bluuebunny/crossref_metadata_2025 huggingface dataset:
Second messenger production in avian medullary nephron segments in response to peptide hormones
Authors: Goldstein David L. , Reddy Vishala , Plaga Kimberly
Published: December 2017

We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow ( Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 ± 56, 147 ± 31, and 151 ± 41 fmol ⋅ mm−1⋅ 30 min−1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10−6M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.
Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded rat
Authors: van Dokkum Richard P. E. , Sun Cheng-Wen , Provoost Abraham P. , Jacob Howard J. , Roman Richard J.
Published: December 2017

The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contributes to the development of renal damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of whole kidney, cortical, and medullary blood flow and PGCwere compared in young (12 wk old) FHH and fawn-hooded low blood pressure (FHL) rats in volume-replete and volume-expanded conditions. Baseline RBF, cortical and medullary blood flow, and PGCwere significantly greater in FHH than in FHL rats. Autoregulation of renal and cortical blood flow was significantly impaired in FHH rats compared with results obtained in FHL rats. Myogenically mediated autoregulation of PGCwas significantly greater in FHL than in FHH rats. PGCrose from 46 ± 1 to 71 ± 2 mmHg in response to an increase in renal perfusion pressure from 100 to 150 mmHg in FHH rats, whereas it only increased from 39 ± 2 to 53 ± 1 mmHg in FHL rats. Isolated perfused renal interlobular arteries from FHL rats constricted by 10% in response to elevations in transmural pressure from 70 to 120 mmHg. In contrast, the diameter of vessels from FHH rats increased by 15%. These results indicate that the myogenic response of small renal arteries is altered in FHH rats, and this contributes to an impaired autoregulation of renal blood flow and elevations in PGCin this strain.
Role of central melanocortins in endotoxin-induced anorexia
Authors: Huang Qin-Heng , Hruby Victor J. , Tatro Jeffrey B.
Published: December 2017

Inflammation and microbial infection produce symptoms, including fever, anorexia, and hypoactivity, that are thought to be mediated by endogenous proinflammatory cytokines. Melanocortins are known to act centrally to suppress effects on fever and other sequelae of proinflammatory cytokine actions in the central nervous system, but the roles of melanocortins in anorexia and hypoactivity occurring during the acute phase response are unknown. The present study was designed to determine the effects of exogenous and endogenous α-melanocyte stimulating hormone (α-MSH) on lipopolysaccharide (LPS)-induced anorexia in relation to their effects on fever. Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 μg/kg ip), followed 30 min later by intracerebroventricular injection of either α-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. Food intake, locomotor activity, and body temperature (Tb) were monitored during the ensuing 24-h period. Each of two intracerebroventricular doses of α-MSH (30 and 300 ng) potentiated the suppressive effects of LPS on food intake and locomotion, despite the fact that the higher dose alleviated LPS-induced fever. In control rats that were not treated with LPS, only the higher dose of α-MSH significantly inhibited food intake, and Tband locomotor activity were unaffected. To assess the roles of endogenous central melanocortins, LPS-treated rats received intracerebroventricular SHU-9119 (200 ng). Central MC3-R/MC4-R blockade did not affect Tbor food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. Taken together, the results suggest that exogenous and endogenous melanocortins acting centrally exert divergent influences on different aspects of the acute phase response, suppressing LPS-induced fever but contributing to LPS-induced anorexia and hypoactivity.
Intracerebroventricular injection of TNF-α promotes sleep and is recovered in cervical lymph
Authors: Dickstein Jodi B. , Moldofsky Harvey , Lue Franklin A. , Hay John B.
Published: December 2017

Recent studies have shown that the central nervous system (CNS) communicates with the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-α would not only influence the CNS by promoting sleep but also would be directly transmitted into the peripheral immune system. Five hundred nanograms of 125I-labeled TNF-α were injected into the lateral ventricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. 125I-TNF-α was measured in lymph nodes and control fat, skin, and muscle tissues 6 h postinjection.125I-TNF-α was detected in the cervical lymphatics within the first 30 min and peaked within 2–3 h. 125I-TNF-α counts were elevated in the nodes of the head and neck region. Polysomnographic recordings of four animals showed that TNF-α induced a significant increase in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-α and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and peripheral immune functions.
Estrogen enhancement of baroreflex sensitivity is centrally mediated
Authors: Mohamed Mohamed K. , El-Mas Mahmoud M. , Abdel-Rahman Abdel A.
Published: December 2017

