bluuebunny/crossref_metadata_2025 huggingface dataset:
Season and testosterone affect contractile properties of fast calling muscles in the gray tree frogHyla chrysoscelis
Authors: Girgenrath Mahasweta , Marsh Richard L.
Published: March 2015

In anurans, circulating levels of androgens influence certain secondary sexual characteristics that are expressed only during the breeding season. We studied the contractile properties of external oblique muscles (used to power sound production) in a species of North American gray tree frog, Hyla chrysoscelis, during the breeding season and also in testosterone-treated captive males and females after the breeding season. Compared with the muscles of breeding-season males, the trunk muscles of postbreeding-season males have 50% less mass, 60% longer twitches, and 40% slower shortening velocities. Testosterone levels similar to those found in breeding-season male hylid frogs restore the contractile speed and mass of male trunk muscles and also convert the small slow trunk muscles of females into larger fast-contracting muscles. We conclude that androgens likely play a key role in altering the contractile properties of these muscles in males during the annual cycle, allowing them to operate in the breeding season at the frequencies required to produce the characteristic rapidly pulsed calls of this species. Females as well as nonbreeding-season males do not produce advertising calls, and therefore the slower muscles found in these animals may allow more economic operation of these muscles. The effects of testosterone on female trunk muscles indicate the potential of this hormone in contributing to the sexual dimorphism in size and contractile properties of these muscles, but this dimorphism is likely due to the interaction of more than one hormone.
Pressor effect of electroacupuncture on hemorrhagic hypotension
Authors: Syuu Yi , Matsubara Hiromi , Hosogi Shingo , Suga Hiroyuki
Published: March 2015

Neiguan (PC-6) is a traditional acupoint in each forearm and overlies the trunk of the median nerve. Previous studies show that electroacupuncture (EA) at the Neiguan acupoint could improve not only myocardial ischemic dysfunction by inducing a depressor response but also recover hemorrhagic hypotension by inducing a pressor response. However, their physiological mechanisms are not yet elucidated. We investigated the pressor effect of Neiguan EA and its mechanism by focusing on left ventricular (LV) performance in a canine hemorrhagic hypotension model. We hemorrhaged 36 anesthetized and thoracotomized mongrel dogs and decreased LV end-systolic pressure (ESP) to ∼70 mmHg (35% decrease). We obtained LV pressure-volume (P-V) data with a micromanometer catheter and a conductance catheter. One-hour Neiguan EA significantly recovered the decreased ESP, end-diastolic volume, and stroke volume by 32 ± 13%, 27 ± 13%, and 39 ± 17%, respectively ( P < 0.05), without changing heart rate and the slope of the end-systolic P-V relation. Neiguan EA inhibited a hemorrhage-induced increase in plasma catecholamines. However, vecuronium (neuromuscular blocking agent) administration abolished the antihypotension effect of Neiguan EA. Furthermore, Neiguan EA was much more effective than a nonacupoint thigh EA. We conclude that Neiguan EA achieved the antihypotension effect by improving LV filling of the hemorrhage-depressed LV performance despite the inhibition of the hemorrhage-increased plasma catecholamines. This pressor effect seemed to accompany an increased venous return by Neiguan EA-increased vasomotor tone and muscle pump. This study demonstrated a scientific basis for the therapeutic efficacy of acupuncture in the treatment of hemorrhagic hypotension and shock.
IGF-I treatment facilitates transition from parenteral to enteral nutrition in rats with short bowel syndrome
Authors: Gillingham Melanie B. , Dahly Elizabeth M. , Murali Sangita G. , Ney Denise M.
Published: March 2015

The goal of growth factor treatment in patients with short bowel syndrome (SBS) is to facilitate transition from parenteral to enteral feedings. Ideal use of growth factors would be acute treatment that produces sustained effects. We investigated the ability of acute insulin-like growth factor I (IGF-I) treatment to facilitate weaning from total parenteral nutrition (TPN) to enteral feeding in a rat model of SBS. After a 60% jejunoileal resection + cecectomy, rats treated with IGF-I or vehicle were maintained exclusively with TPN for 4 days and transitioned to oral feeding. TPN and IGF-I were stopped 7 days after resection, and rats were maintained with oral feeding for 10 more days. In IGF-I-treated rats, serum concentration of IGF-I and final body weight were significantly greater because of a proportionate increase in carcass lean body mass than in vehicle-treated rats. Acute IGF-I treatment induced sustained jejunal hyperplasia on the basis of significantly greater concentrations of jejunal mucosal protein and DNA without a change in histology or sucrase activity. These results demonstrate that acute IGF-I facilitates weaning from parenteral to enteral nutrition in association with maintenance of a greater body weight and serum IGF-I concentration in rats with SBS.
Brief food restriction increases FA oxidation and glycogen synthesis under insulin-stimulated conditions
Authors: Tucker Michelle Z. , Turcotte Lorraine P.
Published: March 2015

