bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive responses of GLUT-4 and citrate synthase in fast-twitch muscle of voluntary running rats
Authors: Henriksen E. J. , Halseth A. E.
Published: December 2017

Glucose transporter (GLUT-4) protein, hexokinase, and citrate synthase (proteins involved in oxidative energy production from blood glucose catabolism) increase in response to chronically elevated neuromuscular activity. It is currently unclear whether these proteins increase in a coordinated manner in response to this stimulus. Therefore, voluntary wheel running (WR) was used to chronically overload the fast-twitch rat plantaris muscle and the myocardium, and the early time courses of adaptative responses of GLUT-4 protein and the activities of hexokinase and citrate synthase were characterized and compared. Plantaris hexokinase activity increased 51% after just 1 wk of WR, whereas GLUT-4 and citrate synthase were increased by 51 and 40%, respectively, only after 2 wk of WR. All three variables remained comparably elevated (+50-64%) through 4 wk of WR. Despite the overload of the myocardium with this protocol, no substantial elevations in these variables were observed. These findings are consistent with a coordinated upregulation of GLUT-4 and citrate synthase in the fast-twitch plantaris, but not in the myocardium, in response to this increased neuromuscular activity. Regulation of hexokinase in fast-twitch muscle appears to be uncoupled from regulation of GLUT-4 and citrate synthase, as increases in the former are detectable well before increases in the latter.
Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep
Authors: Charles C. J. , Espiner E. A. , Richards A. M. , Nicholls M. G. , Yandle T. G.
Published: December 2017

C-type natriuretic peptide (CNP) is found in abundance in neural tissue and in endothelial cells of vascular tissue, where it may participate in the regulation of vascular tone. However, few studies have examined the metabolism and systemic actions of CNP in conscious animals. Accordingly, we investigated the hemodynamic, renal, and hormonal effects of intravenous CNP-22 administered at two doses (1 and 10 pmol.kg-1.min-1 as dose 1 and dose 10, respectively) in a vehicle-controlled study in normal conscious sheep (n = 8). Plasma CNP levels were raised from a mean baseline level of 2-3 pmol/l (detection limit) to plateau at 10 +/- 1.2 and 115 +/- 18 pmol/l during doses 1 and 10, respectively. Metabolic clearance rates were 3.15 +/- 0.39 and 2.48 +/- 0.36 l/min, respectively. The plasma half-life of CNP on termination of infusion was rapid (1.6 +/- 0.27 min). Dose 10 increased plasma guanosine 3',5'-cyclic monophosphate (P = 0.0002), reduced cardiac output by 18% (P = 0.01), but did not significantly affect mean arterial pressure. Similar suppression (15%) of cardiac output occurred during dose 1 (P = 0.078). Both doses were natriuretic. This study demonstrates that CNP is natriuretic in sheep and lowers cardiac output without significantly affecting arterial pressure. CNP may play an important role in the regulation of regional hemodynamics and fluid homeostasis.
Oral-pharyngeal-esophageal and gastric cues contribute to meal-induced c-fos expression
Authors: Fraser K. A. , Raizada E. , Davison J. S.
Published: December 2017

We recently demonstrated that a meal induces c-fos immunoreactivity in the dorsal motor nucleus of the vagus (DMV), the nucleus of the tractus solitarius (NTS), and the area postrema (AP) of the rat brain stem. This response was not eliminated by the cholecystokinin A (CCK-A) antagonist L-364,718, a finding suggesting that feeding induces c-fos immunoreactivity by a pathway that is largely independent of CCK-A receptor activation. Consequently, the role of alternative gastrointestinal cues in the induction of c-fos was investigated. The induction of c-fos after oral-pharyngeal and esophageal stimuli was examined by use of a sham-feeding procedure via a gastric fistula. Gastric fistula-closed and fed rats displayed c-fos immunoreactivity similar to that of meal-fed rats seen previously. Fistula-open and fed rats showed the same degree of staining in the more rostral section of NTS examined as fistula-closed and fed rats, but fewer c-fos-positive nuclei in the more caudal level of the NTS. The potential for gastric distension to induce c-fos was assessed after the inflation of a gastric balloon. Physiological inflation of the balloon produced marked c-fos induction primarily in the medial NTS.
Interaction of hypertension and caloric restriction on cardiac mass and isomyosin expression
Authors: Swoap S. J. , Boddell P. , Baldwin K. M.
Published: December 2017

Previous studies show that elevations in blood pressure induce concomitant increases in both cardiac mass and slow beta-myosin heavy chain (MHC) expression in rodents, whereas caloric restriction of 50% (CR) causes an increase in beta-MHC while modestly lowering blood pressure in normotensive rats. The goals of this study were to 1) determine if beta-MHC expression could be independently regulated by CR and hypertension when these two interventions are combined and 2) determine if CR exerts a lowering of blood pressure in two contrasting models of rodent hypertension. Rodents were assigned to the following groups: 1) normal control (NC); 2) abdominal aortic constriction (Abcon), a model that induces hypertension via renin-angiotensin II; 3) nephrectomy-deoxycorticosterone acetate treatment (DOCA), a model that induces hypertension through increased salt retention; 4) CR; 5) Abcon+CR; 6) DOCA+CR. Results show that both Abcon and DOCA induced significant increases in systemic blood pressures, left ventricular (LV) weight/body weight, and the relative content of beta-MHC compared with NC. When applied in combination with either Abcon or DOCA, CR significantly blunted the changes observed in both systemic blood pressures and LV weight/body weight. In contrast, CR in conjunction with DOCA augmented % beta-MHC expression relative to either DOCA or CR alone. These data suggest 1) caloric restriction exerts a powerful impact on reducing experimentally induced hypertension in rodents and 2) the regulation of beta-MHC expression appears to be regulated by at least two processes, one associated with the stimulus of hypertension and the other involving an independent pathway linked to caloric restriction.
Effect of liver denervation on glucose production during running in guinea pigs
Authors: Wiersma M. M. , Vissing J. , Mikines K. J. , Steffens A. B. , Galbo H.
Published: December 2017