We have recently shown that estrogen enhances baroreceptor control of reflex bradycardia in conscious rats. The present study replicated this finding in pentobarbital sodium-anesthetized rats, and the study was extended to investigate whether this effect of estrogen is centrally or peripherally mediated. Hemodynamic responses to electrical stimulation of the central end of the aortic depressor or the vagal efferent nerve were evaluated in pentobarbital sodium-anesthetized sham-operated (SO), ovariectomized (OVX), and OVX estradiol-treated Sprague-Dawley rats. Phenylephrine (1–16 μg/kg iv) elicited dose-dependent pressor and bradycardic responses. Regression analysis of the baroreflex curves, relating changes in mean arterial pressure and heart rate, revealed a significantly smaller baroreflex sensitivity in OVX compared with SO anesthetized rats (−0.54 ± 0.05 and −0.91 ± 0.12 beats ⋅ min−1 ⋅ mmHg−1, respectively; P < 0.05). Treatment of OVX rats with 17β-estradiol (E2, 50 μg ⋅ kg−1 ⋅ day−1for 2 days subcutaneously) significantly enhanced baroreflex sensitivity to a level similar to that of SO rats ( P < 0.05). The enhancing effect of E2 on the baroreflex-mediated bradycardia, observed in conscious and anesthetized rats, seems to be selective because the baroreflex-mediated tachycardic responses measured in a separate group of conscious rats were not altered by ovariectomy or E2 administration. Electrical stimulation of the aortic nerve elicited frequency-dependent depressor and bradycardic responses that were significantly smaller in OVX compared with SO values ( P < 0.05). Treatment of OVX rats with E2 restored the hemodynamic responses to aortic stimulation to near SO levels. On the other hand, hemodynamic responses to vagal stimulation were not affected by OVX or treatment with E2. These findings suggest that enhancement of reflex bradycardia by estrogen is centrally mediated and involves interaction with central projections of the aortic nerve.
Fatty acid oxidation affects food intake by altering hepatic energy status
Authors: Friedman Mark I. , Harris Ruth B. , Ji Hong , Ramirez Israel , Tordoff Michael G.
Published: December 2017

Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the same extent as did the low dose but in addition suppressed fatty acid oxidation in muscle and produced a marked depletion of liver glycogen. Dose-related increases in food intake tracked dose-related reductions in liver ATP content, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding behavior by reducing hepatic energy production.
Cardiac inotropic, chronotropic, and dromotropic actions of subretrofacial neurons of cat RVLM
Authors: Campos R. R. , McAllen R. M.
Published: December 2017

The cardiac actions of microinjecting sodium glutamate (0.5–2 nmol) among sympathetic premotor neurons of the subretrofacial nucleus in the rostral ventrolateral medulla (RVLM) were studied in chloralose-anesthetized cats after bilateral vagotomy, sinoaortic denervation, adrenalectomy, and α1-receptor blockade. Glutamate microinjections increased heart rate by 25.9 ± 1.8 beats/min (17.5%), systolic rate of rise in left ventricular pressure (LVdP/d t) by 1,443 ± 110 mmHg/s (119%), and arterial blood pressure by 26.9 ± 1.7 mmHg (50%), whereas they shortened the electrocardiogram P–R interval in 85 of 103 cases by 7.5 ± 1.2 ms (11.4%), triggering junctional rhythms on five occasions. The increase in LVdP/d tusually led the rise in blood pressure, and its magnitude greatly exceeded any increase attributable to changes in heart rate, diastolic filling, or afterload. Right-sided microinjections caused significantly greater tachycardias than did left-sided microinjections, but only left-sided microinjections triggered junctional rhythms (5 of 52 vs. 0 of 51; P < 0.05), whereas microinjections on either side raised LVdP/d tequally. Subretrofacial neurons thus drive positive chronotropic, inotropic, and dromotropic actions via the cardiac sympathetic nerves, whereas subsets among them preferentially control different aspects of cardiac function.
Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep
Authors: de Matteo R. , May C. N.
Published: December 2017

Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate in many species, but the mechanisms involved are unclear. We investigated whether cortisol-induced renal vasodilatation in conscious sheep depends on interactions with prostaglandins or angiotensin II. Intravenous infusion of cortisol (5 mg/h) for 5 h increased renal conductance (RC) by 1.06 ± 0.24 ml ⋅ min−1⋅ mmHg−1more than vehicle. During intrarenal infusion of indomethacin (0.25 mg ⋅ kg−1⋅ h−1), the cortisol-induced increase in RC (0.28 ± 0.21 ml ⋅ min−1⋅ mmHg−1) was significantly reduced. The cortisol-induced rise in RBF (103 ± 17 ml/min) was not significantly reduced by indomethacin treatment (76 ± 9 ml/min). Combined intrarenal infusion of indomethacin (0.25 mg ⋅ kg−1⋅ h−1) with Nω-nitro-l-arginine (2.0 mg ⋅ kg−1⋅ h−1), a nitric oxide synthase inhibitor, abolished the cortisol-induced increases in both RC and RBF. Inhibition of angiotensin II synthesis with intravenous captopril (40 mg/h) blocked the renal vasoconstrictor action of angiotensin I but did not inhibit the cortisol-induced increases in RBF and RC. This study provides evidence that nitric oxide and prostaglandins play a role in cortisol-induced renal vasodilatation but indicates that this response is independent of an interaction with angiotensin.
Somnogenic relationships between tumor necrosis factor and interleukin-1
Authors: Takahashi Satoshi , Kapás Levente , Fang Jidong , Krueger James M.
Published: December 2017

Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines. They also induce each other’s production and both induce nuclear factor kappa B activation, which in turn enhances IL-1 and TNF transcription. We hypothesized that TNF and IL-1 could influence each other’s somnogenic actions. To test this hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sleep deprivation in rabbits. Furthermore, the effects of inhibition of TNF on IL-1-induced sleep and the effects of blocking IL-1 on TNF-induced sleep were determined. A TNF receptor fragment (TNFRF), as a TNF inhibitor, and an IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination of the TNFRF plus the IL-1RF significantly reduced spontaneous non-rapid eye movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits with the combination of TNFRF and IL-1RF also significantly attenuated sleep rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate physiological sleep.
Effects of granulocyte colony-stimulating factor on night sleep in humans
Authors: Schuld A. , Mullington J. , Hermann D. , Hinze-Selch D. , Fenzel T. , Holsboer F. , Pollmächer T.
Published: December 2017

Numerous animal studies suggest that cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mediate increased sleep amount and intensity observed during infection and are, moreover, involved in physiological sleep regulation. In humans the role of cytokines in sleep-wake regulation is largely unknown. In a single-blind, placebo-controlled study, we investigated the effects of granulocyte colony-stimulating factor (G-CSF, 300 μg sc) on the plasma levels of cytokines, soluble cytokine receptors, and hormones as well as on night sleep. G-CSF did not affect rectal temperature or the plasma levels of cortisol and growth hormone but did induce increases in the plasma levels of IL-1 receptor antagonist and both soluble TNF receptors within 2 h after injection. In parallel, the amount of slow-wave sleep and electroencephalographic delta power were reduced, indicating a lowered sleep intensity. We conclude that G-CSF suppresses sleep intensity via increased circulating amounts of endogenous antagonists of IL-1β and TNF-α activity, suggesting that these cytokines are involved in human sleep regulation.
Glucose regulation of the IGF response system in chondrocytes: induction of an IGF-I-resistant state
Authors: Kelley K. M. , Johnson T. R. , Ilan J. , Moskowitz R. W.
Published: December 2017

Nonresponsiveness to the growth-stimulatory actions of insulin-like growth factor (IGF)-I in chondrocytes has been reported in a number of disease states associated with impaired glucose metabolism. Primary rabbit chondrocytes were investigated for changes in their IGF response system [type-I IGF receptor and IGF-binding protein (IGFBP) expression] and in their ability to mount a synthetic response to IGF-I [as35S-labeled proteoglycan ([35S]PG) production] in media containing varying ambient glucose concentrations. Whereas basal [35S]PG synthetic rate was unaffected by glucose concentration, synthetic responsiveness to IGF-I was lost in media containing <5 mmol/l glucose or in media containing a “diabetic” glucose concentration (25 mmol/l). IGFBP expression, as measured by Northern analysis of mRNA levels and Western ligand blotting of secreted protein levels, was not significantly altered in the different glucose media, nor were there any differences in the cell surface localization of IGFBPs as assessed by affinity cross-linking with125I-labeled IGF-I, suggesting that IGFBPs do not induce the IGF-I resistance. The nonresponsiveness to IGF-I in reduced glucose occurred with 25–50% reductions in steady-state levels of IGF type-I receptor mRNA and protein. A significant correlation between IGF receptor mRNA level and synthetic response to IGF-I was observed between 0 and 10 mmol/l glucose concentrations, suggesting that the loss of responsiveness in reduced glucose is manifested at the level of transcription and/or receptor mRNA stability. In contrast, nonresponsiveness to IGF-I in chondrocytes in diabetic glucose concentrations occurred without changes in receptor mRNA and protein levels, suggesting that IGF-I resistance was due to post-ligand-binding receptor defects. It is proposed that IGF-I resistance in chondrocytes subjected to inappropriate glucose levels may constitute an important pathogenic mechanism in degenerative cartilage disorders.
Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake
Authors: DeLany James P. , Blohm Fawn , Truett Alycia A. , Scimeca Joseph A. , West David B.
Published: December 2017

Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects on body fat accumulation. In our previous work, CLA reduced body fat accumulation in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced energy intake, the results suggested that some of the metabolic effects were not a consequence of the reduced food intake. We therefore undertook a study to determine a dose of CLA that would have effects on body composition without affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by weight) were studied in AKR/J male mice ( n = 12/group; age, 39 days) maintained on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups compared with controls. The retroperitoneal depot was most sensitive to the effects of CLA, whereas the epididymal depot was relatively resistant. Higher doses of CLA also significantly increased carcass protein content. A time-course study of the effects of 1% CLA on body composition showed reductions in fat pad weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion, CLA feeding produces a rapid, marked decrease in fat accumulation, and an increase in protein accumulation, at relatively low doses without any major effects on food intake.
Effects of square-wave and simulated natural light-dark cycles on hamster circadian rhythms
Authors: Tang I-Hsiung , Murakami Dean M. , Fuller Charles A.
Published: December 2017

