bluuebunny/crossref_metadata_2025 huggingface dataset:
A construct of interactive feedback control of the GH axis in the male
Authors: Farhy Leon S. , Straume Martin , Johnson Michael L. , Kovatchev Boris , Veldhuis Johannes D.
Published: December 2017

Growth hormone (GH) secretion is controlled by GH-releasing hormone (GHRH), the GH release-inhibiting hormone somatostatin (SRIF), and autofeedback connections. The ensemble network produces sexually dimorphic patterns of GH secretion. In an effort to formalize this system, we implemented a deterministically based autonomous feedback-driven construct of five principal dose-responsive regulatory interactions: GHRH drive of GH pituitary release, competitive inhibition of GH release by SRIF, GH autofeedback via SRIF with a time delay, delayed GH autonegative feedback on GHRH, and SRIF inhibition of GHRH secretion. This formulation engenders a malelike pattern of successive GH volleys due jointly to positive time-delayed feedback of GH on SRIF and negative feedback of SRIF on GH and GHRH. The multipeak volley is explicated as arising from a reciprocal interaction between GH and GHRH during periods of low SRIF secretion. The applicability of this formalism to neuroendocrine control is explored by initial parameter sensitivity analysis and is illustrated for selected feedback-dependent experimental paradigms. The present construct is not overparameterized and does not require an ad hoc pulse generator to achieve pulsatile GH output. Further evolution of interactive constructs could aid in exploring more complex feedback postulates that confer the vivid sexual dimorphism of female GH profiles.
Fetal cerebral and peripheral circulatory responses to hypoxia after nitric oxide synthase inhibition
Authors: Harris Andrew P. , Helou Sabah , Gleason Christine A. , Traystman Richard J. , Koehler Raymond C.
Published: December 2017

The increase in cerebral blood flow (CBF) during hypoxia in fetal sheep at 0.6 gestation is less than the increase at 0.9 gestation when normalized for differences in baseline CBF and oxygen consumption. Nitric oxide (NO) synthase (NOS) catalytic activity increases threefold during this period of development. We tested the hypothesis that administration of the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) decreases the CBF response to systemic hypoxia selectively at 0.9 gestation. We also tested whether any peripheral vasoconstriction during hypoxia is potentiated byl-NAME at 0.9 gestation. Administration ofl-NAME increased arterial blood pressure and decreased microsphere-determined CBF during normoxia in fetal sheep at both 0.6 and 0.9 gestation. With subsequent reduction of arterial oxygen content by ∼50%, the percent increase in forebrain CBF in a control group (57 ± 11%; ± SE) and l-NAME-treated group (51 ± 6%) was similar at 0.6 gestation. Likewise, at 0.9 gestation, the increase in CBF was similar in control (90 ± 25%) andl-NAME (80 ± 28%) groups. At 0.9 gestation,l-NAME treatment attenuated the increase in coronary blood flow and increased gastrointestinal vascular resistance during hypoxia. We conclude that NO exerts a basal vasodilatory influence in brain as early as 0.6 gestation in fetal sheep but is not an important mechanism for hypoxic vasodilation in brain at either 0.6 or 0.9 gestation. Thus the developmental increase in NOS catalytic capacity does not appear to be responsible for developmental increases in the CBF response to hypoxia during this period. In contrast, NO modulates the vascular response to hypoxia in heart and gastrointestinal tract.
Voluntary physical activity prevents stress-induced behavioral depression and anti-KLH antibody suppression
Authors: Moraska Albert , Fleshner Monika
Published: December 2017

The current study addressed whether physical activity can buffer stress-induced “behavioral depression” and immunosuppression. Adult, male Sprague-Dawley rats were housed with either a mobile (physically active) or immobile (sedentary) running wheel and exposed to either stress (inescapable tail shock) or no stress (home cage control). Voluntary wheel running began 4 wk before stressor exposure. Immediately before stress, all rats were administered an intraperitoneal injection of keyhole limpet hemocyanin (KLH; 200 μg), and anti-KLH Ig was measured weekly for 4 wk using ELISA. Prior physical activity reduced the stress-induced behavioral depression and prevented the stress-induced suppression of anti-KLH IgM and IgG2aantibodies. Anti-KLH IgG1was stress insensitive. These data suggest that physical activity can buffer the negative impact of stress on behavior and acquired immune function.
Dietary soy exerts an antihypertensive effect in spontaneously hypertensive female rats
Authors: Martin D. S. , Breitkopf N. P. , Eyster K. M. , Williams J. L.
Published: December 2017

This study tested the hypothesis that dietary soy would attenuate the development of hypertension in female spontaneously hypertensive rats (SHR). Female SHR and control Wistar-Kyoto rats were obtained at 4 wk of age, randomly assigned to either an ovariectomized (OVX) group or a sham-operated group, and placed on a soy diet or control casein diet. After a minimum of 8 wk on their respective diets, mean arterial pressure (MAP) and heart rate (HR) were recorded before and after inhibition of nitric oxide synthase, air-jet stress, or ganglionic blockade. The major finding of this study is that MAP was reduced in the OVX SHR consuming soy diet compared with the casein-fed controls (150 ± 4 vs. 164 ± 3 mmHg). Plasma genistein concentrations were increased in the soy-fed OVX SHR (1.23 ± 0.31 μM) compared with the casein-fed OVX SHR (nondetectable). However, there was no difference in plasma genistein concentrations between sham-operated and OVX SHR (1.37 ± 0.42 vs. 1.23 ± 0.31 μM). Inhibition of nitric oxide synthase increased MAP and decreased HR in all groups; diet did not affect this response. Air-jet stress increased MAP and HR in all groups. However, these responses were exaggerated in the soy-fed SHR. Finally, ganglionic blockade abolished the antihypertensive effect of soy diet in the OVX SHR. These findings indicate that dietary soy exerts an antihypertensive effect in OVX SHR. This effect does not involve the nitric oxide system but may be related to an as yet undefined interaction with the autonomic nervous system.
CNS sympathetic outflow neurons to white fat that express MEL receptors may mediate seasonal adiposity
Authors: Song C. Kay , Bartness Timothy J.
Published: December 2017

