bluuebunny/crossref_metadata_2025 huggingface dataset:
Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro
Authors: Wahlestedt C. , Hakanson R. , Vaz C. A. , Zukowska-Grojec Z.
Published: December 2017

Norepinephrine (NE)-evoked vasoconstrictor and pressor responses are reduced after prolonged exposure; such desensitization is observed both clinically and experimentally. The vasoconstrictor neuropeptide Y (NPY) coexists with NE in perivascular sympathetic nerves, and the results of both in vivo and in vitro studies have indicated functional cooperation between NE and NPY. We propose that NPY becomes increasingly important in situations of high sympathetic activity associated with blunted NE responses. Prolonged NE infusion in conscious rats resulted in adrenergic desensitization; however, NPY administration restored the responsiveness to NE. In naive rats, NE greatly enhanced the pressor action of NPY. An analogous phenomenon was observed in the rabbit isolated pulmonary artery, which failed to respond to NPY unless preexposed to NE; this action of NE was only partly inhibited by conventional adrenoceptor and Ca2+ influx blockade. Conversely, NPY enhanced NE-evoked constriction, in particular when the alpha-adrenoceptor reserve was eliminated. It is proposed that threshold synergism, in part caused by converging stimulation of phospholipase C, accounts for much of the NPY/NE cooperativity. We conclude that 1) NPY and NE cooperate to produce vasoconstriction, both in vivo and in vitro; 2) NPY has the capacity to reverse adrenergic desensitization but not vice versa; 3) NE enhances NPY-evoked vasoconstriction, in part independently of conventional adrenoceptor blockade; 4) threshold synergism phenomena, but not "receptor-receptor interactions," account for (most of) the observed NPY/NE cooperation; and 5) when present, alpha-adrenoceptor reserve prevents the lowering of the NE threshold by NPY.
Training improves glucose homeostasis in rats during exercise via glucose production
Authors: Donovan C. M. , Sumida K. D.
Published: December 2017

The effects of endurance training (running 1 h/day at 35 m/min, 10% grade) on glucose homeostasis during exercise (running 20 m/min) was studied in 30-h fasted rats. Primed-continuous infusion of [6-3H]- and [U-14C]glucose were employed to assess rates of appearance (Ra), disappearance (Rd), and apparent recycling. Training resulted in a 65% increase in skeletal muscle succinate dehydrogenase (SDH) activity but did not significantly influence body weight. Resting blood glucose concentrations were not significantly different between controls, 5.01 +/- 0.19 mM, and trained animals, 4.86 +/- 0.16 mM. Exercise resulted in a more rapid decline in blood glucose levels for control animals, reaching a value of 2.35 +/- 0.39 mM at 60 min, compared with 3.69 +/- 0.47 mM for trained animals. Glucose Ra was not significantly different between groups at rest, and rose for both groups during exercise. However, for controls Ra plateaued between 15 and 60 min of exercise at 11.03 +/- 0.73 mumol.100 g-1.min-1, whereas trained animals demonstrated a continuous rise to 17.13 +/- 1.18 mumol.100 g-1.min-1. Glucose Rd values were not significantly different between groups during the first 30 min of exercise but were significantly higher for trained animals during the final 30 min. As a result of the higher glucose Ra, trained animals demonstrated a smaller mean difference between Ra and Rd during exercise when compared with controls, -0.27 +/- 0.14 vs. -0.96 +/- 0.17 mumol.100 g-1.min-1. Trained animals further demonstrated significantly higher rates of glucose carbon recycling during the final 30 min of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic responses to leukotriene receptor stimulation in conscious rats
Authors: Allen D. E. , Gellai M.
Published: December 2017

We evaluated the effects of leukotrienes (LTs) C4 and D4 on systemic and renal hemodynamics in conscious rats. Intravenous injections of LTC4 or LTD4 (0.5-10 micrograms/kg) caused dose-dependent decreases in cardiac output (CO), renal blood flow (RBF), and heart rate (HR). Flow alterations were accompanied by increased systemic and renal vascular resistances (SVR and RVR) and mean arterial blood pressure (MAP). No secondary hypotensive effect was observed. The HR response was biphasic, with tachycardia replacing the initial brief bradycardia. The changes in RBF and CO were not concurrent; the maximum RBF decrease (47.6 +/- 9.5%, P less than 0.05) occurred when CO was down only by 9.1 +/- 3.6% (P less than 0.05) and RBF had fully recovered in 3-4 min, while CO was still down by 26.3 +/- 3.5% (P less than 0.001). Hematocrit (HCT) increased after the injection of 5 and 10 micrograms/kg doses of LTC4 or LTD4, and its time course of recovery to basal level (30-60 min) paralleled that of CO. Sustained intravenous infusion of the selective LT receptor antagonist, SK&F 104353, dose-dependently inhibited the immediate hemodynamic changes after LTD4 injections. SK&F 104353 also attenuated the increase in vascular permeability and the prolonged decrease in CO, suggesting that the observed cardiac and vascular effects of LTs were mediated by stimulation of LT receptors.
Dehydration increases the density of C receptors for ANF on rat glomerular membranes
Authors: Kollenda M. C. , Vollmar A. M. , McEnroe G. A. , Gerbes A. L.
Published: December 2017

