bluuebunny/crossref_metadata_2025 huggingface dataset:
Human IL-1 receptor antagonist partially suppresses LPS fever but not plasma levels of IL-6 in Fischer rats
Authors: Smith B. K. , Kluger M. J.
Published: December 2017

A human recombinant interleukin-1 receptor antagonist (IL-1ra) recognizes the two known IL-1 receptors and blocks the binding and many biological effects of both IL-1 alpha and IL-1 beta. The effectiveness of IL-1ra in modifying the fever and plasma IL-6 responses elicited by lipopolysaccharide (LPS) in vivo was tested in Fischer 344 rats. Animals that received IL-1ra 0.5 mg/kg intraperitoneally followed 10 min later by 10 micrograms/kg of LPS displayed significantly lower mean fever responses 2-4 h after injection than rats that received vehicle and LPS (0.48 +/- 0.13 vs. 0.95 +/- 0.16 degrees C, P = 0.016). Plasma levels of IL-6 at 4 h after injection were not different in IL-1ra-treated rats compared with controls (407,725 vs. 729,169 U/ml). Based on our previous finding that preadministration of antiserum to IL-1 beta markedly suppressed plasma IL-6 after LPS, and recent evidence that molar excesses of IL-1ra blocked IL-1-induced circulating IL-6 levels, the possibility that IL-1 is responsible for the induction of bioactive IL-6 during inflammation cannot be ruled out. Similarly, the inability of the IL-1ra to completely suppress the febrile responses of rats to LPS in the present study may be dose related. Alternatively, the induction of bioactive IL-6 by IL-1 in the rat may be mediated primarily through some receptor other than the type I (e.g., the type II receptor).
Hypoxia attenuates the renin response to hemorrhage
Authors: Eichinger M. R. , Claybaugh J. R.
Published: December 2017

We studied hypoxia and hypotensive hemorrhage in conscious female goats. After control, goats continued an experimental period in normoxia or hypoxia [fractional inspired oxygen concentration (FIO2) = 0.10] for 120 min. After 60 min in the experimental period, a hemorrhage (0.5 ml.kg-1.min-1 for 30 min) was initiated (normoxic hemorrhage, NH; hypoxic hemorrhage, HH). Heart rate (HR) increased 51 +/- 18 beats/min with NH after 30 min of hemorrhage. HR increased 40 +/- 10 beats/min after hypoxic gas introduction, with no further increase during HH. Mean arterial blood pressure (MABP) was reduced 23 +/- 7 mmHg 30 min after completion of blood loss with normoxia but was reduced 23 +/- 7 mmHg at 20 min of HH. Arginine vasopressin (AVP) was increased to 2.60 +/- 2.08 and 160.40 +/- 49.74 microU/ml after 10 and 20 min of HH, respectively, and was only increased after 30 min (87.33 +/- 67.18 microU/ml) of NH. Unexpectedly, plasma renin activity (PRA) increased in parallel in both groups and was doubled at 30 min of hemorrhage. Atrial natriuretic factor was reduced to 8.8 +/- 1.6 pg/ml by 10 min of NH and to 11.4 +/- 3.3 pg/ml at 30 min of HH. Thus hypoxia leads to an earlier development of hypotension and increase in AVP with blood loss but may attenuate the PRA response to blood pressure reduction.
Determining energy expenditure in preterm infants: comparison of 2H(2)18O method and indirect calorimetry
Authors: Jensen C. L. , Butte N. F. , Wong W. W. , Moon J. K.
Published: December 2017

The doubly labeled water (2H(2)18O) method used to estimate total energy expenditure (EETotal) is particularly sensitive to analytic error in preterm infants, because of their high percentage of body water and the high ratio of water flux to CO2 production. To evaluate further use of this method, the EE of 12 preterm infants was measured by indirect calorimetry and 2H(2)18O simultaneously and continuously for 5 days. Initial infant weight, age, and postconceptional age were (means +/- SD) 1,674 +/- 173 g, 4.4 +/- 2.6 wk, and 34.6 +/- 1.6 wk, respectively. The indirect calorimeter system included an air-temperature-controlled chamber and heart rate monitor. EE was measured by indirect calorimetry for 85.6 +/- 4.7% of study time and estimated from the linear regression of heart rate on EE for 14.4 +/- 4.7% of study time. The 2H(2)18O method entailed an initial dose of 100 mg 2H2O and 250 mg 18O/kg and a final dose of 75 mg 18O/kg; urine was collected twice daily. 2H and 18O enrichments were measured by gas-isotope-ratio mass spectrometry. EE was calculated from measured 2H and 18O dilution spaces (NH, NO), turnover rates (kH, kO), and measured respiratory quotient. The ratio of 2H to 18O dilution spaces was 1.01 +/- 0.01 and the ratio of kO to kH was 1.16 +/- 0.04. Estimation of EE from 2H(2)18O and indirect calorimetry agreed within 1%, although individual variability in methods was large.
Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha and TNF-alpha fragments
Authors: Kapas L. , Hong L. , Cady A. B. , Opp M. R. , Postlethwaite A. E. , Seyer J. M. , Krueger J. M.
Published: December 2017

Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of generalized infections such as fever, increased sleep, and anorexia. The aim of the present work was to localize these effects of TNF-alpha to specific amino acid sequences of the parent molecule by characterizing the in vivo and in vitro activities of several synthetic TNF-alpha fragments. Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited monophasic fevers. All of the somnogenic fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF-alpha increased the expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell line. In contrast, none of the fragments possessed these in vitro activities. Our in vivo results support the concept that there are biologically active regions in the TNF-alpha molecule.
Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis
Authors: Weglicki W. B. , Phillips T. M.
Published: December 2017

During the progression of Mg deficiency in a rodent model, we have observed dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk on a Mg-deficient diet. Sequential analyses of these cytokine changes in the serum of rats revealed an initial rise at day 12, followed by a major elevation in all three cytokine levels by day 21. Of greater interest was an early peak in the serum level of the neuropeptide substance P after only 5 days on the diet. This “neuronal” tachykinin is thought to be released from neural tissues, and it is known to stimulate production of certain cytokines, including IL-1, IL-6, and TNF-alpha. In addition, there was a concomitant increase in histamine levels, which may have resulted from stimulation and degranulation of mast cells by substance P. Thus we hypothesize that the release of substance P may be the earliest pathophysiological event leading to stimulation of the inflammatory cytokines, which may then stimulate the free radical mechanisms of injury previously confirmed by our work.
Whole body insulin sensitivity in Osborne-Mendel and S 5B/Pl rats eating a low- or high-fat diet
Authors: Buchanan T. A. , Fisler J. S. , Underberger S. , Sipos G. F. , Bray G. A.
Published: December 2017

To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high-fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic effects of central angiotensin I, II, and III in conscious rabbits
Authors: Head G. A. , Williams N. S.
Published: December 2017

We have examined the hemodynamic effects of intraventricular angiotensins in conscious rabbits. Fourth ventricular injections of angiotensin II (ANG II, 8 fmol to 25 pmol) produced dose-dependent pressor responses at doses 400 times less than equipressor intravenous doses. Lateral ventricle administration of doses up to 1,000 pmol had little effect on mean arterial pressure (maximum +7 +/- 3 mmHg, P < 0.05, n = 9). Comparison of dose-response curves to ANG I, II, and III showed that all three had similar maximum pressor effects (27 +/- 3 mmHg), with ANG I being four times less potent than ANG II, and ANG III as potent as ANG II. Central pretreatment with the ANG-converting enzyme inhibitor enalapril abolished the pressor response to ANG I, suggesting that it was mediated entirely through ANG II. Examination of the hemodynamic changes after ANG I, II, and III in rabbits instrumented with aortic, mesenteric, or hindquarter flow probes showed that the rise in blood pressure to all three agents was due entirely to a decrease in total peripheral conductance, since cardiac output and heart rate fell. Peripheral conductance changes were not uniform, with the mesenteric bed showing an average 20 +/- 3% fall in conductance, while the hindquarter conductance increased (+12 +/- 3%). In sinoaortic-denervated rabbits, however, central angiotensins reduced conductance equally in the hindlimb and mesenteric beds, suggesting that the hindlimb dilatation in the baroreceptor intact rabbit was due to baroreflex buffering of the pressor effect. In conclusion, these studies suggest that the main sites for ANG effects on the cardiovascular system are located in the brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)
Intraventricular CCK-8 reduces single meal size in the baboon by interaction with type-A CCK receptors
Authors: Figlewicz D. P. , Nadzan A. M. , Sipols A. J. , Green P. K. , Liddle R. A. , Porte D. , Woods S. C.
Published: December 2017

Intraventricular cholecystokinin COOH-terminal octapeptide (CCK-8) decreases meal size in the meal-trained baboon. In the present study, we tested whether this action is mediated by CCK-A receptors, CCK-B receptors, or both. Intraventricular administration of the selective CCK-A receptor agonist A71623 at 1 and 10 nmol/kg suppressed 30-min meal size 69 +/- 22% and 75 +/- 7%, respectively. Additionally, intraventricular A71623 was equipotent to CCK-8 at 1 nmol/kg (% suppression of meal by CCK = 59 +/- 17). However, intraventricular administration of the CCK-B receptor agonist A63387 at 10 nmol/kg had no effect on 30-min meal size (% suppression = 18 +/- 29). Intravenous administration of 10 nmol/kg A71623 did not result in an alteration of meal size, but prandial plasma insulin and glucose responses were delayed and blunted. Basal plasma insulin levels doubled after intravenous administration of A71623. Both behavioral and metabolic responses to A71623 in the baboon are virtually identical to those we have previously observed after CCK-8 treatment. Thus we conclude that the predominant receptor population with which intraventricular CCK-8 interacts are type-A CCK receptors that are accessible to the ventricular system of the baboon.
Ontogeny of renal response to specific dopamine DA1-receptor stimulation in sheep
Authors: Segar J. L. , Smith F. G. , Guillery E. N. , Jose P. A. , Robillard J. E.
Published: December 2017

The present study was designed to characterize the developmental changes in the renal responses to dopamine DA1-receptor activation in chronically instrumented preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting that the effect of fenoldopam on MABP was not directly related to activation of DA1-receptors. Fenoldopam infusion had no significant effects on renal function parameters in preterm fetuses. In near-term fetuses, however, fenoldopam increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion had no significant effects on plasma renin activity and plasma aldosterone concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and 6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect of DA1-receptor activation is age dependent and that stimulation of DA1-receptor in near-term fetuses is associated with a diuresis and natriuresis that seem to be independent of renal hemodynamics and adrenal effects.
Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma
Authors: Faden A. I. , Tzendzalian P. A.
Published: December 2017