Many animals show seasonal changes in adiposity that are triggered by changes in the photoperiod. For example, in short “winterlike” days, the nocturnal duration of pineal melatonin (MEL) secretion increases ultimately resulting in body fat decreases by Siberian hamsters. These decreases in body fat are mediated through increases in the sympathetic drive on white adipose tissue (WAT). The central nervous system (CNS) origins of the sympathetic outflow from brain to WAT include the suprachiasmatic nucleus (SCN), an area necessary for the reception of season-encoded MEL signals in Siberian hamsters. Therefore, we tested whether SCN neurons that are part of the sympathetic outflow to WAT also express MEL receptors (MEL1a). This was accomplished by labeling the sympathetic outflow from brain to WAT using a transsynaptic retrograde tract tracer, the pseudorabies virus (PRV), injected into inguinal WAT combined with labeling of brain MEL1areceptors using in situ hybridization. We found PRV-labeled neurons that also expressed MEL1a-receptor mRNA in several brain regions including the SCN. Thus the increased duration of MEL secretion in short days may increase MEL1a-receptor stimulation that, in turn, increases the sympathetic drive on WAT, thereby increasing lipolysis and decreasing adiposity.
Differential control of sympathetic outflow
Authors: Morrison Shaun F.
Published: December 2017

With advances in experimental techniques, the early views of the sympathetic nervous system as a monolithic effector activated globally in situations requiring a rapid and aggressive response to life-threatening danger have been eclipsed by an organizational model featuring an extensive array of functionally specific output channels that can be simultaneously activated or inhibited in combinations that result in the patterns of autonomic activity supporting behavior and mediating homeostatic reflexes. With this perspective, the defense response is but one of the many activational states of the central autonomic network. This review summarizes evidence for the existence of tissue-specific sympathetic output pathways, which are likely to include distinct populations of premotor neurons whose target specificity could be assessed using the functional fingerprints developed from characterizations of postganglionic efferents to known targets. The differential responses in sympathetic outflows to stimulation of reflex inputs suggest that the circuits regulating the activity of sympathetic premotor neurons must have parallel access to groups of premotor neurons controlling different functions but that these connections vary in their ability to influence different sympathetic outputs. Understanding the structural and physiological substrates antecedent to premotor neurons that mediate the differential control of sympathetic outflows, including those to noncardiovascular targets, represents a challenge to our current technical and analytic approaches.
Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects
Authors: Décombaz Jacques , Schmitt Beat , Ith Michael , Decarli Bernard , Diem Peter , Kreis Roland , Hoppeler Hans , Boesch Chris
Published: December 2017

The hypotheses that postexercise replenishment of intramyocellular lipids (IMCL) is enhanced by endurance training and that it depends on fat intake were tested. Trained and untrained subjects exercised on a treadmill for 2 h at 50% peak oxygen consumption, reducing IMCL by 26–22%. During recovery, they were fed 55% (high fat) or 15% (low fat) lipid energy diets. Muscle substrate stores were estimated by1H (IMCL)- and13C (glycogen)-magnetic resonance spectroscopy in tibialis anterior muscle before and after exercise. Resting IMCL content was 71% higher in trained than untrained subjects and correlated significantly with glycogen content. Both correlated positively with indexes of insulin sensitivity. After 30 h on the high-fat diet, IMCL concentration was 30–45% higher than preexercise, whereas it remained 5–17% lower on the low-fat diet. Training status had no significant influence on IMCL replenishment. Glycogen was restored within a day with both diets. We conclude that fat intake postexercise strongly promotes IMCL repletion independently of training status. Furthermore, replenishment of IMCL can be completed within a day when fat intake is sufficient.
Effects of lower body positive pressure on muscle sympathetic nerve activity response to head-up tilt
Authors: Fu Qi , Iwase Satoshi , Niimi Yuki , Kamiya Atsunori , Kawanokuchi Jun , Cui Jian , Mano Tadaaki , Suzumura Akio
Published: December 2017

The present study was performed to test the hypothesis that application of lower body positive pressure (LBPP) during orthostasis would reduce the baroreflex-mediated enhancement in sympathetic activity in humans. Eight healthy young men were exposed to a 70° head-up tilt (HUT) on application of 30 mmHg LBPP. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve, along with hemodynamic variables. We found that in the supine position with LBPP, MSNA remained unchanged (13.4 ± 3.3 vs. 11.8 ± 2.3 bursts/min, without vs. with LBPP; P > 0.05), mean arterial pressure was elevated, but arterial pulse pressure and heart rate did not alter. At 70° HUT with LBPP, the enhanced MSNA response was reduced (33.8 ± 5.0 vs. 22.5 ± 2.2 bursts/min, without vs. with LBPP; P < 0.05), mean arterial pressure was higher, the decreased pulse pressure was restored, and the increased heart rate was attenuated. We conclude that the baroreflex-mediated enhancement in sympathetic activity during HUT was reduced by LBPP. Application of LBPP in HUT induced an obvious cephalad fluid shift as well as a restoration of arterial pulse pressure, which reduced the inhibition of the baroreceptors. However, the activation of the intramuscular mechanoreflexes produced by 30 mmHg LBPP might counteract the effects of baroreflexes.
Parathyroid hormone-related protein: a calcium regulatory factor in sea bream (Sparus aurataL.) larvae
Authors: Guerreiro Pedro M. , Fuentes Juan , Power Deborah M. , Ingleton Patricia M. , Flik Gert , Canario Adelino V. M.
Published: December 2017

