bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced lactate transport in denervated rat skeletal muscle
Authors: McCullagh K. J. , Bonen A.
Published: December 2017

The purpose of this study was to investigate the effect of the neural regulation of contractile activity on lactate transport in skeletal muscle. Contractile activity of the rat soleus muscle was abolished by denervating the hindlimb muscles in one leg (3 days) while the sham-operated contralateral hindlimb muscles served as a control. Three days after surgery, lactate transport into the soleus muscle was measured in vitro, using incubated soleus muscle strips. Lactate uptake by the denervated soleus muscle was reduced compared with control (P < 0.05). The diffusive component of lactate transport was unaltered by denervation (P > 0.05). These results translated into a reduction in lactate carrier-mediated transport capacity (-68%) in the denervated soleus (P < 0.05). These studies indicate that loss of contractile activity results in a decrement of lactate transport, which is probably due to a reduction in the number of lactate carriers in the sarcolemma. Our results suggest that the inherent activity of the muscle is important in maintaining the lactate transport system.
Hepatomesenteric release and removal of norepinephrine in swine
Authors: Aneman A. , Eisenhofer G. , Fandriks L. , Friberg P.
Published: December 2017

Release and removal of norepinephrine (NE) by hepatomesenteric organs in anesthetized swine were examined using measurements of NE in arterial, portal, and hepatic venous plasma. NE spillover from the liver and mesenteric organs increased during splanchnic nerve stimulation, validating these measurements as indexes of sympathetic outflow. Administration of the neuronal uptake-blocking drug desipramine reduced mesenteric NE extraction more than hepatic extraction, suggesting that neuronal uptake was more important for NE removal in mesenteric organs than in the liver. Circulating NE was removed by the liver more efficiently than by mesenteric organs, whereas mesenteric NE spillover (2.46 nmol/min) exceeded liver NE spillover (0.74 nmol/min). Hepatomesenteric NE spillover represented 53% of total body spillover; NE clearance was 42% of total body clearance. Because of efficient hepatic extraction of NE released by mesenteric organs, the sum of mesenteric and hepatic NE spillovers (3.20 pmol/min) exceeded net hepatomesenteric spillover estimated using arterial and hepatic venous measurements alone (1.96 pmol/min). Thus valid assessment of the substantial amounts of NE released by hepatomesenteric organs requires separate examination of mesenteric and hepatic spillovers.
Effects of age and gender on brown fat and skeletal muscle metabolic responses to cold in F344 rats
Authors: Gabaldon A. M. , Florez-Duquet M. L. , Hamilton J. S. , McDonald R. B. , Horwitz B. A.
Published: December 2017

Older male Fischer 344 (F344) rats do not maintain core temperature as well as do older females during cold exposure. To elucidate factors contributing to the decreased thermoregulatory ability of older males, the metabolic potentials of interscapular brown adipose tissue (IBAT) and skeletal muscle were evaluated at rest (26 degrees C) and during 4 h of cold (6 degrees C) in male and female F344 rats, aged 6, 12, and 26 mo. Compared with 26-mo-old females, cold-exposed 26-mo-old males exhibited a greater drop in core temperature and lower amounts of IBAT mitochondrial uncoupling protein (UCP) and IBAT thyroxine 5'-deiodinase (T5'D) activity. Unlike females, 26-mo-old males showed no cold-induced increase in total IBAT UCP or T5'D activity. In contrast, plasma norepinephrine was higher in cold-exposed 26-mo-old males vs. females, whereas plasma insulin and thyroxine did not differ with gender. Skeletal muscle oxidative capacity (measured by citrate synthase activity) and carbohydrate availability (measured by muscle glycogen and plasma glucose levels) did not differ between the 26-mo-old males and females. Our data suggest that altered regulation of IBAT UCP levels during cold exposure of aged rats, due at least in part to attenuated cold-induced IBAT T5'D activity, contributes to the gender difference in thermoregulatory ability of older males vs. females.
Inhibition of basal and reflex-mediated sympathetic activity in the RVLM by nitric oxide
Authors: Zanzinger J. , Czachurski J. , Seller H.
Published: December 2017

We examined possible functional roles for nitric oxide (NO) in the rostral ventrolateral medulla (RVLM), which is the final area for integration of sympathetic nerve activity (SNA) within the brain stem. Chloralose-anesthetized cats were completely baro- and chemoreceptor denervated, the RVLM was exposed for microinjections, and preganglionic SNA was recorded from the white ramus of the 3rd thoracic segment. Injections of NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, but not of NG-nitro-D-arginine, caused distinct increases in SNA and arterial blood pressure (BP). Excitatory somatosympathetic reflex amplitudes evoked by electrical stimulation of the 4th intercostal nerve were significantly increased by L-NNA whereas inhibitory responses to baroreflex activation by stimulation of the carotid sinus nerve were not affected. The effects of L-NNA were counteracted by the NO-donor compounds glyceryltrinitrate and S-nitroso-N-acetylpenicillamine, which decreased BP and SNA below control values at higher doses. These results suggest that endogenous NO, in addition to its peripheral actions, modulates the central nervous control of cardiovascular functions by reduction of basal sympathetic tone and by attenuation of excitatory reflex responses.
Low-conductance anion channel activated by cAMP in teleost Cl- -secreting cells
Authors: Marshall W. S. , Bryson S. E. , Midelfart A. , Hamilton W. F.
Published: December 2017

