bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioid peptides mediate heat stress-induced immunosuppression during pregnancy
Authors: Nakamura Hiroyuki , Nagase Hirofumi , Yoshida Masami , Ogino Keiki , Seto Toshio , Hatta Kotaro , Matsuzaki Ichiyo
Published: December 2017

To clarify the involvement of the opioid system in enhanced immunosuppression induced by heat stress during pregnancy, we examined the effects of heat exposure and intraperitoneal administration of opioid receptor antagonist naloxone on β-endorphin (β-EP) in blood, pituitary lobes, and placenta as well as splenic natural killer cell activity (NKCA) and placental steroids in pregnant rats at 15–16 days gestation. Two-way analysis of variance revealed significant increases in blood β-EP induced by heat and naloxone and a significant interaction between heat and naloxone on blood β-EP and progesterone (P). Whereas heat reduced NKCA, intraperitoneal administration of naloxone reversed it. Significant increases in blood and placental β-EP induced by both heat and naloxone administration and a significant interaction on blood and placental β-EP was observed. These results suggest that immunosuppression produced by heat stress during pregnancy is mediated by the opioid system. A positive correlation between β-EP in blood and placenta during heat and naloxone administration suggests that increased placental β-EP during heat results in hypersecretion of β-EP into blood. P increased by heat during pregnancy may be involved in the immunosuppression.
K+ channel blockade in the NTS alters efficacy of two cardiorespiratory reflexes in vivo
Authors: Butcher James W. , Paton Julian F. R.
Published: December 2017

We investigated the role of potassium conductances in the nucleus of the solitary tract (NTS) in determining the efficacy of the baroreceptor and cardiopulmonary reflexes in anesthetized rats. The baroreceptor reflex was elicited with an intravenous injection of phenylephrine to evoke a reflex bradycardia, and the cardiopulmonary reflex was evoked with a right atrial injection of phenylbiguanide. Microinjection of two Ca-dependent potassium channel antagonists (apamin and charybdotoxin) into the NTS potentiated the baroreceptor reflex bradycardia. This may reflect the increased neuronal excitability observed previously in vitro with these blockers. In contrast, the Ca-dependent potassium channel antagonists attenuated the cardiopulmonary reflex, whereas voltage-dependent potassium channel antagonists (4-aminopyridine and dendrotoxin) attenuated both the baro- and cardiopulmonary reflexes when microinjected into the NTS. The possibility that the reflex attenuation observed indicates a predominant distribution of certain potassium channels on γ-aminobutyric acid interneurons is discussed.
Taste reactivity responses in rats: influence of sex and the estrous cycle
Authors: Clarke Sharon N. D. A. , Ossenkopp Klaus-Peter
Published: December 2017

Gonadal hormones (e.g., estradiol) may regulate feeding by producing a shift in the taste or palatability of food items. This study examined the impact of endogenous gonadal hormones on palatability by investigating sex differences in taste responsivity, as well as the effect of the estrous cycle on taste responsivity, in a rodent model. In the taste reactivity test, male and female Long-Evans rats received a brief (1 min) intraoral infusion of one of three tastants: sucrose (0.3 M), quinine (0.0003 M), and a sucrose-quinine mixture (0.3 M sucrose and 0.0003 M quinine). Statistical analyses indicated that female rats tested during diestrus or proestrus produced significantly more ingestive responses than did male rats and fewer aversive responses than did both male rats and female rats tested during estrus or metestrus ( P < 0.05). These results indicate a sex difference in taste responsivity in the rat that is modulated by the reproductive status of female rats. This finding implies a role of gonadal hormones in the regulation of taste responsivity in the rat.
Isolation, visualization, characterization, and osmotic reactivity of crayfish BLMV
Authors: Wheatly Michele G. , Weil Jennifer R. , Douglas Phyllis B.
Published: December 2017