The effects of an N-terminal peptide (amino acids 1–38) of Fuguparathyroid hormone-related protein (PTHrP 1–38) on calcium regulation of larval sea bream were investigated in seawater (36‰) and after transfer to dilute seawater (12‰). Exposure to PTHrP 1–38 evoked a 1.5-fold increase in calcium influx in both full-strength and dilute seawater. Calcium influx in dilute seawater-adapted larvae was roughly one-half that observed in full-strength seawater controls. PTHrP 1–38 also reduced drinking of fish in seawater but, at all concentrations tested, was without effect in dilute seawater. The amount of water imbibed was 55% lower in dilute seawater than in seawater. PTHrP 1–38 exposure affected the calcium influx route: the main contribution of calcium uptake shifted from intestinal absorption to extraintestinal uptake, probably by the induction of a dose-dependent increase in branchial (active) transport. Moreover, seawater-adapted fish exposed to 1 nM and 10 mM PTHrP 1–38 experienced a 2.5-fold reduction in overall calcium efflux. Overall, the calciotropic action of PTHrP 1–38 resulted in a dose-dependent increase in net calcium balance.
Age-dependent activation of PKC isoforms by angiotensin II in the proximal nephron
Authors: Boesch Dianne M. , Garvin Jeffrey L.
Published: December 2017

ANG II increases fluid absorption in proximal tubules from young rats more than those from adult rats. ANG II increases fluid absorption in the proximal nephron, in part, via activation of protein kinase C (PKC). However, it is unclear how age-related changes in ANG II-induced stimulation of the PKC cascade differ as an animal matures. We hypothesized that the response of the proximal nephron to ANG II decreases as rats mature due to a reduction in the amount and activation of PKC rather than a decrease in the number or affinity of ANG II receptors. Because PKC translocates from the cytosol to the membrane when activated, we first measured PKC activity in the soluble and particulate fractions of proximal tubule homogenates exposed to vehicle or 10−10M ANG II from young (26 ± 1 days old) and adult rats (54 ± 1 days old). ANG II increased PKC activity to the same extent in homogenates from young rats (from 0.119 ± 0.017 to 0.146 ± 0.015 U/mg protein) ( P < 0.01) and adult rats (from 0.123 ± 0.020 to 0.156 ± 0.023 U/mg protein) ( P < 0.01). Total PKC activity did not differ between groups (0.166 ± 0.018 vs. 0.181 ± 0.023). We next investigated whether activation of the α-, β-, and γ-PKC isoforms differed by Western blot. In homogenates from young rats, ANG II significantly increased activated PKC-α from 40.2 ± 6.5 to 60.2 ± 9.5 arbitrary units (AU) ( P < 0.01) but had no effect in adult rats (46.1 ± 5.1 vs. 48.5 ± 8.2 AU). Similarly, ANG II increased activated PKC-γ in proximal tubules from young rats from 47.9 ± 13.2 to 65.6 ± 16.7 AU ( P < 0.01) but caused no change in adult rats. Activated PKC-β, however, increased significantly in homogenates from both age groups. Specifically, activated PKC-β increased from 8.6 ± 1.4 to 12.2 ± 2.1 AU ( P < 0.01) in homogenates from nine young rats and from 19.0 ± 5.5 to 25.1 ± 7.1 AU ( P < 0.01) in homogenates from 12 adult rats. ANG II did not alter the amount of soluble PKC-α, -β, and -γ significantly. The total amount of PKC-α and -γ did not differ between homogenates from young and adult rats, whereas the total amount of PKC-β was 59.7 ± 10.7 and 144.9 ± 41.8 AU taken from young and adult rats, respectively ( P < 0.05). Maximum specific binding and affinity of ANG II receptors were not significantly different between young and adult rats. We concluded that the primary PKC isoform activated by ANG II changes during maturation.
Spinal and cranial contributions to total cerebrospinal fluid transport
Authors: Bozanovic-Sosic R. , Mollanji R. , Johnston M. G.
Published: December 2017

In this study, we quantified cerebrospinal fluid (CSF) transport from the cranial and spinal subarachnoid spaces separately in sheep and determined the relative proportion of total CSF drainage that occurred from both CSF compartments. Cranial and spinal CSF systems were separated by placement of an extradural ligature over the spinal cord between C1 and C2. In one approach, two different radiolabeled human serum albumins (HSA) were introduced into the appropriate CSF compartment by a perfusion system ( method 1) or as a bolus injection ( method 2). Plasma tracer recoveries in conjunction with a mass balance equation were used to estimate CSF transport. In method 3, catheters connected to reservoirs filled with artificial CSF were introduced into the cranial and spinal CSF compartments. Incremental CSF pressures were established in each CSF system, and the corresponding steady-state flow rates were measured. Total CSF drainage ranged from 0.51 to 0.75 ml · h−1 · cmH2O−1. Expressed as a percentage of the total CSF transport, the ratios of cranial-to-spinal clearance estimated from methods 1, 2, and 3 were 75:25, 88:12, and 75:25, respectively. Primarily on the basis of the data derived from methods 1 and 3, we conclude that the spinal subarachnoid compartment has an important role in CSF clearance and is responsible for approximately one-fourth of total CSF transport.
Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks
Authors: Concannon P. , Levac K. , Rawson R. , Tennant B. , Bensadoun A.
Published: December 2017