To determine the effects of brief food restriction on fatty acid (FA) metabolism, hindlimbs of F344/BN rats fed either ad libitum (AL) or food restricted (FR) to 60% of baseline food intake for 28 days were perfused under hyperglycemic-hyperinsulinemic conditions (20 mM glucose, 1 mM palmitate, 1,000 μU/ml insulin, [3-3H]glucose, and [1-14C]palmitate). Basal glucose and insulin levels were significantly lower ( P < 0.05) in FR vs. AL rats. Palmitate uptake (34.3 ± 2.7 vs. 24.5 ± 3.1 nmol/g/min) and oxidation (3.8 ± 0.2 vs. 2.7 ± 0.3 nmol · g−1· min−1) were significantly higher ( P < 0.05) in FR vs. AL rats, respectively. Glucose uptake was increased in FR rats and was accompanied by significant increases in red and white gastrocnemius glycogen synthesis, indicating an improvement in insulin sensitivity. Although muscle triglyceride (TG) levels were not significantly different between groups, glucose uptake and total preperfusion TG concentration were negatively correlated ( r2= 0.27, P < 0.05). In conclusion, our results show that under hyperglycemic-hyperinsulinemic conditions, brief FR resulted in an increase in FA oxidative disposal that may contribute to the improvement in insulin sensitivity.
Membrane potential controls calcium entry into descending vasa recta pericytes
Authors: Zhang Zhong , Rhinehart Kristie , Pallone Thomas L.
Published: March 2015

We tested the hypothesis that constriction of descending vasa recta (DVR) is mediated by voltage-gated calcium entry. K+channel blockade with BaCl2(1 mM) or TEACl (30 mM) depolarized DVR smooth muscle/pericytes and constricted in vitro-perfused vessels. Pericyte depolarization by 100 mM extracellular KCl constricted DVR and increased pericyte intracellular Ca2+([Ca2+]i). The KATPchannel opener pinacidil (10−7-10−4M) hyperpolarized resting pericytes, repolarized pericytes previously depolarized by ANG II (10−8M), and vasodilated DVR. The DVR vasodilator bradykinin (10−7M) also reversed ANG II depolarization. The L-type Ca2+channel blocker diltiazem vasodilated ANG II (10−8M)- or KCl (100 mM)-preconstricted DVR, and the L-type agonist BayK 8644 constricted DVR. The plateau phase of the pericyte [Ca2+]iresponse to ANG II was inhibited by diltiazem. These data support the conclusion that DVR vasoreactivity is controlled through variation of membrane potential and voltage-gated Ca2+entry into the pericyte cytoplasm.
Uterine artery blood flow and renal sympathetic nerve activity during exercise in rabbit pregnancy
Authors: O'Hagan Kathleen P. , Alberts Jennifer A.
Published: March 2015

The uterine artery blood flow (UtBF) and renal sympathetic nerve activity (SNA) responses to treadmill exercise were evaluated in 12 nonpregnant (NP) and 17 term pregnant (P) rabbits. UtBF was monitored continuously with a Transonic flowprobe. Rabbits underwent three exercise trials (5-min duration) that varied in absolute workload. The rise in renal SNA with exercise was intensity related. Pregnancy did not affect the average steady-state renal SNA response expressed relative to maximum activity (P 24 ± 1% vs. NP 23 ± 2% of maximum smoke-elicited activity) and increased the average renal SNA response expressed relative to resting activity (P +155 ± 19% vs. NP +84 ± 23% from rest, P = 0.03) At rest, UtBF (P 13 ± 3 vs. NP 1.9 ± 0.3 ml/min) and uterine artery conductance (UtC; P 22 ± 5 vs. NP 2.8 ± 0.5 ml · min-1·mmHg-1× 10-2) were elevated in the P rabbits. The average exercise-related decreases in UtBF (P -16 ± 4% vs. NP -48 ± 4%) and UtC (P -27 ± 4% vs. NP -54 ± 4%) were attenuated in the P rabbits. Pregnancy does not impair the ability to raise renal SNA but attenuates the uterine artery constrictor response to moderate to heavy dynamic exercise in rabbits. Under normal conditions, the pregnant uterine circulatory bed may be relatively protected from exercise-related redistribution of blood flow.
Anterior paraventricular thalamus modulates light-induced phase shifts in circadian rhythmicity in rats
Authors: Salazar-Juárez Alberto , Escobar Carolina , Aguilar-Roblero Raúl
Published: March 2015

The reciprocal connections between the paraventricular thalamic nucleus (PVT) and the suprachiasmatic nuclei suggest that PVT may participate in the regulation of circadian rhythms. We studied in rats the effect of lesions of the anterior and midposterior regions of the PVT on phase shifts of drinking circadian rhythm induced by light pulses at circadian times 6, 12, and 23, as well as the phase shifts produced by electrical or glutamatergic stimulation of the anterior PVT at the same circadian times. Lesion of the anterior PVT abolishes the advances induced by light during late subjective night, whereas midposterior PVT lesions did not affect the phase shifts. Electrical stimulation or glutamate injections in the anterior PVT mimic the phase-shifting effects of light pulses. These results indicate the participation of the anterior PVT as a modulator of entrainment of circadian rhythms to light.
A new obesity-prone, glucose-intolerant rat strain (F.DIO)
Authors: Levin Barry E. , Dunn-Meynell Ambrose A. , McMinn Julie E. , Alperovich Michael , Cunningham-Bussel Amy , Chua Streamson C.
Published: March 2015

