bluuebunny/crossref_metadata_2025 huggingface dataset:
Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis
Authors: Jandziszak Karina , Suarez Carlos , Wasserman Ethan , Clark Ross , Baker Bonnie , Liu Frances , Hintz Raymond , Saenger Paul , Brion Luc P.
Published: December 2017

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from ∼5 to ∼12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.
AP lesions block suppression of estrous behavior, but not estrous cyclicity, in food-deprived Syrian hamsters
Authors: Panicker Anitha K. , Mangels Robert A. , Powers J. Bradley , Wade George N. , Schneider Jill E.
Published: December 2017

Food deprivation inhibits ovulatory cycles and estrous behavior in Syrian hamsters. Lesions of the area postrema (AP) prevented the suppression of estrous behavior in food-deprived hamsters, but they did not prevent the suppression of estrous cyclicity or the increase in running-wheel activity caused by food deprivation. Food deprivation or treatment with pharmacological inhibitors of glycolysis and fatty acid oxidation decreased estrogen-receptor immunoreactivity (ERIR) in the ventromedial hypothalamus (VMH), increased ERIR in the arcuate nucleus (Arc) and the posterior parvicellular paraventricular nucleus (PaPo), but had no effect on ERIR in the posterodorsal medial amygdala or the anterior parvicellular paraventricular nucleus. Lesions of the AP prevented the food deprivation-induced decrease in VMH ERIR and the increase in Arc ERIR, but they did not prevent the increase in ERIR in the PaPo. Thus, whatever physiological cues are produced by food deprivation, an intact AP is required for their transmission to the neural circuits controlling estrous behavior, VMH ERIR, and Arc ERIR. The AP is not essential for transmission of this information to the neural circuits controlling estrous cyclicity, running-wheel activity, or PaPo ERIR.
Role of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat
Authors: Huang Chunlong , Johns Edward J.
Published: December 2017

This study examined the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of ANG II was blocked peripherally or selectively within the brain. Activation of skin somatosensory receptors caused a transient reversible 10–15% increase in blood pressure, and while renal perfusion pressure was regulated at control levels, there was a transient fall in urine flow and sodium excretion even though both renal blood flow and glomerular filtration rate were unchanged. These reflexly induced excretory responses were abolished when the renal nerves were sectioned. Administration of the ANG II AT1-receptor antagonist, losartan, either intravenously at 3 or 10 mg/kg or locally into the lateral cerebroventricles at 15 μg plus 7.5 μg/h, had no effect on capsaicin-induced vasopressor responses but blocked the reductions in urine flow and sodium excretion. These findings are consistent with ANG II being involved in at least two stages in the reflex, one centrally and one at the periphery.
Plasma metabolites of quercetin and their antioxidant properties
Authors: Morand Christine , Crespy Vanessa , Manach Claudine , Besson Catherine , Demigné Christian , Rémésy Christian
Published: December 2017

Quercetin is one of the most widely distributed flavonoids present in fruits and vegetables. The present experiments were performed on rats adapted for 3 wk to a semipurified diet supplemented with 0.2% quercetin. The major part of the circulating metabolites of quercetin (91.5%) are glucurono-sulfo conjugates of isorhamnetin (3′-O-methyl quercetin; 89.1 ± 2.1 μM) and of quercetin (14.7 ± 1.7 μM); the minor part (8.5%) is constituted by glucuronides of quercetin and its methoxylated forms (9.6 ± 2.3 μM). Conjugated dienes formation, resulting from Cu2+-catalyzed oxidation of rat very low density lipoproteins + low density lipoproteins (LDL), was effectively inhibited in vitro by conjugated metabolites of quercetin. These metabolites appeared to be four times more potent than trolox in inhibiting LDL oxidation. Moreover, the plasma from rats adapted to a diet containing 0.2% quercetin exhibited a total antioxidant status markedly higher than that of control rats (+60%). This study shows that ubiquitous quercetin is conjugated in vivo, yielding metabolites that exhibit antioxidant properties. Thus the health benefits of flavonoids in foods can be due to the antioxidant properties of their metabolites.
Constitutive expression of cyclooxygenase-2 in rat vas deferens
Authors: McKanna James A. , Zhang Ming-Zhi , Wang Jun-Ling , Cheng H.-F. , Harris Raymond C.
Published: December 2017

Prostaglandins, lipoid substances discovered in human semen as modulators of uterine muscle contractility, are known to play significant roles in virtually all mammalian organ systems, but their male reproductive functions are unclear. Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, occurs in two isoforms distinguished on the basis of constitutive (COX-1) or inducible (COX-2) expression patterns in mammalian tissues. However, in the adult rat male reproductive system, immunohistochemistry and Western and Northern analysis showed that COX-2 is the predominant isoform and is heavily localized to the epithelium of the distal vas deferens, where constitutive expression is manyfold greater than in any other organs of the body. COX-2 is not detected in the proximal one-half of the vas nor in the testis, epididymis, seminal vesicles, or prostate. Elimination of luminal sperm by vasectomy does not affect COX-2 levels, whereas castration severely depletes COX-2 and androgen replacement after castration restores COX-2, indicating that COX-2 expression in the vas is androgen dependent. Because the distal vas also comprises an extensive submucosal venous plexus connected to the penile corpora cavernosa, prostaglandins from the vas may play a role in erection.
Increased physical activity and the growth hormone-IGF-I axis in adolescent males
Authors: Eliakim Alon , Brasel Jo Anne , Mohan Subburaman , Wong Wai Lee T. , Cooper Dan M.
Published: December 2017