Male woodchucks ( Marmota monax) were maintained in northern vs. southern hemisphere photoperiods, provided feed and water ad libitum, and evaluated every 2 wk for 23 mo for body weight, absolute and relative food intake, body temperature, serum testosterone, and serum concentrations of leptin measured using an anti-mouse leptin enzyme-linked immunoassay. During late spring and summer, body weight increased 56 ± 4% above winter nadirs, and during the autumn and early winter weights decreased 27 to 43% below midsummer maxima. Serum leptin initially increased during increases in body weight, in the late spring, reached peak values (490 ± 32 pg/ml) in summer during the initial decline in body weight, and later decreased along with body weight to reach basal values (20 ± 5 pg/ml) in late winter. Spontaneous declines in food intakes in summer began 2–6 wk before resulting declines in body weight and occurred during increases in leptin >100 pg/ml. The rate of decline in food intakes was greatest when serum leptin was at or near peak values. Food intake increased in late winter when leptin was low and 7–10 wk before resulting increases in body weight. Testis recrudescence occurred when leptin was declining to near basal levels. The results suggest that leptin is involved in the hormonal regulation of the circannual cycle in the drive for voluntary food intake in this species.
Corticosterone and insulin interact to regulate glucose and triglyceride levels during stress in a bird
Authors: Remage-Healey Luke , Romero L. Michael
Published: December 2017

Captive European starlings ( Sturnus vulgaris) were exposed to the stress of handling and restraint while corticosterone, glucose, and triglyceride concentrations were monitored in blood plasma. In saline-injected controls, basal samples were taken within 3 min of disturbance with subsequent samples taken at 40, 70, and 150 min. This was repeated at two times during the daily cycle (day and night) on two different photoperiods: short and long days. During both photoperiods, corticosterone concentrations approximately tripled (compared with a sixfold increase in free-living starlings) and triglyceride concentrations decreased 25–45% in response to stress at both times of the day, whereas an ∼25% stress-induced hyperglycemia occurred only at night. Exogenous corticosterone (200 μg), 1.0 or 4.0 IU/kg of insulin, or a combination of corticosterone with each insulin dose was then separately administered to alter the above responses. Insulin did not affect corticosterone or triglyceride concentrations but resulted in a dose-dependent hypoglycemia of 10–40%. Injected corticosterone resulted in supraphysiological corticosterone concentrations (three- to fivefold higher than normal), yet it did not affect the already altered plasma glucose or triglyceride concentrations. This suggests that glucose output and triglyceride decreases were already maximal in response to handling and restraint. However, the low glucose concentrations resulting from exogenous insulin returned to basal quicker with exogenous corticosterone but only during the day. No response to either hormone showed photoperiodic differences. These data suggest that corticosterone's role in metabolism changes to meet varying energetic demands throughout the day.
Hypocretin/orexin suppresses corticotroph responsiveness in vitro
Authors: Samson Willis K. , Taylor Meghan M.
Published: December 2017

The hypocretin/orexins (Hcrts/ORXs) are peptides produced in neurons in the lateral hypothalamic area that project to neuroendocrine centers in the hypothalamus. Hcrt/ORX receptors are present in the hypothalamus and anterior pituitary gland. We examined the possibility that the Hcrts/ORXs, which we have demonstrated previously to act in the brain to stimulate sympathetic function, could alter stress hormone secretion by a direct pituitary action. In vitro studies revealed a dose-related inhibitory effect of the Hcrts/ORXs on corticotropin-releasing hormone-stimulated ACTH secretion that appeared to be mediated via the orexin-1 receptor and to be expressed at doses (threshold dose 1 nM orexin A) similar to the affinity constant for the receptor. The effect was not due to abrogation of the cAMP response of the corticotroph to corticotropin-releasing hormone and was not pertussis toxin sensitive, suggesting a non-Gi-mediated mechanism. Instead, a Gq-mediated signaling mechanism was indicated by the ability of protein kinase C blockade with calphostin C to reverse the inhibitory action of orexin A. Orexin A and orexin B did not significantly alter basal ACTH secretion in vitro and did not alter basal or releasing factor-stimulated secretion of luteinizing hormone, prolactin, thyroid-stimulating hormone or growth hormone from cells harvested from male or random-cycle female donors. Our data suggest a direct, pituitary action of the Hcrts/ORXs to modulate the endocrine response to stress and identify the potential cellular mechanism of a unique biological action of the peptides in the anterior pituitary gland.
Na+-K+-ATPase gene expression in the avian eggshell gland: distinct regulation in different cell types
Authors: Lavelin Irena , Meiri Noam , Genina Olga , Alexiev Rosaly , Pines Mark
Published: December 2017

The avian eggshell gland (ESG) is a tissue specialized in transporting the Ca2+required for eggshell formation and represents a unique biological system in which the calcification process takes place in a circadian fashion. With the use of RNA fingerprinting, a set of genes differentially induced at the time of calcification was detected, one of which was identified as the α1-subunit of Na+-K+-ATPase. The gene was expressed in a circadian manner in both cell types populating the ESG, but in different temporal patterns, suggesting distinct mechanisms of regulation. Ca2+flux and mechanical strain were found to regulate gene expression in the inner glandular epithelium and the pseudostratified epithelium facing the lumen, respectively. Mechanical strain also affected gene expression in cell layers facing the lumen in other parts of the oviduct. Only the α1-isoform, not the α2- or α3-isoform, of Na+-K+-ATPase was expressed in the ESG. In summary, we demonstrate that the α1-subunit Na+-K+-ATPase gene is expressed in different epithelial cell types in the ESG and is regulated by various mechanisms, which may reflect the disparity in the physiological roles of the cells in the process of eggshell formation.
Estrogen and progesterone effects on transcapillary fluid dynamics
Authors: Stachenfeld Nina S. , Keefe David L. , Palter Steven F.
Published: December 2017