Procedures were developed to isolate basolateral membrane vesicles (BLMV) from gill, hepatopancreas, and antennal gland of intermolt freshwater crayfish, Procambarus clarkii. Individual procedures involved a discontinuous sucrose gradient (gill), a 65% sucrose cushion (hepatopancreas), or differential centrifugation (antennal gland). BLMV were visualized, characterized (37°C), and tested for osmotic reactivity with a view to using them for Ca2+uptake studies. Mean diameters of BLMV were 159 nm (gill), 363 nm (hepatopancreas), and 226 nm (antennal gland). Enrichments of basolateral membranes and mitochondria in BLMV were, respectively, 18- and 1.7-fold for gill, 9- and 0.4-fold for hepatopancreas, and 10- and 1-fold for antennal gland. Apical contamination was negligible in BLMV. Percentages of resealing of vesicles as inside out, right side out, or leaky/sheets were 17:27:56% (gill), 14:26:60% (hepatopancreas), and 21:39:40% (antennal gland). Vesicles exhibited osmotic reactivity, as indicated by a linear relationship between vesicular45Ca2+uptake and osmolality. Nonspecific45Ca2+binding was 20% in gill, 39% in hepatopancreas, and 31% in antennal gland. Data were compared with published values for marine crustaceans.
Vitamin E ameliorates enhanced renal lipid peroxidation and accumulation of F2-isoprostanes in aging kidneys
Authors: Reckelhoff Jane F. , Kanji Vijaya , Racusen Lorraine C. , Schmidt Ann Marie , Du Yan Shu , Morrow Jason , Roberts L. Jackson , Salahudeen Abdulla K.
Published: December 2017

Aging results in progressive glomerular sclerosis and reductions in glomerular filtration rate (GFR). Oxidative stress may be an important mechanism for the aging process, but to date the role of oxidative stress on renal aging has not been determined. The present study was performed to determine whether age-related alterations in renal hemodynamics and morphology were associated with oxidative stress and whether this could be attenuated by chronic administration of vitamin E. Rats, aged 13 mo, were given either control diet containing vitamin E 50 IU/kg ( n = 6) or a high-vitamin E diet (5,000 IU/kg; n = 6) for 9 mo. Another group of rats (3–4 mo old; n = 7) served as young controls. Aging was accompanied by a 60% reduction in GFR, a threefold increase in renal F2isoprostanes, newly discovered vasoconstrictive F2-like prostaglandins generated by free radical-mediated lipid peroxidation. Renal aging was also associated with an increase in oxidant-sensitive heme oxygenase, advanced glycosylation end products (AGEs), and the AGE receptor, RAGE. AGE-RAGE interaction has been shown to induce oxidative stress. With high-vitamin E diet, GFR was increased by 50%, F2isoprostanes were suppressed, and expression of heme oxygenase and RAGE was attenuated. There was also a tendency for glomerular sclerosis to be attenuated. These data demonstrate that age-related decline in renal function is accompanied by oxidative stress and that administration of antioxidants, such as vitamin E, could attenuate the decline in renal function.
Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression
Authors: Kaiser Jeffrey R. , Cox Blair E. , Roy Timothy A. , Rosenfeld Charles R.
Published: December 2017

In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady-state responses to intravenous ANG II (0.229–1.72 μg/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently ( P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently ( P = 0.02), but responses were less than umbilical ( P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 μg) inhibited all responses ( P< 0.001); however, 1,000 μg of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled ( P = 0.001) after systemic infusion of only 50 μg of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.
Functional role of ecto-ATPase activity in goldfish hepatocytes
Authors: Schwarzbaum Pablo J. , Frischmann Michael E. , Krumschnabel Gerhard , Rossi Rolando C. , Wieser Wolfgang
Published: December 2017

Extracellular [γ-32P]ATP added to a suspension of goldfish hepatocytes can be hydrolyzed to ADP plus γ-32Pidue to the presence of an ecto-ATPase located in the plasma membrane. Ecto-ATPase activity was a hyperbolic function of ATP concentration ([ATP]), with apparent maximal activity of 8.3 ± 0.4 nmol Pi⋅ (106cells)−1⋅ min−1and substrate concentration at which a half-maximal hydrolysis rate is obtained of 667 ± 123 μM. Ecto-ATPase activity was inhibited 70% by suramin but was insensitive to inhibitors of transport ATPases. Addition of 5 μM [α-32P]ATP to the hepatocyte suspension induced the extracellular release of α-32Pi[8.2 pmol ⋅ (106cells)−1⋅ min−1] and adenosine, suggesting the presence of other ectonucleotidase(s). Exposure of cell suspensions to 5 μM [2,8-3H]ATP resulted in uptake of [2,8-3H]adenosine at 7.9 pmol ⋅ (106cells)−1⋅ min−1. Addition of low micromolar [ATP] strongly increased cytosolic free Ca2+([Formula: see text]). This effect could be partially mimicked by adenosine 5′- O-(3-thiotriphosphate), a nonhydrolyzable analog of ATP. The blockage of both glycolysis and oxidative phosphorylation led to a sixfold increase of[Formula: see text] and an 80% decrease of intracellular ATP, but ecto-ATPase activity was insensitive to these metabolic changes. Ecto-ATPase activity represents the first step leading to the complete hydrolysis of extracellular ATP, which allows 1) termination of the action of ATP on specific purinoceptors and 2) the resulting adenosine to be taken up by the cells.
A prostaglandin, not NO, mediates endothelium-dependent dilation in ventral aorta of shark (Squalus acanthias)
Authors: Evans David H. , Gunderson Mark P.
Published: December 2017