Insulin-like growth factor-I (IGF-I) is associated with muscle hypertrophy, and circulating IGF-I levels are correlated with fitness. To test the hypothesis that IGF-I increases with increased physical activity in adolescent males, 38 subjects (16 ± 0.7 yr old) were randomized to control ( n = 18) or increased physical activity groups for 5 wk. Before and after the intervention, we measured thigh muscle volume using magnetic resonance imaging and serum levels of mean growth hormone (GH) by overnight multiple sampling, GH binding protein (GHBP), IGF-I, and IGFBPs 1–5 by standard assays. Energy expenditure was assessed with the doubly labeled water technique toward the end of the study. In the training subjects there was 1) a significant increase in thigh muscle volume (+3.6 ± 1%), 2) 15.5 ± 3.3% greater energy expenditure than in controls, and 3) no evidence of weight loss (+1.44 ± 0.4%). In contrast to our hypothesis, but similar to our recent observations in adolescent females, training decreased IGF-I (−12 ± 4%, P < 0.005). Moreover, training substantially reduced GHBP (−21 ± 4%, P < 0.00002) and increased IGFBP-2 (+40 ± 16%, P < 0.008). Brief training increased muscle volume in weight-stable adolescent males and, surprisingly, influenced not only IGF-I but GHBP and IGFBP-2 as well in a manner typically found in energy-deficient states.
“Biphasic” fevers often consist of more than two phases
Authors: Romanovsky Andrej A. , Simons Christopher T. , Kulchitsky Vladimir A.
Published: December 2017

This paper disproves the common belief that all doses of lipopolysaccharide (LPS) that are commonly referred to as biphasic fever inducing (≥2 μg/kg) cause truly biphasic responses. A catheter was implanted into the right jugular vein of several strains of adult male rats, and the animals were habituated to the experimental conditions. At an ambient temperature of 30.0°C, loosely restrained animals were injected with a 10 μg/kg dose of LPS (various preparations), and their colonic (Tc) and tail skin temperatures were monitored (from ≥1 h before to ≥7 h after the injection). The results are presented as time graphs and phase-plane plots; in the latter case the rate of change of Tc is plotted against Tc. In experiment 1 the intravenous injection of LPS (from Escherichia coli 0111:B4, phenol extract) into the rats (Bkl:Wistar) induced a triphasic febrile response, as is obvious from time graphs of Tc (3 peaks), time graphs of effector activity (3 waves of tail skin vasoconstriction), and phase-plane plots (3 complete loops); the injection of saline (control) induced no Tc changes. We analyzed whether the triphasic pattern was due to some peculiarities of the experimental design, i.e., the pyrogen preparation used ( experiment 2) or the rat strain tested ( experiment 3) or whether this pattern reflects a more general law. In experiment 2 we used the same (phenol) preparation of different LPS (from Shigella flexneri 1A and Salmonella typhosa) and a different preparation (TCA extract) of the same LPS ( E. coli). Regardless of the LPS used, rats of the Bkl:Wistar strain responded to the 10 μg/kg dose with the triphasic fever. In experiment 3, rats of other strains [Bkl:Sprague-Dawley and Sim:(LE)fBR(Black-hooded)] were tested. Again, all animals responded to the 10 μg/kg dose of E. coli LPS (phenol extract) with the triphasic fever. Because all fevers caused by four different LPS preparations in three rat strains were triphasic, the triphasic pattern is likely to constitute an intrinsic characteristic of the febrile response.
Effect of calcium on development of amiloride-blockable Na+transport in axolotl in vitro
Authors: Takada Makoto , Yai Hideko , Komazaki Shinji
Published: December 2017

The axolotl, Ambystoma mexicanum, which has no specific calcium-containing sieve layer in the dermis, provides useful material for the study of the effect of Ca2+on the development of amiloride-blockable active Na+transport across the skin of amphibians. We raised axolotls in thyroid hormone or aldosterone or cultured the skin with corticoid plus one of several Ca2+concentrations and found that 1) although the short-circuit current (SCC) was increased by both aldosterone and 3,3′,5-triiodo-l-thyronine in vivo, only corticoid was necessary for such an increase in vitro; 2) the development of the SCC in vitro was both corticoid and Ca2+dependent, because the SCC was well developed with over 100 μM Ca2+but not with under 10 μM Ca2+in the presence of corticoid, nor even with 300 μM Ca2+without corticoid; and 3) Ca2+, but not corticoid, was necessary for the formation of cell-to-cell junctions, because the resistance of the skin was well developed with 300 μM Ca2+without corticoid.
Resetting of renal blood autoregulation during acute blood pressure reduction in hypertensive rats
Authors: Iversen Bjarne M. , Kvam Fred Ivan , Matre Knut , Ofstad Jarle
Published: December 2017