The purpose of this study was to determine estrogen (E2) and progesterone (P4) effects on atrial natriuretic peptide (ANP) control of plasma volume (PV) and transcapillary fluid dynamics. To this end, we suppressed reproductive function in 12 women (age 21–35 yr) using a gonadotropin releasing-hormone (GnRH) analog (leuprolide acetate) for 5 wk. During the 5th week, the women either received 4 days of E2administration (17β-estradiol, transdermal patch, 0.1 mg/day) or 4 days of E2 with P4 administration (vaginal gel, 90 mg P4 twice per day). At the end of the 4th and 5th week of GnRH analog and hormone administration, we determined PV (Evans blue dye) and changes in PV and forearm capillary filtration coefficient (CFC) during a 120-min infusion of ANP (5 ng · kg body wt−1 · min−1). Preinfusion PV was estimated from Evans blue dye measurement taken over the last 30 min of infusion based on changes in hematocrit. E2 treatment did not affect preinfusion PV relative to GnRH analog alone (45.3 ± 3.1 vs. 45.4 ± 3.1 ml/kg). During ANP infusion CFC was greater during E2 treatment compared with GnRH analog alone (6.5 ± 1.4 vs. 4.9 ± 1.4 μl · 100 g−1 · min−1 mmHg−1, P < 0.05). The %PV loss during ANP infusion was similar for E2 and GnRH analog-alone treatments (−0.8 ± 0.2 and −1.0 ± 0.2 ml/kg, respectively), indicating the change in CFC had little systemic effect on ANP-related changes in PV. Estimated baseline PV was reduced by E2-P4treatment. During ANP infusion CFC was ∼30% lower during E2-P4 (6.0 ± 0.5 vs. 4.3 ± 4.3 μl · 100 g−1 · min−1mmHg−1, P < 0.05), and the PV loss during ANP infusion was attenuated (−0.9 ± 0.2 and −0.2 ± 0.2 ml/kg for GnRH analog-alone and E2-P4treatments, respectively). Thus the E2-P4treatment lowered CFC and reduced PV loss during ANP infusion.
Prostanoid receptors: ontogeny and implications in vascular physiology
Authors: Wright D. Hamish , Abran Daniel , Bhattacharya Mousumi , Hou Xin , Bernier Sylvie G. , Bouayad Asmàa , Fouron Jean-Claude , Vazquez-Tello Alejandro , Beauchamp Martin H. , Clyman Ronald I. , Peri Krishna , Varma Daya R. , Chemtob Sylvain
Published: December 2017

Prostanoids exert significant effects on circulatory beds. They play a role in the response of the vasculature to adjustments in perfusion pressure and oxygen and carbon dioxide tension, and they mediate the actions of numerous factors. The role of prostanoids in governing circulation of the perinate is suggested to surpass that in the adult. Prostanoids are abundantly generated in the perinate. They have been implicated in autoregulation of blood flow as studied in brain and eyes. Prostaglandins are also dominant regulators of ductus arteriosus tone. The effects of these autacoids are mediated through specific G protein-coupled receptors. In addition to the pharmacological characterization of the prostanoid receptors, important advances in understanding the biology of these receptors have been made in the last decade. Their cloning and the development of animals with disrupted genes of these receptors have been very informative. The involvement of prostanoid receptors in the developing subject, especially on brain and ocular vasculature and on ductus arteriosus, has also begun to be investigated; the expression of these receptors changes with development. Some but not all of the ontogenic changes in these receptors are attributed to homologous regulation. Interestingly, in the process of elucidating their effects, functional perinuclear prostaglandin E2receptors have been uncovered. This article reviews prostanoid receptors and addresses implications on the developing subject with attention to vascular physiology.
Peripheral urocortin inhibits gastric emptying and food intake in mice: differential role of CRF receptor 2
Authors: Wang Lixin , Martínez Vicente , Rivier Jean E. , Taché Yvette
Published: December 2017

Intraperitoneal urocortin inhibits gastric emptying and food intake in mice. We investigated corticotropin-releasing factor receptor (CRF-R) subtypes involved in intraperitoneal urocortin actions using selective CRF-R antagonists. Gastric emptying was measured 2 h after a chow meal, and food intake was measured hourly after an 18-h fast in mice. Urocortin (3 μg/kg ip) inhibited gastric emptying by 88%. The CRF-R1/CRF-R2 antagonist astressin B (30 μg/kg ip) and the selective CRF-R2 antagonist antisauvagine-30 (100 μg/kg ip) completely antagonized urocortin action, whereas the selective CRF-R1 antagonist CP-154,526 (10 mg/kg ip) had no effect. Urocortin (1–10 μg/kg ip) dose dependently decreased the 2-h cumulative food intake by 30–62%. Urocortin (3 μg/kg)-induced hypophagia was completely antagonized by astressin B (30 μg/kg ip) and partially (35 and 31%) by antisauvagine-30 (100 or 200 μg/kg ip). The CRF-R1 antagonists CP-154,526 or DMP904 (10 mg/kg ip) had no effect. Capsaicin did not alter urocortin-inhibitory actions while blocking the satiety effect of intraperitoneal CCK. These data indicate that intraperitoneal urocortin-induced decrease in feeding is only partly mediated by CRF-R2, whereas urocortin action to delay gastric emptying of a meal involves primarily CRF-R2.
Glucose transporter protein responses to selective hyperglycemia or hyperinsulinemia in fetal sheep
Authors: Anderson Marianne S. , Flowers-Ziegler Judy , Das Utpala G. , Hay William W. , Devaskar Sherin U.
Published: December 2017