Previous breeding for the diet-induced obese (DIO) trait from outbred Sprague-Dawley rats produced a substrain with selection characteristics suggesting a polygenic mode of inheritance. To assess this issue further, selectively bred DIO male rats were crossed with obesity-resistant inbred Fischer F344 dams. Male offspring were crossed twice more against female F344 dams. The resultant N3 (F.DIO) rats were then inbred three more times. On low-fat chow, 10-wk-old male and female DIO rats weighed 86 and 59% more than respective F344 rats. By the N3 (F.DIO) generation, they were only 12 and 10% heavier, respectively. After three additional inbreeding cycles, chow-fed F.DIO males had an exaggerated insulin response to oral glucose compared with F344 rats. After 3 wk on a 31% fat (high-energy) diet, male N3 F.DIO rats gained 16-20% more carcass and adipose weight with 98% higher plasma leptin levels, whereas F.DIO females gained 36-54% more carcass and adipose weight with 130% higher leptin levels than comparable F344 rats. After three inbreeding cycles, F.DIO males still gained more weight on high-energy diet and developed a threefold greater insulin response to oral glucose than F344 males. Preservation of the DIO and glucose intolerance traits through successive backcrosses and inbreeding cycles to produce the F.DIO strain lends further support to the idea that they inherited in a polygenic fashion.
Energy restriction with protein restriction increases basal metabolism and meal-induced thermogenesis in rats
Authors: Even Patrick C. , Bertin Eric , Gangnerau Marie-Noelle , Roseau Suzanne , Tomé Daniel , Portha Bernard
Published: March 2015

We previously observed an increased sympathetic nervous system (SNS) activity that was partly responsible for a defect in the insulin secretion response to glucose after postweaning protein-energy restriction (PER) in female rats. These results, together with other data on low-protein feeding, suggested that a low protein-to-energy ratio (P/E) in the diet could stimulate energy expenditure (EE), but direct measurements of EE have never been reported under conditions of PER. The goal of the present study was thus to quantify the changes induced by PER to body composition, the various parameters of EE, and plasma triiodothyronine levels. PER induced severe growth retardation, but the subcutaneous white and interscapular brown adipose tissue masses were preserved. Basal metabolism, meal-induced thermogenesis, and triiodothyronine levels were increased, but substrate utilization by the working muscles was unaffected. Meal-induced thermogenesis was increased by spontaneous activity in PER rats only. These results suggest that rats adapt to a low P/E in the diet by burning part of their excess nonprotein energy and storing the remaining excess in subcutaneous adipose tissue.
Involvement of adrenergic pathways in activation of catalase by myocardial ischemia-reperfusion
Authors: Kim Young-Hoon , Chun Yang-Sook , Park Jong-Wan , Kim Chan-Hyung , Kim Myung-Suk
Published: March 2015

In situ rabbit hearts were subjected to 15 min of regional myocardial ischemia, and at various time points of reperfusion, antioxidant enzyme activity and mRNA expression were measured in ischemic and nonischemic myocardium. Catalase activity increased significantly in both ischemic and nonischemic myocardium, peaking at 1 h after reperfusion and then gradually returning to the control level. Northern blot analysis showed enhanced expression of catalase mRNA in both areas. There were no changes in redox status, because glutathione levels were not altered by ischemia-reperfusion (I/R). We also tested whether catalase activation in the heart results from signaling pathways that might influence not only the heart but also other organs. We found that catalase activity in the brain was increased after myocardial I/R and ischemic stress to the intestine was equipotent to myocardial I/R in catalase activation. We next sought to elucidate the possible involvement of the adrenergic system in catalase stimulation induced by ischemic stimuli. After pretreatment with the α-adrenergic receptor antagonist prazosin, I/R failed to increase catalase activity in the heart and brain. Intravenous norepinephrine increased catalase activity in the heart, brain, and liver. This study shows that brief I/R activates a signaling mechanism to induce catalase activation in multiple organs and the α-adrenergic system is involved as an intermediate pathway in this signal transmission.
Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice
Authors: Yang Runkuan , Gallo David J. , Baust Jeffrey J. , Watkins Simon K. , Delude Russell L. , Fink Mitchell P.
Published: March 2015

We sought to determine whether gut-derived microbial factors influence the hepatic or intestinal inflammatory response to hemorrhagic shock and resuscitation (HS/R). Conventional and gnotobiotic mice contaminated with a defined microbiota without gram-negative bacteria were subjected to either a sham procedure or HS/R. Tissue samples were obtained 4 h later for assessing ileal mucosal permeability to FITC dextran and hepatic and ileal mucosal steady-state IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF mRNA levels. Whereas HS/R significantly increased ileal mucosal permeability in conventional mice, this effect was not apparent in gnotobiotic animals. HS/R markedly increased hepatic mRNA levels for several proinflammatory genes in both conventional and gnotobiotic mice. HS/R increased ileal mucosal IL-6 and COX-2 mRNA expression in conventional but not gnotobiotic mice. If gnotobiotic mice were contaminated with Escherichia coli C25, HS/R increased ileal mucosal permeability and upregulated expression of IL-6 and COX-2. These data support the view that the hepatic inflammatory response to HS/R is largely independent of the presence of potentially pathogenic gram-negative bacteria colonizing the gut, whereas the local mucosal response to HS/R is profoundly influenced by the microbial ecology within the lumen during and shortly after the period of hemorrhage.
Sensitive periods for the effect of dietary sodium restriction on intact and denervated taste receptor cells
Authors: McCluskey Lynnette Phillips , Hill David L.
Published: March 2015

