bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of gill filament blood flow by serotonin in the rainbow trout, Oncorhynchus mykiss
Authors: Sundin L. , Nilsson G. E. , Block M. , Lofman C. O.
Published: December 2017

The effects of exogenously applied serotonin [5-hydroxytryptamine (5-HT)] on the distal arterial vasculature of gill filaments were observed using an epi-illumination microscope equipped with a water-immersion objective and connected to a video camera. In addition, ventral aortic flow (Q) and celiac artery pressure (PCA) were measured. Intra-arterial injection of serotonin (100 nmol/kg) completely stopped the blood flow in the distal part of the filaments and caused a rapid decrease of PCA. Repeatedly, the flow reduction was found to coincide with a constriction of the distal portion of the efferent filamental vasculature. Because there was no concomitant reduction in Q, it is concluded that a redistribution of blood to more proximal parts of the filaments occurred. After treatment with the serotonergic receptor antagonist methysergide, the vasoconstrictor effect of serotonin on the filamental vasculature was eliminated, while a decrease in PCA was still observed. The results demonstrate a specific site(s) for the serotonergic vasoconstriction in the distal portion of the filament.
Responses of the circulatory system and muscle sympathetic nerve activity to head-down tilt in humans
Authors: Nagaya K. , Wada F. , Nakamitsu S. , Sagawa S. , Shiraki K.
Published: December 2017

These experiments were conducted to examine whether changes in central and peripheral hemodynamics were proportional to muscle sympathetic nerve activity (MSNA) during graded head-down tilt (HDT). Twelve healthy males (19-42 yr old) underwent HDT at 15 degrees and 30 degrees for 10 min each with a 10-min rest period between the trials. MSNA at 15 degrees HDT declined by 31 +/- 5% (P < 0.05) for burst rate and by 37 +/- 3% (P < 0.05) for total activity. At 30 degrees HDT, the reduction in MSNA was 51 +/- 5% for burst rate (P < 0.05 vs. 15 degrees HDT) and 46 +/- 5% for total activity (P < 0.05 vs. 15 degrees HDT). Stroke volume increased (P < 0.05) during both 15 degrees and 30 degrees HDT, but heart rate and blood pressure remained unchanged. A concurrent increase in central venous pressure (P < 0.05) and stroke volume with a reduction of thoracic impedance (P < 0.05) suggests that both pressure and volume in the atrium were elevated during HDT, and the magnitude of these changes was greater (P < 0.05) at 30 degrees HDT than at 15 degrees HDT. Forearm blood flow increased during HDT at both 15 degrees and 30 degrees, and the magnitude of the increase was greater (P < 0.05) at 30 degrees HDT. It is concluded that the magnitude of the loading of the cardiopulmonary mechanoreceptors during HDT was higher at 30 degrees in comparison to 15 degrees. This increased the afferent firing rate by the cardiopulmonary receptors and probably inhibited sympathetic outflow in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Interferon-alpha acts at the preoptic hypothalamus to reduce natural killer cytotoxicity in rats
Authors: Take S. , Uchimura D. , Kanemitsu Y. , Katafuchi T. , Hori T.
Published: December 2017

We previously demonstrated that an intracerebroventricular injection of recombinant human interferon-alpha (rhIFN-alpha) reduced the cytotoxicity of splenic natural killer (NK) cells in rats and mice. In the present study, we investigated the brain sites at which rhIFN-alpha acts to suppress splenic NK activity in unanesthetized rats implanted unilaterally with a chronic hypothalamic cannula. A microinjection of 200 U of rhIFN-alpha into the medial part of the preoptic hypothalamus reduced NK activity to approximately 60% of control 30 min after the injection. Administration of 50 U of rhIFN-alpha also decreased NK activity to approximately 80%. The injection of 200 U of rhIFN-alpha into other hypothalamic areas (lateral preoptic hypothalamus, ventromedial hypothalamus, lateral hypothalamus, and paraventricular nucleus) had no effect. The medial preoptic hypothalamus-rhIFN-alpha-induced immunosuppression was completely blocked by splenic denervation, but not by adrenalectomy. These results suggest that IFN-alpha suppresses splenic NK activity predominantly through the medial preoptic hypothalamus-sympathetic pathway.
Glossopharyngeal nerve transection does not compromise the specificity of taste-guided sodium appetite in rats
Authors: Markison S. , St John S. J. , Spector A. C.
Published: December 2017

The chorda tympani nerve (CT) has been shown to be critical in the sodium-specific drinking behavior of sodium-depleted rats, but the role of other gustatory nerves and the contribution of the major salivary glands remain to be elucidated. In this study, rats received either bilateral section of the CT (CTX) or the glossopharyngeal nerve (GLX), extirpation of the sublingual and submaxillary salivary glands (DSAL), or sham surgery. After recovery, rats were sodium depleted with furosemide and tested for their licking responses to 0.05 and 0.3 M NaCl, KCl, CaCl2, and NH4Cl, as well as distilled water in an automated gustometer. Rats that received GLX maintained a specific sodium appetite comparable to controls despite denervation of approximately 64% of the taste buds. In contrast, compared with control rats, CTX and DSAL rats had altered response profiles, showing much smaller differences in licking to NaCl relative to the other stimuli. This was accompanied by a substantially lower lick rate in DSAL rats, raising the possibility that general licking impairments contributed to the decreased NaCl responsiveness in these rats. These findings imply that the CT, but not the glossopharyngeal nerve, is necessary for the maintenance of normal sodium-specific, taste-guided behavior under sodium deplete conditions.
Mechanism of tolerance to tumor necrosis factor: receptor-specific pathway and selectivity
Authors: Takahashi N. , Brouckaert P. , Fiers W.
Published: December 2017