Activity in sympathetic liver nerves has been proposed to be important for glucose production in exercising humans. However, liver denervation does not influence the exercise-induced increase in glucose production in the rat and dog. These species have a poor sympathetic liver innervation in contrast to the rich innervation in humans. The effect of liver denervation on glucose production during exercise was therefore studied in the guinea pig, a species with a rich sympathetic hepatic innervation comparable to that of humans. Guinea pigs were selectively liver denervated (n = 9) or sham operated (n = 8) and instrumented with a carotid and a jugular catheter. One week later they ran on a treadmill at 32 m/min for 20 min. Glucose turnover was evaluated by a primed constant-rate intravenous infusion of [3-3H]glucose. Arterial blood was sampled for analysis of hormones and metabolites. At rest, liver-denervated guinea pigs had lower glucose turnover and plasma concentrations of glucose, glycerol, and cortisol than control animals. During running, the increase in hepatic glucose production was similar in the two groups (4.1 +/- 0.8 vs. 3.8 +/- 0.7 mumol.min-1.100 g-1 in control animals) and so were hepatic (247 +/- 25 vs. 246 +/- 45 mmol glucose units/kg wet wt in control animals) and muscle glycogen concentrations at the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
HSP70 induction during exercise and heat stress in rats: role of internal temperature
Authors: Skidmore R. , Gutierrez J. A. , Guerriero V. , Kregel K. C.
Published: December 2017

The purpose of this study was to determine if the accumulation of the 72-kDa heat shock protein (HSP70) is elevated in response to a prolonged bout of submaximal exercise in which colonic temperature (Tco) remained at control levels. Sprague-Dawley rats were randomly assigned to one of four testing groups [n = 8 per group; ambient temperatures (Ta) for each condition are included]: 1) control (cool/rest; Ta = 24 degrees C); 2) cool and exercise (cool/exercise; Ta = 14 degrees C); 3) nonexertional heating (heat/rest; Ta = 42 degrees C); 4) heat and exercise (heat/exercise; Ta = 32 degrees C). All interventions were approximately 60 min in duration. An exercise bout consisted of treadmill running at 17 m/min and 0% grade, while the heat/rest and heat/exercise experiments consisted of heat exposure that was terminated when Tco reached 41 degrees C. Baseline Tco was similar for all four groups. In the cool/rest and cool/exercise groups, final Tco was not different from the baseline values, nor was it different between these two groups. In the heat/rest and heat/exercise groups, heating rates were similar. Tissue samples were obtained from the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles of the left hindlimb and the left ventricle 30 min after a trial was completed. An enzyme-linked immunosorbent assay specific for HSP70 was used to directly quantitate absolute levels of HSP70 in tissues. There were significant main effects of both heating and exercise for HSP70 levels in the gastrocnemius, soleus, and left ventricle (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of renal medullary blood flow in the development of L-NAME hypertension in rats
Authors: Nakanishi K. , Mattson D. L. , Cowley A. W.
Published: December 2017

The effect of chronic intravenous infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 8.6 mg.kg-1.day-1) on blood pressure, intrarenal blood flow distribution, and sodium and water balance was studied in conscious rats. On the 1st day of intravenous L-NAME infusion, renal medullary blood flow was reduced by 22%, renal cortical blood flow was unaltered, approximately 1 meq of sodium and 12 ml of water were retained, and blood pressure increased from 96 +/- 2 to 118 +/- 2 mmHg. Medullary blood flow was maintained at this decreased level, sodium continued to be retained, body weight continued to increase, and blood pressure remained elevated for the 5 days of L-NAME infusion. During the postcontrol period, blood flow in the renal medulla returned to levels not significantly different from control; the animals went into negative sodium balance and stopped gaining weight, and blood pressure returned to control. The present experiments indicate that decreased renal medullary blood flow and retention of sodium and water play an important role in the development of hypertension during chronic systemic L-NAME administration despite no measurable changes in renal cortical blood flow.
Reduced norepinephrine turnover in organs and brains of obesity-prone rats
Authors: Levin B. E.
Published: December 2017

One-half of the adult male Sprague-Dawley rats fed a diet relatively high in fat, sucrose, and energy content (HE diet) develop diet-induced obesity (DIO). The rest are diet resistant (DR). The role of peripheral and central norepinephrine (NE) activity in predisposing them to these weight gain patterns was assessed before HE diet exposure. Chow-fed male 3-mo-old Sprague-Dawley rats were separated as being prone to become DIO or DR by their high (3.06 +/- 0.14 micrograms) vs. low (1.17 +/- 0.10 micrograms; P = 0.001) 24-h urine NE output, respectively. Turnover of NE, an index of sympathetic activity, was assessed by synthesis inhibition with alpha-methyl-p-tyrosine. DIO-prone rats had significant 53 and 18% reductions in heart and pancreas NE turnover, with interscapular brown adipose tissue turnover comparable to that of DR-prone rats. Hypothalamic NE turnover was significantly decreased by 85 and 60% in the ventromedial nucleus and lateral area vs. DR-prone rats. Although present in DR-prone rats, no turnover was found in the dorsomedial nucleus of DIO-prone rats. Endogenous NE was reduced by 28% in the paraventricular nucleus, whereas arcuate/median eminence turnover was increased by 100% in DIO-prone rats. Amygdalar NE turnover was similar between phenotypes. These intrinsic differences in NE metabolism may play an important role in the development of DIO on HE diets.
Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats
Authors: Klir J. J. , McClellan J. L. , Kozak W. , Szelenyi Z. , Wong G. H. , Kluger M. J.
Published: December 2017