The present study determined the presence of two types of binding sites for atrial natriuretic factor (ANF), the B and C receptor, on rat glomerular membranes. The effect of short-term salt loading and dehydration on these two receptor populations was investigated consecutively. Salt-loaded rats did not show significant changes in plasma ANF concentrations or in the number of ANF binding sites. Water-deprived rats presented significantly lower plasma ANF concentrations (22.0 +/- 1.9 vs. 34.4 +/- 3.8 fmol/ml, P less than 0.01) and an increase in total receptor density (1,860 +/- 398 vs. 987 +/- 143 fmol/mg protein) as compared with the control group. Differentiation of both receptor populations showed that it was the C receptors that accounted for this increase (1,772 +/- 369 vs. 901 +/- 151 fmol/mg protein, P less than 0.05), whereas B-receptor density was unchanged (89 +/- 31 vs. 87 +/- 44 fmol/mg protein). These data suggest that C receptors for ANF are affected by changes of body fluid volume.
Effect of hematocrit on behavioral thermoregulation of the toad Bufo marinus
Authors: Wood S. C.
Published: December 2017

This study tested the hypothesis that the oxygen capacity of blood, indexed by hematocrit, affects the body temperature (Tb) selected by toads (Bufo marinus) in a thermal gradient. Anesthetized toads (Brevital sodium; 40 mg/kg im) were fitted with a cloacal thermistor and femoral artery cannula. After recovery, they were placed in a thermal gradient ranging from approximately 10 to 40 degrees C. Tb was measured for 24 h. Then 1-2 ml blood were withdrawn and replaced with an equal volume of either 0.66% saline or packed red cells from donor toads. Selected Tb was measured for the next 24 h. The mean Tb selected by B. marinus (n = 33) was 24.9 degrees C. Cross-sectional analysis showed no correlation between selected Tb and hematocrit. However, each toad rendered anemic showed a reduction of selected Tb (mean = 22.9 degrees C). The degree of Tb reduction was correlated with the hematocrit reduction, (r = 0.86; P = 0.013). Blood doping did not have a significant effect on selected Tb. The reduction of Tb could be adaptive by reducing oxygen consumption.
Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings
Authors: Vimy M. J. , Takahashi Y. , Lorscheider F. L.
Published: December 2017

In humans, the continuous release of Hg vapor from dental amalgam tooth restorations is markedly increased for prolonged periods after chewing. The present study establishes a time-course distribution for amalgam Hg in body tissues of adult and fetal sheep. Under general anesthesia, five pregnant ewes had twelve occlusal amalgam fillings containing radioactive 203Hg placed in teeth at 112 days gestation. Blood, amniotic fluid, feces, and urine specimens were collected at 1- to 3-day intervals for 16 days. From days 16-140 after amalgam placement (16-41 days for fetal lambs), tissue specimens were analyzed for radioactivity, and total Hg concentrations were calculated. Results demonstrate that Hg from dental amalgam will appear in maternal and fetal blood and amniotic fluid within 2 days after placement of amalgam tooth restorations. Excretion of some of this Hg will also commence within 2 days. All tissues examined displayed Hg accumulation. Highest concentrations of Hg from amalgam in the adult occurred in kidney and liver, whereas in the fetus the highest amalgam Hg concentrations appeared in liver and pituitary gland. The placenta progressively concentrated Hg as gestation advanced to term, and milk concentration of amalgam Hg postpartum provides a potential source of Hg exposure to the newborn. It is concluded that accumulation of amalgam Hg progresses in maternal and fetal tissues to a steady state with advancing gestation and is maintained. Dental amalgam usage as a tooth restorative material in pregnant women and children should be reconsidered.
Acetylcholinesterase inhibitor, pyridostigmine bromide, reduces skin blood flow in humans
Authors: Stephenson L. A. , Kolka M. A.
Published: December 2017

Five subjects exercised on a cycle ergometer for 30 min at 55% peak oxygen consumption on two occasions in an environmental test chamber (ambient temperature = 29 degrees C; dew point temperature = 10 degrees C). Pyridostigmine bromide (PYR), an acetylcholinesterase (AChE) inhibitor, was ingested (30 mg) approximately 150 min before one experiment, and no drug was administered during the other experiment (control). Red blood cell AChE inhibition averaged 40 (+/- 7)% during PYR treatment. Esophageal temperature (Tes), an eight site-derived mean skin temperature, forearm blood flow (FBF; venous occlusion plethysmography), skin blood flow (SkBF; laser-Doppler velocimetry), and metabolic rate (indirect calorimetry) were measured. SkBF decreased 37% after PYR treatment compared with control (P less than or equal to 0.05). The Tes threshold for initiation of cutaneous vasodilation was 36.8 (+/- 0.3) degrees C for the control treatment and 37.0 (+/- 0.3) degrees C for the PYR treatment (P less than or equal to 0.01). FBF was not significantly different between treatments, whereas heart rate was reduced by 7 and 9 beats/min during rest and exercise, respectively (P less than or equal to 0.01). The increased threshold for initiation of cutaneous vasodilation with AChE inhibition by PYR is compatible with nonthermal modulation of the control of thermoregulation through increased acetylcholine (ACh) accumulation. This could potentiate preganglionic transmission to enhance adrenergic vasoconstrictor tone. One suggested mechanism possible at the neuroeffector junction of the sweat gland may be that accumulated ACh diffusion across the adventitia of adjacent arterioles to muscarinic receptors initiates contraction of the smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential osmoresponsiveness of periventricular neurons in duck hypothalamus
Authors: Kanosue K. , Schmid H. , Simon E.
Published: December 2017