Repetitive administration of low doses of tumor necrosis factor (TNF) induces a selective tolerance to some, but not all, of its effects. The aim of the present study was to define the pathways involved in tolerance. We observed that the induction of tolerance is mediated by TNF-R55 triggering. TNF-R75 triggering or the addition of sensitizers can interfere with this induction but does not break an acquired tolerance, inasmuch as tolerant animals were also tolerant to otherwise lethal challenges with the combination of human TNF and the sensitizers interleukin-1 and RU-38486. We further defined the selectivity of the tolerance by examining changes in quantitative parameters such as interleukin-6 induction, hypothermia, and hemoconcentration. The differences between tolerant and nontolerant animals mimicked those observed after administration of human TNF vs. murine TNF and were to be found in the duration rather than in the amplitude of the induced changes. We conclude that tolerance selectively blocks the TNF-R75-mediated pathway, especially the part mimicked by interleukin-1 and RU-38486; this pathway normally leads to a state of unresponsiveness to glucocorticoids.
Vasopressin actions on area postrema neurons in vitro
Authors: Lowes V. L. , Sun K. , Li Z. , Ferguson A. V.
Published: December 2017

The area postrema (AP) is a circumventricular organ located on the dorsal surface of the medulla. Substantial evidence suggests that the AP is an important site involved in cardiovascular regulation. Arginine vasopressin (AVP) is thought to act at the AP to increase the sensitivity of the baroreceptor reflex. We have therefore examined the effects of AVP on AP neurons with the use of extracellular single unit recordings in vitro. Coronal medullary brain slices (thickness = 400 microns) were obtained from male Sprague-Dawley rats and maintained in oxygenated artificial cerebrospinal fluid (aCSF). The slices were perfused with AVP (10(-8) to 10(-6) M), and the effect on single AP neurons was recorded. A total of 79 AP neurons was tested of which 50 (63.3%) were excited by AVP and 5 (6.3%) were inhibited, whereas the remaining 24 (30.3%) cells were unaffected. The excitatory effects of AVP were dose dependent: firing rate increased 92.6 +/- 25.8% at 10(-8) M, 289.4 +/- 53.9% at 10(-7) M, and 456.8 +/- 113.1% at 10(-6) M, respectively. We also examined whether these effects of AVP resulted from direct actions of this peptide on AP cells by testing if responses were retained during blockade of synaptic transmission (achieved by perfusion with a low Ca(2+)-high Mg2+ aCSF) in 11 cells excited by AVP. Nine of these cells were excited by AVP during such synaptic blockade. Finally, we demonstrated that the excitatory responses of five AP cells to AVP were all totally abolished by perfusion of slices with aCSF containing the V1 antagonist ([1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid,2-(O-methyl)tyrosine]-Arg8-vasopressin; Peninsula Laboratories, 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Quantity of sucrose alters the tissue pattern and time course of insulin resistance in young rats
Authors: Pagliassotti M. J. , Prach P. A.
Published: December 2017

To determine the effects of the amount of sucrose in the diet on insulin-stimulated glucose metabolism, euglycemic hyperinsulinemic clamps were performed on male Wistar rats after one of the following dietary treatments (n = 6-8/treatment): 1) high-starch diet (68% of total energy) for 8 wk (ST8), 16 wk (ST16), or 30 wk (ST30); 2) high-sucrose diet (68% of total energy) for 8 wk (SU8), 16 wk (SU16), or 30 wk (SU30); or 3) low-sucrose diet (18% of total energy) for 8 wk (SUL8), 16 wk (SUL16), or 30 wk (SUL30). Body weights were similar in starch- and sucrose-fed rats at 8 wk (502 +/- 9 g), 16 wk (563 +/- 10 g), and 30 wk (607 +/- 26 g). The glucose infusion rate (mumol.g-1.min-1) required to maintain similar glycemia during clamps was 73.1 +/- 8.8 in ST8, 29.7 +/- 4.9 in SU8 (P < 0.05 vs. ST8 and SUL8), and 76.4 +/- 8.2 in SUL8; 69.9 +/- 8.1 in ST16, 35.1 +/- 5.1 in SU16 (P < 0.05 vs. ST16 and SUL16), and 63.2 +/- 6.5 in SUL16; and 65.4 +/- 7.7 in ST30, 26.0 +/- 5.3 (P < 0.05 vs. ST30), and 36.3 +/- 6.0 in SUL30 (P < 0.05 vs. ST30). Impaired suppression of hepatic glucose production accounted for 43, 39, and 34% of the decrease in the glucose infusion rate in SU8 compared with ST8, SU16 compared with ST16, and SU30 compared with ST30, respectively, but 78% in SUL30 compared with ST30. These results suggest that both high- and low-sucrose diets can produce insulin resistance in young rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of effects of adrenalectomy and RU-486 in rats given a choice of maintenance diet and fat supplement
Authors: Trocki O. , Baer D. J. , Castonguay T. W.
Published: December 2017

The effects of adrenalectomy (ADX) and the blockade of glucocorticoid receptors by RU-486 on Sprague-Dawley rats given a choice of a maintenance diet and a fat supplement were studied. Adult male rats were given free access to AIN-76A diet only (CON) or AIN-76A diet and a separate dietary fat option for 4 wk (FAT). They were then assigned to one of the following treatments: ADX, sham operation, ADX with corticosterone (CORT) replacement, RU-486 injections, or vehicle injections. Food intake and body weight were monitored daily for an additional 3 wk. ADX decreased caloric intake and weight gain in the FAT group more than in the CON group. RU-486 also decreased caloric and fat option intakes as well as weight gain. ADX, but not RU-486, reduced body fat content, lowered plasma insulin and triglyceride levels, and decreased glucose intolerance. CORT replacement partially prevented the effects of ADX on weight gain and body fat content. The results of this study indicate that ADX has greater effects on weight gain and body fat accumulation than does RU-486.
Mechanisms of acid release in isolated gas gland cells of the European eel Anguilla anguilla
Authors: Pelster B.
Published: December 2017