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 microliter of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 micrograms/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 micrograms/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 microgram/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 +/- 0.12 degrees C in rats injected with hrTNF and LPS vs. 38.73 +/- 0.04 degrees C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.
Moderate, selective depletion of linoleate and alpha-linolenate in weight-cycled rats
Authors: Chen Z. Y. , Menard C. R. , Cunnane S. C.
Published: December 2017

In rats, the response of adipose tissue composition to a single weight cycle (24-48 h of fasting followed by refeeding) is characterized by a decrease primarily in linoleate and alpha-linolenate, with little or no change in other fatty acids. We tested the hypothesis that during successive weight cycles caused by repeated fasting and refeeding, the depletion of linoleate and alpha-linolenate from whole body stores would be exacerbated despite their adequate availability during the refeeding period. Four complete weight cycles (24-h fasting followed by 72-h ad libitum refeeding) induced a significant quantitative decrease in total n-3 and n-6 polyunsaturates, particularly linoleate and alpha-linolenate, and a simultaneous increase in the accumulation of palmitate, palmitoleate, and oleate in carcass total lipids and in perirenal and epididymal adipose tissue. A significant positive relationship was observed between the increasing ratio of saturates+monounsaturates to n-3 + n-6 polyunsaturates in adipose tissue and the number of weight cycles (r = +0.96, P < 0.0001). The percentage of linoleate and alpha-linolenate in adipose tissue was inversely related to the number of weight cycles. We conclude that, despite providing adequate n-6 and n-3 polyunsaturates in the diet during the refeeding period, weight cycling in young growing rats causes a moderate, selective depletion of linoleate and alpha-linolenate from tissue stores.
Water intake and activity of hypothalamoneurohypophysial system during osmotic and sodium stimulation in rats
Authors: Kadekaro M. , Harris J. , Freeman S. , Terrell M. L. , Koehler E. , Summy-Long J. Y.
Published: December 2017

Intrajugular infusion (200 microliters/min for 10 min) of 0.85 M NaCl or 1.7 M mannitol in conscious adult male Sprague-Dawley rats increased plasma osmolality similarly and had an additive effect when combined. Plasma Na+ concentration, however, increased with infusion of 0.85 M NaCl, decreased with 1.7 M mannitol, and was not significantly altered by the combined solution. Irrespective of changes in plasma Na+ concentration, plasma vasopressin and oxytocin concentrations were elevated to a similar degree after independent infusion of 0.85 M NaCl or 1.7 M mannitol. With the combined infusion, the change in plasma vasopressin was additive but the change in oxytocin tended to be greater. Accordingly, glucose utilization increased throughout the hypothalamoneurohypophysial system after infusion of 0.85 M NaCl and 1.7 M mannitol. With the combined infusion, however, the change in glucose utilization in the paraventricular nucleus was additive but a synergistic effect occurred in the supraoptic nucleus and neural lobe. Drinking responses were similar in all groups receiving hypertonic solutions, with no additive effect after the combined stimulus. Although our results do not completely rule out the participation of cerebrospinal fluid sodium receptors, it is more likely that osmoreceptors regulate the activity of the hypothalamoneurohypophysial system and drinking behavior. Unlike the magnocellular system, however, drinking behavior seems to be negatively influenced by a stress component of the osmotic stimulation.
Role of endogenous central opioid mechanisms in maintenance of body sodium balance
Authors: Kapusta D. R. , Obih J. C.
Published: December 2017

The role of endogenous central opioids in the regulation of renal function was studied in Sprague-Dawley rats. In metabolism studies, changes in sodium balance were examined during normal dietary sodium intake (days 1-7; Na+ of 174 meq/kg) and sodium restriction (days 8-14; Na+ of 4.0 meq/kg). The influence of endogenous central opioids was investigated by repeating the protocol in the same rats during intracerebroventricular infusion of the opioid antagonist naltrexone methylbromide (NMBR). Intracerebroventricular NMBR did not alter sodium balance in rats fed normal sodium chow. In contrast, on low-sodium days 8 and 9, rats exhibited a more negative sodium balance during intracerebroventricular NMBR (day 8; -1,191 +/- 37 mu eq) compared with respective predrug control levels (day 8; -641 +/- 39 mu eq). Subcutaneous NMBR did not alter renal adaptation to sodium restriction. Thus central opioids are not involved in the maintenance of sodium balance during normal sodium intake. However, when dietary sodium is restricted, central opioid pathways are activated as a mechanism to maximally retain sodium.
Interaction of the renal nerves and prostaglandins on the phosphaturic response to PTH in phosphate-deprived rats
Authors: Berndt T. J. , Khraibi A. A. , Knox F. G.
Published: December 2017

