are, however, some species differences concerning the cyclase sensitivity and the hormonal response in this nephron segment. In the mouse, antidiuretic hormone (ADH), parathyroid hormone, glucagon, calcitonin, and isoproterenol stimulate Na+, Cl-, Mg2+, and Ca2+ transports in the cortical TAL, whereas ADH, glucagon, and isoproterenol stimulate NaCl transport only in the medullary TAL. Many of these effects are different from those previously described for the corresponding segments of the rabbit nephron. The close similarity of the cyclase responsiveness to hormones of the mouse and rat TALs makes it possible to interpret the micropuncture data obtained in vivo in the rat superficial (S) and juxtamedullary (JM) nephrons, in the light of the in vitro data obtained in the mouse. Long-term treatment of Brattleboro rats with ADH also elicits differential effects along the TAL. Their consequences on the function of the S and JM nephrons are also examined. There are several indications supporting the view that the newly described hormonal effects in the mouse and rat are of physiological relevance.
Free-running rhythms of melatonin, cortisol, electrolytes, and sleep in humans in Antarctica
Authors: Kennaway D. J. , Van Dorp C. F.
Published: December 2017

The geographic isolation and the prolonged absence of sunlight during winter make Antarctica an interesting environment for studying circadian rhythms. This study explored the effects of wintering on sleep, hormonal, and electrolyte rhythms in four human subjects living in a small Antarctic base. Up to the last sunset sleep, 6-sulfatoxymelatonin, cortisol, sodium, and potassium rhythms were synchronized within clock time. During the 126 days of winter, when there was no sunlight, the circadian rhythms of all measures free ran in each individual. For example, the free-running periods for the cortisol excretory rhythm were 24 h 29 min, 24 h 45 min, 25 h 7 min, and 25 h 14 min for subjects C, J, K, and G, respectively. The period lengths of C, J, and K were significantly different, whereas there was no significant difference between K and G. The phase relationships between each rhythm remained constant in three out of the four subjects. Total daily output and rhythm amplitude for 6-sulfatoxymelatonin, potassium, and sodium remained constant during the entrained and free-running stages of the study. Significant changes in total daily cortisol excretion were observed during the year with one subject producing less and two subjects more while the rhythms were free running. When the sun reappeared during spring, all rhythms again synchronized and entrained to the daylight. These results show that 1) circadian rhythms can free run, even when the subjects have knowledge of time; and 2) within a small communal group, individuals can maintain unique free-running periods.
Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats
Authors: Le Sauter J. , Noh U. , Geary N.
Published: December 2017

Specific antibodies to pancreatic glucagon in a dose sufficient to neutralize 1.5 ng glucagon in vitro were intraportally infused during the first 2 min of spontaneous meals in ad libitum-fed male Sprague-Dawley rats. In separate tests, glucagon antibodies stimulated feeding during the first spontaneous meal of the dark phase (73% mean increase in meal size) and during spontaneous meals in the last quarter of the dark phase (58% increase). These results indicate that a glucagon-sensitive satiety mechanism has a physiological role in the control of nocturnal feeding in rats.
Control of renal handling of potassium loads in ducks with active salt glands
Authors: Simon E. , Gray D. A.
Published: December 2017

Domestic ducks adapted to saline of 400 mosmol/kgH2O as their only water supply received intravenous loads of 100 mM KCl for 2 h while being intravenously infused with 200 mM NaCl at 1.0 ml/min to produce simultaneous salt gland secretion and diuresis-natriuresis. K+ loading did not alter the plasma levels of the osmoregulatory hormones arginine vasotocin, angiotensin II, aldosterone, and atrial natriuretic factor but promptly evoked kaliuresis because of a rise from 17 to 155 mM in urinary K+, with a proportional decrease in urinary Na+. Continuous infusion of amiloride (0.04 mg.min.-1.kg body wt-1 iv) further enhanced diuresis and natriuresis and lowered urinary K+, but the kaliuretic response to K+ loading was only moderately reduced because of enhanced diuresis and a rise in urinary K+ from 3 to 33 mM, with a slight decrease in urinary Na+. Changes in plasma hormone levels reflected dehydration due to excessive diuresis but were not related to kaliuresis. Salt gland secretion was not affected directly by amiloride but was secondarily reduced by the induced dehydration. In amiloride-treated ducks, hyperkalemia in response to K+ loading was exaggerated relative to the modest reduction in K+ excretion and may be attributed to moderate metabolic acidosis and/or general effects of amiloride on K+ metabolism. It is concluded that none of the established osmoregulatory hormones is involved in short-term control of renal K+ handling in ducks and that distal tubular K+ excretion involving amiloride-sensitive Na+ channels is quantitatively unimportant in this avian species.
Integration of vagal afferent responses to gastric loads and cholecystokinin in rats
Authors: Schwartz G. J. , McHugh P. R. , Moran T. H.
Published: December 2017