Single-unit responses to osmotic stimulation were recorded extracellularly in slice preparations from the duck's hypothalamus in the periventricular layer (pl), magnocellular center (mc), and deep periventricular neuropil of the paraventricular nucleus (PVN). The pl neurons were located in the dorsorostral third ventricular region of maximum osmoresponsiveness determined in vivo. Hypertonic stimulation (+20 to +35 mosmol/kgH2O) by excess NaCl in the incubation medium excited 25 and inhibited 4 out of 48 pl neurons. Hypotonic (-10 to -20 mosmol/kgH2O) stimulation inhibited 9 out of 10 neurons activated by hypertonic stimulation. Hypertonic activation of pl neurons was maintained in seven out of nine neurons when NaCl was replaced by LiCl, but replacing NaCl by sucrose was ineffective in each of 10 neurons. Synaptic blockade (Ca2(+)-free/high-Mg2+ medium) did not abolish hypertonic activation in 8 out of 11 pl neurons. Among 30 mc neurons, 2 were activated and 1 inhibited by hypertonic stimulation with NaCl (+20 to +35 mosmol/kgH2O), and among 24 neurons in the periventricular neuropil, 2 were activated and 4 inhibited. The function of osmoresponsive pl neurons as specific receptors would be consistent with their morphological characteristics and with the location and functional properties of the duck's third ventricular osmoresponsiveness in vivo.
Plasma and white adipose tissue lipid composition in marmots
Authors: Florant G. L. , Nuttle L. C. , Mullinex D. E. , Rintoul D. A.
Published: December 2017

White adipose tissue biopsies and plasma samples were obtained from hibernating yellow-bellied marmots (Marmota flaviventris) maintained in the laboratory. In addition, biopsies and plasma samples were obtained from normothermic animals in the field and laboratory. Measurement of plasma free fatty acid (FA) levels indicated that winter laboratory animals exhibited increased lipolysis. Additionally, analysis of white adipose tissue triacylglycerol revealed that the FA composition of the storage fat in animals maintained on the standard laboratory diet is remarkably simple and uniform between different adipose depots in the same animal. Three FAs (palmitic, oleic, and linoleic acids) made up greater than 95% of the total. Triene (alpha-linolenate) was found in newly captured animals, but the percentage of this FA decreased rapidly when the animals were maintained on the standard laboratory diet. Throughout the hibernation season (October to April), white adipose tissue-saturated FA percentage decreased, monoene percentage remained constant, and diene percentage increased. Analysis of plasma FA composition suggested that these animals tended to metabolize saturated FAs from stored lipid during hibernation and that dienes were mobilized briefly after the last arousal from hibernation in spring. From these observations, we hypothesize that marmots preferentially metabolize saturated fats during the hibernation period and that essential FAs of the omega 6 series tend to be metabolized more slowly than other FAs. These characteristics suggest that marmots are a valuable animal model in which to study lipid metabolism.
Renal effects of atrial natriuretic peptide in a marine elasmobranch
Authors: Benyajati S. , Yokota S. D.
Published: December 2017

The effects of atrial natriuretic peptide on the renal function of the spiny dogfish (Squalus acanthias) in seawater were evaluated. A synthetic mammalian peptide, atriopeptin II (2 micrograms/kg), was injected intravascularly into unanesthetized, unrestrained fish prepared for renal clearance studies. The aortic pressure, glomerular filtration rate (GFR), urine flow rate (V), and urinary excretion of sodium, potassium, and total osmolytes were continuously monitored. Atriopeptin II significantly decreased mean aortic pressure (-12%), GFR (-40%), V (-66%), and the absolute excretion rates of sodium (-47%), potassium (-43%), and total osmolytes (-44%). However, the renal effects of atriopeptin II were temporally dissociated from the vasodepressor effect. Mean aortic pressure decreased quickly and returned to control values approximately 2 h after injection, whereas GFR did not decrease significantly until the third hour after injection. The decreases in renal water and solute excretion in response to atriopeptin could be accounted for by the decrease in GFR, since there were no significant changes in fractional water or solute excretion. Similar decreases in GFR were observed during constant infusions of a lower physiological dose of the peptide (80 pg.kg-1.min-1). The observed antidiuretic and antinatriuretic effect of synthetic atriopeptin in the dogfish contrasts with its putative role as a hormone mediating hypervolemic regulation.
Renal interstitial hydrostatic pressure and ANF in exaggerated natriuresis of the SHR
Authors: Khraibi A. A. , Heublein D. M. , Burnett J. C. , Knox F. G.
Published: December 2017

The Okamoto spontaneously hypertensive rat (SHR) has exaggerated natriuretic and diuretic responses to acute volume expansion in comparison with the Wistar-Kyoto (WKY) rat. The objective of these experiments was to determine the role of renal interstitial hydrostatic pressure (RIHP) and atrial natriuretic factor (ANF) in these natriuretic and diuretic responses of the SHR and the WKY rat. Two groups each of SHRs and WKY rats were used in this study. In one group of each, both kidneys were acutely decapsulated, and in the remaining two groups the renal capsules were left intact (control). In both control SHR (n = 6) and WKY (n = 7) groups, volume expansion was associated with a significant increase in RIHP (from 5.0 +/- 0.5 to 7.1 +/- 0.6 mmHg in SHR group and from 6.0 +/- 0.5 to 9.4 +/- 0.3 mmHg in WKY rat group) and a high level of plasma ANF (PANF). The increase in RIHP was significantly lower in the control SHR group compared with that of control WKY rat group (2.1 +/- 0.4 vs. 3.5 +/- 0.3 mmHg; P less than 0.05), whereas PANF was significantly higher in the SHR group (848 +/- 151 pg/ml) compared with that of the WKY group (503 +/- 37 pg/ml) at the end of the volume-expansion period. When the increase in RIHP that occurs during volume expansion in the SHR is blunted by acute bilateral renal decapsulation, the natriuretic and diuretic responses are significantly attenuated despite levels of PANF that are similar to those measured in the control SHR group.(ABSTRACT TRUNCATED AT 250 WORDS)
Halothane sensitivity of young pigs in vivo and in vitro
Authors: Fay R. S. , Gallant E. M.
Published: December 2017