Decrease in systemic blood pressure, duration of pressure decrease, and change in the activity of the renin or the sympathetic nervous system may represent mechanisms involved in resetting the renal blood flow (RBF) autoregulation found in hypertensive rats. Autoregulation of RBF, plasma renin concentration (PRC), and the time needed for resetting to take place were studied in the nonclipped kidney before and after removal of the clipped kidney of two- kidney, one-clip (2K1C) hypertensive rats and before and after mechanical reduction of the renal arterial pressure (RAP) for 10 min in the spontaneously hypertensive rat (SHR) and in the nonclipped kidney of 2K1C hypertensive rats with and without renal denervation. Mean arterial pressure (MAP) fell from 147 to 107 mmHg 30 min after removal of the clipped kidney, and the lower pressure limit of RBF autoregulation decreased from 113 to 90 mmHg ( P < 0.01); PRC fell. Mechanical reductions of RAP from 161 to 120 mmHg in the nonclipped kidney for 10 min did not change RBF, but at 120 mmHg, the lower pressure limit of RBF autoregulation was reduced from 115 mmHg before pressure reduction to 96 mmHg afterwards ( P < 0.02). In SHR, similar pressure reduction for 10 min decreased the lower pressure limit of RBF autoregulation from 106 to 86 mmHg ( P < 0.01). PRC was unchanged in both models, and denervation did not change RBF autoregulation. When RAP was reduced below the lower pressure limit of RBF autoregulation, RBF decreased ∼20%; the lower pressure limit of RBF autoregulation remained unchanged. In normotensive Wistar-Kyoto rats, pressure reduction did not change the range of RBF autoregulation. These results indicate that acute normalization of the pressure range of RBF autoregulation in hypertensive rats is dependent on the degree of pressure reduction of RAP, whereas renal innervation and PRC do not play a major role. We propose that the mechanism of resetting is due to afterstretch of noncontractile elements of the vessel wall or is caused by pure myogenic mechanisms. An effect of intrarenal angiotensin cannot be excluded.
Catechol activation in rat rostral ventrolateral medulla after systemic isocapnic metabolic acidosis
Authors: Rentero N. , Bruandet N. , Milne B. , Quintin L.
Published: December 2017

The catechol signal recorded using in vivo voltammetry within the rat rostral ventrolateral medulla (RVLM) can be interpreted as a catechol-specific index of the integrated activity of RVLM adrenergic barosensitive bulbospinal and nonbulbospinal neurons. To test the hypothesis that systemic acidosis leads to the activation of RVLM adrenergic neurons, the RVLM catechol signal was observed in rats after mild systemic acidosis (pH 7.20–7.25 for 30 min) induced by 1 M HCl under halothane anesthesia, controlled mechanical ventilation, and continuous infusion of Ringer lactate. Particular attention was paid to ensure that changes in mean arterial pressure (MAP) were <15 mmHg during HCl challenge. Saline administration was not associated with any significant change in all considered variables ( n = 5). Mild isocapnic systemic acidosis was associated with an increase in catechol signal ( n = 5), irrespective of carotid sinus nerve section ( n = 5). In keeping with the aim of the study, there were minor (<15 mmHg) but significant changes in MAP among saline, intact, and deafferented groups. Changes in heart rate were not significant. In conclusion, a catechol activation is observed in the RVLM when arterial pressure is maintained during isocapnic systemic metabolic acidosis. This catechol activation appears primarily centrally mediated. Therefore, adrenergic RVLM neurons may relay inputs from the central respiratory generator to the sympathetic system and/or act as chemosensors for H+ next to the surface of the ventrolateral medulla.
Angiotensin II infusion in vivo does not modulate cortisol secretion in the late-gestation ovine fetus
Authors: Poore Kirsten R. , Young I. Ross , Canny Benedict J. , Thorburn Geoffrey D.
Published: December 2017

Maturation of the fetal adrenal gland is critical for the onset of ovine parturition. It has long been proposed that the fetal adrenal gland may be under inhibitory influences during late gestation. In vitro evidence has suggested that angiotensin II may be such an inhibitory factor and may help to prevent a premature increase in cortisol concentrations. The aim of this study was to test the effect of angiotensin II infusion in vivo on basal cortisol concentrations and fetal adrenal responsiveness to an ACTH-(1—24) challenge. Fetuses received a continuous infusion of either angiotensin II (100 ng ⋅ min−1 ⋅ kg−1; n = 7) or saline (2 ml/h; n = 4), which commenced at 140 days of gestation (GA) and continued for a total of 50 h. Adrenal responsiveness to the administration of ACTH-(1—24) (5 μg/kg) was determined during angiotensin II or saline infusions at both 2 and 48 h after infusion onset. Angiotensin II had no significant effect on adrenal responsiveness after acute (2 h) or chronic (48 h) infusion. There was no effect of saline or angiotensin II infusion on basal immunoreactive ACTH or cortisol concentrations after 2 h, but there was a significant increase in basal cortisol concentrations in both treatment groups by 48 h, probably reflecting the normal rise in cortisol concentrations at this GA. Mean arterial blood pressure was significantly increased in angiotensin II-infused fetuses only. This study has therefore found no evidence to suggest that angiotensin II infusion in vivo modulates fetal basal cortisol concentrations or adrenal responsiveness in the last week of gestation, in contrast with previous in vitro studies. These results throw into question the proposed role of angiotensin II as a negative modulator of adrenal function in the ovine fetus.
Vagal and splanchnic afferents are not necessary for the anorexia produced by peripheral IL-1β, LPS, and MDP
Authors: Porter M. H. , Hrupka B. J. , Langhans W. , Schwartz G. J.
Published: December 2017

We investigated the extrinsic gut neural mediation of the suppression of food intake in male Sprague-Dawley rats induced by peripheral intraperitoneal administration of 2 μg/kg interleukin-1β (IL-1β), 100 μg/kg bacterial lipopolysaccharide (LPS), and 2 mg/kg muramyl dipeptide (MDP). Food intake during the first 3 and 6 h of the dark cycle was measured in rats with subdiaphragmatic vagal deafferentation ( n = 9), celiac superior mesenteric ganglionectomy ( n = 9), combined vagotomy and ganglionectomy ( n = 9), and sham deafferentation ( n = 9). IL-1β, LPS, and MDP suppressed food intake at 3 and 6 h in all surgical groups. The results demonstrate that neither vagal nor nonvagal afferent nerves from the upper gut are necessary for the feeding-suppressive effects of intraperitoneal IL-1β, LPS, or MDP in the rat and suggest that peripheral administration of immunomodulators produces anorexia via a humoral pathway.
Acute defense mechanisms against hemorrhage from mechanical gill injury in rainbow trout
Authors: Sundin Lena , Nilsson Göran E.
Published: December 2017