Previous studies demonstrated that catecholamines modulate the phosphaturic response to parathyroid hormone (PTH) in normal rats. The present study was performed to determine the effect of unilateral renal denervation (DNX) and the interaction with prostaglandin synthesis on the blunted phosphaturic response to PTH in phosphate-deprived rats. One week before the acute experiment, rats were anesthetized, and the left kidney was denervated or sham surgery was performed. Rats were fed either a low-phosphate diet (LPD, 0.07%) or a normal-phosphate diet (NPD, 0.7%) for 2 days before the experiment. All rats were thyroparathyroidectomized (TPTX). Control clearances were taken from the left kidney 2 h after TPTX. PTH (33 U/kg + 1 U.kg-1.min-1) was infused for 45 min, and then the urine collections were repeated. In phosphate-deprived rats with an innervated kidney, PTH infusion resulted in a blunted phosphaturic response [changed fractional excretion of phosphate (delta FEPi) of 9.2 +/- 3.7%, n = 9] compared with rats fed NPD (delta FEPi 45.7 +/- 9.3%, n = 6) or those in the phosphate-deprived group with renal DNX (delta FEPi 23.6 +/- 5.0%, n = 12). Indomethacin pretreatment (3 mg/kg) markedly attenuated the phosphaturic response to PTH in phosphate-deprived rats with a denervated kidney (delta FEPi, 3.2 +/- 1.3%, n = 7) but not in animals fed an LPD with innervated kidneys or in rats fed an NPD. Infusion of Iloprost (2 ng.kg-1.min-1), a stable prostaglandin I2 analogue, in indomethacin-treated phosphate-deprived rats enhanced the phosphaturic response to PTH in rats with a denervated kidney (delta FEPi 17.3 +/- 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)
Fever in pregnant, parturient, and lactating rats
Authors: Martin S. M. , Malkinson T. J. , Veale W. L. , Pittman Q. J.
Published: December 2017

Conscious virgin, pregnant, or lactating rats were given intravenous Escherichia coli endotoxin while their temperatures were monitored telemetrically. Virgin females responded to 10-50 micrograms/kg endotoxin with a slight hypothermia, followed by a fever of nearly 2 degrees C magnitude. In pregnant rats given 25 micrograms/kg of the endotoxin, fevers were reduced between 96 h before and 24 h after parturition compared with those seen in virgins or in lactating rats > 24 h postpartum. In the 24-h period before expected time of parturition, no rat developed a fever and the majority of animals became hypothermic; furthermore, in 80% of such animals given 25 micrograms/kg endotoxin, the hypothermia was accompanied by death within 3-15 h. Some mortality and hypothermia were also seen up to 48 h before birth and up to 24 h after birth. No mortality was observed in virgin, pregnant, or lactating rats outside of this time period. We conclude that, around the time of delivery, there is a suppression of fever in the rat and occasional toxic responses to endotoxin.
Central nucleus of the amygdala and the development of hypertension in spontaneously hypertensive rats
Authors: Sharma N. B. , Gelsema A. J.
Published: December 2017

Electrolytic lesions of the central nucleus of the amygdala (ACe) have been shown to attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Whether this was due to destruction of local neurons and/or fibers is unknown. In the present study, neuronal perikarya in the ACe of 4-wk-old SHR were selectively destroyed with ibotenic acid. In two experiments, each comprising lesioned and sham-lesioned SHR, mean arterial blood pressure (MAP) was measured 7 and 15 wk after operation in the second experiment also at 22 wk. In the first experiment, in which rats were fed ad libitum, lesioned SHR had significantly lower body weights from 5 wk postoperation onward, and at 15 wk postoperation their average MAP [173 +/- 7 mmHg (SE)] was significantly lower vs. sham-lesioned SHR (201 +/- 4 mmHg). In the second experiment, food intake, and hence body weight, among the lesioned and sham-lesioned rats was equalized. Average MAP in the lesioned SHR at 7 and 15 wk postoperation was not different vs. sham-lesioned SHR but was significantly higher (191 +/- 6 mmHg) vs. sham-lesioned SHR but was significantly higher (191 +/- 6 mmHg) vs. sham-lesioned SHR (164 +/- 5 mmHg) 22 wk postoperation. These results indicate that destruction of neuronal perikarya in the ACe in young SHR merely delays the development of hypertension, due to a reduced weight gain.
Fish muscle energy metabolism measured during hypoxia and recovery: an in vivo 31P-NMR study
Authors: van Ginneken V. , van den Thillart G. , Addink A. , Erkelens C.
Published: December 2017

Three fish species were exposed to graded hypoxia levels and allowed to recover. Levels of high-energy phosphate compounds in epaxial white muscle were monitored by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Furthermore, O2 consumption of the animals was measured. With increasing hypoxia load, metabolic parameters started to change in the following order: phosphocreatine (PCr)-to-Pi ratio (decrease), O2 consumption (decrease), [PCr] (decrease), intracellular pH (pHi; decrease), Pi (increase), free ADP concentration ([ADP]free; increase), [ATP] (decrease). PCr levels fell with the PO2. After each increment, the [PCr] reached a stable plateau value while, in some cases, a recovery was observed. This recovery could be explained because the balance between anaerobic and aerobic metabolism is continuously fluctuating during hypoxia as a consequence of changes in the activity of the fish. Consequently the [ADP]free are fluctuating, resulting in an activation of the creatine kinase reaction and the anaerobic glycolysis. In all three species, anaerobic glycolysis was activated, but in contrast to anoxia exposure, metabolic suppression was absent. The changes of [ADP]free and [H+] (which influences the position of the creatine kinase equilibrium) are species dependent. Species differences observed in the other parameters were small. It is concluded that the pattern of the activation of anaerobic metabolism under deep hypoxia is different from that under anoxia.
Serotonin3 antagonists block aversion to saccharin in an amino acid-imbalanced diet
Authors: Terry-Nathan V. R. , Gietzen D. W. , Rogers Q. R.
Published: December 2017