The acute effect of selective hyperglycemia or hyperinsulinemia on late gestation fetal ovine glucose transporter protein (GLUT-1, GLUT-3, and GLUT-4) concentrations was examined in insulin-insensitive (brain and liver) and insulin-sensitive (myocardium and fat) tissues at 1, 2.5, and 24 h. Hyperglycemia with euinsulinemia caused a two- to threefold increase in brain GLUT-3, liver GLUT-1, and myocardial GLUT-1 concentrations only at 1 h. There was no change in GLUT-4 protein amounts at any time during the selective hyperglycemia. In contrast, selective hyperinsulinemia with euglycemia led to an immediate and persistent twofold increase in liver GLUT-1, which lasted from 1 until 24 h with a concomitant decline in myocardial tissue GLUT-4 amounts, reaching statistical significance at 24 h. No other significant change in response to hyperinsulinemia was noted in any of the other isoforms in any of the other tissues. Simultaneous assessment of total fetal glucose utilization rate (GURf) during selective hyperglycemia demonstrated a transient 40% increase at 1 and 2.5 h, corresponding temporally with a transient increase in brain GLUT-3 and liver and myocardial GLUT-1 protein amounts. In contrast, selective hyperinsulinemia led to a sustained increase in GURf, corresponding temporally with the persistent increase in hepatic GLUT-1 concentrations. We conclude that excess substrate acutely increases GURfassociated with an increase in various tissues of the transporter isoforms GLUT-1 and GLUT-3 that mediate fetal basal glucose transport without an effect on the GLUT-4 isoform that mediates insulin action. This contrasts with the tissue-specific effects of selective hyperinsulinemia with a sustained increase in GURfassociated with a sustained increase in hepatic basal glucose transporter (GLUT-1) amounts and a myocardial-specific emergence of mild insulin resistance associated with a downregulation of GLUT-4.
Differential induction of peroxisomal β-oxidation enzymes by clofibric acid and aspirin in piglet tissues
Authors: Yu Xing Xian , Odle Jack , Drackley James K.
Published: December 2017

Peroxisomal β-oxidation (POX) of fatty acids is important in lipid catabolism and thermogenesis. To investigate the effects of peroxisome proliferators on peroxisomal and mitochondrial β-oxidation in piglet tissues, newborn pigs (1–2 days old) were allowed ad libitum access to milk replacer supplemented with 0.5% clofibric acid (CA) or 1% aspirin for 14 days. CA increased ratios of liver weight to body weight ( P < 0.07), kidney weight to body weight ( P< 0.05), and heart weight to body weight ( P < 0.001). Aspirin decreased daily food intake and final body weight but increased the ratio of heart weight to body weight ( P < 0.01). In liver, activities of POX, fatty acyl-CoA oxidase (FAO), total carnitine palmitoyltransferase (CPT), and catalase were 2.7-, 2.2-, 1.5-fold, and 33% greater, respectively, for pigs given CA than for control pigs. In heart, these variables were 2.2-, 4.1-, 1.9-, and 1.8-fold greater, respectively, for pigs given CA than for control pigs. CA did not change these variables in either kidney or muscle, except that CPT activity was increased ∼110% ( P < 0.01) in kidney. Aspirin increased only hepatic FAO and CPT activities. Northern blot analysis revealed that CA increased the abundance of catalase mRNA in heart by ∼2.2-fold. We conclude that 1) POX and CPT in newborn pigs can be induced by peroxisomal proliferators with tissue specificity and 2) the relatively smaller induction of POX in piglets (compared with that in young or adult rodents) may be related to either age or species differences.
Peanut lectin binds to a subpopulation of mitochondria-rich cells in the rainbow trout gill epithelium
Authors: Goss Greg G. , Adamia Sophia , Galvez Fernando
Published: December 2017

Fluorescently labeled peanut lectin agglutinin (PNA-FITC) was used to identify a subtype of mitochondria-rich (MR) cells in the gills of freshwater rainbow trout. In situ binding of PNA-FITC was visualized by inverted fluorescence microscopy and found to bind to cells on the trailing edge of the filament epithelium as demonstrated by differential interference contrast optics. The amount of PNA-FITC binding on the filament epithelium increased with cortisol pretreatment concomitant with an increased chloride cell fractional area as demonstrated by scanning electron microscopy. Dispersed gill cells were isolated by trypsinization and separated using a discontinuous Percoll density gradient. Cells migrating to the 1.06–1.09 g/ml interface were found to be MR as demonstrated by staining with the vital mitochondrial dye 4-(4-(dimethylamino)styryl)- N-methylpyridinium iodide and transmission electron microscopy (TEM). However, only ∼40% of the MR cells were found to bind PNA-FITC. Cortisol pretreatment increased the relative numbers of MR cells isolated from the dispersed gill cell population, but the relative proportions of PNA binding cells remained unchanged. Ultrastructural analysis of isolated cells in the TEM demonstrated that the MR cell fraction was comprised of a mixed population of chloride cells and pavement cells.
Cardiac function in rats selectively bred for low- and high-capacity running
Authors: Hussain S. Osman , Barbato John C. , Koch Lauren G. , Metting Patricia J. , Britton Steven L.
Published: December 2017