Circadian rhythms of activity (Act) and body temperature (Tb) were recorded from male Syrian hamsters under square-wave (LDSq) and simulated natural (LDSN, with dawn and dusk transitions) light-dark cycles. Light intensity and data sampling were under the synchronized control of a laboratory computer. Changes in reactive and predictive onsets and offsets for the circadian rhythms of Act and Tb were examined in both lighting conditions. The reactive Act onset occurred 1.1 h earlier ( P < 0.01) in LDSN than in LDSq and had a longer α-period (1.7 h; P < 0.05). The reactive Tb onset was 0.7 h earlier ( P < 0.01) in LDSN. In LDSN, the predictive Act onset advanced by 0.3 h ( P < 0.05), whereas the Tb predictive onset remained the same as in LDSq. The phase angle difference between Act and Tb predictive onsets decreased by 0.9 h ( P < 0.05) in LDSN, but the offsets of both measures remained unchanged. In this study, animals exhibited different circadian entrainment characteristics under LDSq and LDSN, suggesting that gradual and abrupt transitions between light and dark may provide different temporal cues.
Does gender influence the strength and mechanisms of the muscle metaboreflex during dynamic exercise in dogs?
Authors: Laprad Susanne L. , Augustyniak Robert A. , Hammond Robert L. , O’Leary Donal S.
Published: December 2017

Ischemia of active skeletal muscle stimulates neuronal afferents within the muscle, which elicits a reflex increase in sympathetic nerve activity, systemic arterial pressure (SAP), and heart rate (HR), termed the muscle metaboreflex. We retrospectively investigated whether gender influences the activation of the muscle metaboreflex and the primary mechanisms used by this reflex, augmentation of cardiac output (CO) and peripheral vasoconstriction, using 15 female and 13 male chronically instrumented dogs exercising on a treadmill (3.2 km/h, 0% grade). Metaboreflex activation was achieved via progressive partial vascular occlusion of the terminal aorta during exercise. In both females and males, hindlimb ischemia elicited similar substantial increases in SAP (56.1 ± 3.0 and 55.1 ± 4.2 mmHg, respectively), HR (25.8 ± 4.8 and 33.9 ± 2.8 beats/min, respectively), and CO (1.39 ± 0.3 and 1.64 ± 0.2 liters, respectively) and a similar substantial decrease in renal vascular conductance (RVC; 42.7 ± 4.9 and 42.9 ± 5.3%, respectively). Both groups also demonstrated similar metaboreflex thresholds and sensitivities of SAP, HR, CO, and RVC. We conclude that the strength and mechanisms mediating the metaboreflex responses during dynamic exercise in dogs are not affected by gender.
Neonatal uninephrectomy causes hypertension in adult rats
Authors: Woods Lori L.
Published: December 2017

This study was designed to test the hypothesis that a reduced number of nephrons from birth leads to increased arterial pressure in adulthood. Newborn Sprague-Dawley rat pups were uninephrectomized during the first 24 h after birth. In chronically instrumented adult animals (∼22 wk), mean arterial pressure on a normal (0.20%)-Na+diet was higher in uninephrectomized rats (133 ± 2 mmHg vs. 121 ± 2 mmHg in controls, P < 0.0001). Body weights were not significantly different, but the total kidney-to-body weight ratio was significantly reduced by 14% in adult uninephrectomized animals ( P < 0.05). Glomerular filtration rate was reduced by ∼30% in uninephrectomized rats (1.84 ± 0.09 vs. 2.63 ± 0.14 ml/min, P < 0.0002), and effective renal plasma flow was reduced to a lesser degree (6.37 ± 0.38 vs. 7.87 ± 0.51 ml/min, P < 0.03), such that the filtration fraction was also reduced (0.291 ± 0.007 vs. 0.338 ± 0.014, P < 0.01). After 7–10 days on a high (3.15%)-Na+diet, arterial pressure increased more in uninephrectomized animals than in controls (20 ± 3 vs. 1 ± 1 mmHg, P < 0.003). Thus surgical removal of 50% of the nephrons, when done during development, caused reduced renal function and a salt-sensitive hypertension in adulthood. These data suggest that a reduced nephron endowment from birth, caused by genetic and/or perinatal environmental factors, could contribute to essential hypertension in adulthood.
Influence of bioenergetic stress on heat shock protein gene expression in nucleated red blood cells of fish
Authors: Currie Suzanne , Tufts Bruce L. , Moyes Christopher D.
Published: December 2017

The physiological and biochemical signals that induce stress protein (HSP) synthesis remain conjectural. In this study, we used the nucleated red blood cells from rainbow trout, Oncorhynchus mykiss, to address the interaction between energy status and HSP gene expression. Heat shock (25°C) did not significantly affect ATP levels but resulted in an increase in HSP70 mRNA. Hypoxia alone did not induce HSPtranscription in these cells despite a significant depression in ATP. Inhibition of oxidative phosphorylation with azide, in the absence of thermal stress, decreased ATP by 56% and increased lactate production by 62% but did not induce HSP gene transcription. Inhibition of oxidative phosphorylation and glycolysis with azide and iodoacetic acid respectively, decreased ATP by 79% and prevented lactate production, but did not induce either HSP70 or HSP30 gene transcription in these cells. This study demonstrates that a reduction in the cellular energy status will not induce stress protein gene transcription in rainbow trout red blood cells and may, in fact, limit induction during extreme metabolic inhibition.
Brain glucose sensing and body energy homeostasis: role in obesity and diabetes
Authors: Levin Barry E. , Dunn-Meynell Ambrose A. , Routh Vanessa H.
Published: December 2017