Unilateral chorda tympani nerve (CT) section combined with dietary sodium restriction leads to striking alterations in sodium taste function. The regenerated rat CT exhibits deficits in sodium sensitivity, and surprisingly, there are also functional alterations in the intact, contralateral nerve. The studies presented here describe the functional “sensitive periods” for these aberrations and the number of taste buds present during corresponding stages. The regenerated CT is sensitive to dietary sodium restriction during the first 2 wk after denervation, whereas the intact CT is sensitive to dietary manipulation during the first week postsection. Therefore, distinct mechanisms are responsible for the effects of sodium restriction combined with denervation, because separate sensitive periods exist for the regenerated and intact CT nerves. Identification of mature taste buds with an antibody directed at anti-keratin 19 revealed that there is a loss of ∼85% of taste buds on the denervated side of the tongue under control and low-sodium diets within the first week postsection. Thus, sodium restriction does not differentially affect the loss of taste buds following denervation.
Behavioral, plasma, and calorimetric changes related to food texture modification in men
Authors: Labouré Hélène , Van Wymelbeke Virginie , Fantino Marc , Nicolaidis Stylianos
Published: March 2015

We hypothesized that food texture modifications might alter anticipatory reflexes, feeding behavior, and the postabsorptive consequences of ingestion. Two sets of complete meals with different textures but the same macronutrient composition were prepared. The first set was either a soup containing chunks of food (mixture) or the same soup blended until smooth (purée). The second set was either a rusk (R), a sandwich loaf (SL), or a liquid rusk meal (LR). We measured hunger and fullness feelings after ingestion of each food in a calibrated lunch, the ingestion rate, the duration between lunch and a spontaneous dinner request, the energy value, and the macronutrient composition of the ad libitum dinner. We also studied plasma modifications and respiratory gas exchanges from lunch to dinner. Feelings of hunger and fullness were not affected by texture modifications. The purée soup was consumed faster than the mixture ( P < 0.05), and insulin, triacylglycerol, and energy expenditure were greater with the purée ( P < 0.05). LR was less palatable than the other rusk lunch versions ( P < 0.001), and R was ingested more slowly ( P < 0.05). The lowest increase in plasma glucose occurred with SL, and the highest energy expenditure was seen with LR ( P < 0.05). In humans, food texture modification affects not only eating patterns and palatability of ingestants but also metabolic management.
Wavelet analysis of instantaneous heart rate: a study of autonomic control during thrombolysis
Authors: Toledo Eran , Gurevitz Osnat , Hod Hanoch , Eldar Michael , Akselrod Solange
Published: March 2015

Myocardial infarction (MI) is known to elicit activation of the autonomic nervous system. Reperfusion, induced by thrombolysis, is thus expected to bring about a shift in the balance between the sympathetic and vagal systems, according to the infarct location. In this study, we explored the correlation between reperfusion and the spectral components of heart rate (HR) variability (HRV), which are associated with autonomic cardiac control. We analyzed the HR of patients during thrombolysis: nine anterior wall MI (AW-MI) and eight inferoposterior wall MI (IW-MI). Reperfusion was determined from changes in ST levels and reported pain. Reocclusion was detected in four patients. HRV was analyzed using a modified continuous wavelet transform, which provided time-dependent versions of the typically used low-frequency (LF) and high-frequency (HF) peaks and of their ratio, LF/HF. Marked alterations in at least one of the HRV parameters was found in all 18 reperfusion events. Patterns of HRV, compatible with a shift toward relative sympathetic enhancement, were found in all of the nine reperfusion events in IW-MI patients and in three AW-MI patients. Patterns of HRV compatible with relative vagal enhancement were found in six AW-MI patients ( P < 0.001). Significant changes in HRV parameters were also found after reocclusion. Time-dependent spectral analysis of HRV using the wavelet transform was found to be valuable for explaining the patterns of cardiac rate control during reperfusion. In addition, examination of the entire record revealed epochs of markedly diminished HRV in two patients, which we attribute to vagal saturation.
Circadian pattern of ventilation during acute and chronic hypercapnia in conscious adult rats
Authors: Seifert Erin L. , Mortola Jacopo P.
Published: March 2015

Because metabolism is a determinant of the ventilatory chemosensitivity, we tested the hypothesis that the ventilatory response to acute and prolonged hypercapnia is adjusted to the circadian oscillations in oxygen consumption (V˙o2). Adult rats were instrumented for measurements of body temperature (Tb) and activity by telemetry. Pulmonary ventilation (V˙e) was measured by the barometric method and V˙o2by the flow-through method. In the acute experiments, 16 conscious rats entrained to a 12:12-h light (L)-dark (D) cycle (lights on 7:00 AM) were exposed to air, 2%, and then 5% CO2in normoxia (30–45 min each) at 11:00 AM and 11:00 PM. In a separate group of seven rats, simultaneous recordings of all variables were made continuously for 3 consecutive days in air followed by 3 days in 2% CO2in normoxia, in a 12:12-h L-D cycle (lights on 7:00 AM). In air, all variables were significantly higher at night, whether rats were studied acutely or chronically. Acute CO2exposure had similar significant effects at 11:00 AM and 11:00 PM onV˙e (∼25 and 100% increase with 2 and 5% CO2, respectively) and V˙o2(∼8% drop with 5% CO2), such that the hyperventilatory response (% increase inV˙e/V˙o2from air) was similar at both times. Chronic CO2breathing increasedV˙e at all times of the day, but less so during the L phase (∼15 vs. 22% increase in L and D, respectively), when activity was lower. However, V˙o2was reduced from the air level (∼10% drop) in the L, such that theV˙e/V˙o2response was similar between L and D. The same result was obtained when theV˙e/V˙o2response was compared between the L and D phases for the same level of activity. These results suggest that, throughout the day, the hypercapnic hyperpnea, whether during acute or prolonged CO2, is perfectly adjusted to the metabolic level.
VEGF regulates remodeling during permanent anatomic closure of the ductus arteriosus
Authors: Clyman Ronald I. , Seidner Steven R. , Kajino Hiroki , Roman Christine , Koch Cameron J. , Ferrara Napoleone , Waleh Nahid , Mauray Françoise , Chen Yao Qi , Perkett Elizabeth A. , Quinn Timothy
Published: March 2015