Mechanisms of acid production and of acid release have been analyzed in isolated gas gland cells of the eel swimbladder using a cytosensor microphysiometer. Incubation of isolated cells with oxamic acid caused a dose-dependent decrease in the rate of proton release. At the highest oxamic acid concentration used (20 mmol/l), proton release was reduced by approximately 40%; incubation with sodium fluoride (10 mmol/l) or removal of glucose from the extracellular medium caused 60 and 80% reduction, respectively. NaCN had little effect on proton secretion. Proton release of isolated gas gland cells was largely dependent on the extracellular sodium concentration, and this sodium effect was in part inhibitable by amiloride. A 15-20% reduction in the rate of proton secretion was observed in the presence of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, an inhibitor of anion exchange. Inhibition of mammalian H(+)-K(+)-adenosinetriphosphatase with omeprazole had no effect, whereas bafilomycin, an inhibitor of vesicular H(+)-adenosinetriphosphatase, induced a 25% reduction in proton secretion. Ethoxzolamide, a membrane-permeable inhibitor of carbonic anhydrase, caused a 60% reduction in proton secretion (inhibition constant = 54.4 nmol/l). Prontosil-dextran, a membrane-impermeable sulfonamide, also reduced the proton release, thus indicating the presence of a membrane-bound carbonic anhydrase facing the extracellular space.
Hypothalamic neuronal histamine modulates physiological responses induced by interleukin-1 beta
Authors: Kang M. , Yoshimatsu H. , Chiba S. , Kurokawa M. , Ogawa R. , Tamari Y. , Tatsukawa M. , Sakata T.
Published: December 2017

Dynamic involvement of hypothalamic histamine in ingestive behavior and thermogenesis induced by interleukin-1 beta (IL-1 beta) was examined in rats. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta decreased food and water intake and elevated body temperature. However, depletion of neuronal histamine induced by intraperitoneal injection of 160 mumol/rat alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the suppressive effect on drinking, and enhanced the elevating effect on rectal temperature. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta increased hypothalamic histamine turnover rate. The same dose of IL-1 beta also increased activity of HDC and histamine-N-methyltransferase (HMT). These results suggest that IL-1 beta may stimulate synthesis and release of hypothalamic histamine in presynaptic terminals by activation of HDC and facilitate degradation of extracellular histamine by activation of MHT. These changes in the dynamics of hypothalamic histamine modulate IL-1 beta-induced ingestive behavior and body temperature.
CAP2b, a cardioacceleratory peptide, is present in Drosophila and stimulates tubule fluid secretion via cGMP
Authors: Davies S. A. , Huesmann G. R. , Maddrell S. H. , O'Donnell M. J. , Skaer N. J. , Dow J. A. , Tublitz N. J.
Published: December 2017

A cardioacceleratory peptide, CAP2b, identified originally in the lepidopteran Manduca sexta, stimulates fluid secretion by Malpighian tubules of the dipteran Drosophila melanogaster. High-performance liquid chromatography analyses of adult D. melanogaster reveal the presence of a CAP2b-like peptide, that coelutes with M. sexta CAP2b and synthetic CAP2b and that has CAP2b-like effects on the M. sexta heart. CAP2b accelerates fluid secretion in tubules stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) but has no effect on tubules stimulated by guanosine 3',5'-cyclic monophosphate (cGMP), implying that it acts through the latter pathway. By contrast, the action of leucokinin is additive to both cAMP and cGMP but not to thapsigargin, suggesting that leucokinin acts by the elevation of intracellular calcium. CAP2b stimulation elevates tubule cGMP levels but not those of cAMP. By contrast, leucokinin has no effect on levels of either cyclic nucleotide. Both CAP2b and cGMP increase transepithelial potential difference, suggesting that stimulation of vacuolar-adenosinetriphosphatase action underlies the corresponding increases in fluid secretion. Overall, the results show that a Drosophila CAP2b-related peptide acts to stimulate fluid secretion by Malpighian tubules through the cGMP-signaling pathway.
Insulin/IGF-I binding ratio in skeletal and cardiac muscles of vertebrates: a phylogenetic approach
Authors: Parrizas M. , Maestro M. A. , Banos N. , Navarro I. , Planas J. , Gutierrez J.
Published: December 2017

Insulin and insulin-like growth factor (IGF-I) receptor binding and tyrosine kinase activity were characterized in cardiac and skeletal muscles of several vertebrates. Specific insulin binding per unit weight of skeletal muscle was clearly higher in pigeon and rat than in ectothermic vertebrates (32 +/- 5 and 25 +/- 2.7%/100 mg initial tissue in pigeon and rat, respectively, vs. 4.4 +/- 0.2%/100 mg in carp samples). Insulin binding clearly predominated over IGF-I binding in skeletal muscle of endotherms (IGF-I binding was 7.7 +/- 0.5%/100 mg in rat). In ectothermic vertebrates the situation was reversed, and IGF-I binding was higher than insulin binding. In cardiac muscle, specific binding of both insulin and especially IGF-I was higher than the values found in skeletal muscle of the same species (IGF-I binding was 60 +/- 4, 103 +/- 2, and 20 +/- 3%/100 mg in carp, turtle, and rat, respectively). The tyrosine kinase activity of insulin and IGF-I receptors of all species studied presented basal phosphotransferase rates (250-1,600 fmol P.micrograms protein-1.30 min-1) and percentage of stimulation (150-520%) with clear differences between species. The present data suggest that insulin and IGF-I binding to skeletal and cardiac muscles change through the vertebrate scale in both quantity and activity.
Lighting conditions alter Candida albicans-induced sleep responses in rabbits
Authors: Toth L. A. , Krueger J. M.
Published: December 2017