The neurophysiological responses to 2-ml intragastric saline loads and 100-pmol celiac artery infusions of cholecystokinin (CCK) were obtained from 20 vagal afferent fibers in 14 rats. Two groups of fibers were identified. Discharge rates of group I fibers (n = 16) were significantly increased by gastric loading, adapted slowly to maintained gastric volume, and were inhibited by load withdrawal. CCK elicited a significant increase in the discharge rate of these group I fibers. Prior exposure to CCK nearly doubled the response of these fibers to a subsequent gastric load. In contrast, group II fibers (n = 4) increased firing rate only during infusion of a gastric load and showed rapid adaptation and no response to CCK. CCK failed to alter subsequent responses to gastric loads in these fibers. These results 1) demonstrate an integration of signals elicited by exogenous CCK and gastric loads at the level of vagal afferent fibers and 2) imply that aspects of CCK's inhibition of food intake may derive from CCK's ability to mimic and amplify vagal afferent activity provoked by meal-related gastric events.
Electrophysiological evidence of baroreceptor input to area postrema
Authors: Papas S. , Ferguson A. V.
Published: December 2017

Subpopulations of rat area postrema (AP) and nucleus tractus solitarius (NTS) neurons exist that are responsive to changes in blood pressure. The hypothesis that these effects may be mediated by afferent baroreceptor input was examined. Orthodromic responses of AP and NTS neurons to aortic depressor nerve (ADN) stimulation were observed. Sixty-three percent of AP neurons were affected by ADN stimulation, with most exhibiting short-duration excitatory responses (latency, 27 +/- 1 ms; duration, 11 +/- 1 ms). Fifty-five percent of NTS neurons were influenced by ADN stimulation, although effects in this region were more heterogeneous (24% of neurons excited, 31% inhibited). Thus, in the rat, apparently both AP and NTS neurons receive afferent barosensory information.
Lactate metabolism in inactive skeletal muscle during lactacidosis
Authors: Chin E. R. , Lindinger M. I. , Heigenhauser G. J.
Published: December 2017

Contributions of carbohydrate and fat metabolism to the removal of a lactate (Lac-) load were quantified in inactive soleus (SL), plantaris (PL), and white gastrocnemius (WG) rat hindlimb muscle. Male Sprague-Dawley rats were perfused for 60 min with normal perfusate (NP, n = 8) or a high-lactate perfusate (LP, n = 8), simulating ionic conditions found in arterial blood and plasma after intense exercise: Lac- = 11.0 mM, K+ = 7.88 mM, and pH = 7.15. Metabolite fluxes across the hindlimb were calculated from blood flow and arteriovenous differences. In NP, Lac- was continuously released (2.9 +/- 0.2 mumol.min-1 x 100 g-1). However, in LP, a rapid and significant uptake of Lac- increased muscle Lac- fivefold to 39.6 +/- 1.1, 33.1 +/- 2.2, and 28.8 +/- 1.7 mumol/g dry wt in SL, PL, and WG, respectively. Glucose and O2 uptakes were similar during LP and NP perfusion. Glycerol release increased eightfold to 3.3 +/- 0.7 mumol.min-1 x 100 g-1 in response to LP. Muscle ATP, creatine phosphate, glycogen, glycolytic intermediate, and triacylglycerol concentrations did not change. However, muscle lactate-to-pyruvate ratios were elevated in all muscles of the LP group postperfusion, indicating changes in the mass action ratio at the pyruvate dehydrogenase reaction. In LP, of 80 mumol of Lac- taken up, 11% was accounted for by increased muscle Lac-, 12-24% was oxidized, and 5% may have been involved in glycerol release. The remaining Lac- may have been involved in metabolic cycling along the glyconeogenic-glycolytic pathway and/or in triacylglycerol-free fatty acid substrate cycling.
Loss of integrative control of peripheral circulation during desynchronized sleep
Authors: Cianci T. , Zoccoli G. , Lenzi P. , Franzini C.
Published: December 2017