Anatomic remodeling and permanent closure of the newborn ductus arteriosus appears to require the development of intense hypoxia within the constricted vessel wall. Hypoxic ductus smooth muscle cells express vascular endothelial cell growth factor (VEGF). We studied premature baboons and sheep to determine the effects of VEGF inhibition (in baboons) and VEGF stimulation (in sheep) on ductus remodeling in vivo. For study of VEGF inhibition, 13 premature newborn baboons (68% gestation) were treated with inhibitors of both prostaglandin and nitric oxide production to constrict the ductus and induce ductus wall hypoxia. Six received a neutralizing monoclonal antibody against VEGF (A.4.6.1, mAbVEGF), while seven did not. Both groups developed the same degree of ductus constriction, tissue hypoxia, and VEGF expression. The mAbVEGF treatment produced a significant ( P < 0.05) reduction in ductus vasa vasorum ingrowth and neointima formation (due to both a decrease in luminal endothelial cell proliferation and a decrease in smooth muscle cell migration into the neointima). For study of VEGF stimulation, nine sheep fetuses (70% gestation) had their ductus wall injected with either VEGF ( n = 6) or vehicle ( n = 4) in vivo. VEGF administration produced a significant ( P < 0.05) increase in vasa vasorum ingrowth and neointima formation. We conclude that VEGF plays an important role in the formation of neointimal mounds and vasa vasorum ingrowth during permanent ductus closure.
Vestibulosympathetic reflex during orthostatic challenge in aging humans
Authors: Monahan Kevin D. , Ray Chester A.
Published: March 2015

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 ± 1 yr) and 11 older subjects (64 ± 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Δ106 ± 28 vs. Δ20 ± 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Δ53 ± 15%; P < 0.05) but not older subjects (Δ−5 ± 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Δ−6 ± 2 mmHg) and during LBNP (Δ−7 ± 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.
Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats
Authors: Eckel Lisa A. , Houpt Thomas A. , Geary Nori
Published: March 2015

The ovarian hormone estradiol reduces meal size and food intake in female rats, at least in part by increasing the satiating potency of CCK. Here we used c-Fos immunohistochemistry to determine whether estradiol increases CCK-induced neuronal activation in several brain regions implicated in the control of feeding. Because the adiposity signals leptin and insulin appear to control feeding in part by increasing the satiating potency of CCK, we also examined whether increased adiposity after ovariectomy influences estradiol's effects on CCK-induced c-Fos expression. Ovariectomized rats were injected subcutaneously with 10 μg 17β-estradiol benzoate (estradiol) or vehicle once each on Monday and Tuesday for 1 wk ( experiment 1) or for 5 wk ( experiment 2). Two days after the final injection of estradiol or vehicle, rats were injected intraperitoneally with 4 μg/kg CCK in 1 ml/kg 0.9 M NaCl or with vehicle alone. Rats were perfused 60 min later, and brain tissue was collected and processed for c-Fos immunoreactivity. CCK induced c-Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus of the hypothalamus (PVN), and central nucleus of the amygdala (CeA) in vehicle- and estradiol-treated ovariectomized rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, the PVN, and the CeA, but not in the rostral NTS or AP. This action of estradiol was very similar in rats tested before ( experiment 1) and after ( experiment 2) significant body weight gain, suggesting that adiposity does not modulate CCK-induced c-Fos expression or interact with estradiol's ability to modulate CCK-induced c-Fos expression. These findings suggest that estradiol inhibits meal size and food intake by increasing the central processing of the vagal CCK satiation signal.
Endothelin-A receptors and NO mediate decrease in arterial pressure during recovery from restraint
Authors: Yip Avery W. C. , Krukoff Teresa L.
Published: March 2015

We investigated the role of central endothelin-A (ETA) receptors and nitric oxide (NO) in regulating arterial pressure during restraint stress and recovery from stress. Rats received intracerebroventricular (icv) injections of the ETAreceptor antagonist BQ123 (24 μg/kg) and were then subjected to two restraint-rest cycles (1 h of restraint and 1 h of rest/cycle). Although mean arterial pressure (MAP) values in BQ123-treated and control rats increased at the onset of restraint and remained elevated during restraint, MAP values in BQ123-treated rats were consistently greater than in control rats. During rest periods, MAP values in control rats decreased to below baseline levels, whereas those in BQ123-treated rats remained significantly higher. NO content was decreased in the brain stems of BQ123-treated compared with control rats after the 4-h protocol. Injections (icv) of the NO synthase (NOS) inhibitor N G-nitro-l-arginine (l-NNA) eliminated the decreases in MAP values during rest periods in both BQ123-treated and control rats. Inhibition of neuronal NOS with icv injection of 7-nitroindazole sodium salt resulted in MAP values intermediate between control rats and rats receivingl-NNA. These results support the hypothesis that endothelin acts through ETA receptors in the brain, possibly via release of NO, to decrease arterial pressure during restraint and recovery from restraint.
Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite
Authors: Menani José Vanderlei , Barbosa Silas Pereira , De Luca Laurival Antonio , De Gobbi Juliana Irani Fratucci , Johnson Alan Kim
Published: March 2015