To evaluate the influence of light on sleep patterns after microbial challenge, we studied rabbits housed in 12:12-h light-dark (LD), constant light (LL), or constant darkness (DD) before and after intravenous Candida albicans inoculation. Compared with the LD group, uninoculated LL rabbits sporadically increased slow-wave sleep and delta-wave amplitudes during the circadian period previously associated with the dark phase. In contrast, uninfected DD rabbits showed reduced sleep during the circadian period previously associated with the light phase. Inoculation of LD rabbits with Candida approximately 2 h after light onset increased slow-wave sleep and delta-wave amplitudes during hours 4-8 postinoculation and reduced these parameters during hours 20-46. In contrast, Candida-inoculated LL rabbits demonstrated increased slow-wave sleep for up to 28 h after inoculation, with little subsequent reduction; delta-wave amplitudes were similar to those of LD rabbits. Candida-inoculated DD rabbits demonstrated attenuated increases in slow-wave sleep and delta-wave amplitudes, but the suppression phase was not altered. We conclude that lighting conditions modulate microbially induced sleep alterations.
Glucose and oxygen metabolism in the fetal foal during late gestation
Authors: Fowden A. L. , Silver M.
Published: December 2017

With the use of [U-14C]glucose tracer methodology, the rates of umbilical uptake, utilization, oxidation, and production of glucose were determined in nine chronically catheterized fetal foals in the fed state between 268 and 325 days of gestation (term approximately 335 days). At the same time, the rates of umbilical O2 and lactate uptake were measured in all nine fetuses by Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization, and CO2 production from glucose carbon were 36.9 +/- 2.5, 36.4 +/- 1.7, and 117.7 +/- 17.4 mumol.min-1.kg fetal body wt-1, respectively (n = 9). Endogenous glucose production was therefore negligible in the fetal foal in the fed state. Production of CO2 from glucose carbon accounted for 40.9 +/- 6.5% of the umbilical O2 uptake, which averaged 292 +/- 15 mumol.min-1.kg-1 (n = 9). No significant changes in fetal glucose or O2 metabolism were observed with increasing gestational age. The rates of umbilical glucose uptake, glucose utilization, and CO2 production from glucose carbon (P < 0.01), but not the rate of umbilical O2 uptake (P > 0.05), were positively correlated with the fetal blood glucose level. There was a significant umbilical lactate uptake in the fetuses older than 290 days (12.3 +/- 4.1 mumol.min-1.kg-1, n = 5, P < 0.05) but not in the younger animals (6.2 +/- 9.6 mumol.min-1.kg-1, n = 4, P > 0.05). Hence, glucose is used for both oxidative and nonoxidative metabolism in utero and is a major, although not the sole, oxidative substrate in the fetal foal during late gestation.
Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise
Authors: Convertino V. A. , Engelke K. A. , Ludwig D. A. , Doerr D. F.
Published: December 2017

Seven healthy men performed maximal exercise 24 h before the end of 16 days exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that such an exercise technique could restore plasma volume (PV) at the end of a simulated space mission. Exercise consisted of supine cycling with graded work rates increasing by 16 W/min to volitional fatigue and required an average of 16 min. The experimental protocol was a standard cross-over design in which the order of treatment (exercise or control) was counterbalanced across all seven subjects. PV, fluid intake (ad libitum), urine output, renal function, and hormones associated with fluid homeostasis were measured before HDT, 24 h before the end of HDT just prior to exercise, and at the end of HDT 24 h after exercise. HDT reduced PV by 16% in both control and exercise conditions. Maximal exercise completely restored plasma volume within 24 h to 3.9 +/- 3.2% of pre-HDT levels despite continued HDT. Compared with control, exercise induced a 660-ml larger positive fluid balance because of greater fluid intake and reduced urine volume during the 24 h after exercise. These results suggest that one bout of maximal leg exercise before return from 16 days of spaceflight may be completely effective in stimulating thirst and restoring plasma volume to preflight levels.
Entrainment of Syrian hamster circadian activity rhythms by neonatal melatonin injections
Authors: Grosse J. , Velickovic A. , Davis F. C.
Published: December 2017

The circadian rhythms of fetal and neonatal rodents are entrained by their mother. This entrainment is dependent upon the maternal suprachiasmatic nucleus (SCN), but the mechanism of entrainment is unknown. Administration of the pineal hormone melatonin to pregnant, SCN-lesioned female Syrian hamsters entrains the activity rhythms of their hamster pups. The aim of this study was to determine whether melatonin injected directly in neonatal Syrian hamsters is able to entrain circadian rhythms and, if so, for how long this effect persists during development. Injection of melatonin in two groups of hamster pups at opposite phases on postnatal days 1-5 entrained the onset of activity rhythms on the day of weaning to two phases 10.67 h apart. Melatonin injection did not entrain activity rhythms to opposite phases on either postnatal days 6-10 or 21-25. Vehicle injection did not entrain animals to opposite phases at any of the ages studied. These results demonstrate that melatonin is able to act directly on the neonate to cause entrainment and that this effect disappears after postnatal day 6.
Does thromboxane mediate the fetal ACTH response to acidemia?
Authors: Cudd T. A. , Wood C. E.
Published: December 2017