Tissue damage after traumatic brain injury (TBI) results in part from delayed biochemical changes initiated by the insult. Platelet-activating factor (PAF) is an alkylphospholipid that has been implicated in tissue damage after cerebral ischemia. PAF is toxic to certain neuronal cell lines in culture, reduces cerebral blood flow, alters the blood-brain barrier, and can enhance phospholipid hydrolysis. The recent development of receptor antagonists to PAF permits examination of its possible role in delayed tissue injury after neurotrauma. Treatment with the PAF receptor antagonists BN 52021 and WEB 2170 before injury significantly enhanced neurological recovery after fluid percussion-induced TBI in rats. Pretreatment with WEB 2170 also significantly limited alterations in tissue water content and tissue glycine levels after trauma, and reduced posttraumatic levels of extracellular glycine in ipsilateral hippocampus. These findings implicate PAF in the pathophysiology of TBI, through actions at PAF receptors. A possible role for glycine in this process is suggested.
Irradiance responsivity and unequivocal type-1 phase responsivity of rat circadian activity rhythms
Authors: Bauer M. S.
Published: December 2017

Behavioral, neuropharmacological, and molecular studies of light-induced phase shifting of rodent circadian rhythms evaluate carefully the phase dependence of light responsivity. However, much less information is available regarding the dependence of such effects on the duration and irradiance of the photic stimulus used. In this study, very brief (5-min) white light pulses of 50 microW/cm2 (175 lux) administered to hooded rats elicited unequivocal type-1 phase responsivity, without significant changes in period, and with phase shift variability comparable to that in studies using longer, higher intensity pulses. Irradiance dependence was demonstrated in the phase-delay, phase-advance, and crossover portions of the phase-response curve, with minimal phase shifting seen during the dead zone even at very high irradiance. These results indicate that maximal phase-shifting magnitude may be achieved with shorter, less intense photic stimuli than are often used in studies of the neural mechanisms involved in light responsivity of rat circadian rhythms.
Intrarenal pressures during direct inhibition of sodium transport
Authors: Khraibi A. A. , Granger J. P. , Haas J. A. , Burnett J. C. , Knox F. G.
Published: December 2017

Renal interstitial hydrostatic pressure (RIHP) has been implicated in the regulation of sodium excretion. Studies using vasodilators and other maneuvers to increase RIHP have found a significant correlation between RIHP and sodium excretion. Since correlative studies do not prove a cause-and-effect relationship, it is not known whether the rise in sodium excretion in these studies is the result of increases in RIHP or if RIHP is elevated as a result of decreases in sodium and water reabsorption and increases in intratubular pressure. Therefore, the purpose of the present study was to determine whether elevation of intratubular hydrostatic pressures in response to direct inhibition of tubule transport with loop diuretics results in increases in RIHP in dogs and rats. Intrarenal hydrostatic pressures, renal hemodynamics, and sodium and water excretion were examined in dogs during intravenous administration of furosemide (3 mg/kg bolus followed by 0.03 mg.kg-1 x min-1) or bumetanide (60 micrograms/kg bolus followed by 1 microgram.kg-1 x min-1). Furosemide administration increased urinary flow rate (V; 0.10 +/- 0.02 to 4.6 +/- 0.97 ml/min), urinary sodium excretion (UNaV; 16 +/- 5 to 549 +/- 123 mu eq/min), and proximal tubule hydrostatic pressure (PT; 21 +/- 1 to 28 +/- 1 mmHg) but had no effect on RIHP (7.2 +/- 0.6 to 7.4 +/- 0.7 mmHg) or peritubular capillary hydrostatic pressure (14 +/- 1 to 14 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin-induced suppression of renal sympathetic outflow depends on the number of baroafferent inputs in rabbits
Authors: Nishida Y. , Bishop V. S.
Published: December 2017

We tested the hypothesis that the inhibitory action of arginine vasopressin (AVP) on renal sympathetic nerve activity (RSNA) is related to the number of baroreceptor stations. The role of baroreceptor afferents was determined by comparing the effects of AVP on the baroreflex function curves [mean arterial pressure (MAP) vs. %RSNA] obtained in intact conscious rabbits with those obtained in rabbits with one carotid sinus and one aortic nerve intact (1CSN + 1AoN) and in rabbits with only a single carotid sinus nerve intact (1CSN). Baroreflex curves were obtained by relating %RSNA to MAP during ramp increases and decreases in MAP. MAP was increased with phenylephrine and decreased with caval occlusion. In the intact state (n = 7), AVP infusions (0.4, 1.5, and 3.0 mU.kg-1 x min-1) produced dose-dependent reduction in the maximum %RSNA (97 +/- 1 to 85 +/- 6, 68 +/- 6, and 57 +/- 5%, respectively) at minimum MAP and the gain of the baroreflex curve (5.7 +/- 0.2 to 3.9 +/- 0.2, 3.2 +/- 0.3, and 2.2 +/- 0.2 mmHg, respectively) and shifted the midrange of the curves (72 +/- 3 to 68 +/- 4, 68 +/- 2, and 63 +/- 3 mmHg, respectively). However, in the 1CSN + 1AoN state (n = 6), the medium dose of AVP (1.5 mU.kg-1 x min-1) did not significantly alter the maximum %RSNA, the gain of the curve, or the midrange of the curve. The highest dose of AVP (3.0 mU.kg-1 x min-1) still reduced the maximum %RSNA (98 +/- 3 to 75 +/- 3) and the gain of the curve (4.1 +/- 0.4 to 2.7 +/- 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of ventromedial hypothalamic stimulation on glucose transport system in rat tissues
Authors: Takahashi A. , Sudo M. , Minokoshi Y. , Shimazu T.
Published: December 2017