Piglets less than 8 wk of age that are known by genotype to be malignant hyperthermia-susceptible (MHS) do not usually develop characteristic hyperthermia and limb muscle rigidity in response to a brief halothane exposure (5 min of 3%). To determine whether a malignant hyperthermia (MH) episode could nevertheless be provoked by a more rigorous challenge, both genetically MHS (Pietrain) and normal (Yorkshire) 5-wk-old piglets were exposed to a combined halothane-succinylcholine challenge. Only two of eight MHS piglets developed limb rigidity; however, all MHS piglets (and no normal piglets) developed clinical signs of MH episode initiation during the 30-min challenge. Temperatures rose from 37.4 to 38.6 degrees C in MHS piglets while falling slightly in normal piglets. In MHS piglets, venous pH fell from 7.46 +/- 0.02 to 6.88 +/- 0.07, PVCO2 rose from 36 +/- 2 to 126 +/- 17 mmHg, and plasma concentration of K+ rose from 4.0 +/- 0.1 to 7.1 +/- 0.6 mM, whereas all values remained stable in normal piglets. Muscles removed from the same piglets before the halothane-succinylcholine challenge were exposed to halothane in vitro. The muscles from genetically MHS piglets responded to halothane with characteristic depression of tetanic tension and prolonged tetanus relaxation time but did not develop halothane-induced contractures. We conclude that, in the absence of either halothane-induced limb rigidity or in vitro contractures, these young animals were still susceptible to potentially fatal MH episodes on exposure to appropriate triggering agents. The MH defect is apparently partially masked in piglets and expressed fully only in older pigs.
Mechanisms of impaired excretion of a fluid load after cardiac denervation in dogs
Authors: Williams T. D. , Travill C. M. , Noble M. I. , Drake-Holland A. J. , Chalmers J. , Jeffery C. D. , Sutton R. , Lightman S. L.
Published: December 2017

The influence of cardiac innervation on the renal response to volume expansion was investigated. Systemic hemodynamic, plasma hormone, and renal clearance measurements were made before, during, and after intravenous administration of 1,000 ml 0.9% saline over 10 min to six control and six cardiac-denervated, chloralose-anesthetized mongrel dogs. Volume expansion resulted in a two- to threefold rise in plasma atrial natriuretic peptide (ANP) concentrations and a 50% rise in glomerular filtration rate (GFR) in both groups. Plasma renin activity (PRA) and plasma arginine vasopressin remained higher throughout in cardiac-denervated compared with control dogs. The marked increases in urine flow rate and sodium and free water clearances seen in the controls were attenuated or abolished after cardiac denervation. These differences were due to the influence of higher PRA and vasopressin in these animals compared with the controls, rather than differences in hemodynamic responses operating via GFR or in direct humoral responses via ANP secretion.
Influence of temperature on mechanics and energetics of muscle contraction
Authors: Rall J. A. , Woledge R. C.
Published: December 2017

Results gleaned from use of temperature as a probe to study skeletal muscle performance and mechanisms of activation and contraction are reviewed. Steady-state and non-steady-state responses to changes in temperature are considered. Temperature sensitivities, Q10 values, of mechanical and energetic parameters range from nearly 1 to greater than 5 in frog skeletal muscle. Factors that are less temperature sensitive (Q10 less than or equal to 1.5) are peak tetanic force, instantaneous stiffness, curvature of force-velocity relation, magnitude of labile heat, and mechanical efficiency. Rates with intermediate temperature sensitivities (Q10 greater than 2 but less than 3) include rate of isometric force development, maximum shortening velocity, and relaxation from a brief tetanus. Rates with high temperature sensitivities (Q10 greater than 3) include cross-bridge turnover during an isometric tetanus, isometric economy, maximum power output, Ca2+ sequestration by sarcoplasmic reticulum, relaxation from a prolonged tetanus, and recovery metabolism. The observation that the Q10 for relaxation rate depends on tetanic duration can be explained in terms of the possible role of parvalbumin as a soluble relaxing factor.
Relationship between thirst and diazoxide-induced hypotension in rats
Authors: Evered M. D.
Published: December 2017

Diazoxide, a potent vasodilator and antidiuretic, was used to examine the relationship between hypotension and thirst in conscious rats with indwelling arterial and venous catheters. Bolus iv. injections (5-50 mg/kg) caused prompt, long-lasting, and dose-dependent reductions in mean arterial pressure (MAP) and stimulated drinking. Water intake and degree of hypotension were closely correlated when MAP was 10-65 mmHg below normal. At the time of drinking there were no significant changes in central venous pressure, plasma osmolality, or Na+ or K+ concentration. Plasma glucose increased approximately 35%, and blood volume increased approximately 10% (based on hematocrit changes and dilution of Evans blue). Captopril (100 mg/kg sc to block the renin-angiotensin system) enhanced the depressor response to diazoxide but abolished the dipsogenic response over the same range of arterial pressures tested in controls. Angiotensin II iv infusion restored drinking in captopril-treated animals. The combination of captopril and diazoxide did not block drinking to iv infusions of hypertonic saline or water deprivation. These results confirm that hypotension potently stimulates thirst and support the hypothesis that angiotensin II mediates the dipsogenic response in rats.
Central effects of substance P and somatostatin in conscious, streptozotocin-treated rats
Authors: Tomlinson K. C. , Gardiner S. M. , Bennett T.
Published: December 2017