Regional blood flow (BF) changes during sleep were measured in rabbits at low, neutral, and high ambient temperatures (Ta) with radioactive microspheres. At both low and high Ta, peripheral vasomotor changes at the onset of desynchronized sleep (DS) were incompatible with thermoregulatory homeostasis. At low Ta, BF decreased in muscle (with the disappearance of shivering), whereas it increased in the arteriovenous anastomoses (AVA) and in the splanchnic bed. At high Ta, BF decreased in muscle (with the disappearance of panting) and in the AVA, whereas it increased in the splanchnic bed. An impaired central nervous regulation underlies the disruption of peripheral circulation patterns in this sleep stage. The lack of adaptive vasomotor adjustments in DS, which has little consequence in normal conditions, may become relevant in cardiovascular pathophysiology when BF redistribution through increased neurogenic vasomotor activity becomes a major compensating mechanism.
Glucagon in physiological concentrations stimulates brown fat thermogenesis in vivo
Authors: Billington C. J. , Briggs J. E. , Link J. G. , Levine A. S.
Published: December 2017

Our aims were to further characterize the stimulatory effect of glucagon on brown fat and to test the hypothesis that physiological levels of hyperglucagonemia would stimulate brown fat thermogenesis. In the first set of experiments, glucagon (1 mg/kg sc twice daily) or vehicle control was administered three times in 26 h. This large dose of glucagon produced increases in GDP binding to brown fat mitochondria. In addition, Scatchard analysis indicated a glucagon-induced increase in number of GDP binding sites without evidence for alteration in binding site affinity. No consistent increase in brown fat mitochondrial GDP binding was produced 2 h after a single injection of glucagon (1 mg/kg). In the second set of experiments, glucagon was administered intraperitoneally by constant osmotic minipump infusion. Glucagon in a dose of 150 micrograms.kg-1.day-1 for 5 days produced significant increases in GDP binding to brown fat mitochondria, whereas glucagon serum levels were increased but stayed within the usual physiological range. A larger dose of glucagon administered by constant infusion virtually eliminated body weight gain over 7 days while significantly increasing nucleotide binding (GDP) to brown fat mitochondria. An important role for glucagon in thermogenic regulation is suggested.
Bradykinin-induced prostaglandin synthesis is enhanced in keratinocytes and fibroblasts by UV injury
Authors: Pentland A. P. , Jacobs S. C.
Published: December 2017

Ultraviolet (UV) light exposure substantially modifies the host immune response, in part through the synthesis of prostaglandins. Work examining the mechanisms by which UV irradiation stimulates prostaglandin synthesis has focused on mediators that increase in quantity after irradiation. The present work demonstrates that UV irradiation injury increases the sensitivity and maximum response of keratinocytes to bradykinin, suggesting that agonist quantities need not increase in injured tissue to contribute to inflammation. The ability of UV injury to increase bradykinin-stimulated prostaglandin synthesis is not limited to keratinocytes, as irradiation produced a similar response in fibroblasts. Receptor binding studies demonstrate that the enhanced response of irradiated cells is not due to increased bradykinin binding. These data suggest that UV irradiation may cause cells to increase their response to an array of inflammatory mediators present in injured tissue, whether or not the quantity of the mediator increases.
Carbonic acid buffer species measured in real time with an intracellular microelectrode array
Authors: Wietasch K. , Kraig R. P.
Published: December 2017