Electrical stimulation of the ventromedial hypothalamus (VMH) increased the rate constant of glucose uptake in rat heart and brown adipose tissue (BAT), as measured in vivo by the 2-deoxy-D-[3H]glucose method. The increase in glucose uptake in BAT was abolished by local sympathetic denervation. To analyze the mechanism of this hypothalamic modulation, the effects of VMH stimulation and insulin treatment on the number and dissociation constant (Kd) of glucose transporters in the plasma and microsomal membranes were examined by means of [3H]cytochalasin B binding. VMH stimulation did not alter either the number or Kd value of glucose transporters in plasma and microsomal membranes prepared from heart and BAT, whereas insulin treatment increased the number of glucose transporters in the plasma membranes and decreased those in the microsomal membranes. D-Glucose transport activity was also measured with the same plasma membrane vesicles. An apparent functional activity of transporters was detected to be increased in the heart and BAT plasma membranes after VMH stimulation but not after insulin treatment. These results suggest that VMH stimulation enhances glucose utilization in heart and BAT via sympathetic innervation and that the mechanism by which VMH stimulation increases tissue glucose uptake is different from that of insulin, possibly causing an activation of glucose transporters present in the plasma membrane.
Do renal nerves chronically influence renal function and arterial pressure in spinal rats?
Authors: Trostel K. A. , Osborn J. W.
Published: December 2017

Previous studies have demonstrated that renal nerve activity has acute effects on renal function in rats with cervical spinal cord transection (CST). The present study tested the hypothesis that renal nerves chronically influence renal and cardiovascular function in CST rats. Three groups of conscious Sprague-Dawley rats were studied: renal denervated plus CST (RDNX + CST), sham RDNX plus CST (sham + CST), and sham RDNX plus sham CST (intact). CST or sham CST surgeries were performed 8 days after RDNX or sham RDNX. Sodium and water intakes were fixed by intravenous infusion. Mean arterial pressure (MAP) and plasma renin activity (PRA) were measured before and for 9 days after CST/sham CST. In addition, urine flow, urinary sodium excretion, and urine pH were measured in the two groups of CST rats. One day after CST, MAP decreased approximately 25 mmHg in both RDNX + CST and sham + CST groups. PRA had fallen approximately 50% 1 day after CST and was not different between CST groups. PRA remained depressed throughout the study. There were no differences between sham + CST and RDNX + CST rats in any of the renal or cardiovascular variables measured after CST. In summary, we found no evidence for a chronic effect of renal nerves on renal function or arterial pressure in CST rats.
In vivo longitudinal variations in protein synthesis in developing ovine intestines
Authors: Attaix D. , Aurousseau E. , Rosolowska-Huszcz D. , Bayle G. , Arnal M.
Published: December 2017

Changes in fractional rates of protein synthesis (Ks) were investigated at different small and large intestinal sites in 1-, 5-, and 8-wk-old milk-fed and 8-wk-old weaned lambs, a species with early intestinal maturation similar to most domestic animals and humans, with the use of a flooding dose of L-[3H]valine. Between 1 and 8 wk of age, Ks did not change significantly in the duodenum, the cecum, or the colon of milk-fed lambs, but was depressed by 30% in the jejunum and by 39% in the ileum. This was because of reduced ribosomal capacity, i.e., total RNA-to-protein ratio (Cs) in the jejunum, and also alterations in both Cs and protein synthetic efficiency, i.e., rate of synthesis relative to RNA (KRNA) in the ileum. Ks values throughout the small intestine were significantly higher (45-55%) in weaned lambs than in 8-wk-old milk-fed animals. This enhancement of protein synthesis was mainly related to an increase in KRNA (27-40%). Ks decreased by 43% from the duodenum to the ileum in both milk-fed and weaned 8-wk-old animals, but not in 1- and 5-wk-old milk-fed lambs, because of a marked reduction in KRNA. It was concluded that changes in nutrients at weaning, weaning itself, or both, enhanced protein synthesis without any specific effect on small intestinal site. By contrast, intrinsic developmental factors were responsible only for the regional differences in small intestinal Ks that occurred at 8 wk of age. Longitudinal variations in protein synthesis may contribute to the establishment of the well-recognized jejunoileal gradients of brush-border enzymes and villus height that characterize the mature mammalian small intestine.
Effect of beta-endorphin on sympathetic nerve activity to interscapular brown adipose tissue
Authors: Egawa M. , Yoshimatsu H. , Bray G. A.
Published: December 2017