Conditioned taste aversion presumably plays a role in the anorectic responses to amino acid-imbalanced diets that induce acute amino acid deficiency. The serotonin3 (5-HT3) receptor antagonists, tropisetron (Trop), MDL-72222 (MDL), and ondansetron, increase intake of imbalanced amino acid diets. Therefore, we tested whether 5-HT3 receptor antagonists would block an aversion to powdered saccharin after it was included in an amino acid-imbalanced diet. Rats were given an intraperitoneal injection of Trop, MDL, or vehicle (Veh), just before introducing one of four diets: imbalanced amino acid diet +/- saccharin (Imb or ImbSac) or a balanced (corrected) diet +/- saccharin (Cor or CorSac). Subsequent aversion to saccharin was shown in preference tests using Cor and CorSac. Saccharin preference was significantly decreased (8.3% on test day 1) in the Veh/ImbSac group, but the Trop/ImbSac group's saccharin preference (57.8%) was similar to controls (49.6-70.3%); MDL also blocked the aversion to saccharin after ImbSac. This confirms previous reports of conditioned taste aversions with amino acid limitation and suggests a role for the 5-HT3 receptor in the development of these aversions.
Vasoconstrictors alter oxygen, lactate, and glycerol metabolism in the perfused hindlimb of a rat kangaroo
Authors: Ye J. M. , Edwards S. J. , Rose R. W. , Rattigan S. , Clark M. G. , Colquhoun E. Q.
Published: December 2017

The Tasmanian bettong (Bettongia gaimardi) is a small marsupial rat kangaroo without detectable brown adipose tissue (BAT). The hindlimb was perfused with constant flow at 25 degrees C after cannulation under anesthesia of the femoral artery and vein to one hindlimb. Norepinephrine (NE, 25 nM-2.5 microM) and vasopressin (VP, 10 nM-0.1 microM) each increased perfusion pressure, oxygen consumption (VO2), and lactate and glycerol efflux of the perfused hindlimb. NE-mediated increases in VO2 and the efflux of lactate and glycerol were unaffected by propranolol (10 microM) but were completely blocked by the further addition of phentolamine (10 microM). In contrast, serotonin (5-HT; 0.1-2.5 microM) inhibited VO2 and inhibited lactate efflux. The changes induced by NE, VP, and 5-HT were all rapidly reversed by nitroprusside. These results suggest that resting thermogenesis in bettong hindlimb can be differentially controlled by the vasculature, which may also contribute to the induced VO2. This vascular control of skeletal muscle VO2 appears widespread in homeotherm evolution.
Cardiovascular effects of arginine vasotocin, atrial natriuretic peptide, and epinephrine in freshwater eels
Authors: Oudit G. Y. , Butler D. G.
Published: December 2017

The effects of 150 ng/kg iv injections of arginine vasotocin (AVT), eel atrial natriuretic peptide (ANP), and epinephrine (Epi) on the cardiovascular dynamics of resting freshwater eels, Anguilla rostrata were studied. Injection of AVT into the caudal vein significantly increased cardiac output (CO) from 15.3 to 23.6 ml.min-1.kg-1 primarily by increasing stroke volume. Mean dorsal aortic pressure (PDA) also increased. Estimated branchial shunting (2.54 ml.min-1.kg-1) was elevated by 130% because of an increased proportion of CO, indicating a vasoconstriction of the branchial arterioarterial pathway. In contrast, Epi reduced the fraction of CO perfusing the arteriovenous pathway. Epi also produced a positive chronotropic effect, increased CO and systemic vasoconstriction, resulting in a vasopressor response. These changes occurred earlier than those of AVT and ANP. Pressor responses triggered by AVT and Epi preceded the increases in CO. Injections of 150 and 200 ng/kg ANP caused a reduction in PDA due to a decrease in CO (and SV) but failed to modulate systemic resistance. The change in CO was the primary contributor to the pressor (and depressor) responses elicited by the three hormones.
Chemical sympathectomy and maternal separation affect neonatal stress responses and adrenal sensitivity to ACTH
Authors: Walker C. D.
Published: December 2017

The participation of sympathetic adrenal innervation in the control of the neonatal adrenocortical system and in changes in adrenal sensitivity after maternal separation for 24 h was tested in 10- and 23-day-old pups. Chemical sympathectomy by guanethidine (20 mg/kg body wt) decreased basal and stimulated corticosterone compound B (B) secretion without affecting adrenocorticotropic hormone (ACTH) release, abolished the enhanced adrenal sensitivity to ACTH induced by maternal separation in 10-day-old pups, but did not modify adrenal sensitivity following ether stress in 23-day-old pups. Guanethidine treatment did not affect body and adrenal weight or adrenal choline acetyltransferase activity, but it increased tyrosine hydroxylase activity at both ages. Both chronic guanethidine treatment and acute corticotropin-releasing factor immunoneutralization reduced plasma B levels after maternal separation without affecting plasma ACTH levels. Maternal separation in 10-day-old pups enhanced basal and stimulated ACTH and B secretion after exposure to ether vapors and insulin-induced hypoglycemia (IIH). In nonseparated pups, IIH did not stimulate ACTH secretion and caused small increases in B secretion; however, the enhanced response of separated pups to IIH was due to the effects of intraperitoneal injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Upregulation of the GABAA/benzodiazepine receptor during anoxia in the freshwater turtle brain
Authors: Lutz P. L. , Leone-Kabler S. L.
Published: December 2017