Intravenous mineral acid infusions into fetal sheep stimulate increases in plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations that correlate to the induced changes in arterial pH (pHa). We have recently demonstrated that ACTH and cortisol responses to mineral acid infusion in adult sheep are mediated by thromboxane A2 (TxA2). We designed the present experiments to test the hypothesis that fetal ACTH and cortisol responses are also mediated by TxA2. We infused chronically instrumented fetal sheep with 1 N HCl (0.5 ml/min i.v.) for 60 min, with or without pretreatment with the cyclooxygenase inhibitor flunixin-N-methylglucamine. HCl infusion significantly decreased pHa and significantly increased the arterial partial pressure of O2 (PaO2) and CO2 (PaCO2). Flunixin pretreatment significantly decreased fetal plasma thromboxane B2 (TxB2) concentrations but did not significantly alter the blood gas and pH response to HCl. TxB2 is a stable metabolite of TxA2 and was measured as an index of TxA2 generation. HCl increased fetal heart rate only in the flunixin group. Plasma ACTH and cortisol concentrations were increased significantly in both groups; flunixin did not significantly alter the responses. HCl infusion did not significantly alter plasma TxB2 concentrations. We conclude that the fetal ACTH and cortisol responses to HCl infusion are not mediated by TxA2 or other prostanoids whose synthesis depends on cyclooxygenase activity.
Respiratory modulation of sympathetic nerve activity: effect of MK-801
Authors: Morrison S. F.
Published: December 2017

The modulation of splanchnic sympathetic nerve activity (SNA) by brain stem neural networks generating the respiratory rhythm was examined in decerebrate, unanesthetized, vagotomized, artificially ventilated rats before and after blockade of the N-methyl-D-aspartate (NMDA) channel with intravenous administration of dizocilpine (MK-801). NMDA channel blockade 1) prolonged inspiration and reduced the phrenic nerve amplitude, 2) reduced SNA to 40% of control levels, and 3) decreased mean arterial pressure by 20 mmHg. A strong synchronization of SNA to the central respiratory cycle (monitored by the activity on the phrenic nerve) was maintained after MK-801 administration, although a brief inhibition of SNA during early inspiration and a sympathetic excitation during early expiration were eliminated. These results suggest 1) the existence of an NMDA-independent mechanism by which some elements of the brain stem respiratory network excite sympathetic outflow, 2) that the NMDA-mediated influence of specific classes of brain stem respiratory neurons can modulate this excitation during portions of the respiratory cycle, and 3) that an NMDA-dependent excitation in the brain stem or spinal cord plays a significant role in maintaining basal levels of splanchnic SNA.
Cardiovascular and sympathoadrenal responses to heat stress following water deprivation in rats
Authors: Massett M. P. , Johnson D. G. , Kregel K. C.
Published: December 2017

This study was designed to characterize the regional and systemic hemodynamic and sympathoadrenal responses to heating after 24 and 48 h of water deprivation in chloralose-anesthetized, male Sprague-Dawley rats (n = 7 per group). Water deprivation produced significant decreases in body weight of 8.1 and 13.7% in the 24- and 48-h groups (P < 0.05), respectively. After water deprivation, rats were exposed to an ambient temperature of 43 degrees C. After correction for body weight differences, heating rates were faster in the 48-h group compared with both euhydrated and 24-h groups. Mean arterial blood pressure (MAP), heart rate, and colonic (Tco) and tail (Ttail) temperatures increased above baseline in all groups during heating. Renal and mesenteric artery blood flow velocities decreased, and vascular resistances increased in response to heating. Compared with euhydrated controls, 48-h water-deprived rats exhibited attenuated pressor (delta MAP = 36 +/- 3 vs. 18 +/- 3 mmHg) and visceral vasoconstrictor (% delta in mesenteric resistance = 122.6 +/- 27.3 vs. 54.9 +/- 6.9%) responses during heating. Tail-skin blood flow estimated from Ttail was also lower at baseline and the onset of heating in water-deprived rats. However, peak Ttail and Tco values were similar across groups. Plasma catecholamines measured in separate groups of rats (n = 6 per group) were significantly higher at baseline and the end of heating in the 48-h group compared with euhydrated and 24-h groups. Despite this exaggerated sympathoadrenal response, the 48-h group exhibited attenuated hemodynamic responses to nonexertional heating compared with euhydrated and 24-h water-deprived rats. These data suggest that cardiovascular and thermoregulatory adjustments can compensate for small changes in hydration state (i.e., 24 h), but more severe levels of hypohydration significantly alter blood pressure and body temperature regulation during heat stress.
Effect of pioglitazone on vascular reactivity in vivo and in vitro
Authors: Kotchen T. A. , Zhang H. Y. , Reddy S. , Hoffmann R. G.
Published: December 2017

Pioglitazone (a thiazolidinedione derivative) increases insulin sensitivity and prevents hypertension in the Dahl-salt-sensitive (S) rat. The present study was undertaken to determine if pioglitazone modulates pressor responsiveness to vasoactive agents, both in vivo and in vitro. In vivo, pretreatment with pioglitazone inhibited (P < 0.02) pressor responses to both norepinephrine and angiotensin II in conscious Dahl-S, but not in Sprague-Dawley rats. In vitro, pioglitazone augmented the capacity of insulin to inhibit pressor responses of strips of thoracic aortas to norepinephrine, but not to angiotensin. Additionally, in vitro, incubation with insulin plus pioglitazone augmented acetylcholine-induced, but not nitroprusside-induced vasodilation. Pioglitazone pretreatment increased (P < 0.001) in vitro insulin-stimulated glucose uptake in adipose tissue, but not in thoracic aortas of Dahl-S. We hypothesize that pioglitazone attenuates hypertension by modulating the effects of insulin on vascular function, resulting in both blunted vasoconstriction and augmented acetylcholine-induced vasodilation. These alterations are not accounted for by an effect of pioglitazone on glucose uptake by vascular smooth muscle.
Effect of lactate on hepatic insulin clearance in perfused rat liver
Authors: Pagano C. , Rizzato M. , Lombardi A. M. , Fabris R. , Favaro A. , Federspil G. , Vettor R.
Published: December 2017