The brain has evolved mechanisms for sensing and regulating glucose metabolism. It receives neural inputs from glucosensors in the periphery but also contains neurons that directly sense changes in glucose levels by using glucose as a signal to alter their firing rate. Glucose-responsive (GR) neurons increase and glucose-sensitive (GS) decrease their firing rate when brain glucose levels rise. GR neurons use an ATP-sensitive K+channel to regulate their firing. The mechanism regulating GS firing is less certain. Both GR and GS neurons respond to, and participate in, the changes in food intake, sympathoadrenal activity, and energy expenditure produced by extremes of hyper- and hypoglycemia. It is less certain that they respond to the small swings in plasma glucose required for the more physiological regulation of energy homeostasis. Both obesity and diabetes are associated with several alterations in brain glucose sensing. In rats with diet-induced obesity and hyperinsulinemia, GR neurons are hyporesponsive to glucose. Insulin-dependent diabetic rats also have abnormalities of GR neurons and neurotransmitter systems potentially involved in glucose sensing. Thus the challenge for the future is to define the role of brain glucose sensing in the physiological regulation of energy balance and in the pathophysiology of obesity and diabetes.
Effects of acute physical exercise on hepatocyte volume and function in rat
Authors: Latour Martin G. , Brault Antoine , Huet Pierre-Michel , Lavoie Jean-Marc
Published: December 2017

The goal of the present experiment was to measure the volume of the different compartments in liver of exercised rats and to get some insights into the appropriate working of the hepatic function following exercise. Hence, livers from male rats were isolated and perfused after treadmill exercise or rest. This procedure was performed on rats that were overnight semifasted (50% food restriction) or well fed. To evaluate the hepatocyte cell volume, the multiple-indicator dilution curve technique was used after 40 min of perfusion. Radioactive tracers for red blood cells, sucrose, and water were used to measure liver vascular space, liver interstitial space, and water cellular space, respectively. The hepatocyte function was assessed by taurocholate and propanolol clearance. Oxygen consumption, intrahepatic resistance, bile secretion, and lactate dehydrogenase release estimated liver viability. Liver viability and hepatocyte function were not changed following exercise either in the fed or in the semifasted animals. As expected, liver glycogen levels were significantly ( P < 0.01) reduced in the food-restricted rats. Consequently, liver glycogen levels following exercise were decreased significantly ( P < 0.01) only in the fed rats. Despite this, exercise decreased the hepatocyte water space in both food-restricted and fed groups (∼15%; P < 0.01) without altering the sinusoidal and interstitial space. The present data show that acute exercise decreased the hepatocyte volume and that this volume change is not entirely linked to a decrease in hepatic glycogen level.
Magnitude of functional adaptation after intestinal resection
Authors: O’Connor Timothy P. , Lam Mandy M. , Diamond Jared
Published: December 2017

Intestinal adaptation after resection has been much studied, but rarely examined in an integrative context. Hence we assessed the effects of resection and subsequent adaptation on the quantitative relationship between dietary glucose load and gut capacity to transport glucose. The ratio of capacity to load is termed the “safety factor.” Our objectives were to determine 1) the time course of intestinal adaptation after resection, 2) whether adaptation is quantitatively complete, 3) whether survival requires maintaining a safety factor of at least 1.0 for glucose transport, 4) the effect of altered energy demands on adaptation, and 5) the relationship between the amount of tissue removed and the magnitude of functional adaptation. We performed 80% resection of the small intestine on Sprague-Dawley rats and measured small intestinal glucose uptake capacity, dietary glucose load, and gut gross morphology at 1, 5, and 10 wk postsurgery. Nearly all aspects of adaptation were complete by 1 wk postsurgery. After resection, remnant small intestine mass increased by over fivefold within 1 wk, to reach 50–70% of its preresection value. However, mass-specific glucose uptake activity was reduced, so that intestinal regeneration restored uptake capacity to only 33% of control values. Increased energetic demands had only modest effects on intestinal adaptation. Although the safety factor for small intestinal glucose uptake remained <1.0 (i.e., capacity < load) after adaptation to resection, nearly all rats survived. Hindgut fermentation of nonabsorbed nutrients appeared to contribute to that survival, despite inadequate small intestinal capacity. After less massive resection surgeries (25, 50, and 75% resections), the percent increase in glucose uptake capacity increased with the amount of tissue removed.
Resonance in the renal vasculature evoked by activation of the sympathetic nerves
Authors: Malpas Simon C. , Hore Todd A. , Navakatikyan Michael , Lukoshkova Elena V. , Nguang Sing Kiong , Austin Paul C.
Published: December 2017