The freshwater turtle brain survives anoxia by decreasing its energy expenditure. During this anoxic period there is a sustained release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This study investigated whether there was a corresponding change in the binding properties of the GABAA/benzodiazepine (GABA/BDZ) receptor. Turtles (Trachemys scripta) were subjected to a 100% N2 atmosphere for up to 24 h. After exposure, the cerebral cortex was dissected out, and saturation binding assays for GABA/BDZ receptors were performed using the radioligand [3H]flunitrazepam. Control turtles had a dissociation constant (Kd) of 1.97 +/- 0.54 nM and a receptor density (Bmax) of 2,404 +/- 221 fmol/mg protein. The Kd showed no significant change over 24 h of anoxia. However, significant increases were seen in Bmax after 12 h (21%, P < 0.05) and 24 h (29%, P < 0.01) of anoxia. We suggest that a long-term upregulation of GABAA receptors occurs in the anoxic turtle brain that acts to increase the inhibitory effectiveness of the released GABA and thereby contributes to anoxia survival of the turtle.
Effect of elevated ambient temperature on sleep, EEG spectra, and brain temperature in the rat
Authors: Gao B. O. , Franken P. , Tobler I. , Borbely A. A.
Published: December 2017

To examine the relationship between sleep and brain temperature in the rat, the vigilance states, spectral power density of the electroencephalogram (EEG), hypothalamic temperature (T(hy)), and cortical temperature (Tcr) were recorded for 3 days. A 1-day rise of ambient temperature from 23 to 30 degrees C did not affect the percentage of waking, non-rapid eye movement sleep (NREMS), and rapid eye movement sleep (REMS), but increased EEG slow-wave activity in NREMS in the 12-h dark period. T(hy) was invariably higher than Tcr, but at 30 degrees C the difference diminished because of a rise in Tcr. In contrast to Tcr, T(hy) was only slightly increased at 30 degrees C and only during sleep and in the dark period. Although the temperatures changed largely in parallel at vigilance state transitions, Tcr rose more rapidly than T(hy) at NREMS-REMS transitions and more slowly at NREMS-waking transitions. T(hy) declined more rapidly than Tcr at waking-NREMS transitions and more slowly at REMS-NREMS transitions. The results are consistent with a central role of the hypothalamus in the activation and deactivation of the waking state.
Sensitization of nociceptive C-fibers in zinc-deficient rats
Authors: Izumi H. , Mori H. , Uchiyama T. , Kuwazuru S. , Ozima Y. , Nakamura I. , Taguchi S.
Published: December 2017

A marked decrease in zinc concentration was observed in plasma (P < 0.001), hindpaw skin (P < 0.01), and dorsal skin (P < 0.01) in zinc-deficient rats (rats fed a zinc-deficient diet for 3 wk), compared with the control rats fed the same zinc-deficient diet supplemented with ZnCO3 (50 mg/kg diet). The threshold intensity needed to elicit vasodilatation in the hindpaw skin of the zinc-deficient rats on electrical stimulation of the saphenous nerve in a peripheral direction was markedly lower (P < 0.01) than that in the control rats. No difference was observed between control (n = 5) and zinc-deficient rats (n = 5) in the magnitude of the plasma extravasation evoked by either histamine or substance P. There was no difference between control and zinc-deficient rats in terms of the dose-response curve for release of histamine by substance P. Prostaglandin E2 (PGE2) concentration in the hindpaw skin of the zinc-deficient rats was nearly fourfold higher (P < 0.01) than that of the control rats, whereas no difference in the leukotriene B4 level in the hindpaw skin was observed between control and zinc-deficient rats. From the present study, it seems likely that an increased level of PGE2 in the vicinity of the nociceptive C-fiber terminals in the hindpaw skin of zinc-deficient rats may sensitize the terminals of the nociceptive C-fibers of the saphenous afferent nerve in the hindpaw and thus facilitate the production of antidromic vasodilatation.
Stimulation of steroidogenesis in cultured rat adrenocortical cells by unsaturated fatty acids
Authors: Sarel I. , Widmaier E. P.
Published: December 2017

The hypothesis that the stimulatory action of free fatty acids (FFA) in the hypothalamic-pituitary-adrenocortical (HPA) axis occurs in part at the adrenal cortex was evaluated. Pathophysiological concentrations of oleic and linoleic acids, but not stearic or caprylic acid, stimulated steroidogenesis from cultured rat adrenocortical cells (concentrations eliciting 50% of maximal responses, approximately 60 and 120 microM, respectively), with a latency of 90 min. Maximal stimulation of steroidogenesis by both acids was < 50% of that produced by adrenocorticotropic hormone (ACTH) and was blocked by cycloheximide. The maximal steroidogenic response to ACTH was inhibited approximately 50% by oleic acid. The actions of oleic and linoleic acids were not associated with an increase in adenosine 3',5'-cyclic monophosphate (cAMP) secretion but appeared to require intracellular oxidation. None of the lipids influenced cell viability or corticosterone radioimmunoassay. The latency of the steroidogenic response, the putative requirement for intracellular oxidation, and the apparent lack of involvement of cAMP suggest a mechanism of action of FFA distinct from that of ACTH, yet still requiring protein synthesis. It is concluded that the modulation of steroidogenesis by these abundant naturally occurring lipids may be an important component of the control mechanisms within the HPA pathway in disorders of lipid homeostasis (e.g., obesity, starvation, or diabetes).
Relation of membrane potential to basolateral TEA transport in isolated snake proximal renal tubules
Authors: Kim Y. K. , Dantzler W. H.
Published: December 2017