We studied characteristics and modulation of ion channels in primary cultures of opercular epithelium from the euryhaline marine killifish Fundulus heteroclitus. Primary cultures, 17-28 h old, retain mitochondria-rich Cl- cells identifiable by fluorescence microscopy. Cell-attached patches revealed frequent low-conductance 8.1 +/- 0.35 pS channels that usually became inactive on excision; high-conductance anion channels were not apparent. Ion substitution experiments demonstrated selectivity for Cl- over gluconate of 1:0.07. With addition of 1-isobutyl-3-methylxanthine (0.1 mM) and dibutyryladenosine 3',5'-cyclic monophosphate (1.0 mM) to the bath, incidence of the channel increased from 35.3 to 61.9% of total patches (n = 156 and 21, respectively), and incidence of patches with multiple copies of the channel increased markedly from 2.2 to 38.5%. Epithelial Cl- transport was inhibited by mucosally added diphenylamine-2-carboxylic acid (1.0 mM) but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1-1.0 mM). The anion channel was absent from cultured killifish corneal epithelium, a tissue that lacks Cl- cells. We conclude that a low-conductance anion channel of Cl- cells, likely in the apical membrane, may account for adenosine 3',5'-cyclic monophosphate-activated Cl- secretion by marine fish.
Circulating tumor necrosis factor-alpha does not mediate endotoxin-induced hypothermia in rats
Authors: Schotanus K. , Holtkamp G. M. , van Rooijen N. , Tilders F. J. , Berkenbosch F.
Published: December 2017

The present study was designed to investigate the role of macrophages and circulating tumor necrosis factor-alpha (TNF-alpha) in the endotoxin-induced hypothermic responses in rats. Intravenous as well as intraperitoneal administration of endotoxin to male Wistar rats (0.5 mg/kg) led to increased plasma TNF-alpha concentrations and a transient hypothermia, which reached its nadir after 90 min. The hypothermia and plasma TNF-alpha responses to endotoxin were abolished after elimination of peripheral macrophages. Seven days after the first challenge, tolerance of the hypothermic response was found if the same dose was administered intraperitoneally but not if it was administered intravenously. Tolerance of the TNF-alpha response was induced irrespective of the route of endotoxin administration. We hypothesize that, after intravenous administration of endotoxin, macrophage-dependent and -independent mechanisms are activated, whereas the hypothermic response to intraperitoneal endotoxin involves primarily macrophage-dependent mechanisms. These mechanisms may relate to the prime targets reached by endotoxin, such as macrophages and endothelial cells. Because the development of tolerance of the hypothermic response is dependent on the route of endotoxin administration, whereas that of the plasma TNF-alpha response is not, we conclude that circulating TNF-alpha is not the macrophage-derived cryogenic signal that triggers the hypothermic response.
Effect of arterially infused catecholamines and insulin on plasma glucose and free fatty acids in carp
Authors: Van Raaij M. T. , van den Thillart G. E. , Hallemeesch M. , Balm P. H. , Steffens A. B.
Published: December 2017

Common carp (Cyprinus carpio L.), kept at 20 degrees C, were fitted with an indwelling PE-50 cannula in the dorsal aorta. Hormones dissolved in Ringer saline were arterially infused at a rate of 1 microgram.kg-1.min-1 for epinephrine (Epi), 2 micrograms.kg-1.min-1 for norepinephrine (NE), and 1.33 micrograms.kg-1.min-1 for insulin. INfusion of bovine insulin in carp resulted in a long lasting (24 h) decrease of plasma free fatty acids (FFA; -0.41 +/- 0.06 mM) and glucose levels (-3.14 +/- 0.25 mM) compared with preinfusion levels at t = 0. Both Epi and NE induced a marked hyperglycemia although Epi was more potent (+8.2 +/- 0.9 and +6.9 +/- 0.8 mM, respectively). Plasma FFA levels increased by 0.25 +/- 0.03 mM compared with preinfusion levels on Epi infusion. In contrast, during NE infusion, plasma FFA levels decreased significantly by -0.21 +/- 0.03 mM. Plasma insulin titers did not significantly change during infusion of NE or Epi. It is concluded that the ratio of NE to Epi is the major factor that determines the effect of catecholamines on plasma FFA levels in carp. These results may explain species-dependent different effects of hypoxia on FFA metabolism in fish.
Effect of total body core cooling during poly I:C-induced fever in rabbits
Authors: Toien O. , Mercer J. B.
Published: December 2017

At ambient temperature (Ta) 20 and 10 degrees C, metabolic heat production and hypothalamic temperature (Thypo) were measured to determine the fever response in six rabbits injected with polyriboinosinic-polyribocytidylic acid (poly I:C; 5 mg/kg iv). Similar measurements were made in afebrile and febrile animals subjected to 3 h of body cooling, in which heat was extracted with a chronically implanted intravascular heat exchanger in a ramplike manner. The fever time course showed a biphasic pattern. During cooling in the febrile experiments, Thypo remained constant or even slightly increased during the time corresponding to the first phase of fever but rapidly fell during the second phase because of a depressed shivering response. The net effect at the end of the cooling period was that Thypo decreased by 0.4 and 0.6 degree C more than in the afebrile cooling experiments at Ta 20 and 10 degrees C, respectively. The results indicate normal shivering responses during phase I of poly I:C-induced fever and depressed shivering in phase I, possibly because of a reduced thermosensitivity.
Seasonal influences on the control of plasma sex hormone-binding globulin by T4 in male little brown bats
Authors: Damassa D. A. , Gustafson A. W. , Kwiecinski G. G. , Gagin G. A.
Published: December 2017