By cutting gill filaments in anesthetized rainbow trout ( Oncorhynchus mykiss), observing the bleeding through a stereomicroscope, and using blockers of various known endogenous filament artery vasoconstrictors, we have here attempted to characterize hemostatic mechanisms in gills. The immediate hemostatic response to a cut in a gill filament artery was a local vasoconstriction, stopping the hemorrhage within ∼20 s. In heparinized fish, the hemorrhage recommenced after ∼8 min, suggesting that the vasoconstriction soon subsides and blood clotting becomes responsible for the hemostasis. Antagonists of acetylcholine, adenosine, and serotonin receptors were unable to block the hemostatic vasoconstriction. Also, tetrodotoxin was without effect, indicating a nonnervous origin. By contrast, indomethacin significantly affected the measured bleeding times, suggesting that eicosanoids play a significant role in this process (possibly by stimulating vasoconstriction and/or by inducing local thrombocyte aggregation). By possessing several hundred virtually identical filaments with readily observable vasculature, the fish gill appears to be a good experimental model for studying hemostatic mechanisms.
Ontogeny of neuropeptide Y expression in response to deprivation in lean Zucker rat pups
Authors: Kowalski Timothy J. , Houpt Thomas A. , Jahng Jeongwon , Okada Nori , Chua Streamson C. , Smith Gerard P.
Published: December 2017

Hypothalamic neuropeptide Y (NPY) activity is believed to play an important role in the response to food deprivation in adult rats. Little is known, however, about the role of the hypothalamic NPY system in the control of food intake in the preweanling rat. To address this issue, we examined the effect of deprivation on arcuate nucleus preproNPY expression in lean Zucker rat pups, using in situ hybridization. PreproNPY expression within the arcuate nucleus was localized to cells in the medial portion. Twenty-four hours of food, water, and maternal deprivation significantly increased the relative abundance of preproNPY mRNA in pups on postnatal day (P) 2, P9, P12, and P15 by 14–31%. This response, however, was not observed on P5. The absence of an effect on P5 and the magnitude of the response at the other ages tested were not correlated with the amount of weight lost during deprivation.
Divergence of the feeding and thermogenic pathways influenced by NPY in the hypothalamic PVN of the rat
Authors: Kotz Catherine M. , Briggs Jacqueline E. , Grace Martha K. , Levine Allen S. , Billington Charles J.
Published: December 2017

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) increases feeding and decreases brown adipose tissue (BAT) uncoupling protein (UCP) and lipoprotein lipase (LPL) mRNA. Previously we reported that the feeding and BAT effects induced by NPY in the PVN are blocked by 50 μg naltrexone (NTX) in the rostral nucleus of the solitary tract (rNTS). We sought to determine whether the effect of rNTS NTX on PVN NPY-induced alterations in energy metabolism occurred at lower doses of NTX. Male Sprague-Dawley rats were fitted with cannulas into two sites: PVN and rNTS. Feeding response, BAT UCP, and LPL mRNA were measured after injection of 0, 5, 10, and 25 μg NTX in the rNTS ± 1 μg NPY in the PVN. One-hour feeding response to PVN NPY was significantly and dose dependently decreased by 10 and 25 μg rNTS NTX (−23 and −31%, respectively). However, rNTS NTX did not block the PVN NPY-induced decrease in BAT UCP or LPL mRNA. BAT β-actin mRNA (as a measure of overall changes in gene expression) was unchanged among treatment groups. These results indicate a possible divergence in the PVN NPY feeding-stimulatory/BAT-inhibitory pathway, such that PVN NPY feeding effects may be routed through the rNTS whereas BAT effects may be due to alterations at another neural site.
Amygdaloid-lesion hyperphagia: impaired response to caloric challenges and altered macronutrient selection
Authors: King Bruce M. , Rossiter Kirk N. , Stines Samuel G. , Zaharan Gelana M. , Cook Jack T. , Humphries Misty D. , York David A.
Published: December 2017

Lesions of the most posterodorsal aspects of the amygdala in female rats result in hyperphagia and moderate obesity. In the present study, rats with amygdaloid lesions did not increase their daily food intake when their powdered diet was diluted with 25 or 50% nonnutritive bulk. Control animals adjusted their food intake appropriately. In a second study, rats with lesions ate less food (lab chow pellets) than controls when allowed to eat for only 1 h/day for 10 days. In experiment 3, rats were offered a three-choice macronutrient diet. Whereas four of six control animals preferred the high-fat diet, all eight of the rats with amygdaloid lesions displayed a distinct preference for the high-carbohydrate diet, including those that had preferred the high-fat diet before surgery. These results, along with the previous finding that identical lesions result in hyperinsulinemia, indicate that the amygdala is involved in both the homeostatic regulation of food (caloric) intake and the selection of macronutrients.
Systemic α-MSH suppresses LPS fever via central melanocortin receptors independently of its suppression of corticosterone and IL-6 release
Authors: Huang Qin-Heng , Hruby Victor J. , Tatro Jeffrey B.
Published: December 2017