Carbonic acid buffer anions, HCO3- and CO3(2-), play an instrumental role in a host of vital processes in animal cells and tissues. Yet study of carbonic acid buffer species is hampered because no means are available to simultaneously monitor them at a cellular level in a rapid and dynamic fashion. An ion-selective cocktail, previously reported to measure changes in bicarbonate activity (alpha HCO3-), was instead shown to be principally selective for alpha CO3(2-). Ion-selective micropipettes (ISMs) based on this exchanger and consisting of a 3:1:6 (volume) mixture of tri-n-octylpropylammonium chloride, 1-octanol, and trifluoroacetyl-p-butylbenzene showed no significant interference from bicarbonate, chloride, phosphate, ascorbate, lactate, glutamate, acetate, or hydroxyl ions at concentrations expected in vivo. Intracellular and triple-barrel ISMs, consisting of a CO3(2-) sensitive, pH-sensitive, and reference barrel, were fabricated. Skeletal muscle cells (n = 17) were penetrated in vivo and showed values of 74 +/- 7 mV for membrane potential, 6.94 +/- 0.09 pHi, and 11 +/- 5 microM intracellular alpha CO3(2-), from which intracellular alpha HCO3- of 25 +/- 10 mM and CO2 tension of 120 +/- 55 Torr were calculated. All ion measurements reached a new steady state in 9 +/- 2 s after cell penetration. Thus measurements of intracellular alpha CO3(2-) and pH and associated levels of alpha HCO3(2-) and CO2 tension can be determined in biological tissues and cells with a spatial and temporal resolution previously unattainable.
Restricted feeding entrains circadian wheel-running activity rhythms of the kowari
Authors: Kennedy G. A. , Coleman G. J. , Armstrong S. M.
Published: December 2017

The effect of daily restricted feeding (RF) on the circadian wheel-running rhythms of the kowari, Dasyuroides byrnei, was examined in two experiments. Kowaris were presented with a preferred food (determined in a pilot study) during a daily 2-h meal in the light period of a 14:10 light-dark (LD) cycle (expts 1 and 2), during constant dark (DD) immediately after termination of the LD cycle (expt 1), and during DD when kowaris were free running (expt 1). Results showed that 1) RF elicited anticipatory activity similar in duration and phasing to that observed in the rat; 2) cycles of meal-associated activity free ran for up to 6 days after the termination of RF; 3) activity persists at a phase near that of the former mealtime during periods of food deprivation; and 4) activity indicative of beating between two pacemakers occurred when feeding was restricted to the L period of LD cycles. Together these observations suggest that the activity rhythms of the kowari may be controlled by separate, but possibly coupled, light-entrainable and food-entrainable pacemakers, as are those of the rat.
Corticotropin-releasing factor in the ovine fetus and pregnant ewe: role of placenta
Authors: Keller-Wood M. , Wood C. E.
Published: December 2017

In the sheep, maternal plasma adrenocorticotropic hormone and cortisol are increased in late pregnancy, and fetal plasma cortisol and adrenocorticotropic hormone rise precipitously in late gestation. To test whether the ovine placenta secretes corticotropin-releasing factor (CRF) into either the maternal or fetal circulation, pregnant ewes and their fetuses were prepared with femoral arterial catheters and uterine and umbilical venous catheters. Samples were taken from all sites before and during hypoxia. There was no difference in CRF concentration across the placenta in the mothers or the fetuses under resting or hypoxemic conditions, but maternal and fetal arterial plasma CRF concentrations increased between 128 and 145 days. In a second study, maternal and fetal femoral venous plasma CRF concentrations were measured 1-19 days before spontaneous parturition. The mean concentration increased 8.6 +/- 0.6 pg/ml 11-19 days before parturition to 13.0 +/- 1.0 and 13.2 +/- 1.4 pg/ml in fetuses 4-8 and 1-3 days before parturition, respectively. Maternal plasma concentrations did not significantly increase in the days closer to parturition. These studies demonstrate that there are low but measurable CRF concentrations in fetal and maternal sheep plasma but that these are not the result of tonic placental secretion of CRF.