We examined the ability of different frequencies in sympathetic nerve activity (SNA) to induce oscillations in renal blood flow (RBF). In anesthetized rabbits the renal nerves were stimulated using modulated sine patterns (base frequency 5 Hz, 5-ms duration pulses) that varied in amplitude between 0 and 10 V at a frequency between 0.04 and 1.0 Hz. The strengths of the induced oscillations in RBF were calculated using spectral analysis. Although faster rhythms in simulated SNA >0.6 Hz contributed to the level of vascular tone, 95% of the power in the frequency response curve was below this frequency, indicating a low-pass filtering/integrating characteristic of the vasculature. Frequencies <0.6 Hz were associated with increasing ability to induce oscillations in RBF. The ability of an SNA rhythm at 0.6 Hz to induce a rhythm in RBF was 21 times less than that at 0.25 Hz. At 0.16 Hz there was a distinct peak in the frequency response curve, indicating the vasculature was more sensitive in this frequency band to sympathetic stimulation. Blockade of endogenous nitric oxide by N G-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg) did not alter resting RBF levels nor was the low-pass filtering/integrating characteristic of the vasculature to nerve stimulation changed (i.e., the curve was not shifted left or right); however, there was a selective increase in the sensitivity to stimulation at 0.16 Hz, i.e., larger oscillations in RBF were evoked. These results indicate an ability of SNA to induce resonant oscillations in the renal vasculature and that there may be active and passive modulators of these responses. Naturally occurring oscillations in SNA <0.6 Hz are likely to contribute to the dynamic control of RBF, ensuring it responds rapidly and with high gain to the stimuli of daily life, while filtering out the faster oscillations ensures stable glomerular filtration.
Exogenous calmodulin potentiates vasodilation elicited by phospholipid-associated VIP in vivo
Authors: Ikezaki Hiroyuki , Patel Manisha , Önyüksel Hayat , Akhter Syed R. , Gao Xiao-Pei , Rubinstein Israel
Published: December 2017

The purpose of this study was to determine whether exogenous calmodulin potentiates vasoactive intestinal peptide (VIP)-induced vasodilation in vivo and, if so, whether this response is amplified by association of VIP with sterically stabilized liposomes. Using intravital microscopy, we found that calmodulin suffused together with aqueous and liposomal VIP did not potentiate vasodilation elicited by VIP in the in situ hamster cheek pouch. However, preincubation of calmodulin with liposomal, but not aqueous, VIP for 1 and 2 h and overnight at 4°C before suffusion significantly potentiated vasodilation ( P < 0.05). Calmodulin-induced responses were significantly attenuated by calmidazolium, trifluoperazine, and NG-nitro-l-arginine methyl ester (l-NAME) but notd-NAME. The effects ofl-NAME were reversed byl- but notd-arginine. Indomethacin had no significant effects on calmodulin-induced responses. Calmodulin had no significant effects on adenosine-, isoproterenol-, acetylcholine-, and calcium ionophore A-23187-induced vasodilation. Collectively, these data indicate that exogenous calmodulin amplifies vasodilation elicited by phospholipid-associated, but not aqueous, VIP in the in situ peripheral microcirculation in a specific, calmodulin active sites-, and nitric oxide-dependent fashion. We suggest that extracellular calmodulin, phospholipids, and VIP form a novel functionally coordinated class of endogenous vasodilators.
Changes in the glomerulosa cell phenotype during adrenal regeneration in rats
Authors: Engeland W. C. , Levay-Young B. K.
Published: December 2017

In situ hybridization was used to examine cellular differentiation during rat adrenal regeneration, defining zona glomerulosa [cytochrome P-450 aldosterone synthase ( P-450aldo) mRNA positive], zona fasciculata [cytochrome P-450 11β-hydroxylase ( P-45011β) mRNA positive], or zona intermedia [negative for both but 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA positive]. After unilateral adrenal enucleation with contralateral adrenalectomy (ULE/ULA), the expression of all mRNA was reduced at 2 days. From 5 to 10 days, P-45011β and 3β-HSD mRNA increased while P-450aldo remained low; at 20 days, all mRNA were increased. From 2 to 10 days, cells adjacent to the capsule showed intermedia cell differentiation; by 20 days, the subcapsular glomerulosa cells reappeared. This suggests that after enucleation the glomerulosa dedifferentiates to zona intermedia. The experiment was repeated in rats where the postenucleation ACTH rise was prevented. Rats underwent ULE with sham ULA (ULE/SULA) or ULE/SULA with ACTH treatment. Adrenals from ULE/SULA rats expressed increased P-450aldo mRNA at 10 days and reduced P-45011β mRNA and adrenal weight at 30 days. ACTH treatment reversed the pattern toward that seen in ULE/ULA. These findings show that the enucleation-induced dedifferentitation of the glomerulosa cell may result in part from elevated plasma ACTH and that prevention of dedifferentiation may result in impaired regeneration.
Roles of aldosterone and angiotensin in maturation of sodium appetite in furosemide-treated rats
Authors: Rowland Neil E. , Morian Kenneth R.
Published: December 2017