beta-Endorphin was injected into the third cerebroventricle to investigate its effects on sympathetic nerve activity to interscapular brown adipose tissue (IBAT) in rats. Multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically in anesthetized rats. The intracerebroventricular injection of beta-endorphin (125, 250, and 500 pmol/rat in 10 microliters) suppressed sympathetic nerve activity in a dose-related fashion (-23.9 +/- 20.4, -38.7 +/- 7.1, and -66.7 +/- 7.6% 30 min after injection) compared with preinjection baseline. N-acetyl-beta-endorphin (250 pmol) had no effect on sympathetic nerve activity to IBAT. The intraperitoneal injection of naloxone (5.0 mg/rat) did not affect sympathetic nerve activity, but preinjection of naloxone inhibited the suppressive effect of intracerebroventricular injection of beta-endorphin (250 pmol). We conclude that the intracerebroventricular administration of beta-endorphin suppressed the sympathetic nerve activity to IBAT through opioid receptors. The results of this experiment are consistent with the hypothesis that beta-endorphin has a reciprocal effect on food intake and the sympathetic nervous system.
Suppression by central AVP of prostaglandin E1 hyperthermia in one-kidney, one-clip Goldblatt hypertensive rats
Authors: Fyda D. , Veale W. , Pittman Q.
Published: December 2017

We have investigated the ability of the one-kidney, one-clip (1K,1C) hypertensive rat to develop a hyperthermic response to intracerebroventricular injection of prostaglandin (PG) E1. Accordingly, core temperature was monitored in response to PGE1 injections both preoperatively and on days 4, 8, 12, and 18 after either unilateral nephrectomy or the induction of hypertension due to nephrectomy plus renal artery clipping. Temperature responses to PGE1 were similar throughout each test day in normotensive, unilaterally nephrectomized control rats. In contrast, 1K,1C rats became hypertensive within 4 days of renal artery clipping, and at this time the hyperthermic response to PGE1 was virtually abolished. A reduced hyperthermic response was also seen at 8 and 12 days after clipping; by 18 days responses were again similar to controls. To determine whether central arginine vasopressin (AVP) was involved in the suppression of the hyperthermic response, we pretreated other hypertensive rats centrally with the V1-AVP antagonist [d(CH2)5Tyr(Me)]AVP before PGE1 injection. In 1K,1C animals thus treated, temperature responses 4-12 days after clipping were indistinguishable from those of similarly treated normotensive control rats. We suggest that the reduced hyperthermic responses to PGE1 seen in the 1K,1C rats during the initial development of hypertension may be due to activation of brain AVP pathways.
Effects of alpha- and beta-adrenergic antagonists on rise in body temperature induced by psychological stress in rats
Authors: Nakamori T. , Morimoto A. , Morimoto K. , Tan N. , Murakami N.
Published: December 2017

We investigated the effects of intraperitoneal injection of alpha- and beta-adrenergic antagonists on psychological stress-induced responses in free-moving rats. Psychological stress was induced by immersion in 2-cm-deep water. The intraperitoneal injection of the alpha-adrenergic blocker, phentolamine (10 mg/kg), attenuated the stress-induced rise in body temperature and hypertension but enhanced tachycardia. In contrast, intraperitoneal injection of the beta-adrenergic blocker, propranolol (1 mg/kg), suppressed tachycardia but had no effect on rise in body temperature and hypertension during stress. The intraperitoneal injection of both blockers had no effect on the increase in metabolic rate (O2 consumption) induced by stress. The intravenous injection of propranolol (1 mg/kg) suppressed the stress-induced rise in body temperature. We then examined the effect of intracerebroventricular injection of propranolol on the stress-induced rise in body temperature and found that intracerebroventricular injection of propranolol (50 micrograms) suppressed the stress-induced rise in body temperature. These results support the following hypotheses: 1) Systemic injection of phentolamine suppresses the psychological stress-induced rise in body temperature by facilitating heat-loss; 2) Peripheral beta-adrenergic stimulation probably does not contribute to psychological stress-induced rises in body temperature; and 3) central beta-adrenergic receptors are important in stress-induced increases in body temperature.
HPA axis responses to acute stress and adrenalectomy during adjuvant-induced arthritis in the rat
Authors: Harbuz M. S. , Rees R. G. , Lightman S. L.
Published: December 2017

Adjuvant-induced arthritis results in chronic activation of the hypothalamo-pituitary-adrenal (HPA) axis. In the Piebald-Viral-Glaxo (PVG) rat, however, corticotropin-releasing factor (CRF) mRNA in the parvocellular paraventricular nucleus (pPVN) of the hypothalamus was reduced, and the normal corticosterone and CRF mRNA responses to acute stress were inhibited. The proenkephalin A mRNA response to stress in the pPVN was maintained, implying a specific inhibition of the CRF mRNA responses in this pathological situation. Adrenalectomy at day 0 (the time of adjuvant injection), day 13 (just before inflammation), or day 19 (submaximal inflammation) resulted in a marked increase in CRF mRNA compared with day 21 adrenal-intact arthritic animals. However, levels were below those of nonarthritic adrenalectomized rats, demonstrating that the inhibition of CRF mRNA associated with arthritis is not simply due to changes in glucocorticoid feedback. Proopiomelanocortin mRNA in the anterior pituitary was markedly increased in all adrenalectomized arthritic animals above the increase seen in sham-adrenalectomized day-21 arthritic rats. Adrenalectomy was always associated with an increase in the severity of the disease.
Gastric branch vagotomy blocks nutrient and cholecystokinin-induced suppression of gastric emptying
Authors: Schwartz G. J. , Berkow G. , McHugh P. R. , Moran T. H.
Published: December 2017

Pages R630–R637: G. J. Schwartz, G. Berkow, P. R. McHugh, and T. H. Moran. “Gastric branch vagotomy blocks nutrient and cholecystokinin-induced suppression of gastric emptying.” Page R361: An incorrect formula was used to calculate the volume remaining. The correct formula appears below.