Male little brown bats showed a well-defined seasonal cycle of plasma thyroxine (T4). Total T4 concentrations increased during hibernation, reached peak levels in May at spring emergence, and subsequently declined to lowest levels in September. Thyroxine-binding globulin (TBG) activity increased only in summer, and seasonal changes in non-TBG-bound T4 generally paralleled those of total T4. During the fall and early hibernation period, bats studied under feral conditions or following photoperiod manipulation showed coincident changes in plasma T4 and sex hormone-binding globulin (SHBG) levels. In contrast, males studied during late hibernation or following spring arousal exhibited declining plasma T4 levels during periods of increased SHBG activity. Additionally, the prehibernation decline in SHBG did not depend on changing environmental conditions. Bats maintained under summerlike conditions during the fall showed normal seasonal reductions in SHBG and T4. These studies indicate that T4 is the likely physiological regulator of plasma SHBG activity during the fall and early hibernation, but that other factors modulate the timing of SHBG induction in the spring.
Regulation of neurohypophysial hormone secretion in an Australian marsupial
Authors: Bathgate R. A. , Sernia C.
Published: December 2017

The brushtail possum secretes the typically reptilian mesotocin (MT) and arginine vasopressin (AVP) as its neurohypophysial hormones. In this study we have looked at the regulation of MT and AVP secretion in conscious possums by studying the effects of surgical stress and handling of animals, hypertonic saline infusion, hemorrhage, and angiotensin II (ANG II) infusion on the plasma concentrations of MT and AVP. Surgical insertion of a jugular catheter and handling stress increased MT secretion for 3 days after surgery without affecting plasma AVP concentrations. Hypertonic saline infusion induced a gradual increase in plasma osmolarity and Na+ concentration throughout the infusion, which steadily increased plasma AVP without affecting plasma K+ or hematocrit. The relationship between plasma osmolarity and AVP was exponential. Plasma MT was stimulated only by supraphysiological plasma osmolarities. ANG II increased plasma MT and AVP concentrations equipotently throughout the infusion. Hemorrhage was a relatively specific stimulus for AVP secretion, but MT secretion was highly stimulated during severe hypovolemia. It was concluded that MT and AVP secretion is differentially regulated in the possum.
Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats
Authors: Tagliaferro A. R. , Ronan A. M. , Payne J. , Meeker L. D. , Tse S.
Published: December 2017

Young adult male rats were treated with 4 mg dehydroepiandrosterone (DHEA)/100-g diet for 4 wk or were fed the same purified diet unadulterated (51 carbohydrate:20 fat: 23.5 protein; wt/wt). After 1 wk body weight and fat mass of the DHEA-fed rats were significantly less than the controls. By the end of week 3, fat-free mass of the DHEA rats was less than the controls. Neither food intake nor resting metabolism, measured by indirect calorimetry, was different between groups. Isolated epididymal adipocytes of DHEA rats were significantly smaller and isoproterenol (x 10(7) M) stimulation of glycerol release was 53% greater (P < 0.01) than the controls. Basal rate of glycerol release increased significantly for both groups in response to the adenosine inhibitor adenosine deaminase; there were no significant interaction effects. Inhibition of lipolysis by the adenosine analogue phenylisopropyladenosine was similar between groups. Findings support the hypothesis that DHEA reduces adiposity directly by increased lipolysis, but the mechanism of action does not involve a change in the antilipolytic function of adenosine.
NPY increases food intake in white-crowned sparrows: effect in short and long photoperiods
Authors: Richardson R. D. , Boswell T. , Raffety B. D. , Seeley R. J. , Wingfield J. C. , Woods S. C.
Published: December 2017

To determine if altered sensitivity to neuropeptide Y (NPY) underlies premigratory fattening, white-crowned sparrows held on short day length (9:15-h light-dark) received injections into the third ventricle (ivt) of saline or several doses of NPY. An inverted-U function occurred with food intake increasing 30 and 60 min after doses of 1.0 and 2.0 micrograms NPY. When photostimulated (20:4-h light-dark), birds increased daily caloric intake and gained weight rapidly. Birds maintained on long day lengths significantly increased food intake after 0.25 and 0.5 micrograms of NPY and did not respond to higher doses. The effective dose range for NPY to increase food intake moved to the left, suggesting an increase in sensitivity to the peptide on long day lengths. In summary, white-crowned sparrows consume more food when administered NPY ivt and have increased sensitivity when photostimulated and gaining weight. Hence NPY may be a natural stimulator of food intake in this species.
Sympatholytic effect of tricyclic antidepressants: site and mechanism of action in anesthetized rats
Authors: Huangfu D. , Goodwin W. B. , Guyenet P. G.
Published: December 2017