In mammals, the vascular endothelium releases a variety of paracrine factors, including the vasodilatory prostaglandin (PG)I2and nitric oxide (NO), which is generally accepted as the major endothelium-derived relaxing factor (EDRF) in mammals. Current evidence for the vascular NO-EDRF system in fishes is contradictory. In addition, the role of PGs in the control of fish vascular tension is also unclear. We have utilized isolated rings of the ventral aorta of the spiny dogfish shark to examine the ability of various components of the NO system to dilate this vessel. Neither the NO precursorl-arginine, the NO donor sodium nitroprusside, nor NO itself dilated the rings. The Ca2+ionophore A-23187 did produce an endothelium-dependent dilation that was not inhibited by the NO synthase inhibitor NG-nitro-l-arginine methyl ester but was inhibited by the cyclooxygenase inhibitor indomethacin, suggesting that PGs are involved. PGE1and carbaprostacyclin, but not PGI2, produced concentration-dependent dilation, and intact aortic rings secreted five times as much PGI2as PGE in both the unstimulated state and after stimulation with A-23187. Our data suggest strongly that a PG, most probably PGI2, is the EDRF in the ventral aorta of this shark species.
Whole cell patch-clamp study of putative vasomotor neurons isolated from the rostral ventrolateral medulla
Authors: Lipski Janusz , Kawai Yoshinori , Qi Jianguo , Comer Alison , Win Joe
Published: December 2017

A distinct subpopulation of neurons in the rostral and ventrolateral part of the medulla oblongata (RVL) plays a key role in controlling sympathetic vasomotor tone. To characterize these neurons under conditions in which all cell-to-cell interactions are eliminated, RVL neurons were acutely dissociated from 13- to 19-day old rats. Cells projecting to the upper thoracic segments were retrogradely labeled with fluorescent beads. Fifty-two percent (17/33) of examined spinally projecting neurons were catecholaminergic, as demonstrated by single-cell reverse transcription-polymerase chain reaction or immunocytochemistry. No spontaneous (capacitive) spikes were revealed in the tight seal cell-attached configuration. Whole cell recordings were made from 54 spinally projecting neurons using Cs+- or K+-containing pipettes. No spontaneous firing was observed in current-clamp mode with K+-based pipettes (membrane potential, −61.5 ± 2.3 mV). Step depolarizations (300- or 400-ms pulses, up to 100 pA) evoked regular firing or one to four spikes. Several voltage-gated currents, resembling the transient and persistent Na+, delayed rectifier and low- and high-threshold Ca2+, were revealed in voltage-clamp mode. These results show that isolated spinally projecting RVL neurons display no pacemaker-like activity. Because data from the literature indicate that these neurons are capable of generating such activity under different experimental conditions, the factors responsible for different behavior need to be determined. Dissociated RVL neurons provide a useful new model for studying biophysical and other properties of neurons involved in blood pressure control.
Primary vagally mediated decelerations in heart rate during tonic rapid eye movement sleep in cats
Authors: Verrier Richard L. , Lau T. Rern , Wallooppillai Umesha , Quattrochi James , Nearing Bruce D. , Moreno Ricardo , Hobson J. Allan
Published: December 2017

Rapid eye movement (REM) sleep results in profound state-dependent alterations in heart rate. The present study describes a novel phenomenon of a primary deceleration in heart rate that is not preceded or followed by increases in heart rate or arterial blood pressure and occurs primarily during tonic REM sleep. The goals were to characterize the primary decelerations and to provide insights on the underlying central and peripheral autonomic mechanisms. Cats were chronically implanted with electrodes to record electroencephalogram, pontogeniculooccipital wave activity in lateral geniculate nucleus, hippocampal theta rhythm, electromyogram, electrooculogram, respiration (diaphragm), and electrocardiogram. Arterial blood pressure was monitored from a carotid artery catheter. R-R interval fluctuations were continuously tracked using customized software. The muscarinic blocking agent glycopyrrolate (0.1 mg/kg iv) and the β-adrenergic blocking agent atenolol (0.3 mg/kg iv) were administered in alternating sequence with a 90- to 120-min interval. Glycopyrrolate immediately eliminated the decelerations during REM sleep. Atenolol alone had no effect on their frequency. These findings suggest that a change in the centrally induced pattern of autonomic activity to the heart is responsible for the primary decelerations, namely, a bursting of cardiac vagal efferent fiber activity.
Central nitric oxide attenuates the baroreceptor reflex in conscious rabbits
Authors: Matsumura Kiyoshi , Abe Isao , Tsuchihashi Takuya , Fujishima Masatoshi
Published: December 2017