V = (Cs/Ci){[5/(1 – Co/Cs)] – 5}

where Cs, is the concentration of dye in the stomach before saline rinse. The other factors remain as described in the article. This error resulted in a small underestimation of the magnitude of the reported phenomena in a few cases and does not alter the main findings, conclusions, or interpretations of this study.
Brain sensitivity to anoxia in fish as reflected by changes in extracellular K+ activity
Authors: Nilsson G. E. , Perez-Pinzon M. , Dimberg K. , Winberg S.
Published: December 2017

Most vertebrates have a very limited tolerance to anoxia. The only exceptions to this rule are found among ectothermic species, notably crucian carp (Carassius carassius) and freshwater turtles. It has been assumed that the brains of these species are less sensitive to anoxia than ectothermic brains in general. However, it has not been possible to exclude that anoxia-intolerant species like rainbow trout (Oncorhynchus mykiss) die from heart failure rather than brain failure during anoxia, and that the average ectothermic brain is actually rather insensitive to anoxia. By simultaneously measuring the effect of anoxia on brain extracellular K+ activity ([K+]o), blood pressure, and heart rate in rainbow trout, we show that the rainbow trout brain rapidly loses ion homeostasis during anoxia, despite an initial increase in blood pressure. The rainbow trout brain showed a sudden transient increase in [K+]o (suggesting a rapid depolarization) after approximately 30 min of anoxia at 10 degrees C. At the same time the blood pressure was still close to the normoxic value. In a comparative experiment, crucian carp was found to maintain a low brain [K+]o for at least 6 h of anoxia. Thus the results suggest that the rainbow trout brain is anoxia-intolerant in itself, and that its ability to maintain ion gradients during anoxia is very much lower than that of crucian carp. If temperature differences are taken into account, the anoxia sensitivity of the rainbow trout brain is comparable to that of mammals.
Role of somatostatin in glucose regulation during endotoxicosis in the rat
Authors: Yelich M. R. , Umporowicz D. M. , Drolet B. A.
Published: December 2017

This study assessed the role of somatostatin in regulating glucose homeostasis during endotoxicosis in the rat. Plasma levels of somatostatin, glucose, lactate, insulin, and glucagon were measured in control and endotoxin-treated rats. Cysteamine was used to block endogenous somatostatin release before endotoxin treatment. Early during the course of endotoxicosis, plasma levels of somatostatin-like immunoreactivity (SLI) were significantly elevated along with glucose, lactate, insulin, and glucagon. Pretreatment of endotoxic rats with cysteamine virtually blocked the elevated SLI levels and prevented the early appearance of hyperglycemia. Endotoxin-induced increases in lactic acid and glucagon levels were attenuated by cysteamine pretreatment, but elevated insulin levels were not appreciably altered. Elevated somatostatin levels appeared to support the occurrence of the early hyperglycemia and prevent the development of late hypoglycemia during endotoxicosis by sustaining elevated glucagon levels and thus facilitating the maintenance of glucose levels. The results suggest that somatostatin plays a significant role in the glucoregulatory response to endotoxicosis. Endotoxicosis may alter the relative "physiological" ability of somatostatin to inhibit the secretion of insulin and glucagon.
A natriuretic factor is released by saline infusion into rat renal artery
Authors: Bullivant E. M. , Munoz D. J.
Published: December 2017

Saline (154 mM NaCl) infused into one renal artery of anesthetized rats produced a prompt and substantial increase in sodium excretion without significant alteration of arterial pressure, renal blood flow, or glomerular filtration rate. A 1-h infusion at rates of 0.0375, 0.05, or 0.1 ml/min increased sodium excretion by the infused kidney from 0.15 +/- 0.04 to 0.70 +/- 0.12, from 0.45 +/- 0.10 to 2.17 +/- 0.40, and from 0.27 +/- 0.06 to 4.29 +/- 0.80 mumol/min, respectively. Natriuresis also occurred in the contralateral kidney. No comparable responses resulted from infusions at 0.0375 ml/min into the jugular vein, inferior vena cava, or carotid artery. Cross-circulation of blood from infused rats increased sodium excretion in uninfused recipients from 0.36 +/- 0.11 to 1.43 +/- 0.43 mumol.min-1.kidney-1. Isovolemic exchange-transfusion of blood from infused donor rats increased sodium excretion in uninfused recipients from 0.30 +/- 0.05 to 0.51 +/- 0.09 mumol.min-1.kidney-1. In both experiments, aortic infusions below the renal artery produced no comparable effect in recipient rats. Infusion of 300 mM glucose was not natriuretic. Infusion of two NaCl loads, 5.8 and 15.4 mumol/min, each at two different rates, increased sodium excretion in proportion to the load of NaCl and not to the rate of infusion. Infusions of a protein-free artificial rat plasma or of 140 mM NaCl, both with the sodium concentration of rat plasma, produced very little increase in sodium excretion. Infusion of 154 mM sodium lactate produced an increase in sodium excretion comparable to that produced by 154 mM NaCl. Reducing the infusion rate of 154 mM NaCl from 0.05 to 0.01 ml/min produced a rapid decline in the rate of sodium excretion. We conclude that renal arterial saline infusion activates a mechanism that increases sodium excretion by the infused kidney and concurrently causes the release of a natriuretic factor. Increased sodium concentration in renal arterial blood was the only stimulus found to produce the effect.
Evaluation of renal hormones in natriuresis induced by renal arterial saline infusion
Authors: Bullivant E. M. , Munoz D. J.
Published: December 2017