Cardiovascular responses to intracerebroventricular (icv) injections of substance P and somatostatin were measured in Long-Evans and Brattleboro rats treated with streptozotocin (STZ) or saline. Substance P icv evoked similar pressor responses and tachycardia in STZ-treated and saline-treated Long-Evans rats, together with signs of behavioral activation (i.e., arousal). As a group, Brattleboro rats did not respond significantly to icv substance P, although some individual rats showed clear cardiovascular and behavioral responses. These findings may indicate a reduced sensitivity to icv substance P in Brattleboro rats but show no differences attributable to STZ treatment. Hence, diminished pressor responses to icv angiotensin II (observed previously) may be specific to sympathoadrenal activation associated with drinking. Somatostatin caused a pressor effect in saline-treated, but not in STZ-treated, Long-Evans rats, which was probably due to arginine vasopressin (AVP)-mediated mechanisms because it was not present in either saline-treated or STZ-treated Brattleboro rats. Both control and STZ-treated Long-Evans rats showed a bradycardic response to somatostatin that was not seen in Brattleboro rats. These results indicate that different AVP-mediated mechanisms might be responsible for the pressor and bradycardic effects of icv somatostatin. It is possible that impairment of central somatostatin-mediated AVP release contributes to the diminished role of AVP in blood pressure recovery following ganglion blockade in STZ-treated rats described previously.
Interleukin 1 alpha and an interleukin 1 beta fragment are somnogenic
Authors: Obal F. , Opp M. , Cady A. B. , Johannsen L. , Postlethwaite A. E. , Poppleton H. M. , Seyer J. M. , Krueger J. M.
Published: December 2017

The somnogenic activity of interleukin 1 beta (IL-1 beta) has previously been established. Interleukin 1 alpha (IL-1 alpha) is a distinct gene product that possesses similar biological activities. We report here that IL-1 alpha, like IL-1 beta, has the capacity in rabbits to enhance non-rapid-eye-movement sleep, electroencephalographic slow-wave (0.5-3.5 Hz) voltages, and body temperatures and to inhibit rapid-eye-movement sleep. After IL-1 alpha, sleep remained episodic, and at the doses used no abnormal behavior was observed. Several synthetic IL-1 alpha and IL-1 beta peptides were also tested in vivo for somnogenic and pyrogenic activity and in vitro for their ability to stimulate prostaglandin E2 (PGE2) production by fibroblasts and proliferation of T-cells. Only IL-1 beta-(208-240) enhanced non-rapid-eye-movement sleep and body temperature, although both IL-1 beta-(208-240) and IL-1 alpha-(223-250) stimulated PGE2 production; both of these peptides failed to stimulate T-cell production. In contrast, four other IL-1 peptides were nonpyrogenic and somnogenically inactive yet stimulated T-cell proliferation. We conclude that the components of IL-1 required for sleep and temperature activities are different from those required for T-cell proliferation.
Effects of glucoprivation on gastric motility and pituitary oxytocin secretion in rats
Authors: Cato R. K. , Flanagan L. M. , Verbalis J. G. , Stricker E. M.
Published: December 2017

Pharmacological doses of insulin (3-25 U/kg sc) elicited feeding and increased gastric motility in rats. In contrast, the glucose analogue 2-deoxy-D-glucose (2-DG), given ip in doses known to increase food intake, had dose-dependent effects on gastric motility: 100 and 200 mg/kg 2-DG increased gastric motility, whereas 500 mg/kg 2-DG virtually eliminated gastric contractions. This latter result resembled the known effects on gastric motility of cholecystokinin (CCK) and LiCl. Moreover, like CCK and LiCl, 500 mg/kg 2-DG stimulated pituitary oxytocin (OT) secretion, and its effects on gastric motility and OT secretion were potentiated by pretreatment with the opioid antagonist naloxone. In contrast, OT secretion was not affected by insulin-induced hypoglycemia with or without naloxone pretreatment. These results suggest that there are two components to the effects of 2-DG on gastric motility: an insulin-like excitatory component and a CCK-LiCl-like inhibitory component. The latter inhibitory component may be mediated by the paraventricular nucleus of the hypothalamus, which has already been implicated in the inhibitory control of gastric motility.
Characterization of feeding behavior induced by central injection of GRF
Authors: Dickson P. R. , Vaccarino F. J.
Published: December 2017

The behavior resulting from injection of rat hypothalamic growth hormone-releasing factor (GRF) (0, 0.01, 0.1, 1.0 pmol) into the suprachiasmatic nucleus-medial preoptic area (SCN/MPOA) or the paraventricular nucleus (PVN) of the hypothalamus was examined. After injections of GRF, feeding and other behavioral responses of male Wistar rats were observed for 90 min. In the SCN/MPOA, GRF dose dependently increased food intake, increasing mean meal length at 0.1 pmol and increasing rate of eating with no effect on meal length at 1.0 pmol. Other behavioral measures were unaffected by GRF. There was no effect after injections into the PVN. These data are taken as confirmation that the SCN/MPOA region of the hypothalamus is important for the central stimulatory effects of GRF on feeding. The possibility that the PVN is involved in the expression of feeding derived from intra-SCN/MPOA GRF injections is discussed.
Endocrine and fluid-balance responses to amniotic and allantoic fluid loss in sheep
Authors: Dickson K. A. , Hooper S. B. , McMillen I. C. , Harding R.
Published: December 2017

Our aim was to determine fetal and maternal endocrine and fluid-balance responses to prolonged loss of amniotic and allantoic fluids in sheep. In seven sheep, amniotic and allantoic fluids were drained [379.1 +/- 20.1 (SE) ml/day] from 107 to 135.3 +/- 0.6 days of gestation (term: 145 days). The results from these sheep were compared with those from seven control sheep. Maternal water intake, urine production, and urine osmolality were not altered by fluid drainage, nor were fetal and maternal arterial blood gases, pH, or plasma osmolalities. Fluid drainage increased amniotic, but not allantoic, fluid osmolality. Maternal plasma cortisol concentration increased with fluid drainage, but maternal plasma concentrations of prolactin and arginine vasopressin were unchanged. Fluid drainage increased prolactin concentrations in fetal plasma and amniotic fluid, but fetal plasma concentrations of cortisol (hydrocortisone), arginine vasopressin, norepinephrine, and epinephrine were unchanged. Our results show that the fetus is capable of maintaining its plasma osmolality despite prolonged loss of fluid from its amniotic and allantoic sacs and that this is associated with alterations in the production rate and the composition of amniotic fluid.
Functional recovery of the gustatory system after sodium deprivation during development: how much sodium and where
Authors: Przekop P. , Mook D. G. , Hill D. L.
Published: December 2017