Intravenous desipramine (DMI) and amitriptyline, but not fluoxetine, dose dependently inhibited splanchnic sympathetic nerve discharge (sSND; -64 +/- 3% after 4 mg/kg iv DMI, 172 ng/ml plasma) in urethan-anesthetized debuffered rats. Inhibition was reversed or prevented by microinjection of the alpha 2-adrenergic receptor (alpha 2-AR) antagonist 2-methoxyidazoxan (MOI) into the rostral ventrolateral medulla (RVLM, 1 nmol/side). sSND inhibition (-58 +/- 12%) by baclofen (8 mg/kg iv, a gamma-aminobutyric acid-B receptor agonist) was unaffected by MOI. MOI alone raised sSND 46 +/- 9%. Microinjection of 6-hydroxydopamine into the RVLM (2 micrograms/side, 10-13 days, to destroy noradrenergic terminals) did not change the effect of intravenous DMI or MOI on sSND. Slow-firing presympathetic neurons of the RVLM were activated by iontophoretic MOI (26 +/- 4%) and inhibited by 4 mg/kg iv DMI (-44 +/- 12%, effect reversed by alpha 2-AR antagonists iv). We interpret these findings as follows: 1) alpha 2-ARs in the RVLM are activated at rest, probably by catecholamines released by C1 adrenergic cells, 2) this activation reduces sSND, 3) DMI and amitriptyline reduce sSND by increasing alpha 2-AR activation in the RVLM, and 4) these effects are due to neither serotonin uptake inhibition nor blockade of norepinephrine uptake by noradrenergic fibers.
Modulation of feeding by beta 2-microglobulin, a marker of immune activation
Authors: Plata-Salaman C. R. , Sonti G. , Borkoski J. P.
Published: December 2017

Increased levels of beta 2-microglobulin (part of the class I major histocompatibility complex molecules) in body fluids are associated with activation of the immune system and pathophysiological processes. Various anorexigenic cytokines, including interferon-gamma and tumor necrosis factor-alpha, induce the expression of class I molecules. Therefore, it is possible that beta 2-microglobulin may participate in the feeding suppression induced by cytokines or may have direct effects on feeding. In the present study, the effects of beta 2-microglobulin on the central regulation of feeding were investigated. Intracerebroventricular (ICV) microinfusion of beta 2-microglobulin (0.01-5.0 micrograms/rat) suppressed the nighttime food intake dose dependently. The most effective dose of beta 2-microglobulin, 5.0 micrograms/rat, decreased nighttime feeding by 38% and total daily food intake by 28%. Computerized analysis of behavioral patterns demonstrated that beta 2-microglobulin decreased meal size and meal frequency during the initial 4-h interval, but decreased only meal size during the second 4-h interval after the ICV microinfusion of 5.0 micrograms beta 2-microglobulin/rat; meal duration was not significantly affected in any interval. For the complete nighttime period, only meal size was significantly decreased. Cerebrospinal fluid-brain and rectal temperatures did not change significantly. ICV microinfusion of heat-treated beta 2-microglobulin or intraperitoneal administration of beta 2-microglobulin, in doses equivalent to those administered centrally, had no effect on food intake. The results suggest that beta 2-microglobulin may act centrally to decrease feeding, and this effect may participate in the anorexia frequently accompanying pathological processes.
Corticosterone regulates behavioral effects of lipopolysaccharide and interleukin-1 beta in mice
Authors: Goujon E. , Parnet P. , Aubert A. , Goodall G. , Dantzer R.
Published: December 2017

The modulatory role of endogenous corticoids in the behavioral effects of lipopolysaccharide (LPS) and recombinant human interleukin-1 beta (IL-1 beta) was studied in mice. Adrenalectomy enhanced the depression of social exploration induced by subcutaneous injection of 200 ng of IL-1 beta or 2 micrograms of LPS. This effect was mimicked by an acute injection of the progesterone antagonist RU-38486 (0.25-1 mg). Chronic replacement with a 15-mg corticosterone pellet abrogated the enhanced susceptibility of adrenalectomized animals to 200 ng of IL-1 beta but had only partial protective effects on their response to 400 ng of IL-1 beta and LPS. These results suggest that the pituitary-adrenal response to cytokines exerts an inhibitory feedback on the cell targets that mediate the behavioral effects of LPS and IL-1 beta.
Hypoxemia in the absence of blood loss or significant hypotension causes inflammatory cytokine release
Authors: Ertel W. , Morrison M. H. , Ayala A. , Chaudry I. H.
Published: December 2017

Although hemorrhagic shock causes a significant elevation of circulating levels of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6], it remains unknown whether hypoxemia per se in the absence of blood loss activates macrophages (Mo) to release increased amounts of these mediators. To study this, hypoxemia was induced in C3H/HeN mice by placing them in a plastic box that was flushed with a gas mixture containing 95% N2-5% O2 for 60 min, followed by return of the mice to room air. For control animals, the plastic box was flushed with room air. At 0, 2, or 24 h thereafter, blood samples were obtained, plasma was separated, and then peritoneal Mo (pMo) and Kupffer cells (KC) were isolated and incubated at 37 degrees C for 24 h with lipopolysaccharide. The Mo supernatants, as well as plasma samples, were assayed for TNF-alpha, IL-1 beta, and IL-6 with the use of specific bioassays. Hypoxemia induced a significant (P < 0.05) increase in plasma TNF-alpha levels during the entire study period while circulating IL-6 was elevated by 313% (P < 0.01) at 24 h after hypoxemia compared with shams. Moreover, the release of TNF-alpha, IL-1 beta, and IL-6 by pMo and KC was markedly increased after hypoxemia compared with shams. Thus, hypoxemia in itself, in the absence of any blood loss or tissue injury, induces release of proinflammatory cytokines, which may contribute to systemic inflammation following hypoxemia.
Voluntary exercise increases gonadotropin secretion in male Golden hamsters
Authors: Pieper D. R. , Ali H. Y. , Benson L. L. , Shows M. D. , Lobocki C. A. , Subramanian M. G.
Published: December 2017