Low rates of unilateral renal arterial infusion with isotonic saline (154 mM NaCl) produce a natriuresis in both kidneys in anesthetized rats, with the involvement of a blood-borne factor. We investigated whether this response was modulated by known renal or adrenal hormones. The response to saline infusion at 0.05 ml/min was tested after acute adrenalectomy (n = 7), in the presence of various blocking agents [captopril (3 mg.kg-1.h-1, n = 7), indomethacin (5 mg/kg, n = 8), aprotinin (25 KIU/min, n = 8), propranolol (1 micrograms/min, n = 6), or benserazide (15 micrograms/min, n = 6)], and after lignocaine infusion around the renal artery (12.5 micrograms/min, n = 5). In all cases, the overall increase in sodium excretion by both kidneys was not significantly less (alpha < or = 0.01) than that in untreated rats; it was increased by aprotinin, renal nerve blockade, and propranolol. Plasma levels of angiotensin II, aldosterone, and atrial natriuretic peptide were unchanged by renal arterial saline infusion. We conclude that the saline-induced natriuresis is not reduced by inhibition of the production of angiotensin II, prostaglandins, kinins, dopamine, or adrenal hormones, or by factors released by the renal nerves, indicating that none of these is directly responsible for the saline-induced natriuresis.
Intravenous infusion of bombesin reduces food intake in humans
Authors: Muurahainen N. E. , Kissileff H. R. , Pi-Sunyer F. X.
Published: December 2017

Infusion of bombesin into healthy young men at two dosages (1.33 and 4.0 ng.kg-1.min-1) resulted in a significant 135-g reduction in intake of a yogurt and fruit blend, compared with saline infusions, at the higher dose, but only a 20-g (nonsignificant) reduction at the lower dose. There were no overt side effects, although half of the subjects reported a slightly elevated (mean elevation = 0.5 on a 1-5 category scale) sick sensation when receiving bombesin at the higher dose, but not when receiving saline. At the higher dose, the mean palatability of the test meal was reduced by 0.5 units on a nine-point scale of liking. This study demonstrates for the first time in humans that a slow intravenous infusion of bombesin can decrease spontaneous food intake when infused at the rate of 4 ng.kg-1.min-1 beginning at the onset of a meal. These results confirm that the short-term satiety effect of peripherally administered bombesin previously reported in animals can be obtained in humans.
Independence of salt intake induced by calcium deprivation from the renin-angiotensin-aldosterone system
Authors: Tordoff M. G. , Pilchak D. M. , Hughes R. L.
Published: December 2017

We investigated whether the elevated NaCl intake shown by calcium-deprived rats is mediated by the renin-angiotensin-aldosterone system. First, we looked for manifestations of altered renin-angiotensin-aldosterone system activity during the progression of calcium deficiency. There were no differences between control and calcium-deprived rats in plasma aldosterone concentrations, plasma renin activity, plasma sodium concentrations, sodium balance, or blood pressure. Second, we used selective pharmacological antagonists to examine whether disruption of the renin-aldosterone-angiotensin system influenced salt intake. Blockade of aldosterone receptors with spironolactone (25 mg.kg-1 x day-1 sc for 7 days) had no effect on NaCl intake of control or calcium-deprived rats. Angiotensin AT1 receptor blockade with losartan potassium (0.5-10 mg/kg orally) had no effect on NaCl intake of control or calcium-deprived rats but doses > 0.5 mg/kg decreased NaCl intake of adrenalectomized rats. Taken together, these findings indicate that the renin-angiotensin-aldosterone system does not mediate the increased NaCl intake produced by calcium deficiency. The appetite for salt produced by calcium deficiency involves a different physiological substrate from most other models of NaCl intake.
Independence of salt intake from the hormones regulating calcium homeostasis
Authors: Tordoff M. G. , Hughes R. L. , Pilchak D. M.
Published: December 2017

Rats deprived of dietary calcium increase voluntary intake of NaCl solutions. We investigated whether the major hormones controlling calcium homeostasis are responsible for this increase in salt intake. Removing endogenous sources of calcitonin and parathyroid hormone by thyroidectomy and/or parathyroidectomy had no effect on NaCl intake. The surgically compromised rats and their intact controls drank similar amounts of NaCl in response to manipulations of diet calcium content. Despite normal NaCl intakes, rats with parathyroidectomy had low plasma calcium concentrations and a strong appetite for 50 mM CaCl2 solution. Chronic infusion of parathyroid hormone into rats with thyroparathyroidectomy decreased NaCl intake. Intact rats fed an American Institute of Nutrition (AIN)-76A-based vitamin D-deficient diet increased NaCl intake slightly and showed a strong appetite for CaCl2, but other rats maintained normocalcemic by the addition of calcium, phosphorus, and lactose to the vitamin D-deficient diet had normal NaCl and CaCl2 intakes. Chronic infusions of 1,25-dihydroxyvitamin D3 into intact rats had no effect on NaCl intake. Taken together, these results indicate that the increase in NaCl intake produced by calcium deprivation is not mediated by changes in circulating levels of calcium, calcitonin, parathyroid hormone, or 1,25-dihydroxyvitamin D3. Furthermore, the major calcium-regulating hormones are not involved in the control of "spontaneous" NaCl intake in the rat.
C-type natriuretic peptide and atrial natriuretic peptide receptors of rat brain
Authors: Brown J. , Zuo Z.
Published: December 2017