We measured the effects of changes in bath K+ concentration ([K+]) on basolateral membrane potential difference (PD) and [3H]tetraethylammonium (TEA) transport in isolated snake (Thamnophis) proximal renal tubules (25 degrees C; pH 7.4). Increasing bath [K+] from 3 to 65 mM decreased PD from -60 mV (inside of cells negative) to -20 mV and 2-min uptake of [3H]TEA by approximately 25%, indicating that PD influences TEA entry into the cells. Uptake of [3H]TEA was inhibited similarly at both K+ concentrations by unlabeled TEA, indicating that uptake is carrier mediated. Kt (approximately 18 microM) for 2-min uptake of [3H]TEA in 3 mM K+ increased significantly in 65 mM K+, suggesting that the decrease in PD or the increase in [K+] alters the affinity of the transporter for TEA. The steady-state cell-to-bath ratio for [3H]TEA with 3 mM K+ (-60 mV PD) was approximately 16, significantly above the ratio of 10 predicted for passive distribution at electrochemical equilibrium. With 65 mM K+ (-20 mV PD) this ratio decreased to approximately 6, again significantly above the predicted ratio of 2. These data suggest that the PD can account for much, but not all, of the steady-state uptake of TEA. Efflux of [3H]TEA across the basolateral membrane was identical with either 3 or 65 mM K+ in the bath but was almost completely inhibited in either case by tetrapentylammonium, a potent inhibitor of TEA uptake. These data indicate that virtually all TEA transport across the basolateral membrane is carrier mediated and that transport out of the cells is unaffected by PD.
Mechanisms of proximal proton secretion in BBM of herbivorous, omnivorous, and carnivorous species
Authors: Duplain M. , Noel J. , Fleser A. , Marshansky V. , Gougoux A. , Vinay P.
Published: December 2017

The mechanisms of proton secretion by the proximal brush-border membrane (BBM) were compared in carnivorous (dog), omnivorous (human, pig, rat), and herbivorous (rabbit, hamster) species. The activity of the proton pump (V-type bafilomycin-sensitive H(+)-adenosinetriphosphatase) and of the Na+/H+ exchanger (amiloride-sensitive quenching of acridine orange fluorescence), the two major proton secretion mechanisms, was measured. The enzymatic activity of the H(+)-adenosinetriphosphatase activity was measured in intact (endosomes) and solubilized (0.1% deoxycholate or Triton X-100) BBM vesicles isolated by conventional Mg2+ precipitation techniques. In all species, but not in humans, the fraction of the ATP turnover energizing the proton pump (bafilomycin-sensitive respiration) was also measured in isolated proximal tubules. Significant differences in acid transport mechanisms were noted between species, with the proton pump predominating in the BBM of carnivorous species and the Na+/H+ exchanger predominating in the BBM of herbivorous species. The fraction of respiration suppressible by bafilomycin in proximal tubules was also different in all the species considered. This may indicate a different organization of proximal H+ transport related to the species-specific menace to acid-base balance.
Autonomic nervous system activity in weight gain and weight loss
Authors: Arone L. J. , Mackintosh R. , Rosenbaum M. , Leibel R. L. , Hirsch J.
Published: December 2017

Studies in both animals and humans indicate that the autonomic nervous system (ANS) responds to changes in systemic energy balance. In the present study, ANS response to weight change was examined by sequential blockade of cardiac autonomic innervation with parasympathetic (atropine) and sympathetic (esmolol) blockers. Change in heart period (interbeat interval) from baseline after atropine defined the amount of parasympathetic control (PC), and the subsequent change after esmolol defined the amount of sympathetic control (SC). In nonobese subjects, weight gain to 10% above initial body weight resulted in a decrease in PC and an increase in SC, and conversely, weight loss to 10% below initial weight resulted in an increase in PC and a decrease in SC. In obese subjects, weight loss resulted in the same pattern of changes in PC and SC. The major changes were in the parasympathetic arm of the ANS. These findings support the hypothesis that the ANS acts to oppose weight change.
Cardiovascular effects of serotonin in the nucleus of the solitary tract
Authors: Feldman P. D. , Galiano F. J.
Published: December 2017

The cardiovascular regulatory role of serotonin [5-hydroxytryptamine (5-HT)] in the solitary tract nucleus (NTS) was investigated in urethan-anesthetized Wistar rats. Unilateral microinjection of 5-HT (5 nmol in 50 nl) into the NTS evoked depressions of both arterial pressure (-20 +/- 1 mmHg) and heart rate (-43 +/- 6 beats/min). Induction of bradycardia and hypotension was repeatable and consistently obtained with injections into the NTS but not into neighboring structures. Microinjection of the nonselective 5-HT receptor antagonist methiothepin or the 5-HT1A/5-HT1B antagonist pindolol prevented any cardiovascular change by subsequent microinjection of 5-HT into the NTS. In contrast, microinjection of the 5-HT2-selective antagonist ketanserin or the 5-HT1A antagonist spiroxatrine had no effect on the subsequent effects of 5-HT. Bilateral vagal denervation prevented the bradycardia induced by 5-HT, whereas the vasodepression remained intact. These data provide evidence that 5-HT in the NTS evokes vagal chronotropic cardioinhibition and sympathetic withdrawal and suggest that this action is mediated by 5-HT1 serotonergic receptors, possibly of the 5-HT1B subtype.
Implication of L-type Ca2+ channels in noncholinergic adrenal catecholamine secretion by endothelin-1 in vivo
Authors: Yamaguchi N.
Published: December 2017