To determine the effect of voluntary exercise and food restriction on reproductive hormone secretion, 48 adult male hamsters were placed in cages with (EX) or without (SED) running wheels. One-half of the animals in each exercise group was fed ad libitum, and the other half was food restricted to reduce their body weight to 90 g over 4 wk. After 10 wk, the EX ad libitum-fed group had much larger testes and much higher serum follicle-stimulating hormone and testosterone levels than the other three groups, but these values in the EX food-restricted hamsters were similar to those in the SED food-restricted group. In experiment 2, 20 adult male hamsters were castrated and later implanted with silicone rubber capsules containing testosterone. Two weeks after implantation of the capsules, the serum follicle-stimulating hormone levels were higher in the EX than in the SED group of testosterone-treated hamsters, but not in animals receiving blank capsules. These data suggest that exercise increases gonadotropin secretion by inhibiting the negative feedback of testosterone.
Blood pressure and fluid-electrolyte balance in ANF-transgenic mice on high- and low-salt diets
Authors: Veress A. T. , Chong C. K. , Field L. J. , Sonnenberg H.
Published: December 2017

Transgenic mice overexpressing an atrial natriuretic factor (ANF) fusion gene (TTR-ANF) and their nontransgenic siblings were placed on a high- (8%) or low (< 0.008%)-salt diet for 14 days to determine whether the lifelong elevation of ANF in the transgenic animals compromised their ability to maintain fluid-electrolyte balance. Steady-state dietary intake and urinary output of sodium and chloride were not statistically different between TTR-ANF and control groups on either diet. By contrast, water intake and urine volume were markedly elevated in the TTR-ANF group on either diet. Arterial blood pressure, measured in anesthetized mice at the end of the dietary regimen, was significantly and similarly reduced in the TTR-ANF compared with control groups on either diet, although high salt intake was associated with increased pressure in both groups. Renal excretion of fluid and electrolytes was studied in the anesthetized mice before and after acute blood volume expansion. Although the absolute increase in fluid and electrolyte excretion was much greater on the high- than on the low-salt diet in both groups, TTR-ANF mice had an exaggerated response relative to controls on either diet. On the basis of these results, we conclude the following. 1) When they are stimulated, renal salt-conserving mechanisms are sufficiently powerful to overcome the expected natriuretic effects of chronic elevation of plasma ANF; however, the natriuretic potential of ANF can be expressed in the short term when the counterregulatory mechanisms are inactivated. 2) ANF exerts a chronic hypotensive effect that is independent of changes in renal salt excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Control of renal medullary blood flow by vasopressin V1 and V2 receptors
Authors: Nakanishi K. , Mattson D. L. , Gross V. , Roman R. J. , Cowley A. W.
Published: December 2017

Experiments were performed in anesthetized renal-denervated rats to determine the contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the regulation of renal medullary blood flow. Renal medullary interstitial infusion of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1) significantly decreased outer medullary blood flow by 15% and inner medullary blood flow by 35%, as measured with implanted optical fibers for laser-Doppler flowmetry. Medullary interstitial infusion of equimolar doses of arginine vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased inner medullary blood flow by only 17%, a decrease significantly less than that during the infusion of the V1 agonist. These results were confirmed in videomicroscopy experiments on the exposed papilla, which demonstrated that the V1 agonist and AVP decreased descending and ascending vasa recta capillary red blood cell velocity and calculated blood flow, with greater decreases during infusion of the V1 agonist. In further laser-Doppler flowmetry studies, stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D-arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present experiments indicate that vasopressin V1 receptor stimulation serves to decrease renal medullary blood flow while V2 receptor stimulation appears to increase renal medullary blood flow; however, the net effect of AVP is to decrease renal medullary blood flow.
TNF soluble receptor and antiserum against TNF enhance lipopolysaccharide fever in mice
Authors: Kozak W. , Conn C. A. , Klir J. J. , Wong G. H. , Kluger M. J.
Published: December 2017

We tested the effects of tumor necrosis factor (TNF) soluble receptor (sTNFR) and anti-TNF serum (anti-TNF) administered intraperitoneally on fever induced by lipopolysaccharide (LPS) in mice. Both agents have been shown to block bioactivity of mouse TNF-alpha. Core temperature (Tb) and locomotor activity in unrestrained mice were measured by biotelemetry. Within 1 h from the LPS injection (2.5 mg/kg ip) Tb decreased below normal for 5-6 h and motor activity was depressed for the following 48 h. After this initial reduction, Tb increased and reached a peak at approximately 24 h postinjection. Anti-TNF and sTNFR blocked this "hypothermic phase" after LPS, and the fevers started sooner; however, the levels and time of peak temperature did not change markedly. In addition, a human recombinant TNF-alpha given intraperitoneally abolished fever and prolonged the fall of Tb in mice after LPS. We conclude that the reduction of Tb soon after injection of LPS in mice is dependent on TNF-alpha.
Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue
Authors: Matz J. M. , Blake M. J. , Tatelman H. M. , Lavoi K. P. , Holbrook N. J.
Published: December 2017