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 μg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.
Differential activation of mTOR signaling by contractile activity in skeletal muscle
Authors: Parkington Jascha D. , Siebert Adam P. , LeBrasseur Nathan K. , Fielding Roger A.
Published: March 2015

The cellular mechanisms by which contractile activity stimulates skeletal muscle hypertrophy are beginning to be elucidated and appear to include activation of the phosphatidylinositol 3-kinase signaling substrate mammalian target of rapamycin (mTOR). We examined the time course and location of mTOR phosphorylation in response to an acute bout of contractile activity. Rat hindlimb muscle contractile activity was elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Plantaris (Pla), tibialis anterior (TA), and soleus (Sol) muscles from stimulated and control limbs were collected immediately or 6 h after stimulation. HFES resulted in mTOR phosphorylation immediately after (3.4 ± 0.9-fold, P < 0.01) contractile activity in Pla, whereas TA was unchanged compared with controls. mTOR phosphorylation remained elevated in Pla (3.6 ± 0.6-fold) and increased in TA (4.6 ± 0.9-fold, P < 0.05) 6 h after HFES. Interestingly, mTOR activation occurred predominantly in fibers expressing type IIa but not type I myosin heavy chain isoform. Furthermore, HFES induced modest ribosomal protein S6 kinase phosphorylation immediately after exercise in Pla (0.4 ± 0.1-fold, P < 0.05) but not TA and more markedly 6 h after in both Pla and TA (1.4 ± 0.4-fold vs. 2.4 ± 0.3-fold, respectively, P < 0.01). Akt/PKB phosphorylation was similar to controls at both time points. These results suggest that mTOR signaling is increased after a single bout of muscle contractile activity. Despite reports that mTOR is activated downstream of Akt/PKB, in this study, HFES induced mTOR signaling independent of Akt/PKB phosphorylation. Fiber type-dependent mTOR phosphorylation may be a molecular basis by which some fiber types are more susceptible to contraction-induced hypertrophy.
Role of thromboxane receptors in the dipsogenic response to central angiotensin II
Authors: Kitiyakara Chagriya , Welch William J. , Verbalis Joseph G. , Wilcox Christopher S.
Published: March 2015

Central angiotensin II (ANG II) regulates thirst. Because thromboxane A2-prostaglandin H2 (TP) receptors are expressed in the brain and mediate some of the effects of ANG II in the vasculature, we investigated the hypothesis that TP receptors mediate the drinking response to intracerebroventricular (icv) injections of ANG II. Pretreatment with the specific TP-receptor antagonist ifetroban (Ifet) decreased water intake with 50 ng/kg icv ANG II (ANG II + Veh, 7.2 ± 0.7 ml vs. ANG II + Ifet, 2.8 ± 0.8 ml; n = 5 rats; P < 0.001) but had no effect on water intake induced by hypertonic saline (NaCl + Veh, 8.4 ± 1.1 ml vs. NaCl + Ifet, 8.9 ± 1.8 ml; n = 5 rats; P = not significant). Administration of 0.6 μg/kg icv of the TP-receptor agonist U-46,619 did not induce drinking when given alone but did increase the dipsogenic response to a near-threshold dose of 15 ng/kg icv ANG II (ANG II + Veh, 1.1 ± 0.7 vs. ANG II + U-46,619, 4.5 ± 0.9 ml; n = 5 rats; P < 0.01). We conclude that central TP receptors contribute to the dipsogenic response to ANG II.
Cortisol alters carbonic anhydrase-mediated renal sulfate secretion
Authors: Pelis Ryan M. , Goldmeyer James E. , Crivello Joseph , Renfro J. Larry
Published: March 2015

Active transepithelial sulfate secretion rate by winter flounder renal proximal tubule epithelium in primary culture (fPTC) is dependent on intracellular carbonic anhydrase (CA) and enhanced by cortisol. To further evaluate this relationship, a partial cDNA clone (327 bp) of carbonic anhydrase II (CAII) with high sequence similarity to CAII from numerous species including fish, chicken, and human was obtained from fPTCs. The majority of CA activity and CAII protein was present in the cytosol of fPTCs; however, significant amounts of both (in addition to SDS-resistant CA activity, i.e., CAIV-like isoform) were present in concentrated plasma membranes. CAII from concentrated membranes migrated differently than purified CAII on nondenaturing PAGE gels, suggesting that CAII associates with another membrane component. Treatment of fPTCs with the cell-soluble CA inhibitor methazolamide (100 μM) caused a 58% reduction in active transepithelial SO42-secretion. fPTCs that were previously cultured under high-cortisol concentrations, when subjected to 5 days of low physiological levels of cortisol, had decreased CA activity (28%), CAII protein abundance (65%), and net active SO42-secretion (28%), with no effect on epithelial differentiation. Methazolamide and low-cortisol treatment in combination inhibited net active SO42-secretion 56%, which was not different than the effect of methazolamide treatment alone. These data indicate that cortisol directly increases renal CA activity, CAII protein abundance, and CA-dependent SO42-secretion in the marine teleost renal proximal tubule.
Baroreflex modulation of sympathetic nerve activity to muscle in heat-stressed humans
Authors: Cui Jian , Wilson Thad E. , Crandall Craig G.
Published: March 2015