We examined the role of central nitric oxide (NO) in the baroreceptor reflex in conscious rabbits. Intracerebroventricular infusion of 20 μmol of N ω-nitro-l-arginine methyl ester (l-NAME) to block central NO resulted in increases in arterial pressure, renal sympathetic nerve activity (RSNA), and plasma catecholamine levels, and the pressor response was suppressed by pretreatment with pentolinium (5 mg/kg iv). On the other hand, a subpressor dose of intracerebroventricular l-NAME (10 μmol/h) caused significant increases in baroreflex sensitivities assessed by RSNA and heart rate compared with vehicle infusion [maximum gain: −18.2 ± 0.9 vs. −9.6 ± 0.9%/mmHg ( P < 0.001) and −14.3 ± 2.3 vs. −5.7 ± 0.4 beats ⋅ min−1 ⋅ mmHg−1( P < 0.05), respectively]. Conversely, an intracerebroventricular infusion of Et2N[N(O)NO]Na, an NO donor (1 μmol/h) significantly attenuated the baroreflex sensitivities. However, intracerebroventricular infusion of N ω-nitro-d-arginine methyl ester (10 μmol/h), an enantiomer ofl-NAME, failed to alter the baroreflex sensitivities. These results suggest that 1) the pressor response induced by inhibition of central NO synthesis is mainly mediated by the enhanced sympathetic outflow and 2) central NO attenuates the baroreflex control of RSNA and heart rate in conscious rabbits.
Behaviors of hypoglossal hyoid motoneurons in laryngeal and vestibular reflexes and in deglutition and emesis
Authors: Umezaki Toshiro , Nakazawa Ken , Miller Alan D.
Published: December 2017

Reflex responses of hypoglossal motoneurons innervating the geniohyoid (GH) and thyrohyoid (TH) muscles from the superior laryngeal (SLN) and vestibular nerves and their behaviors during fictive swallowing and vomiting were examined by recording both the extracellular activities of 11 single cells in the hypoglossal nucleus and GH and TH muscle nerve activity in eight decerebrate, paralyzed, and artificially ventilated cats. The majority of TH motoneurons were either active and/or exhibited shortened antidromic latencies during early expiration. In contrast, GH motoneurons did not exhibit any respiratory-related activity. Electrical single-shock stimulation of the SLN never evoked an excitatory reflex response on GH or TH motoneurons but rather evoked inhibitory responses on the THs. Unlike other hypoglossal motoneurons, GH and TH motoneurons do not appear to receive vestibular inputs. However, they can exhibit robust activities during fictive swallowing and vomiting, particularly during expulsion. Thus these motoneurons may play an important role in airway protection during swallowing and vomiting but not in controlling upper airway patency regulated by vestibular afferents.
Mechanisms of the antidiabetic effects of the β3-adrenergic agonist CL-316243 in obese Zucker-ZDF rats
Authors: Liu Xilin , Pérusse Fleurette , Bukowiecki Ludwik J.
Published: December 2017