Restriction of maternal dietary sodium beginning on or before embryonic day 8 and continued thereafter results in reduced taste responses of the chorda tympani nerve to NaCl in the offspring. The effects of deprivation, however, are reversible. A single ingestive bout of 30 ml isotonic NaCl was sufficient to restore normal sodium taste, and the restorative effects of the single exposure apparently persisted throughout multiple generations of taste receptor cells. Furthermore, the recovery apparently did not depend on direct receptor cell-stimulus interactions. Rats permitted to drink 30 ml of isotonic NaCl, but not allowed to retain it, did not recover normal sodium taste responses, suggesting that factors other than taste stimulation are important in the restorative effects of sodium.
Chronic lymph flow and transcapillary fluid flux during angiotensin II hypertension
Authors: Valenzuela-Rendon J. , Manning R. D.
Published: December 2017

The roles of the transvascular fluid flux and lymph flow in the distribution of extracellular fluid volume during angiotensin II (ANG II) hypertension were evaluated in 11 conscious dogs. Similarly, the factors regulating the distribution of plasma protein across the microvasculature were assessed. By the second day of ANG II infusion, the thoracic duct lymph flow had increased 58% above control, transcapillary fluid flux had increased 45%, and plasma volume, sulfate space, and interstitial fluid volume remained close to control. In addition, the thoracic duct lymph protein transport had increased 34%, and the accompanying increase in transcapillary protein flux prevented any change in plasma protein mass. Also, at this time, the lymph flow and protein transport from subcutaneous tissue in the hind limb were not increased, and the permeability-surface area product of this region decreased 40%. The origin of the increased thoracic duct lymph flow on day 2 probably was from the splanchnic bed. In conclusion, the increased lymph flow during ANG II hypertension compensated for the increase in transcapillary fluid flux, thus preventing edema formation.
Learning to sham feed: behavioral adjustments to loss of physiological postingestional stimuli
Authors: Davis J. D. , Smith G. P.
Published: December 2017

The progressive increase in intake of a concentrated (0.8 M sucrose) solution seen when rats are first exposed to the sham-feeding procedure can be prevented by interspersing two real-feeding tests between each sham-feeding test. Under these conditions, sham intake is significantly larger than real intake but significantly smaller than intake on the fifth consecutive sham-feeding test. This result indicates that there is a learned negative-feedback signal based on the association of the taste and postingestive effects of 0.8 M sucrose which extinguishes under consecutive sham-feeding tests. Analysis of the rate of ingestion during the tests revealed that the conditioned negative-feedback signal operates during the first 6 min of a sham-feeding test that follows real-feeding tests. The effect of the absence of an unconditional negative-feedback signal appears from approximately 6 to approximately 20 min during a sham-feeding test.
Efferent mechanisms mediating renal sodium and water excretion induced by centrally administered serotonin
Authors: Montes R. , Johnson A. K.
Published: December 2017

Treatments that increase central extracellular serotonin (5-HT) also increase Na excretion. Efferent renal sympathetic nerve activity (ERSNA) contributes to the control of Na and water reabsorption. To determine whether renal nerves play a role in the 5-HT-induced natriuresis, we examined the effect of intracerebroventricular (icv) injection of vehicle or 5-HT (20 micrograms) on Na, K, and urine excretion rates, as well as mean arterial pressure and heart rate in unanesthetized, hydrated rats with renal nerves intact or sectioned. Renal denervation attenuated the natriuresis produced by 5-HT but not the antidiuresis observed 15-30 min after injection. Central 5-HT produced brief pressor and bradycardic responses, followed by continued bradycardia and hypotension, which were more pronounced in intact rats. In other experiments, circulating levels of arginine vasopressin (AVP) and plasma atrial natriuretic polypeptide (ANP) were measured 15 min after icv injection of 5-HT. 5-HT significantly increased circulating AVP, but plasma ANP remained unchanged. These results suggest that renal nerves participate in the natriuresis elicited by centrally administered 5-HT through a decrease in ERSNA. The antidiuresis observed after central 5-HT may be due to an increase in AVP release.
Macrophages produce somnogenic and pyrogenic muramyl peptides during digestion of staphylococci
Authors: Johannsen L. , Wecke J. , Obal F. , Krueger J. M.
Published: December 2017

Muramyl peptides have a variety of biological effects in mammals, including enhancement of the immune response, sleep, and body temperature. Although mammals lack biosynthetic pathways for muramyl peptides, they are found in mammals and are well known as components of bacterial cell walls. This suggests that phagocytic mammalian cells digest bacterial cell walls and produce biologically active muramyl peptides. Staphylococcal cell walls were radioactively labeled during growth of the bacteria. During the digestion of these radiolabeled bacteria, murine bone marrow macrophages produced low-molecular-weight substances that coeluted chromatographically with the radioactive cell wall marker. Further separation of these substances using reversed-phase high-performance liquid chromatography resulted in the isolation of substances with high specific biological activity. Intracerebroventricular injection of rabbits with these substances induced an increase in slow-wave sleep and body temperature and a suppression of rapid-eye-movement sleep. The characteristics of the biological responses and the chromatographic behavior of the active components are consistent with those of muramyl peptides. The ability of macrophages to tailor muramyl peptides from peptidoglycan may provide an amplification step for the immune response. Muramyl peptides released by macrophages may also act as mediators for various facets of the acute phase response elicited by bacterial infections such as fever and sleep.
Macronutrient intake and utilization by rats: interactions with type I adrenocorticoid receptor stimulation
Authors: Devenport L. , Knehans A. , Thomas T. , Sundstrom A.
Published: December 2017