To identify whether whole body heating alters arterial baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA and beat-by-beat arterial blood pressure were recorded in seven healthy subjects during acute hypotensive and hypertensive stimuli in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature ( P < 0.01), MSNA ( P < 0.01), heart rate ( P< 0.01), and skin blood flow ( P < 0.001), whereas mean arterial blood pressure did not change significantly ( P > 0.05). During both normothermic and heat stress conditions, MSNA increased and then decreased significantly when blood pressure was lowered and then raised via intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure during heat stress (−128.3 ± 13.9 U · beats−1 · mmHg−1) was similar ( P = 0.31) with normothermia (−140.6 ± 21.1 U · beats−1 · mmHg−1). Moreover, no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that arterial baroreflex modulation of MSNA and heart rate are not altered by whole body heating, with the exception of an upward shift of these baroreflex curves to accommodate changes in these variables that occur with whole body heating.
Compensation for partial lipectomy in mice with genetic alterations of leptin and its receptor subtypes
Authors: Harris Ruth B. S. , Hausman Dorothy B. , Bartness Timothy J.
Published: March 2015

One hypothesis for the regulation of total body fat suggests that leptin is a lipostatic feedback signal that acts at brain sites involved in regulation of energy balance. The importance of leptin in recovery from partial surgical lipectomy was tested by performing bilateral epididymal lipectomy or sham surgery on wild-type and leptin-deficient ob/ob mice. Eight weeks later, nonexcised pads of lipectomized mice were increased but total carcass fat was lower than in sham-operated ob/ob mice. In experiment 2, ob/ob mice, wild-type mice, and two db/db mutants, C57BL/6J dbLepr/dbLepr (BL/6J) mice possessing short-form and circulating leptin receptors and C57BL/6J db3J/db3J (BL/3J) mice expressing only circulating receptors, were lipectomized or sham operated. Sixteen weeks later, body mass and carcass lipid were not different between sham and lipectomized ob/ob mice, wild-type mice, or BL/6J db/db mice, whereas there was incomplete (decreased carcass fat) but suggestive recovery (increased retroperitoneal fat mass and cell number) in lipectomized BL/3J db/db mice. These data indicate that leptin is not required for the regulation of total body fat.
Glutamate receptors in RVLM modulate sympathetic baroreflex in conscious rabbits
Authors: Mayorov Dmitry N. , Head Geoffrey A.
Published: March 2015

In this study, we examined the effect of excitatory amino acid (EAA) receptor blockade in the rostral ventrolateral medulla (RVLM) on the renal sympathetic baroreflex in conscious rabbits. Rabbits were implanted with guide cannulas for bilateral microinjections into the RVLM (+2 to +3 mm from the obex, n = 8) or into the intermediate ventrolateral medulla (IVLM; 0 to +1 mm from the obex, n = 5) and with an electrode for measuring renal sympathetic nerve activity (RSNA). After 7 days of recovery, microinjection of the EAA receptor antagonist kynurenate (10 nmol) into the RVLM did not affect resting RSNA or arterial pressure. Kynurenate decreased the gain of the RSNA baroreflex by 53% but did not change the reflex range. By contrast, injection of kynurenate into the IVLM increased resting arterial pressure and RSNA by 27 mmHg and 88%, respectively, but did not alter the RSNA baroreflex gain or range. Pentobarbital sodium anesthesia attenuated the gain and range of the RSNA baroreflex by 78 and 40%, respectively. Under these conditions, microinjection of kynurenate into the RVLM did not cause any further change in the gain of this reflex. These results suggest that endogenous EAA neurotransmitters in the RVLM are important in modulating the sympathetic baroreflex in conscious rabbits. Anesthesia can mask the functional significance of EAAs in the RVLM in modulating the baroreflexes, which may explain why previous studies in anesthetized animals found no effect of blocking EAA receptors in the RVLM on sympathetic baroreflexes.
Sleep in mice with nonfunctional growth hormone-releasing hormone receptors
Authors: Obal Ferenc , Alt Jeremiah , Taishi Ping , Gardi Janos , Krueger James M.
Published: March 2015