Previous studies have demonstrated that chronic cold exposure activates the sympathetic nervous system, increases energy expenditure, improves glucose tolerance, enhances insulin sensitivity, and stimulates glucose uptake in peripheral tissues [brown and white adipose tissues (BAT and WAT) and muscles] of normal rats. The goal of the present studies was to test whether the selective β3-adrenergic agonist CL-316243 (CL) would mimic the beneficial effects of cold exposure in lean and obese ZDF/Gmi- fa male (ZDF) rats, a new model of type II diabetes. In obese ZDF rats, chronic infusion of CL (1 mg ⋅ kg−1⋅ day−1for 14 days) significantly decreased body weight gain, food intake, and WAT weight. It also increased total tissue cytochrome oxidase activity, not only in BAT (15 times), but also in WAT (2–4 times), suggesting that it progressively enhanced mitochondriogenesis in adipose tissues. CL treatment normalized hyperglycemia and reduced hyperinsulinemia and circulating free fatty acid (FFA) levels. It also improved glucose tolerance and reduced insulin response during an intravenous glucose tolerance test. In general, the beneficial effects of CL were more pronounced in obese than in lean rats. Hyperinsulinemic-euglycemic glucose clamps combined with the [2-3H]deoxyglucose method revealed that CL markedly improved insulin responsiveness in obese rats (3–4 times) and increased glucose uptake in BAT (21 times), WAT (3 times), skeletal muscles (2–3 times), and in the diaphragm (2.8 times), but not in the heart. It is concluded that chronic CL treatment improves glucose tolerance and insulin responsiveness in obese ZDF rats by a mechanism similar to that induced by chronic cold exposure, i.e., by stimulating facultative thermogenesis, mitochondriogenesis, and glucose utilization in BAT and WAT. In addition to this mechanism, the reduction in plasma FFA levels induced by chronic CL treatment may further contribute to enhance glucose uptake in skeletal muscles (a tissue that does not express typical β3-adrenoceptors) via the “glucose-fatty acid” cycle. The antiobesity and antidiabetic properties of CL suggest that selective β3-adrenergic agonists may represent useful agents for the treatment of type II diabetes.
Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal afferent signals in rat
Authors: Schwartz Gary J. , Moran Timothy H.
Published: December 2017

Volume and chemical characteristics of meals in the gut have been proposed to generate vagal afferent signals that mediate the negative feedback control of ingestion and gastric emptying. Furthermore, duodenal nutrients elicit changes in gastrointestinal motility that may stimulate mechanosensitive vagal afferents. The degree to which the activity of an individual vagal afferent fiber can be modified by both mechanical and nutrient properties in the gut remains unclear. The present studies evaluated the relationships between distal antral and proximal duodenal load-sensitive vagal afferent activity and gastroduodenal motility in response to duodenal nutrient exposure in ketamine-xylazine-anesthetized rats. Duodenal carbohydrate (glucose) and amino acid (peptone) infusions (0.2 ml/min, 0.2–0.5 kcal/ml) stimulated concentration-dependent increases in 1) antroduodenal contractions and 2) antral and duodenal vagal afferent activity beyond those attributable to osmolarity alone. In addition, duodenal peptone was more effective than equicaloric glucose in eliciting this vagal activity. These data demonstrate that the proximal duodenum can discriminate its nutrient chemical contents and that gastroduodenal load-sensitive vagal afferents indirectly transduce nutrient chemical information.
Contribution of renal nerves to renal blood flow variability during hemorrhage
Authors: Malpas Simon C. , Evans Roger G. , Head Geoff A. , Lukoshkova Elena V.
Published: December 2017

We have examined the role of the renal sympathetic nerves in the renal blood flow (RBF) response to hemorrhage in seven conscious rabbits. Hemorrhage was produced by blood withdrawal at 1.35 ml ⋅ min−1 ⋅ kg−1for 20 min while RBF and renal sympathetic nerve activity (RSNA) were simultaneously measured. Hemorrhage was associated with a gradual increase in RSNA and decrease in RBF from the 4th min. In seven denervated animals, the resting RBF before hemorrhage was significantly greater (48 ± 1 vs. 31 ± 1 ml/min intact), and the decrease in RBF did not occur until arterial pressure also began to fall (8th min); however, the overall percentage change in RBF by 20 min of blood withdrawal was similar. Spectral analysis was used to identify the nature of the oscillations in each variable. Before hemorrhage, a rhythm at ∼0.3 Hz was observed in RSNA, although not in RBF, whose spectrogram was composed mostly of lower-frequency (<0.25 Hz) components. The denervated group of rabbits had similar frequency spectrums for RBF before hemorrhage. RSNA played a role in dampening the effect of oscillations in arterial pressure on RBF as the transfer gain between mean arterial pressure (MAP) and RBF for frequencies >0.25 Hz was significantly less in intact than denervated rabbits (0.83 ± 0.12 vs. 1.19 ± 0.10 ml ⋅ min−1 ⋅ mmHg−1). Furthermore, the coherence between MAP and RBF was also significantly higher in denervated rabbits, suggesting tighter coupling between the two variables in the absence of RSNA. Before the onset of significant decreases in arterial pressure (up to 10 min), there was an increase in the strength of oscillations centered around 0.3 Hz in RSNA. These were accompanied by increases in the spectral power of RBF at the same frequency. As arterial pressure fell in both groups of animals, the dominant rhythm to emerge in RBF was centered between 0.15 and 0.20 Hz and was present in intact and denervated rabbits. It is speculated that this is myogenic in origin. We conclude that RSNA can induce oscillations in RBF at 0.3 Hz, plays a significant role in altering the effect of oscillations in arterial pressure on RBF, and mediates a proportion of renal vasoconstriction during hemorrhage in conscious rabbits.
Fos expression following isotonic volume expansion of the unanesthetized male rat
Authors: Randolph R. R. , Li Q. , Curtis K. S. , Sullivan M. J. , Cunningham J. T.
Published: December 2017

Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide binding to circumventricular organs may mediate the central response to volume expansion, a condition common to pregnancy, exercise training, and congestive heart failure. This study used Fos immunocytochemistry to examine brain regions activated by volume expansion. Male Sprague-Dawley rats were infused with isotonic saline equal to 10% of their body weight in 10 min followed by a maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h infusions at 0.01 ml/min. Five minutes after the start of volume expansion, central venous pressure of expanded animals was significantly greater than control animals. The volume-expanded group exhibited significantly greater Fos activation ( P < 0.05) in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and perinuclear zone of the supraoptic nucleus. Double labeling indicates that oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain regions known to inhibit both sympathetic activity and vasopressin release show increased Fos expression following isotonic volume expansion.
Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats
Authors: Moffitt J. A. , Foley C. M. , Schadt J. C. , Laughlin M. H. , Hasser E. M.
Published: December 2017

The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 ± 11.9 vs. 342 ± 30.6% baseline LSNA), as was maximum reflex gain (−4.0 ± 0.6 vs. −7.8 ± 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 ± 10.8 vs. 453 ± 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (−2 ± 2.8 vs. 13 ± 4.5% baseline RSNA), and maximum gain (−5.8 ± 0.5 vs. −13.6 ± 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.
Exercise effects on lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity
Authors: Davis J. M. , Kohut M. L. , Jackson D. A. , Colbert L. H. , Mayer E. P. , Ghaffar A.
Published: December 2017

This study examined the effects of moderate and prolonged exercise on 1) lung tumor metastases and 2) alveolar macrophage antitumor response in vitro. C57Bl/6 mice were assigned to either Ex-30 (30-min run), Ex-F (run to fatigue), Ex-F-24 h (run to fatigue 24 h before tumor injection), or Con (rested in lanes above the treadmill). Mice received intravenous injections of syngeneic B16 melanoma cells 30 min postexercise. Lungs were removed 7 or 10 days later, and tumor foci were counted. Ex-F had fewer tumors than either Ex-30 or Con, whereas Ex-F-24 h also showed a strong trend toward fewer tumors. The initial localization of tumor cells in the lungs after injection was not different among groups. For the in vitro experiment, mice were killed immediately after exercise or 8 h later. Alveolar macrophages were removed and cultured in vitro with B16 melanoma cells. The growth of the tumors cultured with macrophages from Ex-F was lower than Con after exercise and, to a lesser extent, 8 h later. In Ex-30, this effect was only found immediately after exercise. The data suggest that prolonged exercise has a protective effect on lung tumor metastases and enhances alveolar macrophage antitumor cytotoxicity.
Regulation of intracellular pH in proximal tubules of avian long-looped mammalian-type nephrons
Authors: Brokl Olga H. , Martinez Christina L. , Shuprisha Apichai , Abbott Diane E. , Dantzler William H.
Published: December 2017

In nonperfused proximal tubules isolated from chicken long-looped mammalian-type nephrons, intracellular pH (pHi), measured with the pH-sensitive fluorescent dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, was ∼7.3 under control conditions (HEPES-buffered medium with pH 7.4 at 37°C) and was reduced to ∼7.0 in response to NH4Cl pulse. The rate of recovery of pHi from this level to the resting level was 1) significantly reduced by the removal of Na+ from the bath, 2) significantly increased by the removal of Cl− from the bath, 3) unchanged by the removal of both Na+ and Cl− from the bath, 4) significantly reduced by the addition of either ethylisopropylamiloride or DIDS to the bath, 5) significantly increased by a high bath K+ concentration, and 6) unchanged by the addition of Ba2+ to the bath. These data suggest that both Na+-coupled and Cl−-coupled basolateral acid-base fluxes are involved in determining the rate of recovery of pHi after acidification. The most likely ones to be important in regulating pHi are a Na+/H+exchanger and a Na+-coupled Cl−/[Formula: see text]exchanger. In birds, long-looped mammalian-type nephrons resemble short-looped transitional nephrons but differ markedly from superficial loopless reptilian-type nephrons.
Evidence for a role of kallikrein-kinin system in patients with shock after blunt trauma
Authors: Sugimoto Katsuhiko , Hirata Mitsuhiro , Majima Masataka , Katori Makoto , Ohwada Takashi
Published: December 2017