When rats are treated with furosemide, there is a rapid natriuresis. However, increased sodium appetite does not occur until some time later. One hypothesis to explain this delay is that increased circulating levels of the hormones of sodium depletion prime or sensitize the brain circuits involved in sodium appetite, perhaps by induction of target gene(s). In the present study, we describe the time course of the temporal maturation of sodium appetite after furosemide treatment and the associated changes in plasma levels of ANG II and aldosterone and in plasma volume. Sodium appetite is modest 3 h after furosemide treatment, is increased after 12 h, and is still larger after 24 h. This pattern is evident with repeated testing. Plasma levels of aldosterone and plasma renin activity are substantially increased 3 h after furosemide treatment, and so the NaCl appetite cannot result simply from progressively increasing levels of these hormones. Furthermore, activation of the subfornical organ and the ventral lamina terminalis, assessed with c-Fos immunocytochemistry, did not differ across these three times. Metyrapone, an inhibitor of adrenal steroid synthesis, was used to examine sodium appetite in the absence of elevations in aldosterone after furosemide treatment. Although metyrapone effectively blocked the increase in aldosterone, it was without effect on the appetite 3 or 24 h after furosemide treatment. Furthermore, elevations of plasma aldosterone by the use of minipumps for several days before furosemide treatment did not prime or potentiate but instead tended to inhibit the induced sodium appetite, despite achieving levels of aldosterone and plasma renin activity typically associated with a robust sodium appetite. Infusions of DOCA gave a similar result. Lastly, minipump infusions of ANG II also did not potentiate sodium appetite. Thus neither addition nor subtraction of these hormones alone influenced sodium appetite under these conditions.
Heat acclimation increases the basal HSP72 level and alters its production dynamics during heat stress
Authors: Maloyan Alina , Palmon Aaron , Horowitz Michal
Published: December 2017

It has been previously shown that heat acclimation leads to an elevated basal level of 72-kDa heat shock protein (HSP72). Augmented expression of HSP72 is considered as a cytoprotective response. This led us to hypothesize that alterations in the heat shock protein (HSP) defense pathway are an integral part of the heat acclimation repertoire. To investigate this, we studied the temporal profile of basal HSP expression upon acclimation and the dynamics of their accumulation subsequent to acute heat stress (HS). In parallel, HSP72 mRNA level before and after HS was measured. For comparison, HSC mRNA [the constitutive member of 70-kDa HSP (HSP70) family] was measured in similar conditions. Heat acclimation was attained by continuous exposure of rats to 34°C for 0, 1, 2, and 30 days. HS was attained by exposure to 41 or 43°C for 2 h. Thermoregulatory capacity of the rats was defined by rectal temperature, heating rate, and the cumulative heat strain invoked during HS. HSP72 and HSP70 gene transcripts were measured in the left ventricle of the heart by means of Western immunoblotting and semiquantitative RT-PCR, respectively. The resultant acclimatory change comprised a higher resting level of the encoded 72-kDa protein (Δ175%, P < 0.0001). After HS, peak HSP72 mRNA level was attained, 40 and 20 min post-HS at 41 and 43°C, respectively, vs. 60 and 40 min in the nonacclimated group. The subsequent HSP synthesis, however, was dependent on the severity of the cumulative heat strain. At the initial phase of heat acclimation, augmented HSP72 transcription unaccompanied by HSP synthesis was observed. It is concluded that upon heat acclimation, the HSP defense pathway is predisposed to a faster response. At the initial phases of heat acclimation, inability to elevate the HSP cytosolic level rules out their direct cytoprotective role.
Biphasic changes in left ventricular function during hyperdynamic endotoxemia
Authors: Ishihara Satoshi , Ward John A. , Tasaki Osamu , Pruitt Basil A. , Javors Martine A. , Cassidy Richard A. , Mozingo David W.
Published: December 2017

Cardiac contractility was studied in a clinically relevant conscious swine model simulating human hemodynamics during endotoxemia. The slope of the end-systolic pressure-volume relationship [end-systolic elastance ( EES)] was used as a load-independent contractility index. Chronic instrumentation in 10 pigs included two pairs of endocardial ultrasonic crystals for measuring internal major and minor axial dimensions of the left ventricle, a micromanometer for left ventricular pressure measurement, and a thermodilution pulmonary artery catheter. After a 10-day recovery period, control measurements of cardiac hemodynamic function were obtained. The following week, Escherichia coli endotoxin (10 μg ⋅ kg−1⋅ h−1) was administered intravenously for 24 h. EESincreased 1 h after endotoxin infusion and decreased beyond 7 h. The later hemodynamic changes resembled human cardiovascular performance during endotoxemia more closely than the changes during the acute phase. EESdecreased in the later phase. A similar biphasic response of EEShas been reported during a tumor necrosis factor-α (TNF) challenge. Even though plasma TNF was highest at 1 h and declined thereafter in this study, no consistent relationship between TNF and EESwas identified, and TNF levels did not correlate directly with the changes in EES.
Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2
Authors: Gutzwiller Jean-Pierre , Drewe Jürgen , Göke Burkhard , Schmidt Harald , Rohrer Beat , Lareida Jürg , Beglinger Christoph
Published: December 2017