The aim of our study was to investigate whether sodium lactate has any effect on hepatic insulin dynamics in perfused rat liver. Rat livers were perfused in situ with saline or increasing concentrations of sodium lactate, and hepatic insulin extraction was calculated from the difference in insulin concentration between the portal and the suprahepatic vein. Our results show that hepatic insulin extraction at the three lactate concentrations added was higher than in the control experiments (lactate 1 mmol/l: 263 +/- 51 vs. 765 +/- 114, P < 0.005; lactate 5 mmol/l: 341 +/- 80 vs. 906 +/- 109; P < 0.005; lactate 15 mmol/l: 438 +/- 21 vs. 981 +/- 66 microIU.g-1.30 min-1, P < 0.005). No significant differences were observed in net glucose balance across the liver during perfusion with lactate. Moreover perfused liver displayed a net lactate production during infusion with saline or lactate added at the lower concentrations (1 and 5 mM), whereas at the highest (15 mM), a net lactate uptake by the liver was observed (P < 0.05). Our results suggest that, in perfused rat liver, lactate may increase hepatic insulin clearance. Thus energy fuels such as lactate and nonesterified fatty acid have opposite effects on hepatic insulin clearance and may therefore contribute to the regulation of posthepatic insulin delivery.
Gastric emptying of ingested fat emulsion in rats: implications for studies of fat-induced satiety
Authors: Friedman M. I. , Ramirez I. , Tordoff M. G.
Published: December 2017

Evidence that ingested fat acts in the intestine to produce satiety stems from studies showing that intraintestinal infusion of fat emulsion inhibits eating behavior of rats. In this study, we determined the appropriateness of infusion parameters used in these behavioral studies by measuring gastric emptying rates of both the aqueous and lipid components of Intralipid ingested normally by rats. Stomach contents were collected at different times 0-40 min after rats ingested Intralipid containing [14C]polyethylene glycol (PEG) and phenol red (PR) and were assayed for PEG, PR, and fat. The proportion of ingested fat remaining in the stomach was significantly greater than the proportion of ingested PEG or PR at all time points examined. Despite initial gastric emptying of fat during ingestion, consumption of Intralipid (0.5 or 1.1 kcal/ml) did not suppress subsequent solid food intake. The results indicate that 1) ingested fat emulsion rapidly partitions in the rat stomach into an aqueous phase, which empties rapidly, and a lipid phase, which empties slowly, and 2) normal ingestion of Intralipid is not immediately satiating. These observations raise questions about the physiological significance of the rapid and marked suppression of feeding behavior produced by intraintestinal infusion of Intralipid.
Chronic food restriction and acute food deprivation decrease mRNA levels of opioid peptides in arcuate nucleus
Authors: Kim E. M. , Welch C. C. , Grace M. K. , Billington C. J. , Levine A. S.
Published: December 2017

Although opioid administration induces food intake, the relationship between endogenous opioid synthesis and food consumption is unclear. Two studies examined the effects of food restriction and deprivation on opioid mRNA levels in the arcuate nucleus (ARC) of the rat. Body weight significantly decreased following food restriction and deprivation (P < 0.0001). In experiment 1, food restriction of 10,20,30, and 40% (g) of ad libitum intake for 14 days decreased proDynorphin (proDyn), proEnkephalin (proEnk), and proOpiomelanocortin (POMC) mRNA levels in a linear fashion relative to changes in body weight (r = 0.398, P = 0.0011; r = 0.455, P = 0.0028; r = 0.292, P = 0.0642, respectively). In experiment 2, 48 h deprivation significantly decreased mRNA levels of proDyn and POMC by 23.7% (P < 0.05) and 45.6% (P < 0.01), respectively, whereas 24 h food deprivation decreased POMC mRNA by 43.% (P < 0.01). proEnk mRNA was not affected by 24- or 48-h food deprivation. Restricting food intake suppressed mRNA levels of proDyn, proEnk, and POMC by 29.7, 22.3, and 44.4%, respectively, in 20% restricted rats and by 35.5, 26.8, and 45.6%, respectively, in 40%restricted rats (P < 0.01). It appears that ARC mRNA levels of proDyn, proEnk, and POMC are directly related to the amount of food consumed and/or changes in body weight in food-restricted and food-deprived rats.
Comparison of trophic effects of norepinephrine, insulin, and IGF-1 in mouse brown adipocytes
Authors: Desautels M. , Bhaumick B. , Ram J. I.
Published: December 2017

The objective of this work was to evaluate whether insulin, like norepinephrine (NE), exerts direct growth effects in brown adipocytes, as assessed by changes in rates of protein labeling with [35S]methionine. Mouse brown adipocytes isolated by tissue collagenase digestion were incubated for up to 24 h with or without NE in Dulbecco's modified Eagle's medium with albumin, calf serum, and antibiotics. There was a 40% cell loss and a 50% decrease in cell content of succinate dehydrogenase (SDH) activity over 24 h. Both cell recovery and SDH content significantly improved in the presence of NE. In addition, NE increased [35S]methionine incorporation into proteins in both cytosolic and mitochondrial compartments. These effects of NE were inhibited by propranolol. Both insulin and insulin-like growth factor-1 (IGF-1) receptors were detected in brown adipocytes, with insulin receptors in much greater concentration. Increased protein labeling was observed when brown adipocytes were incubated for 4 h with 0.2-5 nM insulin in the absence of serum. This effect was small (30% stimulation) compared with the 200-350% increase observed with NE, and 5 nM IGF-1 had no effect. These results indicate direct trophic actions of both NE and insulin in mouse brown adipocytes, with the effects of NE an order of magnitude greater than those of insulin.
Acceptance of minerals and other compounds by calcium-deprived rats: 24-h tests
Authors: Coldwell S. E. , Tordoff M. G.
Published: December 2017