Systemically administered α-melanocyte-stimulating hormone (α-MSH) inhibits endotoxin (lipopolysaccharide; LPS)- or interleukin (IL)-1-induced fever and adrenocortical activation, but the sites of these actions and the mechanisms involved are unknown. The aims of this study were, first, to determine whether melanocortin receptors (MCR) located within the central nervous system mediate the suppressive effects of peripherally administered α-MSH on LPS-induced fever and activation of the pituitary-adrenal axis and, second, to determine whether systemic α-MSH suppresses the LPS-induced rise in plasma IL-6 levels, potentially contributing to its antipyretic effect. Male rats received Escherichia coli LPS (25 μg/kg ip). Core body temperatures (Tb) were determined hourly by radiotelemetry (0–8 h), and blood was withdrawn via venous catheters for plasma hormone immunoassays (0–2 h) and IL-6 bioassay (0–8 h). α-MSH (100 μg/kg ip) completely prevented the onset of LPS-induced fever during the first 3–4 h after LPS and suppressed fever throughout the next 4 h but did not affect Tb in afebrile rats treated with intraperitoneal saline rather than LPS. Intraperitoneal α-MSH also suppressed the LPS-induced rise in plasma IL-6, ACTH, and corticosterone (CS) levels. Intracerebroventricular injection of SHU-9119, a potent melanocortin-4 receptor (MC4-R)/MC3-R antagonist, completely blocked the antipyretic effect of intraperitoneal α-MSH during the first 4 h after LPS but had no effect on α-MSH-induced suppression of LPS-stimulated plasma IL-6 and CS levels. Taken together, the results indicate that the antipyretic effect of peripherally administered α-MSH during the early phase of fever is mediated by MCR within the brain. In contrast, the inhibition of LPS-induced increases in plasma CS and IL-6 levels by intraperitoneal α-MSH appears to be mediated by a different mechanism(s), and these effects do not contribute to its antipyretic action.
Effect of changing body temperature on the ventilatory and metabolic responses of lean and obese Zucker rats
Authors: Maskrey Michael , Megirian David , Farkas Gaspar A.
Published: December 2017

We measured body temperature (Tb) and ventilatory and metabolic variables in lean ( n = 8) and obese ( n = 8) Zucker rats. Measurements were made while rats breathed air, 4% CO2, and 10% O2. Under control conditions, Tbin obese rats was always less than that of their lean counterparts. Obese rats adopted a more rapid, shallow breathing pattern than lean rats in air and had a lower ventilation rate in 4% CO2. Respiration in 10% O2was similar for the two groups. Metabolic variables did not differ between lean and obese rats whatever the gas breathed. When lean rats were cooled to match Tbin control obese rats with an implanted abdominal heat exchanger, they increased ventilation and metabolism in air; there was no effect of cooling on responses to 4% CO2; and ventilation increased while metabolism decreased in 10% O2. When obese rats were warmed to match Tbin control lean rats, trends in ventilation and metabolism resulted in a tendency toward hyperventilation in air and 4% CO2, but not in 10% O2. Taken overall, matching Tbin lean and obese rats accentuated differences in respiratory and metabolic variables between the two groups. We conclude that differences in respiration between lean and obese Zucker rats are not due to the difference in Tb.
Chronic ingestion of dietary fat is a prerequisite for inhibition of feeding by enterostatin
Authors: Lin Ling , York David A.
Published: December 2017

Enterostatin (Ent), the activation pentapeptide from procolipase, inhibits the intake of dietary fat. The selectivity of the response to fat suggests that the rat must recognize a permissive signal related to dietary fat for the Ent biological response. To investigate the nature of this signal, we studied the effects of Ent in rats that were adapted to either a high-fat (HF) or high-carbohydrate/low-fat (HC) diet and then naively exposed to either HF or HC diets. Ent (1 nmol) was injected into the lateral ventricle of overnight-fasted rats, and food intake was measured. Rats adapted to HF diet and tested with HC diet responded to Ent, but rats adapted to HC diet and tested with HF did not respond to Ent. The groups were maintained on their new test diets for up to 21 days and tested again for their response to Ent at 3, 7, 14, and 21 days. Ent response did not appear in HC-adapted rats switched to HF diet before 21 days. Conversely, the HF-adapted rats, which responded to Ent when tested with HC diet for the first time, did not respond at any subsequent testing time. The data suggest that chronic ingestion of dietary fat is required for Ent action and that chronic consumption of fat initiates a postingestion metabolic, endocrine, or neurochemical change that is required for the biological response to Ent.
EAA receptors in the dorsomedial hypothalamic area mediate the cardiovascular response to activation of the amygdala
Authors: Soltis Robert P. , Cook Jennifer C. , Gregg Adam E. , Stratton James M. , Flickinger Kathleen A.
Published: December 2017

The role of excitatory amino acid (EAA) receptors in the dorsomedial hypothalamus (DMH) in mediating the cardiovascular response to activation of the basolateral amygdala (BLA) was examined using conscious rats. Microinjection of the nonselective EAA receptor antagonist kynurenic acid (0.1–10 nmol) into the DMH blocked or reversed the increases in heart rate and arterial pressure resulting from injection of the GABAA receptor antagonists bicuculline methiodide (BMI; 100 pmol) and picrotoxin (100 pmol) into the BLA. Similar injections of kynurenic acid at sites lateral or dorsal to the DMH or injection of the inactive analog xanthurenic acid into the DMH were less effective in blocking the cardiovascular changes resulting from intra-amygdalar injection of BMI. Hypothalamic injection of the NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10 pmol) or thedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (50 pmol) at doses shown to be selective for their respective EAA receptor subtypes attenuated the cardiovascular changes associated with intra-amygdalar injection of BMI. Therefore, EAA receptors in the area of the DMH appear to be involved in mediating the cardiovascular changes resulting from activation of the amygdala.
Evidence that decreased heart rate in thyroid hormone receptor-α1-deficient mice is an intrinsic defect
Authors: Johansson Catarina , Vennström Björn , Thorén Peter
Published: December 2017