Corticosterone-free (adrenalectomized, ADX) and intact rats were offered experimentally compounded diets in which 65% of available calories were supplied by a single macronutrient (single-diet study). ADX impaired the intake, weight gain (especially as body fat), and efficient utilization of high-protein and high-fat diets. In contrast, no behavioral, metabolic, or compositional changes could be found among ADX rats maintained on a diet high in carbohydrates. When ADX rats were given separate sources of macronutrients (self-selection study) they did not self-select a high-carbohydrate diet. Instead, they displayed a strong fat avoidance and a relative increase in protein intake, the macronutrient they utilize least efficiently. Separate groups of ADX animals were continuously infused with 25 or 125 micrograms.kg-1.day-1 aldosterone, a specific type I adrenocorticoid receptor agonist. Type I receptor stimulation eliminated all ADX-related deficiencies found in the single-diet and self-selection studies: caloric intake, feeding efficiency, carcass composition, and macronutrient preferences were restored to or beyond the corresponding values of adrenal-intact rats. The normal rat's ability to ingest and utilize macronutrients optimally is dependent on corticosterone's stimulation of type I receptors.
Fatigue and recovery of rat soleus muscle are influenced by inhibition of an intracellular carbonic anhydrase isoform
Authors: Fremont P. , Riverin H. , Frenette J. , Rogers P. A. , Cote C.
Published: December 2017

Carbonic anhydrase III (CA III; EC 4.2.1.1) is the most abundant cytosolic enzyme in type I skeletal muscle fibers. Methazolamide, a specific CA inhibitor, was used to characterize the effects of inhibiting CA III on the resistance to fatigue and recovery of the rat soleus muscle using a 60-min fatigue protocol performed in vitro at 25 degrees C. Incubation with 10(-3) M methazolamide resulted in a smaller decrease in tension production during the fatigue protocol, thereby increasing the total tension-time integral for the fatigue test. However, the rate and extent of recovery after the test were lower in the experimental group compared with the control group. A similar effect was observed at physiological temperature (35 degrees C). The results indicate that inhibition of CA III significantly influences tension production as early as 30 s into the stimulation protocol. Inhibition of CA III only during the recovery period did not influence the recovery profile, thereby indicating that the impaired recovery was related to the presence of methazolamide during the stimulation period.
Endothelium-derived vasoactive factors and the renal vasculature
Authors: King A. J. , Brenner B. M.
Published: December 2017

The endothelium is now recognized to transduce intravascular hemodynamic and chemical signals into appropriate changes in vascular smooth muscle (VSM) tone. The effector branch of this transduction is due, at least in part, to endothelial release of potent soluble vasoactive mediators. Two such mediators, endothelium-derived relaxing factor (EDRF) and endothelin, have markedly different chemical composition and contrasting effects on VSM tone. EDRF, identified to be nitric oxide or a nitrosothiol, is a vasodilator, whereas endothelin, a 21-amino acid polypeptide, is the most potent vasoconstrictor yet described. Considerable evidence has been amassed to suggest that these molecules play an important role in the regulation of basal renal hemodynamics and in the pathogenesis of acute renal failure. The purpose of this editorial review is to examine the data supporting a role for the endothelium in the regulation of renal hemodynamics in normal and pathological states.
Cholecystokinin-A receptor mediation of food intake in cats
Authors: Bado A. , Durieux C. , Moizo L. , Roques B. P. , Lewin M. J.
Published: December 2017

The selective cholecystokinin (CCK)-B-receptor agonist and antagonist, BC 264 and L 365260, respectively, and the CCK-A-receptor antagonist, L 364718, were used to investigate the possible involvement of different classes of CCK receptors in the control of food intake induced by exogenous CCK octapeptide (CCK-8) in the cat with gastric fistula. Intravenous infusion of CCK-8 dose dependently inhibited milk intake under sham-feeding conditions, maximal inhibition reaching 52 +/- 7% (P less than 0.001) with 0.88 nmol.kg-1.h-1. L 364718 prevented this inhibition, whereas L 365260 was ineffective over the dose range tested. The reversal effect of L 364718 on 0.88 nmol.kg-1.h-1 CCK-8-induced inhibition of milk intake was observed at doses as low as 0.44 nmol.kg-1.h-1. The selective CCK-B-receptor agonist, BC 264, in doses ranging from 0.88 to 7 nmol.kg-1.h-1, had no effect on milk intake under sham-feeding conditions, although it dose dependently stimulated gastric acid output. Furthermore, neither L 364718 nor L 365260 (88 nmol.kg-1.h-1 iv) stimulated milk intake when given in the absence of CCK-8. We conclude that exogenous CCK-8 causes satiety in the cat through activation of peripheral CCK-A receptors.
Effects of pH on phosphate transport by flounder renal tubule primary cultures
Authors: Gupta A. , Renfro J. L.
Published: December 2017