We measured 24-h spontaneous intake of four to eight concentrations of 31 different solutions by groups of rats fed control or low-calcium diets. Relative to controls, those fed low-calcium diet had increased acceptance of one or more concentrations of sodium chloride, sodium acetate, and sodium bicarbonate, but not sodium gluconate. Differences in palatability between these sodium salts were unimportant because the rats fed low-calcium diet consumed more sodium chloride even if this was made less acceptable by adulteration with citric acid. The possibility that calcium-deprived rats have an enhanced general cation or mineral appetite was supported by findings of increased acceptance of one or more concentrations of nine of ten chloride minerals tested (aluminum chloride, ammonium chloride, ferric chloride, ferrous chloride, magnesium chloride, sodium chloride, potassium chloride, strontium chloride, zinc chloride). However, there were no differences in acceptance of any concentration of cesium chloride, magnesium sulfate, or lead acetate. Moreover, calcium-deprived rats drank more hydrochloric acid and malic acid than did controls. Thus the effect of calcium deficiency on intake was not confined to minerals. Acidity or bitterness did not appear important because there was no difference between the groups in intake of sulfuric acid, citric acid, or quinine hydrochloride. Consistent with the exacerbating effects of phosphates on calcium deprivation, deprived rats had decreased intakes of phosphates (sodium phosphate, potassium phosphate). However, they also had decreased intakes of sucrose and saccharin. It is clear that calcium deprivation does not induce a general increase in acceptance of all taste solutions, but there appears to be no simple explanation for what these animals consume.
Regulation of glucose turnover and hormonal responses during electrical cycling in tetraplegic humans
Authors: Kjaer M. , Pollack S. F. , Mohr T. , Weiss H. , Gleim G. W. , Bach F. W. , Nicolaisen T. , Galbo H. , Ragnarsson K. T.
Published: December 2017

To examine the importance of blood-borne vs. neural mechanisms for hormonal responses and substrate mobilization during exercise, six spinal cord-injured tetraplegic (C5-T1) males (mean age: 35 yr, range: 24-55 yr) were recruited to perform involuntary, electrically induced cycling [functional electrical stimulation (FES)] to fatigue for 24.6 +/- 2.3 min (mean and SE), and heart rate rose from 67 +/- 7 (rest) to 107 +/- 5 (exercise) beats/min. Voluntary arm cranking in tetraplegics (ARM) and voluntary leg cycling in six matched, long-term immobilized (2-12 mo) males (Vol) served as control experiments. In FES, peripheral glucose uptake increased [12.4 +/- 1.1 (rest) to 19.5 +/- 4.3 (exercise) mumol.min-1.kg-1; P < 0.05], whereas hepatic glucose production did not change from basal values [12.4 +/- 1.4 (rest) vs. 13.0 +/- 3.4 (exercise) mumol.min-1.kg-1]. Accordingly, plasma glucose decreased [from 5.4 +/- 0.3 (rest) to 4.7 +/- 0.3 (exercise) mmol/l; P < 0.05]. Plasma glucose did not change in response to ARM or Vol. Plasma free fatty acids and beta-hydroxybutyrate decreased only in FES experiments (P < 0.05). During FES, increases in growth hormone (GH) and epinephrine and decreases in insulin concentrations were abolished. Although subnormal throughout the exercise period, norepinephrine concentrations increased during FES, and responses of heart rate, adrenocorticotropic hormone, beta-endorphin, renin, lactate, and potassium were marked. In conclusion, during exercise, activity in motor centers and afferent muscle nerves is important for normal responses of GH, catecholamines, insulin, glucose production, and lipolysis. Humoral feedback and spinal or simple autonomic nervous reflex mechanisms are not sufficient. However, such mechanisms are involved in redundant control of heart rate and neuroendocrine activity in exercise.
Acute and chronic angiotensin hypertension: neural and nonneural components, time course, and dose dependency
Authors: Li Q. , Dale W. E. , Hasser E. M. , Blaine E. H.
Published: December 2017

We examined the mechanisms mediating hypertension in conscious rats during acute and chronic infusion of angiotensin II (ANG II) at pressor doses (50, 100, and 200 ng.kg-1.min-1). Trimethaphan-induced blood pressure reduction was inversely related to the acute dose of ANG II, consistent with a constrictor action of ANG II on vascular smooth muscle and withdrawal of sympathetic tone. During chronic ANG II infusion, the entire increase in mean arterial pressure (MAP) was inhibited by trimethaphan, consistent with neural mediation. During acute ANG II hypertension, the AT1-specific receptor blocker losartan induced a large fall in MAP (64 +/- 4 mmHg) in ganglion-blocked (chlorisondamine) rats, whereas, during chronic ANG II hypertension, losartan had only a small hypotensive effect (11 +/- 3 mmHg). To determine the time course of the change from vascular smooth muscle action to neural action, we measured MAP in response to trimethaphan during the first 24 h of ANG II infusion. After 5 h, the minimal MAP in response to trimethaphan was significantly higher than that before ANG II. After 10 h of infusion, trimethaphan decreased MAP to pre-ANG II levels. That is, the neural component was fully active after only 10 h of infusion in rats. Finally, chronic administration of ANG II resulted in a dose-related increase in MAP that, at all doses, was completely inhibited by trimethaphan. These findings are consistent with ANG II acting primarily on vascular smooth muscle during acute infusion and via neural pathways during chronic treatment. The transition from direct smooth muscle to indirect neural action is rapid in rats (< 10 h), and the MAP and neural responses to ANG II are dose related during chronic hypertension.
Heterogeneity and lability of endogenous digitalis-like substances in the plasma of the toad, Bufo marinus
Authors: Butler V. P. , Morris J. F. , Akizawa T. , Matsukawa M. , Keating P. , Hardart A. , Furman I.
Published: December 2017