The accumulation of heat shock proteins (HSPs) after the exposure of cells or organisms to elevated temperatures is well established. It is also known that a variety of other environmental and cellular metabolic stressors can induce HSP synthesis. However, few studies have investigated the effect of cold temperature on HSP expression. Here we report that exposure of Institute of Cancer Research (ICR) mice to cold ambient temperatures results in a tissue-selective induction of HSPs in brown adipose tissue (BAT) coincident with the induction of mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is associated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to heat and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to cold exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic receptors through, as yet, undetermined signal transduction pathways. Thermogenesis results from an increase in activity and synthesis of several metabolic enzymes in BAT of animals exposed to cold challenge. The concomitant increase in HSPs may function to facilitate the translocation and activity of the enzymes involved in this process.
A long-lasting change in the excitability of fetal brain neurons following activation of dam's hypothalamus in rats
Authors: Nakamura S. , Arakawa S. , Nishiike S.
Published: December 2017

The influence of the dam's brain on the electrical activity of brain neurons was examined in the rat fetus while the fetus was still connected to the dam by the umbilical cord. Under urethan anesthesia, the spontaneous or glutamate-induced discharge of single brain stem neurons in fetuses was decreased by electrical stimulation of the dam's hypothalamus (Hyp). The changes occurred 21-122 s after start of the stimulation and persisted throughout the recording until the cells were lost after 2.4-9.5 min. The effects of electrical stimulation of dam's midbrain reticular formation (MRF) were much weaker and of shorter duration compared with Hyp stimulation. The dam's blood pressure was increased immediately after the beginning of MRF or Hyp stimulation. The change was always greater with MRF than with Hyp stimulation. Activation of the dam's MRF and Hyp had no marked influence on the blood flow in the fetal brain. These results indicate the presence of a functional interaction between the brain of the dam and that of its fetus mediated through the placenta.
Energy, protein, and substrate metabolism in simulated microgravity
Authors: Acheson K. J. , Decombaz J. , Piguet-Welsch C. , Montigon F. , Decarli B. , Bartholdi I. , Fern E. B.
Published: December 2017

Whole body protein turnover and energy expenditure before and during an oral glucose tolerance test (1 g/kg body wt) were studied on separate occasions in six healthy young men before and during 3 days of simulated microgravity using the 6 degrees head-down tilt (HDT) method. After 42-47 h of HDT, basal insulin concentrations increased significantly from 9.4 +/- 1.9 to 13.1 +/- 0.1 microU/ml (P < 0.002). No significant differences in glycemia, insulinemia, or free fatty acid concentrations were observed in response to the oral glucose load. With HDT, increases were observed in basal postabsorptive resting metabolic rate (8%; P < 0.05), lipid oxidation (33 +/- 2 to 51 +/- 5 mg/min; P < 0.02), and the thermic effect of glucose (7.7 +/- 1 to 10.7 +/- 0.6%; not significant). Protein turnover (arithmetic mean of ammonia and urea flux rates) was unchanged by HDT, but a significant increase was seen when calculated from ammonia alone (P < 0.02). The present data show that HDT results in an increased energy requirement through elevations in both the basal metabolic rate and the thermic response to food ingestion. These changes may have been brought about by a cephalic shift of body fluids similar to that experienced in microgravity.
Ventricular sensory neurons in canine dorsal root ganglia: effects of adenosine and substance P
Authors: Huang M. H. , Sylven C. , Horackova M. , Armour J. A.
Published: December 2017

Effects elicited by adenosine and substance P on ventricular sensory endings of 14 dorsal root ganglion afferent neurons were studied in situ in anesthetized dogs. Sensory-field application of adenosine (1 microM) increased the activity of these neurons by 179%. Application of a nonspecific adenosine antagonist to epicardial sensory fields suppressed ongoing activity in all 14 neurons by 39%. Application of an A1- or A2-adenosine-receptor antagonist suppressed activity generated by 10 of these neurons by 44 and 59%, respectively. Adenosine applied after A1- or A2-receptor blockade increased activity in 10 neurons by 131 and 145%, respectively, indicating that A1- and A2-receptor effects were not additive. Application of substance P (1 microM) to identified sensory fields increased activity in 12 of these neurons by 169%, whereas application of a substance P-receptor antagonist reduced activity generated by these neurons by 75%. Myocardial ischemia increased activity of nine neurons associated with left ventricular sensory fields by 320%, an effect that was counteracted by the nonspecific adenosine-receptor antagonist. It is concluded that A1- and A2-adenosine receptors, as well as substance P receptors, are present on ventricular epicardial sensory nerve endings of dorsal root ganglion neurons that are tonically active during normal states, becoming further activated during ischemia.
Sympathetic vasoconstrictive responses to high- and low-sodium diets in diabetic and normal subjects
Authors: Miller J. A.
Published: December 2017