Transepithelial phosphate (Pi) fluxes were determined in primary monolayer cultures of the winter flounder proximal tubule in Ussing chambers. Net Pi secretion, peritubular (P)-to-lumen (L) net flux (Jnet = 17.0 +/- 3.77 nmol.cm-2.h-1), was strongly stimulated by lowering peritubular pH to 6.5 (pHP 6.5 vs. pHL 7.5) compared with control tissues at pH 7.5 (pHP 7.5 vs. pHL 7.5) where net reabsorption (L-to-P Jnet = 1.10 +/- 0.36 nmol.cm-2.h-1) occurred. The stimulation of net secretion by pHP 6.5 was inhibited to 27% of control by 200 microM amiloride. The imposition of a reversed pH gradient (pHL 6.5 vs. pHP 7.5) did not stimulate Pi secretion. Preincubation with 0.5 U/ml phospholipase C caused a nearly fivefold stimulation of Pi secretion compared with the untreated controls. H-7 (100 microM), a protein kinase inhibitor, caused a 2.5-fold reduction in phorbol ester (PE)-induced stimulation of Pi secretion. H-7 also significantly inhibited Pi secretion (50% reduction) when peritubular pH was lowered to 6.5. PE-induced net Pi secretion was significantly lower when luminal pH was lowered to 5.5 compared with controls where luminal pH was kept at 7.5. Amiloride (200 microM) significantly inhibited the PE-induced net Pi secretion in the presence of luminal pH 7.5 but had no significant effect at luminal pH 5.5. Replacement of luminal NaCl with LiCl or isosmolar mannitol significantly reduced net phosphate secretion under the conditions of lowered peritubular pH. Net Pi secretion was also dependent on the maintenance of a cellular Na+ gradient, since 100 microM ouabain inhibited PE-induced net Pi secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic and hemodynamic responses to endogenous and exogenous catecholamines in formerly obese subjects
Authors: Leibel R. L. , Berry E. M. , Hirsch J.
Published: December 2017

Formerly or reduced-obese (RO) subjects exhibit diminished systemic energy requirements for weight maintenance. Based on studies in animals and humans, there is reason to believe that the autonomic nervous system (ANS) plays an important role in coordinate regulation of energy metabolism and may be altered in the RO state. We have, therefore, investigated aspects of autonomic physiology in obese (OB), RO, and never obese (NO) subjects subjected to insulin-mediated hypoglycemia and incremental intravenous infusions of epinephrine. Total catecholamine secretion during insulin-induced hypoglycemia was significantly lower in the RO. The RO showed increased sensitivity to in vivo lipolytic and cardiovascular effects of endogenous and infused catecholamines. In these studies, OB subjects responded more like the NO subjects than did the RO. The RO display characteristic changes in autonomic status that may play a role in their enhanced energy efficiency.
Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans
Authors: Esler M. D. , Wallin G. , Dorward P. K. , Eisenhofer G. , Westerman R. , Meredith I. , Lambert G. , Cox H. S. , Jennings G.
Published: December 2017

In isolated organs, or when given in low dose intra-arterially, tricyclic antidepressant drugs are known to block reuptake of norepinephrine into sympathetic nerve varicosities, with a resultant increased norepinephrine washout. On the other hand, systemic administration of such drugs in humans reduces norepinephrine spillover to plasma. To clarify these seemingly contradictory findings, we have measured concurrently muscle sympathetic activity in the peroneal nerve (microneurography) and rates of norepinephrine spillover to plasma for the body as a whole and for the heart, the kidneys, and the forearm (radiotracer technique), both before and after intravenous infusion of desipramine, 0.5 mg/kg. Desipramine lowered the overflow of norepinephrine to plasma for the body as a whole and from the forearm and the kidneys (by 30-50%) but increased cardiac norepinephrine spillover by 25%. Both the number of sympathetic bursts per min in the peroneal nerve and their mean voltage amplitudes were markedly reduced after desipramine; total activity (bursts/min x mean burst amplitude) fell by approximately 90%. The effects of desipramine on norepinephrine spillover are explicable in terms of inhibition of central sympathetic outflow, balanced against the local blockade of transmitter reuptake. In most sites, the predominant effect is a reduction of norepinephrine overflow. For the heart, where reuptake is so important in transmitter disposition, the net effect is increased overflow.
Characterization of angiotensin receptors mediating prostaglandin synthesis in C6 glioma cells
Authors: Jaiswal N. , Diz D. I. , Tallant E. A. , Khosla M. C. , Ferrario C. M.
Published: December 2017

The heptapeptide angiotensin (ANG)-(1-7) mimics some but not all the central actions of ANG II, suggesting that receptor subtypes may exist. The effects of ANG-(1-7), ANG II, and ANG I on prostaglandin (PG) E2 and prostacyclin (PGI2) synthesis were investigated in neurally derived rat C6 glioma cells. All three ANG peptides stimulated PG release in a dose-dependent manner with the order of potency ANG-(1-7) greater than ANG I greater than ANG II. PGE2 release induced by ANG-(1-7) (10(-7) M) was partially blocked by [Sar1,Ile8]ANG II (10(-6) M), [Sar1,Thr8]ANG II (10(-6) M), or the subtype 1 selective antagonist Du Pont 753 (10(-5) M) but not by the subtype 2 selective antagonist CGP 42112A (10(-7)-10(-5) M). PGI2 release was inhibited only by [Sar1,Thr8]ANG II. ANG II-induced PGE2 release was blocked by [Sar1,Thr8]ANG II (10(-6) M), [Sar1,Ile8]ANG II (10(-6) M), or Du Pont 753 (10(-7) M) but not by CGP 42112A (10(-7)-10(-5) M). In contrast, ANG II-induced PGI2 release was blocked by Du Pont 753 (10(-7) M) as well as [Sar1,Ile8]ANG II (10(-6) M) but not by [Sar1,Thr8]ANG II or CGP 42112A. Thus ANG II-stimulated PGE2 and PGI2 syntheses in C6 glioma cells are mediated via receptor subtype 1. ANG-(1-7)-induced PGE2 synthesis is also mediated via subtype 1 receptors; however, PGI2 release was blocked by [Sar1,Thr8]ANG II only.(ABSTRACT TRUNCATED AT 250 WORDS)