Three major groups of endogenous digitalis-like substances (EDLS) have been identified in the plasma of the toad, Bufo marinus. One group of compounds, present in fresh plasma, is composed of chromatographically homogeneous polar conjugates, principally bufadienolide 3-sulfates, which exhibit relatively weak Na(+)-K(+)-adenosinetriphosphatase (ATPase) inhibitory activity. A second and larger group of compounds, also found in fresh plasma, includes chromatographically heterogeneous conjugates, which are effective inhibitors of Na(+)-K(+)-ATPase; these compounds possess properties similar to those of bufotoxins. The third group of EDLS consists of free unconjugated bufadienolides, which are also effective Na(+)-K(+)-ATPase inhibitors. These unconjugated bufadienolides are present in relatively low concentrations in fresh toad plasma, but appreciable quantities are enzymatically generated from conjugates (believed to consist principally of bufotoxins) during the in vitro incubation of plasma. We suggest that the extent to which circulating polar EDLS are enzymatically deconjugated in vivo may be important in the regulation of the digitalis-sensitive Na(+)-K(+)-ATPase of toad brain, the only known digitalis-sensitive Na(+)-K(+)-ATPase in the toad.
Basal and glucoprivic-induced changes in extracellular GABA in the ventral hypothalamus of Zucker rats
Authors: Specter S. E. , Horwitz B. A. , Beverly J. L.
Published: December 2017

The diminished sensitivity of genetically obese (fa/ fa) Zucker rats to the glucoprivic agent 2-deoxy-D-glucose (2-DG) may involve impaired release of the neurotransmitter gamma-aminobutyric acid (GABA) in discrete regions of the hypothalamus. Extracellular GABA concentrations in the medial (MH) and lateral (LH) hypothalamus of lean (Fa/Fa) and age-matched obese (fa/fa) male Zucker rats before and after 2-DG (1.2 mmol/kg i.v.). Basal GABA concentrations were higher (P < 0.05) in the MH of obese vs. lean rats. No differences were noted in LH GABA levels between lean and obese rats or in baseline extracellular GABA levels between brain regions in lean rats. In lean rats, a characteristic bimodal increase in GABA concentrations was apparent in the MH, whereas GABA concentrations decreased in the LH during the 60 min after 2-DG. No changes in GABA concentrations in dialysate from the MH or LH of obese rats were observed after 2-DG. The alterations in basal activity and responsiveness to glucoprivic stimuli by GABAergic system in the MH of obese rats may reflect a defect in central glucostatic control of food intake and, ultimately, in the hypothesized autonomic imbalance in fa/fa Zucker rat.
Cardiovascular effects of serotonin and DP-5-CT in conscious Long-Evans and Brattleboro rats
Authors: Anderson I. K. , Ramage A. G. , Gardiner S. M.
Published: December 2017

The regional hemodynamic changes caused by intracerebroventricular 5-hydroxytryptamine (5-HT) were investigated in conscious Long-Evans and Brattleboro rats with chronically implanted Doppler flow probes. In both strains, a low dose of 5-HT (4 nmol/kg) caused a pressor response associated with tachycardia, mesenteric vasoconstriction, and a transient hindquarters vasodilatation. In Long-Evans rats, higher doses of 5-HT (40 and 120 nmol/kg) caused a pressor response, a bradycardia, mesenteric vasoconstriction, and maintained hindquarters dilatation. The bradycardia and mesenteric vasoconstriction caused by 40 nmol/kg of 5-HT in Long-Evans rats were attenuated by d(CH2)5Tyr(Me)arginine vasopressin, a V1-receptor antagonist. In Brattleboro rats the high doses of 5-HT failed to cause a pressor response but caused a delayed depressor response, a transient tachycardia, less mesenteric vasoconstriction, and a larger initial hindquarters dilatation compared with Long-Evans rats. The initial part of the hindquarters vasodilator response caused by 120 nmol/kg of 5-HT in Brattleboro rats was attenuated by the beta 2-adrenoceptor antagonist ICI-118551. In Long-Evans rats, N,N-di-n-propyl-5-carboxamidotryptamine maleate (DP-5-CT; 3, 30, and 100 nmol/kg icv), a 5-HT1A receptor agonist, caused a tachycardia associated with a marked hindquarters vasodilatation. These changes were accompanied by a weak mesenteric vasoconstriction and, for the highest dose of DP-5-CT, a pressor response. These data overall are consistent with the hemodynamic effects of intracerebroventricular 5-HT contingent on vasopressin release and, along with DP-5-CT, sympathoadrenal excitation; however, additional mechanisms are indicated.
Immobilization increases norepinephrine release and reduces NK cytotoxicity in spleen of conscious rat
Authors: Shimizu N. , Kaizuka Y. , Hori T. , Nakane H.
Published: December 2017

The purpose of this study was to investigate whether immobilization stress would affect the cytotoxic activity of natural killer (NK) cells through the changes in norepinephrine release in the spleen. An in vivo microdialysis technique consisting of high-performance liquid chromatography with electrochemical detection was used to examine norepinephrine levels in the spleen of the conscious rat. The results of the physiological and pharmacological manipulations indicated that norepinephrine recovered in the dialysis solution was mainly derived from the nerve terminals of the splenic sympathetic nerve. Immobilization stress rapidly increased norepinephrine levels to 817.4 +/- 181.7% of baseline in conjunction with the suppression of NK cytotoxicity. Both the increased levels of norepinephrine and the immunosuppression of NK cytotoxicity by immobilization stress were significantly attenuated after surgical denervation of the splenic sympathetic nerve. The results suggest that immobilization-induced suppression of splenic NK cytotoxicity is mediated predominantly through enhanced activity of the splenic sympathetic nerve.