Bradykinin (BK) is activated via plasma and/or tissue kallikrein-kinin (K-K) system pathways during hypotension after blunt trauma. The precise role of the K-K system in human subjects has not been defined. We developed a new method for measuring levels of BK in the blood and examined the role of the K-K system in patients with shock after trauma. Eight patients were entered into this study. We measured the levels of a high-molecular-weight kininogen (HMWK), a low-molecular-weight kininogen (LMWK), BK, and (1—5)-BK in the blood of patients in an unstable state (Pre) and a stable state (Post). At Pre, the blood BK level was significantly elevated, the HMWK and LMWK levels were significantly lower, and the (1—5)-BK level was significantly higher than the respective levels at Post. Our data suggest a significant role for the K-K system in the pathogenesis of shock after blunt trauma. This newly developed method for determination of the activation of the plasma K-K system appears to be useful for determining the severity of a trauma.
Tubuloglomerular feedback in Dahl rats
Authors: Karlsen Finn M. , Leyssac Paul P. , Holstein-Rathlou Niels-Henrik
Published: December 2017

We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response to perturbations around the natural operating point, with a TGF response that was more efficient than in normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in hypertensive Dahl-S rats was found. The results suggest that the loss of autoregulation in hypertensive Dahl-S rats is due to a compromised myogenic response. We also measured the free-flow proximal intratubular pressure in Dahl rats. Perfectly regular oscillations were demonstrated in all Dahl series, including the hypertensive Dahl-S rats. This is the first demonstration of regular oscillations in an experimental rat model of hypertension.
Ca2+uptake and Cd2+accumulation in larval tilapia (Oreochromis mossambicus) acclimated to waterborne Cd2+
Authors: Chang Min-Hwang , Lin Hui-Chen , Hwang Pung-Pung
Published: December 2017

The present study compares the rates of Ca2+uptake and Cd2+accumulation in tilapia ( Oreochromis mossambicus) between larvae preexposed to Cd2+and naive larvae. Preexposure to Cd2+induces some form of adaptation that attenuates the effects of Cd2+later on. Exposure to Cd2+decreased the uptake of Ca2+but did not suppress the accumulation rate of Cd2+. A 12-fold increase in 96-h half-maximal lethal concentration was found in tilapia larvae preexposed to 0.45 μM Cd2+from hatching for 3 days in comparison with naive 3-day-old larvae. The effects of Cd2+on Ca2+influx kinetics in larvae preexposed to 0.18 μM Cd2+for 3 days were examined. The Michaelis constant for Ca2+in the 0.18 μM Cd2+preexposed larvae did not change significantly in the presence of Cd2+, whereas maximal velocity increased by ∼23%. An enhanced Ca2+uptake efficiency (∼18%) was found in these Cd2+-acclimated larvae. The criterion that determines the survival of tilapia larvae encountering Cd2+challenge is the degree of interference with Ca2+homeostasis instead of the absolute amount of Cd2+accumulated.
Effect of acute food deprivation on lactational infertility in rats is reduced by leptin administration
Authors: Woodside Barbara , Abizaid Alfonso , Jafferali Shelina
Published: December 2017

The goals of these experiments were to determine whether lactational anestrus would be prolonged by a 48-h fast at days 13 and 14 postpartum (pp) and, if so, to determine whether this effect could be reversed by treatment with the Ob protein leptin. We found that food deprivation on days 13 and 14 pp prolonged lactational infertility by 7 days and that the nutritional experience of both the dam and her litter contributed to this effect. Leptin administration (2.5 mg ⋅ kg−1 ⋅ day−1) during food deprivation was sufficient to reduce the length of lactational infertility compared with vehicle-treated food-deprived rats ( P < 0.05). Similar leptin treatment in ad libitum-fed animals reduced food intake ( P < 0.05) and litter growth ( P < 0.05) but had no statistically significant effect on maternal weight gain or length of lactational infertility. Food-deprived lactating animals had lower circulating leptin levels than ad libitum-fed lactating animals on day 15 pp ( P < 0.05), as determined by RIA. Levels in nonlactating rats were higher than in either lactating group ( P < 0.05).
Hemodilution mediates changes in renal hemodynamics after acute volume expansion in rats
Authors: Franchini Kleber G.
Published: December 2017