Rat genetic models of intrinsic (i.e., untrained) low-capacity runners (LCR) and high-capacity runners (HCR) are being developed by artificial selective breeding for treadmill running. At generation 3, these lines differed in running capacity by 114%. We used generation 3 rats to test the hypotheses that HCR, relative to LCR, have 1) greater isolated cardiac performance and 2) more resistance to myocardial ischemic insult. The LCR ran for 227 ± 7 m, and the HCR ran 994 ± 11 m at exhaustion (337% difference, P < 0.001). Isolated heart performance was assessed from cardiac output (CO) generated at constant preload (15 mmHg) and afterload (70 mmHg) using a Langendorff-Neely working heart preparation. CO averaged 33.5 ± 2.0 ml · min−1· g−1in LCR hearts and 49.9 ± 1.4 ml · min−1· g−1in HCR hearts (49% difference, P < 0.001). Recovery of CO after 25 min of global ischemia was not different between the lines. These results suggest that 1) increased cardiac performance accounts for part of the difference in running capacity between the lines; and 2) unlike exercise training, genetically determined intrinsic capacity for exercise does not influence the recovery from 25 min of global low-flow cardiac ischemia.
Oxidative stress enhances the production and actions of adenosine in the kidney
Authors: Chen Ya-Fei , Li Pin-Lan , Zou Ai-Ping
Published: December 2017

The purpose of this study was to determine whether superoxide anions (O[Formula: see text]·) activate 5′-nucleotidase (5′-ND), thereby increasing the production of renal adenosine and regulating renal function. Using HPLC analysis, we found that incubation of renal tissue homogenate with the O[Formula: see text]· donor KO2doubled adenosine production and increased the maximal reaction velocity of 5′-ND from 141 to 192 nmol · min−1· mg protein−1. The O[Formula: see text]·-generating system, xanthine/xanthine oxidase increased the maximal reaction velocity of 5′-ND from 122 to 204 nmol · min−1· mg protein−1. Superoxide dismutase (SOD) with catalase produced a concentration-dependent reduction of 5′-ND activity in renal tissue homogenate, while the SOD inhibitor diethyldithiocarbamic acid significantly increased 5′-ND activity. Inhibition of disulfide bond formation by thioredoxin or thioredoxin reductase significantly decreased xanthine/xanthine oxidase-induced activation of renal 5′-ND. In in vivo experiments, inhibition of SOD by diethyldithiocarbamic acid (0.5 mg · kg−1· min−1iv) enhanced renal vasoconstriction induced by endogenously produced adenosine and increased renal tissue adenosine concentrations under control condition and in ischemia and reperfusion. We conclude that oxidative stress activates 5′-ND and increases adenosine production in the kidney and that this redox regulatory mechanism of adenosine production is important in the control of renal vascular tone and glomerular perfusion.
Intracerebroventricular CART peptide reduces food intake and alters motor behavior at a hindbrain site
Authors: Aja Susan , Sahandy Shirin , Ladenheim Ellen E. , Schwartz Gary J. , Moran Timothy H.
Published: December 2017

Peptides from cocaine- and amphetamine-regulated transcript (CART) reduce food intake in rats when injected into the lateral ventricle. Hypothalamic and hindbrain sites important in the control of feeding contain CART-immunoreactive fibers. To further define the site of CART's anorectic action, we compared feeding and other behavioral responses to third or fourth ventricular (3V, 4V) CART-(55–102) in 6-h food-deprived rats, both before and after cerebral aqueduct occlusion. 3V CART reduced the volume of Ensure consumed and resulted in fewer observations of eating and grooming within the 30-min test session. These reductions were significantly attenuated by aqueduct obstruction. 4V CART suppressed Ensure intake and resulted in decreased observations of feeding both with and without aqueduct blockade. 3V CART produced flat-backed postures and movement-associated tremors that were prevented by aqueduct obstruction. 4V CART also produced these signs, both with and without aqueduct blockade. We conclude that the major hypophagic effect of intracerebroventricular CART is mediated at a hindbrain site. The association of CART-induced feeding suppression with altered motor behavior questions the specificity of intracerebroventricular CART for actions on feeding.
Functional properties of an agouti signaling protein variant and characteristics of its cognate radioligand
Authors: Yang Ying-Kui , Dickinson Chris , Lai Yu-Mei , Li Ji-Yao , Gantz Ira
Published: December 2017

Agouti signaling protein (ASIP), the human (h) homolog of agouti, is an endogenous melanocortin peptide antagonist. To date, characterization of this protein has been performed with recombinant protein only and without the availability of an ASIP/agouti radioligand. In this report we describe the functional characteristics of a chemically synthesized truncated ASIP variant, ASIP-[90–132 (L89Y)], and the binding characteristics of its cognate radioligand,125I-ASIP-[90–132 (L89Y)]. Similar to full-length recombinant ASIP/agouti, ASIP-[90–132 (L89Y)] was a potent inhibitor of α-melanocyte-stimulating hormone cAMP generation at the cloned human melanocortin receptor (hMCR) subtypes hMC1R and hMC4R. It also displayed a lesser degree of inhibition at the hMC3R and hMC5R. However, ASIP-[90–132 (L89Y)] was found to be less potent than full-length recombinant ASIP and, surprisingly, only exhibited weak inhibitory activity at the hMC2R. In competition binding assays with the radioligand125I-ASIP-[90–132 (L89Y)], ASIP-[90–132 (L89Y)] displayed a hierarchy of binding affinity that roughly paralleled its rank order of inhibitory potency at the various MCR subtypes, i.e., hMC1R ≈ hMC4R > hMC3R ≈ hMC5R > hMC2R. Structure-activity studies revealed that ASIP-[90–132 (L89Y)] possessed greater pharmacological potency than either the further truncated ASIP variants ASIP-(116–132) or cyclo(CRFFRSAC). Interestingly, the latter molecules were both weak agonists at the hMC1R. These studies further support the concept that ASIP/agouti inhibits melanocortin action by directly binding to target MCRs and provide additional insight into the structural requirements for maximal inhibitory potency.
Comparative actions of adrenomedullin and nitroprusside: interactions with ANG II and norepinephrine
Authors: Charles Christopher J. , Nicholls M. Gary , Rademaker Miriam T. , Richards A. Mark
Published: December 2017