Glucagon-like peptide-1-(7—36) amide (GLP-1) is an incretin hormone of the enteroinsular axis. Recent experimental evidence in animals and healthy subjects suggests that GLP-1 has a role in controlling appetite and energy intake in humans. We have therefore examined in a double-blind, placebo-controlled, crossover study in 12 patients with diabetes type 2 the effect of intravenously infused GLP-1 on appetite sensations and energy intake. On 2 days, either saline or GLP-1 (1.5 pmol ⋅ kg−1 ⋅ min−1) was given throughout the experiment. Visual analog scales were used to assess appetite sensations; furthermore, food and fluid intake of a test meal were recorded, and blood was sampled for analysis of plasma glucose and hormone levels. GLP-1 infusion enhanced satiety and fullness compared with placebo ( P = 0.028 for fullness and P = 0.026 for hunger feelings). Energy intake was reduced by 27% by GLP-1 ( P = 0.034) compared with saline. The results demonstrate a marked effect of GLP-1 on appetite by showing enhanced satiety and reduced energy intake in patients with diabetes type 2.
Central leptin modulates behavioral and neural responsivity to CCK
Authors: Emond Michael , Schwartz Gary J. , Ladenheim Ellen E. , Moran Timothy H.
Published: December 2017

The mechanisms through which leptin, the protein product of the ob gene, affects food intake remain to be determined. To assess whether the actions of leptin depend on modulation of within-meal satiety signals, we measured the effect of third ventricular leptin administration on the satiety actions of CCK. Leptin (10 μg) administered 1 h before 30-min access to a liquid diet had no effect on intake when administered alone, but doses of 3.5 or 10 μg dose dependently increased the suppression of intake produced by 1 nmol/kg CCK. Examination of patterns of c-Fos activation induced by 3.5 μg leptin and 1 nmol/kg CCK revealed that the combination produced significant c-Fos activation within the area postrema and the caudal and medial nucleus of the solitary tract (NST) compared with either leptin or CCK treatments alone. The leptin-CCK combination also resulted in increased c-Fos activation within the paraventricular nucleus of the hypothalamus above that produced by leptin alone. These data suggest that the actions of leptin in food intake are mediated through its ability to modulate responsivity to within-meal satiety signals.
CNS origins of the sympathetic nervous system outflow to brown adipose tissue
Authors: Bamshad Maryam , Song C. Kay , Bartness Timothy J.
Published: December 2017

Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha’s K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.
Osmolality: a physiological long-term regulator of lumbar sympathetic nerve activity and arterial pressure
Authors: Scrogin Karie E. , Grygielko Eugene T. , Brooks Virginia L.
Published: December 2017

Acute infusion of hypertonic fluid increases mean arterial pressure (MAP) in part by elevating nonrenal sympathetic activity. However, it is not known whether chronic, physiological increases in osmolality also increase sympathetic activity. To test this hypothesis, MAP, heart rate (HR), and lumbar sympathetic nerve activity (LSNA) were measured in conscious, 48-h water-deprived rats (WD) during a progressive reduction in osmolality produced by a 2-h systemic infusion (0.12 ml/min) of 5% dextrose in water (5DW). Water deprivation significantly increased osmolality (308 ± 2 vs. 290 ± 2 mosmol/kgH2O, P < 0.001), HR (453 ± 7 vs. 421 ± 10 beats/min, P < 0.05), and LSNA (63.5 ± 1.8 vs. 51.9 ± 3.8% baroreflex maximum, P < 0.01). Two hours of 5DW infusion reduced osmolality (−15 ± 5 mosmol/kgH2O), LSNA (−23 ± 3% baseline), and MAP (−10 ± 1 mmHg). To evaluate the role of vasopressin in these changes, rats were pretreated with a V1-vasopressin receptor antagonist. The antagonist lowered MAP (−5 ± 1 mmHg) and elevated HR (32 ± 7 beats/min) and LSNA (11 ± 3% baseline) in WD ( P < 0.05), but not in water-replete, rats. 5DW infusion had a similar cumulative effect on all variables in V1-blocked WD rats, but had no effect in water-replete rats. Infusion of the same volume of normal saline in WD rats did not change osmolality, LSNA or MAP. Together these data indicate that, in dehydrated rats, vasopressin supports MAP and suppresses LSNA and HR and that physiological changes in osmolality directly influence sympathetic activity and blood pressure independently of changes in vasopressin and blood volume.
Vestigial respiratory burst activity in wound macrophages
Authors: Nessel Christopher C. , Henry William L. , Mastrofrancesco Balduino , Reichner Jonathan S. , Albina Jorge E.
Published: December 2017

Macrophages from experimental wounds in rats were tested for their capacity to generate reactive oxygen intermediates. Measurements of superoxide and H2O2release, [Formula: see text]-dependent lucigenin chemiluminescence, oxygen consumption, hexose monophosphate shunt flux, and NADPH oxidase activity in cell lysates indicated, at best, the presence of a vestigial respiratory burst response in these cells. The inability of wound cells to release[Formula: see text] was not rekindled by priming with endotoxin or interferon-γ in vivo or in vitro. NADPH oxidase activity in a cell-free system demonstrated that wound macrophage membranes, but not their cytosols, were capable of sustaining maximal rates of [Formula: see text] production when mixed with their corresponding counterparts from human neutrophils. Immune detection experiments showed wound macrophages to be particularly deficient in the cytosolic component of the NADPH oxidase p47- phox. Addition of recombinant p47- phox to the human neutrophil-cell membrane/wound macrophage cytosol cell-free oxidase assay, however, failed to support[Formula: see text] production. Present findings indicate an unexpected deficit of wound macrophages in their capacity to generate reactive oxygen intermediates.