Uncomplicated insulin-dependent diabetes mellitus (IDDM) is associated with a suppressed reflex response to sympathetic nervous system (SNS) stimulation and an enhanced pressor response to catecholamines. This study examined the SNS in subjects with IDDM (duration < 5 yr, n = 9) to determine the responsible mechanism within the cardiopulmonary baroreflex arc and the role played by extracellular fluid volume (ECFV) expansion. The reflex arc was tested by examining the plasma norepinephrine (PNE) and forearm vascular (FVR) responses to 60 min of cardiopulmonary baroreceptor unloading by lower body negative pressure (LBNP) at -15 mmHg. The effector limb was tested by measuring the PNE, FVR, and mean arterial pressure (MAP) response to the cold pressor test (CPT). The postganglionic neuroeffector junction was tested by measuring the venoconstrictive response to local norepinephrine infusion. ECFV was varied by altering dietary sodium. In IDDM subjects on a 250 mmol sodium diet, PNE and FVR responses to LBNP (delta PNE = 0.15 +/- 0.05; delta FVR = 4.3 +/- 1.2) were attenuated compared with controls (delta PNE = 0.36 +/- 0.23; delta FVR = 11.56 +/- 2.72). MAP and FVR responses to the CPT were intact (delta MAP = 9.74 +/- 1.9; delta FVR = 7.02 +/- 3.11) compared with controls (delta MAP = 10.74 +/- 2.69; delta FVR = 8.26 +/- 2.94), but the PNE response was attenuated. The peripheral vasculature was hyperresponsive to norepinephrine infusion in IDDM subjects [mean effective dose (ED50) = 57 +/- 10 ng/min] compared with controls (ED50 = 133 +/- 30 ng/min). Sodium restriction (20 mmol/day) normalized the FVR response to LBNP and the venous response to norepinephrine infusion. The PNE response both to LBNP and the CPT remained attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)
Myometrium of the spiny dogfish Squalus acanthias: peptide and steroid regulation
Authors: Sorbera L. A. , Callard I. P.
Published: December 2017

The phylogenetic age of endocrine control of viviparous reproduction in vertebrates may be estimated by examination of elasmobranch models. We have shown in pregnant Squalus acanthias that Squalus relaxin (sRLX) significantly decreased the frequency of myometrial contractions in a dose-dependent reversible manner in vitro and in vivo, without altering the intensity or duration of contractions. In contrast, neurointermediate lobe extract provoked a marked and reversible enhancement of the duration and intensity of contractions but was ineffective in altering the frequency of contractions. In steroid-primed animals, untreated and estradiol-17 beta (E2)-treated animals exhibited a decrease in the frequency of activity after injection of sRLX in vivo while pretreatment with progesterone (P4) alone or in combination with E2 fully suppressed the effects of sRLX. These results suggest that homologous sRLX slows the frequency of spontaneous uterine contractions in third-trimester sharks (stage C) in which endogenous P4 is reduced and E2 levels are rising. These data demonstrate the physiological importance of these hormones and the antiquity of reproductive tract control mechanisms.
Time course for entry of intestinally infused lipids into blood of rats
Authors: Greenberg D. , Kava R. A. , Lewis D. R. , Greenwood M. R. , Smith G. P.
Published: December 2017

The early time course of the absorption of duodenally infused 14C-labeled Intralipid into either the hepatic portal circulation or systemic circulation was measured. Plasma radioactivity did not increase significantly at either site until 30 min after the intestinal infusion began and was maximal between 60 and 120 min. In studies on the effects of intestinal lipid infusions on sham feeding in rats we find significant suppressions of sham feeding after only 10 min. Thus the time course for lipid absorption is different from that of the satiating effects of duodenally infused fats. These results are consistent with the hypothesis that the satiating effect of fats infused into the small intestine occurs before entry of absorbed fats into the blood and is not dependent on recently absorbed circulating fat.
Regulation of beta 3-adrenergic receptor mRNA by sympathetic nerves and glucocorticoids in BAT of Zucker obese rats
Authors: Onai T. , Kilroy G. , York D. A. , Bray G. A.
Published: December 2017

Impaired brown adipose tissue (BAT) thermogenesis in the genetically obese Zucker fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the role of the sympathetic nervous system in modulating the effects of adrenalectomy by studying beta3-adrenergic receptor (AR) and uncoupling protein (UCP) mRNA levels in unilaterally sympathectomized interscapular BAT of lean and obese rats. UCP mRNA levels were increased by adrenalectomy. Sympathetic denervation prevented this adrenalectomy-induced increase in lean rats but not in obese rats. beta 3-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decreased and denervation increased beta 3-AR mRNA in lean rats but the opposite response was observed to both of these manipulations in obese rats. beta 3-AR mRNA and UCP mRNA were negatively correlated in lean rats but positively correlated in obese rats. Norepinephrine increased UCP mRNA levels in denervated BAT of both lean and obese rats and decreased beta 3-AR mRNA in lean rats but not obese rats. These data suggest that the regulation of the beta 3-AR gene in response to sympathetic stimuli and glucocorticoids is abnormal in the obese rat.
Multiple mechanisms mediate antipyretic action of glucocorticoids
Authors: Coelho M. M. , Luheshi G. , Hopkins S. J. , Pela I. R. , Rothwell N. J.
Published: December 2017

Glucocorticoids inhibit various components of the acute phase response, particularly the increase in body temperature (fever) induced by a variety of stimuli. In the present study these observations have been extended, and we have determined the effect of glucocorticoid treatment or surgical adrenalectomy on the cytokine and prostaglandin (PG) concentrations in plasma and cerebrospinal fluid (CSF) during the febrile response to endotoxin. Dexamethasone treatment, either before or after endotoxin injection, markedly inhibited fever and the increased plasma interleukin (IL)-6 and CSF IL-6, PGE2, and PGF2 alpha concentrations. Adrenalectomized (ADX) rats showed higher fevers and plasma and CSF IL-6, PGE2, and PGF2 alpha, concentrations compared with sham-operated animals and exhibited a lower plasma-to-CSF IL-6 ratio than sham-operated animals. Dexamethasone pretreatment also inhibited fever induced by centrally injected TNF-alpha, IL-1 beta, or IL-6. Pyrogenic response to IL-8 was not modified by indomethacin but was markedly inhibited by prior treatment with dexamethasone. These results support the hypothesis that endogenous glucocorticoids function as part of an inhibitory feedback system involved in the modulation of fever and that multiple mechanisms may be involved in their antipyretic effect.
A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt
Authors: Engelke K. A. , Doerr D. F. , Convertino V. A.
Published: December 2017