The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in arterial pressure (8–10 mmHg, both P < 0.001) ADM and NP induced similar increases in heart rate. ADM increased cardiac output ( P < 0.001), and the fall in calculated peripheral resistance was greater with ADM than NP ( P = 0.013). ADM infusions raised plasma ADM levels ( P < 0.001), plasma renin activity ( P = 0.001), and ANG II ( P < 0.001) but tended to blunt any concurrent rise in aldosterone compared with NP ( P = 0.056). ADM maintained both urine flow ( P < 0.001) and sodium excretion ( P = 0.01) compared with falls observed with NP. ADM attenuated the vasopressor actions of exogenous ANG II ( P = 0.006) but not norepinephrine. In addition, ADM antagonized the ANG II-induced rise in plasma aldosterone ( P < 0.001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis.
Daily hypothermia and torpor in a tropical primate: synchronization by 24-h light-dark cycle
Authors: Perret M. , Aujard F.
Published: December 2017

To study the temporal organization of daily hypothermia and torpor in a nocturnal Malagasy primate, the gray mouse lemur, body temperature (Tb) and locomotor activity were recorded using telemetry on 39 males held in 24-h light-dark cycles of different photoperiods. Under free-running condition, the circadian Tb and locomotor activity rhythms had a period shorter than 24 h. Circadian daily hypothermia started by a rapid drop in Tb (0.24°C/10 min) at the end of subjective night (13 h 25 ± 20 min) and was characterized by minimal Tb values 3 h 20 ± 5 min later. Spontaneous arousal from daily hypothermia occurred at a fixed time (6 h 05 ± 15 min, n = 7) after the beginning of subjective day. In animals exposed to 24-h light-dark cycles with night duration varying from 10 to 14 h, locomotor activity was strictly restricted to dark time, but the temporal organization of daily hypothermia was not modified, although changes in amplitude of Tb rhythm were observed. Daily hypothermia was directly induced by light and lasted 5 h 10 ± 10 min, with minimal Tb values 3 h 30 ± 30 min ( n = 28) after lights on, on condition that nighttime did not exceed the duration of subjective night. However, in animals exposed to 24-h light-dark cycles with night duration varying from 10 to 5 h, the limit of induction of daily hypothermia by light was ∼9 h after the beginning of night. Finally, under short days (14:10-h light-dark cycle), long bouts (6 h 50 ± 40 min) of actual torpor (minimum Tb 27.6 ± 0.9°C) were observed and would involve mechanisms depending on physiological changes induced by short day exposure.
α-Adrenergic contribution to the cardiovascular response to acute hypoxemia in the chick embryo
Authors: Mulder A. L. M. , van Goor C. A. , Giussani D. A. , Blanco C. E.
Published: December 2017

Fetal responses to acute hypoxemia include bradycardia, increase in blood pressure, and peripheral vasoconstriction. Peripheral vasoconstriction contributes to the redistribution of the cardiac output away from ancillary vascular beds toward myocardial, cerebral, and adrenal circulations. We investigated the effect of α-adrenergic receptor blockade on this fetal response. Fluorescent microspheres were used to measure cardiac output distribution during basal and hypoxemic conditions with and without phentolamine treatment. Phentolamine altered basal cardiac output distribution, indicating a basal α-adrenergic tone, but this was mainly noted at the earlier stages of incubation. During hypoxemia, phentolamine prevented vasoconstriction in the carcass. At day 19 of incubation, the percent cardiac output distributed to the carcass increased by 20% compared with a decrease in the control group by 17%. Phentolamine markedly attenuated the subsequent redistribution of the cardiac output toward the brain (from +102% in the control group to −25% in the phentolamine-treated group) and the heart (from +196% in the control group to +69% in the phentolamine-treated group). In the chick embryo, α-adrenergic mechanisms contribute to the maintenance of basal vascular tone and to the redistribution of the cardiac output away from the peripheral circulations toward the brain and heart during hypoxemic conditions.
Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy
Authors: Madiehe Abram M. , Lin Ling , White Christy , Braymer H. Doug , Bray George A. , York David A.
Published: December 2017

Removal of adrenal steroids by adrenalectomy (ADX) slows or reverses the development of many forms of obesity in rodents, including those that are leptin or leptin receptor deficient. Obesity is associated with hyperleptinemia and leptin resistance. We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The inhibitory effect of leptin (2.5 μg icv) on food intake was enhanced in ADX rats. A combination of ribonuclease protection assays, RT-PCR, Western blots, and mobility shift assays was used to evaluate the leptin signaling pathway in whole hypothalami from sham-operated, ADX and corticosterone-replaced ADX (ADX-R) Sprague-Dawley rats that were treated acutely with either saline vehicle or leptin intracerebroventricularly. ADX increased the expression of leptin receptor mRNA, increased STAT-3 mRNA and protein levels, induced constitutive STAT-3 phosphorylation and DNA binding activity, and also reduced suppressor of cytokine signaling-3 (SOCS-3) mRNA and protein levels. ADX and leptin treatment increased STAT-3 phosphorylation, but with no concomitant increase in DNA binding activity. Leptin and ADX decreased NPY mRNA expression, but their combination did not further decrease NPY mRNA. Corticosterone supplementation of ADX rats partially reversed many of these effects. In conclusion, ADX through activation of STAT-3 and inhibition of SOCS-3 activates the JAK-STAT signaling pathway. These effects most probably explain the ability to prevent the development of obesity by removal of adrenal steroids.