Natriuretic peptide receptors in rat brain were mapped by in vitro autoradiography using 125I-labeled [Tyr0]CNP-(1-22) to bind atrial natriuretic peptide receptor (ANPR)-B and ANPR-C receptors selectively, and 125I-labeled alpha-ANP to select ANPR-A and ANPR-C receptors. Des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23)-amide (C-ANP) was used for its selectivity for ANPR-C over ANPR-A. Specific binding of 125I-[Tyr0]CNP-(1-22) with a dissociation constant (Kd) approximately 1 nM occurred in olfactory bulb, cerebral cortex, lateral septal nucleus, choroid plexus, and arachnoid mater. This binding was abolished by C-type natriuretic peptide [CNP-(1-22)], alpha-ANP and C-ANP, and conformed to ANPR-C. 125I-alpha-ANP bound to all structures that bound 125I-[Tyr0]CNP-(1-22). This binding was also inhibited by both CNP-(1-22) and C-ANP, confirming the presence of ANPR-C-like binding sites. However, ANPR-C-like binding sites were heterogenous because only some had high affinities for 125I-[Tyr0]CNP-(1-22) and CNP-(1-22). 125I-alpha-ANP also bound sites without affinities for C-ANP or CNP-(1-22). These sites were consistent with ANPR-A. They occurred mainly on the olfactory bulb, the choroid plexus, and the subfornical organ. Guanosine 3',5'-cyclic monophosphate production was strongly stimulated by alpha-ANP but not by CNP-(1-22) in olfactory bulb. Neither ligand stimulated it in cortical tissue. Thus the natriuretic peptide binding sites of rat brain conformed to ANPR-A and to heterogenous ANPR-C-like sites. No ANPR-B were detected.
Endogenous angiotensin II modulates the effect of atrial natriuretic peptide on extracellular fluid partition
Authors: Valentin J. P. , Nafrialdi N. , Ribstein J. , Mimran A.
Published: December 2017

Atrial natriuretic peptide (ANP) has been shown to promote a fluid shift from the intravascular toward the interstitial compartment and to interact with the renin-angiotensin system at the renal as well as the extrarenal level. In the present studies, the interaction between the renin-angiotensin system and the effects of ANP infusion (100 ng.kg-1 x min-1 for 45 min) on arterial pressure and hematocrit were assessed in bilaterally nephrectomized, anesthetized rats. In a first series of experiments, suppression of angiotensin II generation was achieved by chronic (10 days) treatment by the angiotensin-converting-enzyme inhibitor (ACEI) captopril in rats maintained on a low-sodium diet. ACEI pretreatment prevented the rise in hematocrit associated with ANP infusion (+2.1 +/- 0.1 vs. +5.8 +/- 0.2%, P < 0.05), without influencing the effect of ANP on arterial pressure. In ACEI-pretreated rats, acute administration of angiotensin II at a subpressor dose (2.5 ng.kg-1 x min-1) restored the ANP-induced increase in hematocrit. In a second series of experiments, acute blockade of the renin-angiotensin system was obtained by the ACEI enalaprilat or the nonpeptide angiotensin II receptor antagonist losartan (both 1 mg/kg i.v. bolus). In the presence of either enalaprilat or losartan, the ANP-induced increase in hematocrit was similarly prevented. These results indicate that the effect of ANP on vascular permeability is modulated by endogenous angiotensin II, possibly due to distinct influences of the two peptides at the level of pre- and postcapillary resistances.
The effect of a low essential fatty acid diet on hibernation in marmots
Authors: Florant G. L. , Hester L. , Ameenuddin S. , Rintoul D. A.
Published: December 2017

We investigated the effect of an essential fatty acid (EFA)-deficient diet on hibernation patterns in yellow-bellied marmots (Marmota flaviventris). Fatty acid (FA) analysis of white adipose tissue (WAT) from animals maintained for 2 mo on the EFA-deficient diet suggested that little or no EFAs were present in the gonadal or omental fat depots. Hibernation about lengths of the EFA-deficient animals were significantly shorter (P < 0.01) than control animals. Stated another way, these animals aroused twice as frequently compared with control animals and used more energy to survive winter. Analysis of WAT composition and blood samples revealed that animals were highly lipolytic during winter. Furthermore, the release of FAs was not random: linoleate (cis-9,cis-12-octadecadienoic acid; 18:2, a diene EFA) was significantly (P < 0.05) under-represented in venous outflow from the gonadal WAT pad based on the percentage of this species in WAT. The concentration of saturated FAs was higher than that predicted from the WAT-FA composition. We conclude that linoleate is preferentially retained within WAT and that concentrations of this EFA may influence hibernation behavior. Thus EFAs may have a thermoregulatory role in hibernation in addition to their role as essential precursors for physiologically important lipids after hibernation is over.