Using a telemetry system with implantable transmitters, we recorded heart rate, electrocardiogram (ECG), body temperature, and locomotor activity continuously in awake, freely moving mice deficient in the thyroid hormone receptor-α1 (TRα1). We have previously reported that the TRα1-deficient mice have a 20% lower mean heart rate and a 0.5°C lower body temperature compared with wild-type control animals. In this study we found that when 3,5,3′-triiodothyronine (T3) was given once a day, there was a parallel increase in heart rate (occurring 1 day later in the TRα1-deficient mice than in controls) and body temperature. Analysis of single-lead ECG revealed a prolonged QRS and Q-Tend time in the TRα1-deficient mice, which was shortened after T3 treatment. Monophasic action potential durations, measured in hearts from anesthetized mice at 90% of repolarization, were significantly prolonged in TRα1-deficient mice. Air-jet stress and a single injection of an anticholinergic agent induced a parallel increase, and a β-adrenergic receptor blocker induced a decrease in heart rate in both groups. There was no difference in β-adrenergic receptor density. The results indicate that the TRα1-deficient mice have a specific defect in intrinsic heart rate regulation.
Circadian system of mice integrates brief light stimuli
Authors: Van Den Pol Anthony N. , Cao Vinh , Heller H. Craig
Published: December 2017

Light is the primary sensory stimulus that synchronizes or entrains the internal circadian rhythms of animals to the solar day. In mammals photic entrainment of the circadian pacemaker residing in the suprachiasmatic nuclei is due to the fact that light at certain times of day can phase shift the pacemaker. In this study we show that the circadian system of mice can integrate extremely brief, repeated photic stimuli to produce large phase shifts. A train of 2-ms light pulses delivered as one pulse every 5 or 60 s, with a total light duration of 120 ms, can cause phase shifts of several hours that endure for weeks. Single 2-ms pulses of light were ineffective. Thus these data reveal a property of the mammalian circadian clock: it can integrate and store latent sensory information in such a way that a series of extremely brief photic stimuli, each too small to cause a phase shift individually, together can cause a large and long-lasting change in behavior.
Coordination of autonomic and behavioral thermoregulatory responses during exposure to a novel stimulus in rats
Authors: Dymond Karin E. , Fewell James E.
Published: December 2017

The induction of psychological stress in rats is accompanied by an elevation of core temperature. Our experiments were carried out to determine whether the latency, duration, magnitude, or effector mechanisms of the core temperature response to psychological stress would be altered when rats were allowed to use behavioral as well as autonomic thermoregulation. Core temperature, oxygen consumption, and ambient temperature were measured in adult rats before and after handling and a sham intraperitoneal injection. Seven rats were studied in a thermocline (gradient of 7 to 42°C) and eight rats were studied in a metabolic chamber (25°C). The rats studied in the thermocline selected a warm ambient temperature following the sham intraperitoneal injection and exhibited an increase in core temperature of shorter latency, greater magnitude, and greater duration than those studied in the metabolic chamber. The rats studied in the metabolic chamber exhibited an oxygen consumption response of greater magnitude and duration than the animals studied in the thermocline. Thus the characteristics in addition to the effector mechanisms of the core temperature response to psychological stress are altered when rats are allowed to use behavioral as well as autonomic thermoregulatory effectors.
Evolution in functional complexity of heart rate dynamics: a measure of cardiac allograft adaptability
Authors: Kresh J. Yasha , Izrailtyan Igor
Published: December 2017

The capacity of self-organized systems to adapt is embodied in the functional organization of intrinsic control mechanisms. Evolution in functional complexity of heart rate variability (HRV) was used as measure of the capacity of the transplanted heart to express newly emergent regulatory order. In a cross-sectional study of 100 patients after (0–10 yr) heart transplantation (HTX), heart rate dynamics were assessed using pointwise correlation dimension (PD2) analysis. A new observation is that, commencing with the acute event of allograft transplantation, the dynamics of rhythm formation proceed through complex phase transitions. At implantation, the donor heart manifested metronome-like chronotropic behavior (PD2 ∼1.0). At 11–100 days, dimensional complexity of HRV reached a peak (PD2 ∼2.0) associated with resurgence in the high-frequency component (0.15–0.5 Hz) of the power spectral density. Subsequent dimensional loss to PD2 ∼1.0 at 20–30 mo after HTX was followed by a progressive near-linear gain in system complexity, reaching PD2 ∼3.0 7–10 yr after HTX. The “dynamic reorganization” in the allograft rhythm-generating system, seen in the first 100 days, is a manifestation of the adaptive capacity of intrinsic control mechanisms. The loss of HRV 2 yr after HTX implies a withdrawal of intrinsic autonomic control and/or development of an entrained dynamic pattern characteristic of extrinsic sympathetic input. The subsequent long-term progressive rise in dimensional complexity of HRV can be attributed to the restoration of a functional order patterning parasympathetic control. The recognition that the decentralized heart can restitute the multidimensional state space of HR generator dynamics independent of external autonomic signaling may provide a new perspective on principles that constitute homeodynamic regulation.
Human duodenogastric reflux, retroperistalsis, and MMC
Authors: Dalenbäck Jan , Abrahamson Hasse , Björnson Einar , Fändriks Lars , Mattsson Anna , Olbe Lars , Svennerholm A.-M. , Sjövall Henrik
Published: December 2017