The role of the somatotropic axis in sleep regulation was studied by using the lit/lit mouse with nonfunctional growth hormone (GH)-releasing hormone (GHRH) receptors (GHRH-Rs) and control heterozygous C57BL/6J mice, which have a normal phenotype. During the light period, the lit/lit mice displayed significantly less spontaneous rapid eye movement sleep (REMS) and non-REMS (NREMS) than the controls. Intraperitoneal injection of GHRH (50 μg/kg) failed to promote sleep in the lit/lit mice, whereas it enhanced NREMS in the heterozygous mice. Subcutaneous infusion of GH replacement stimulated weight gain, increased the concentration of plasma insulin-like growth factor-1 (IGF-1), and normalized REMS, but failed to restore normal NREMS in the lit/lit mice. The NREMS response to a 4-h sleep deprivation was attenuated in the lit/lit mice. In control mice, intraperitoneal injection of ghrelin (400 μg/kg) elicited GH secretion and promoted NREMS, and intraperitoneal administration of the somatostatin analog octretotide (Oct, 200 μg/kg) inhibited sleep. In contrast, these responses were missing in the lit/lit mice. The results suggest that GH promotes REMS whereas GHRH stimulates NREMS via central GHRH-Rs and that GHRH is involved in the mediation of the sleep effects of ghrelin and somatostatin.
Vascular reactivity in intrapulmonary arteries of chicken embryos during transition to ex ovo life
Authors: Villamor Eduardo , Ruijtenbeek Karin , Pulgar Victor , De Mey Jo G. R. , Blanco Carlos E.
Published: March 2015

The present study aimed to characterize pulmonary vascular reactivity in the chicken embryo from the last stage of prenatal development and throughout the perinatal period. Isolated intrapulmonary arteries from non-internally pipped embryos at 19 days of incubation and from internally and externally pipped embryos at 21 days of incubation were studied. Arterial diameter and contractile responses to KCl, endothelin-1, and U-46619 increased with incubation but were unaffected by external pipping. In contrast, the contractions induced by norepinephrine, phenylephrine, and electric field stimulation decreased with development. No developmental changes were observed in endothelium-dependent [acetylcholine (ACh) and cyclopiazonic acid] or endothelium-independent [sodium nitroprusside (SNP)] relaxation. These relaxations were abolished by the soluble guanylate cyclase inhibitior 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Endothelium-dependent relaxation was unaffected by blockade of cyclooxygenase or heme oxygenase but was significantly reduced by nitric oxide (NO) synthase inhibitors. Reduction of O2concentration from 95 to 5% produced a marked reduction in ACh and SNP-induced relaxations. Chicken embryo pulmonary arteries show a marked endothelium-dependent relaxation that is unaffected by transition to ex ovo life. Endothelium-derived NO seems to be the main mediator responsible for this relaxation.
Central mineralocorticoid receptor blockade decreases plasma TNF-α after coronary artery ligation in rats
Authors: Francis Joseph , Weiss Robert M. , Johnson Alan Kim , Felder Robert B.
Published: March 2015

The Randomized Aldactone Evaluation Study (RALES) demonstrated a substantial clinical benefit to blocking the effects of aldosterone (Aldo) in patients with heart failure. We recently demonstrated that the enhanced renal conservation of sodium and water in rats with heart failure can be reduced by blocking the central nervous system effects of Aldo with the mineralocorticoid receptor (MR) antagonist spironolactone (SL). Preliminary data from our laboratory suggested that central MR might contribute to another peripheral mechanism in heart failure, the release of proinflammatory cytokines. In the present study, SL (100 ng/h for 21 days) or ethanol vehicle (Veh) was administered via the 3rd cerebral ventricle to one group of rats after coronary ligation (CL) or sham CL (Sham) to induce congestive heart failure (CHF). In Veh-treated CHF rats, tumor necrosis factor-α (TNF-α) levels increased during day 1 and continued to increase throughout the 3-wk observation period. In CHF rats treated with SL, started 24 h after CL, TNF-α levels rose initially but retuned to control levels by day 5 after CL and remained low throughout the study. These findings suggest that activation of MR in the central nervous system plays a critical role in regulating TNF-α release in heart failure rats. Thus some of the beneficial effect of blocking MR in heart failure could be due at least in part to a reduction in TNF-α production.
Chronic measurement of cardiac output in conscious mice
Authors: Janssen B. , Debets J. , Leenders P. , Smits J.
Published: March 2015

We describe the feasibility of chronic measurement of cardiac output (CO) in conscious mice. With the use of gas anesthesia, mice >30 g body wt were instrumented either with transit-time flow probes or electromagnetic probes placed on the ascending aorta. Ascending aortic flow values were recorded 6–16 days after surgery when probes had fully grown in. In the first set of experiments, while mice were under ketamine-xylazine anesthesia, estimates of stroke volume (SV) obtained by the transit-time technique were compared with those simultaneously obtained by echocardiography. Transit-time values of SV were similar to those obtained by echocardiography. The average difference ± SD between the methods was 2 ± 7 μl. In the second set of studies, transit-time values of CO were compared with those obtained by the electromagnetic flow probes. In conscious resting conditions, estimates (±SD) of cardiac index (CI) obtained by the transit-time and electromagnetic flow probes were 484 ± 119 and 531 ± 103 ml · min−1 · kg body wt−1, respectively. Transit-time flow probes were also implanted in mice with a myocardial infarction (MI) induced by ligation of a coronary artery 3 wk before probe implantation. In these MI mice ( n = 7), average (±SD) resting and stimulated (by volume loading) values of CO were significantly lower than in noninfarcted mice ( n = 15) (resting CO 16 ± 3 vs. 20 ± 4 ml/min; stimulated CO 20 ± 5 vs. 26 ± 6 ml/min). Finally, using transfer function analysis, we found that, in resting conditions for both intact and MI mice, spontaneous variations in CO (>0.1 Hz) were mainly due to those occurring in SV rather than in heart rate. These data indicate that CO can be measured chronically and reliably in conscious mice, also in conditions of heart failure, and that variations in preload are an important determinant of CO in this species.