The aim of the present study was to investigate if either dihydropyridine-sensitive L-type Ca2+ channels or cholinergic receptor-mediated mechanisms are implicated in endothelin-1 (ET)-induced adrenal catecholamine (CA) secretion in anesthetized dogs. ET was locally administered to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. In the control group, local infusion (1 min, 0.5 ml/min) of ET (the fixed total dose of 0.5 microgram given to the gland or approximately 0.0197 microgram/kg of body weight) resulted in a sharp increase in the basal CA output, followed by a rapid decline, and a relatively slow secondary response lasted over a period of 15-30 min. In the second group treated with nifedipine (5 micrograms or approximately 0.207 microgram/kg) similarly administered 10 min before ET infusion, the ET-induced first steep increase in CA output was significantly attenuated by approximately 75% (P < 0.05, n = 6). In dogs similarly receiving either pentolinium (1 mg or approximately 0.041 mg/kg) or atropine (0.5 mg or approximately 0.018 mg/kg), the ET-induced CA response remained unchanged. The results indicate that ET-induced adrenal CA release was largely mediated by the activation of dihydropyridine-sensitive L-type Ca2+ channels. Furthermore, neither nicotinic nor muscarinic receptors were functionally implicated in the CA response to ET. The study suggests the existence of noncholinergic mechanisms involved in the secretory action of ET on the adrenal medulla in the dog in vivo.
Stimulation of cholinergic receptors in the medial preoptic area affects sleep and cortical temperature
Authors: Imeri L. , Bianchi S. , Angeli P. , Mancia M.
Published: December 2017

The medial preoptic area (MPA), a cholinoceptive brain area devoid of cholinergic cells, plays an important role in the regulation of different physiological functions, particularly sleep control and thermoregulation. To investigate the effects of the stimulation of cholinergic receptors in this area on sleep and cortical temperature (Tcort), carbachol (a mixed cholinergic agonist) was directly microinjected into the MPA of freely moving rats. Carbachol (0.25 and 0.5 microgram, corresponding to 1.37 and 2.74 nmol) microinjection induced an increase in wakefulness and an inhibition of both slow wave and desynchronized sleep phases. The temperature of the cerebral cortex was reduced in comparison with control conditions (saline microinjection). Sterile needle insertion and saline microinjections induced a significant increase in Tcort, but no changes in the sleep-wake cycle compared with the handling of the animal. The results suggest that 1) carbachol microinjection into the MPA can activate an arousal-generating system and affect thermoregulatory mechanisms, and 2) sleep and temperature responses may be dissociated.
Paracellular solute uptake by the freshwater zebra mussel Dreissena polymorpha
Authors: Dietz T. H. , Byrne R. A. , Lynn J. W. , Silverman H.
Published: December 2017

A hyperosmotic solution of mannitol or glucose (100 mM) in pond water caused an increase in paracellular solute movement between the bathing medium and body fluids of Dreissena polymorpha. Small molecules (< 5,000 Da) in the bath entered the mussel, and 80-85% of the sodium and chloride in the blood was lost within 12 h. Blood total solute was elevated within 4 h of exposure to hyperosmotic conditions, but the rise was attributed to the gain of glucose or mannitol from the bath and not to an elevation of ion concentration as a result of the osmotic loss of water. Lanthanum in the bathing solution was able to penetrate the paracellular junctional complex between gill epithelial cells in mussels exposed to hyperosmotic conditions but was rarely observed in pond water-acclimated animals. Colloidal gold (6 nm diam) was unable to penetrate the paracellular space but was accumulated in endocytotic vesicles in many epithelial cells. The "leakiness" of the epithelial tissue may be a critical factor in the low blood solute concentrations in freshwater mussels despite high rates of ion transport in these animals.
Urate transport in Homarus americanus hepatopancreas: studies on membrane vesicles and R cells
Authors: Nies A. T. , Kinne R. K. , Kinne-Saffran E. , Grieshaber M. K.
Published: December 2017

[2-14C]urate uptake was studied in hepatopancreatic basolateral membrane vesicles and in R cell suspensions of the American lobster by Millipore filtration techniques. Unspecific binding of urate to the vesicular membrane was 25.5 +/- 3.0% of equilibrium. Vesicular uptake showed a diffusional and a saturable component (Km) 0.37 +/- 0.04 mM and maximal velocity (Vmax) 16.5 +/- 1.2 pmol urate.mg protein-1.s-1). [2-14C]urate uptake was significantly trans-stimulated by urate. Purine analogues, probenecid, p-aminohippuric acid, pyrazinoic, and oxonic acid cis-inhibited urate transport. Urate uptake was not affected by Na+ or K+ transmembrane gradients but stimulated by 1 mM 2-oxoglutarate at the cis-side in Na(+)-containing media. Cellular urate uptake was inhibited by pyrazinoic acid. Uptake was saturable (Km 0.53 +/- 0.11 mM and Vmax 3.7 +/- 0.4 pmol urate.mg protein-1.s-1) and Na(+)-independent. However, 2-oxoglutarate stimulated uptake in Na(+)-containing media. These results suggest that urate uptake across the basolateral membrane occurs via a specific, Na(+)-independent transport system that may operate in the exchange mode accepting 2-oxoglutarate as countertransported substrate. In vivo, urate uptake thereby would be a tertiary active system driven by a 2-oxoglutarate gradient established across the cell membrane by the operation of a Na(+)-2-oxoglutarate cotransport system.