The aim of this study was to determine to what extent human migrating motor complex (MMC)-related secretory phenomena are influenced by a recently discovered period of duodenal retroperistalsis during late phase III. A constant-flow perfusion technique was used to measure gastric appearance of acid, bicarbonate, pepsin, bilirubin, IgA, and duodenally infused [14C]polyethylene glycol (PEG) 4000 in 12 healthy volunteers. Interdigestive gastroduodenal motility was recorded by digital manometry. During late antral phase II and III, the gastric lumen was acidified ( P < 0.005 phase III vs. phase I) together with a marked increase in luminal pepsin output (3.1 ± 1.2 during phase III vs. 0.25 ± 0.08 kU/5 min in phase I, P < 0.01), followed by a realkalinization due to a simultaneous reduction of acid secretion and a duodenogastric reflux, aided by retrograde peristalsis, of bicarbonate and IgA but not of bilirubin, at the end of antral phase III ( P < 0.05 phase III vs. phase I values). This physiological duodenoantral reflux phenomenon may play an important role in the chemical and immunological restitution of the antral mucosal barrier function after the exposure to high acid and pepsin concentrations during antral phase III activity.
Ablation of posterior atrial ganglionated plexus potentiates sympathetic tachycardia to behavioral stress
Authors: Randall David C. , Brown David R. , Li Sheng-Gang , Olmstead Matthew E. , Kilgore Jay M. , Sprinkle Aletia G. , Randall Walter C. , Ardell Jeffrey L.
Published: December 2017

The role of the posterior atrial ganglionated plexus (PAGP) in heart rate (HR) control was tested in unanesthetized dogs ( n = 8). Resting HR was unchanged before (85 ± 20 beats/min, mean ± SD) versus after (87 ± 18 beats/min) surgical ablation of these intrinsic cardiac ganglia (PAGPX). However, the peak tachycardia to a 30-s stressful stimulus was significantly increased ( P < 0.05) from +53 ± 22 beats/min before the denervation to +77 ± 13 beats/min after PAGPX. Conversely, the peak HR increase during the stress after β-adrenergic blockade was the same before (36 ± 24 beats/min) versus after (38 ± 14 beats/min) PAGPX. Moreover, the HR response to a neutral behavioral stimulus, which is mediated primarily by withdrawal of parasympathetic inhibition of the sinoatrial (SA) node, was unaltered by PAGPX. Thus the augmented tachycardia subsequent to PAGPX was attributable primarily to increased sympathetic action at the SA node. These findings indicate that a major role of PAGP parasympathetic neurons is to inhibit sympathoexcitatory effects on HR, probably either via interactions between neurons comprising the intrinsic plexus(es) or perhaps via presynaptic inhibition of sympathetic neurotransmitter release. This organization would allow parasympathetic ganglia within the PAGP to selectively modify sympathetic input to the SA node independent of direct vagal inhibition of pacemaker activity.
Blockade of corticotropin-releasing hormone receptors reduces spontaneous waking in the rat
Authors: Chang Fang-Chia , Opp Mark R.
Published: December 2017

We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. To further elucidate this role for CRH, we administered intracerebroventricularly into rats two specific CRH-receptor antagonists, α-helical CRH-(9—41) (α-hCRH) or astressin, and determined changes in electroencephalogram-defined waking and sleep. Our results indicate that both of these receptor antagonists reduce the amount of time spent awake in a dose-related manner when administered before the dark period of the light-dark cycle. However, the time courses for these effects differ between antagonists; effective doses of α-hCRH reduce waking during the first 2 h postinjection, whereas effective doses of astressin reduce waking during postinjection hours 7–12. In contrast to dark-onset administrations, the amount of waking is not altered by either CRH-receptor antagonist when administered before the light period. These results support our hypothesis that CRH contributes to the regulation of physiological waking, since interfering with the binding of CRH to its receptor reduces spontaneous waking.
Effect of ventilation style on cardiovascular and renal adaptation in preterm newborn lambs
Authors: Wada Norihisa , Ervin M. Gore , Ikegami Machiko
Published: December 2017

Renal adaptive responses during the 24 h after delivery in term newborn lambs include marked increases in both glomerular filtration rate (GFR) and sodium reabsorption. This study investigated the effects of ventilation style on cardiovascular, renal, and endocrine adaptations in preterm newborn lambs. Lambs ( n = 62) were delivered by cesarean section at 131 days gestation (term = 150 days), treated with surfactant, and randomized to one of three ventilation strategies: high-frequency oscillation (12 Hz), high rate (50 breaths/min; tidal volume = 8 ml/kg), or low rate (15 breaths/min; tidal volume = 15 ml/kg). Lambs (5 or 6/group) were ventilated for 2, 5, 10, and 24 h to maintain arterial[Formula: see text] between 45 and 50 mmHg. Plasma vasopressin levels decreased to <25 pg/ml by 10 h, and fractional sodium excretion decreased to <1% by 16 h in all groups. However, cardiac output, renal plasma flow, and GFR values did not change over time for any of the groups. The style of ventilation employed had no measurable effects on overall cardiovascular, renal, or endocrine function. We conclude in ventilated preterm lambs that 1) the ventilation style does not affect the time course for postnatal adaptation, 2) adaptive changes in renal tubular sodium reabsorption are evident by 16 h after birth, and 3) changes in preterm newborn renal sodium reabsorption occur in the absence of postnatal changes in renal plasma flow or GFR.
Acute stressor exposure both suppresses acquired immunity and potentiates innate immunity
Authors: Fleshner Monika , Nguyen Kien T. , Cotter Crystal S. , Watkins Linda R. , Maier Steven F.
Published: December 2017