We tested the hypothesis that one bout of maximal exercise performed 24 h before reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated baroreflex function was assessed in seven subjects before and after two periods of HDT separated by 11 mo. On the last day of one HDT period, subjects performed a single bout of maximal cycle ergometry (exercise). Subjects did not exercise after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was evaluated using a neck collar device. Integrated baroreflex function was assessed by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated vasoconstriction was assessed by measuring the late phase II rise in MAP. Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0 ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8 beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or exercise. The late phase II increase of MAP was 71% greater after exercise compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary tract of behaving rats
Authors: Nakamura K. , Norgren R.
Published: December 2017

The activity of single taste neurons was recorded from the nucleus of the solitary tract before (n = 41) and after (n = 58) awake, behaving rats were switched to a sodium-free diet. During sodium deprivation, the spontaneous activity of the neurons increased (142%), but responses to water and sapid stimuli decreased. For all neurons in the sample, the mean response to water decreased to 72% of its predeprivation level, NaCl dropped to 53%, sucrose to 41%, citric acid to 68%, and quinine HCl to 84%. Despite the drop in magnitude, the response profiles of the taste neurons were not changed by the dietary condition. In the Na-replete state, 61% of the activity elicited by NaCl occurred in NaCl-best cells and 33% in sucrose-best neurons. In the depleted state, these values were 60 and 26%, respectively. Nevertheless, at the highest concentrations tested, deprivation did alter the relative responsiveness of the gustatory neurons to sucrose and NaCl in specific categories of neurons. Compared with acute preparations, dietary sodium deprivation in awake, behaving rats produced a more general reduction in the gustatory responses of neurons in the nucleus of the solitary tract. The largest reductions in elicited activity occurred for the "best stimulus" of a particular neuron, thus leading to smaller differences in response magnitude across stimuli, particularly at the highest concentrations tested.
Lack of relationship between opioid-induced changes in fetal breathing and plasma glucose levels
Authors: Szeto H. H. , Cheng P. Y. , Soong Y. , Wu D. L.
Published: December 2017

The mechanisms by which opioids increase or decrease fetal breathing remain unclear. Fetal plasma glucose is known to modulate breathing activity, and opioids have been reported to alter glucose regulation in the adult. In this study, we investigated whether alterations in fetal breathing by opioids may be explained by changes in plasma glucose levels. We compared the effects of morphine (nonselective), [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-selective), and [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) on fetal breathing and plasma glucose in unanesthetized fetal sheep. Whereas morphine at 1.2 and 5.0 mg/h iv resulted in an increase in breath number (P < 0.01), plasma glucose was decreased after 1.2 mg/h (P = 0.006) but increased after 5.0 mg/h (P = 0.008). DAMGO (100 micrograms/h icv) increased plasma glucose (P = 0.001) but reduced fetal breathing (P < 0.001). In contrast, DPDPE (30 micrograms/h icv) increased fetal breathing (P = 0.026) but had no effect on plasma glucose concentration. These data demonstrate that the actions of opioids on fetal glucose regulation and breathing are dependent on dose and receptor selectivity. However, there is no relationship between the effects of opioids on fetal breathing and plasma glucose concentration.
Pregnancy enhances the pressor response to thromboxane analogues in rabbits
Authors: Losonczy G. , Singh J. P. , Schoenl M. , Mucha I. , Venuto R. C.
Published: December 2017

In this study, we first tested the hypothesis that the previously demonstrated circulatory failure and thrombocytopenia induced by intracaval administration of thromboxane A2 (TxA2) analogues in nonpregnant (NP) rabbits [G. Losonczy, I. Mucha, J. DiPirro, J. Sweeney, G. Brown, J. Brentjens, and R. Venuto. Am. J. Physiol. 265 (Regulatory Integrative Comp. Physiol. 34): R772-R780, 1993] could be avoided if the compounds were given instead into the aortic arch. Conscious New Zealand White rabbits received bolus injections of U-46619 (5-20 micrograms) through a previously implanted catheter threaded into the aortic arch. Indeed, mean arterial pressure (MAP) rose modestly, and thrombocytopenia did not develop. Next, we compared the blood pressure responses of pregnant (P) rabbits with those of NP rabbits to intra-aortic U-46619 and I-BOP, because they had been found to be resistant to both the hypotensive and platelet aggregatory effects of intracaval U-46619. Resting blood pressure was lower in P than in NP rabbits (74 +/- 3 vs. 95 +/- 2 mmHg), but showed a greater increase in response to U-46619. For example, following a 20-micrograms dose blood pressure rose 20 +/- 0.3 mmHg in P vs. 12 +/- 2.1 mmHg in NP rabbits (P < 0.02). Similar results were obtained with the second TxA2 analogue I-BOP. Pregnancy-induced enhancement of blood pressure elevation may be the consequence of peripheral vasoconstriction, which was not seen in NP rabbits. Thus the actions of TxA2 analogues U-46619 and I-BOP are markedly influenced by the route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)