Acute stressor exposure alters immune function. Rats exposed to inescapable tail shock stress (IS) generate less antibody to a benign, antigenic protein, keyhole limpet hemocyanin (KLH). The following studies examined the effect of IS on peritoneal cavity, spleen, and mesenteric lymph node cell number, interferon-γ (IFN-γ) production, and nitrite production. Rats were injected intraperitoneally with KLH (200 μg) or saline immediately before IS exposure and killed 0, 48, and 96 h after IS termination. KLH immunization resulted in elevated cell numbers and IFN-γ levels 2–4 days later in nonstressed control rats. In contrast, rats exposed to IS failed to increase cell number and IFN-γ levels in response to KLH. The T cell subpopulations affected were CD4 T cells, specifically the Th1-like subset. In addition, in rats exposed to IS + KLH, nitrite production was potentiated 2–4 days after stressor termination. IS had little effect on these measures in saline-injected rats. These data support the conclusion that exposure to IS suppresses the expansion of anti-KLH lymphocytes, possibly anti-KLH Th1 cells. In addition, stressor exposure potentiates the production of nitrite. Importantly, this potentiated response occurred only in KLH-immunized animals, suggesting that macrophages may be primed by stressor exposure and thus respond more vigorously to antigen. The potential links between these changes are discussed.
Mechanisms of spontaneous baroreflex impairment in Lyon hypertensive rats
Authors: Lantelme Pierre , Cerutti Catherine , Lo Ming , Paultre Christian Z. , Ducher Michel
Published: December 2017

This experiment aimed at 1) comparing the spontaneous baroreflex sensitivity (SBRS) in Lyon genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats and 2) assessing some aspects of the mechanisms of its impairment in LH rats. Baroreflex was studied in control animals after an early chronic converting enzyme inhibition with perindopril and after a 4-wk infusion of ANG II in perindopril-treated rats. The SBRS was determined with a previously validated method, using statistical dependence between blood pressure (BP) and heart rate values recorded in freely moving animals. LH rats exhibited high BP, cardiac hypertrophy, and decreased SBRS (LH, 1.3 ± 0.2; LN, 2.5 ± 0.4; LL, 2.2 ± 0.4 beats ⋅ min−1 ⋅ mmHg−1). Perindopril prevented the development of hypertension and cardiac hypertrophy and normalized SBRS. BP rose in LH and LL rats after ANG II infusion, but only LH rats, which developed a cardiac hypertrophy, had an impaired SBRS (LH, 1.1 ± 0.2; LN, 2.5 ± 0.2; LL, 2.8 ± 0.3 beats ⋅ min−1 ⋅ mmHg−1). This impairment was partially reversed by an acute ANG II blockade with losartan. These results demonstrate that high BP does not account for the decreased SBRS in LH rats. SBRS impairment could result either from cardiac hypertrophy or from the direct effect of ANG II on the baroreflex loop.
Acidic fibroblast growth factor activates adrenomedullary secretion and sympathetic outflow in rats
Authors: Matsumoto Itsuro , Niijima Akira , Oomura Yutaka , Sasaki Kazuo , Tsuchiya Katsuhiko , Aikawa Tadaomi
Published: December 2017

Effects of exogenous acidic fibroblast growth factor (aFGF), which is increased in the brain by food intake, on the plasma levels of catecholamines and on sympathetic efferent outflow were examined in anesthetized rats. A guide cannula was inserted into the cerebral third ventricle, and a vascular indwelling catheter was inserted into the right atrium from the jugular vein. Plasma epinephrine (Epi) and norepinephrine (NE) increased markedly in a dose-dependent manner for up to 120 min after intracerebroventricular or intravenous administration of aFGF (6–667 fmol/rat). Concomitant increases occurred in the efferent activity in the sympathetic nerves supplying the adrenal, spleen, and interscapular brown adipose tissue after the above administrations of aFGF. Both intravenous and intracerebroventricular administration of 10 ng basic FGF (bFGF) also increased sympathetic adrenal efferent activity and plasma Epi and NE concentrations. However, the increases induced by 10 ng bFGF were smaller than those induced by 10 ng aFGF. Bilateral splanchnicotomy completely prevented the increases in Epi induced by intracerebroventricular or intravenous aFGF but had less effect on the increases in NE. Pretreatment with an antibody against corticotropin-releasing factor (CRF), given via the intracerebroventricular route, significantly attenuated the increases in Epi and NE evoked by intracerebroventricular or intravenous administration of aFGF. Hepatic vagotomy also greatly reduced the increases in both catecholamines and the increases in sympathetic efferent firing rates evoked by intravenous administration of aFGF. These findings indicate that 1) aFGF administered intracerebroventricularly activates adrenomedullary secretion and sympathetic outflow via CRF release and 2) aFGF injected intravenously also induces sympathoadrenomedullary activation via centrally released CRF. The idea is discussed that sympathetic activation induced either by endogenous aFGF after feeding or by exogenously administered aFGF may play roles both in energy expenditure after overeating and in the modulation of immune functions.