The present study examined the factors responsible for triggering renal hemodynamic adjustments during acute volume expansion. The renal hemodynamic effects of graded volume expansion with 0.9% saline (Sal; 1, 2, and 4% of body wt), 7% BSA solution (0.35, 0.70, and 1.4% body wt), or whole blood from a donor rat (WBL; 0.35, 0.70, and 1.4% body wt) were compared in rats anesthetized with pentobarbital sodium. Neural influences on the kidney were eliminated by vagus nerves, baro/chemoreceptor afferents, and renal nerves section, and renal perfusion pressure was controlled at constant level (∼120 mmHg) throughout the experiments. In Sal- and BSA-expanded rats, renal blood flow (RBF) increased (Sal: 15, 40, 71%; BSA 17, 49, 107%) and renal vascular resistance (RVR) decreased in parallel with the degree of volume expansion (RVR: Sal 17, 31, 44%; and BSA: 15, 35, 54%). Renal hemodynamics remained unaltered after expansion with WBL. In rats expanded with Sal or BSA, correction of the fall of hematocrit restored RBF and RVR to control levels. Interference with tubuloglomerular feedback by uretheral obstruction had no effect on the decrease in RVR with Sal or BSA. Inhibition of the vascular tone by intrarenal papaverine infusion also did not alter the renal hemodynamic response to volume expansion with Sal or BSA. These findings suggest that the changes in renal hemodynamics after acute expansion are likely mediated by changes in rheologic properties of the blood rather than by changes in active vascular tone.
Further evidence that BAT thermogenesis modulates cardiac rate in infant rats
Authors: Sokoloff Greta , Kirby Robert F. , Blumberg Mark S.
Published: December 2017

Previous research in infant rats suggested that brown adipose tissue (BAT), by providing warm blood to the heart during moderate cold exposure, protects cardiac rate. This protective role for BAT thermogenesis was examined further in the present study. In experiment 1, 1-wk-old rats in a warm environment were pretreated with saline or chlorisondamine (a ganglionic blocker), and then BAT thermogenesis was stimulated by injection with the β3-agonist CL-316243. In experiment 2, pups were pretreated with chlorisondamine and injected with CL-316243, and after BAT thermogenesis was stimulated the interscapular region of the pups was cooled externally with a thermode. In both experiments, cardiac rate, oxygen consumption, and physiological temperatures were monitored. Activation of BAT thermogenesis substantially increased cardiac rate in saline- and chlorisondamine-treated pups, and focal cooling of the interscapular region was sufficient to lower cardiac rate. The results of these studies support the hypothesis that BAT thermogenesis contributes directly to the modulation of cardiac rate.
Duodenal nutrient infusions differentially affect sham feeding and Fos expression in rat brain stem
Authors: Phifer Curtis B. , Berthoud Hans-Rudolf
Published: December 2017

Duodenal infusions of macronutrients inhibit sham and normal feeding. Neural substrates of this response were studied by infusing glucose, linoleic acid, an amino acid mixture, saline, or water into the duodenum of unanesthetized rats and then measuring sham feeding of 30% sucrose or Fos expression in the dorsal vagal complex. Linoleic acid and amino acids (both 1.5 kcal) and glucose (4.5 kcal) suppressed sham feeding relative to control infusions, and all three macronutrients triggered Fos expression in the nucleus of the solitary tract and area postrema. Although there were significant quantitative differences, the subnuclear distribution pattern of Fos-expressing neurons was not different for the three macronutrients and was largely localized to the medial, dorsomedial, and commissural subnuclei of the nucleus of the solitary tract and the area postrema. Linoleic acid suppressed intake and stimulated Fos expression similarly to glucose infusions of three times the caloric value. Amino acids strongly suppressed sham feeding but triggered relatively little Fos expression. These results indicate that the intake-suppressing potency of duodenal macronutrients is dependent on nutrient type, rather than simply caloric value, and that amino acids, although potent inducers of satiety, affect ingestion by processes different from those subserving lipids and carbohydrates. Furthermore, the similar patterns of neuronal activation after different duodenal infusions may indicate a large degree of convergence at the level of primary and second-order sensory neurons, whereas the distinctly different pattern obtained earlier with gastric distension indicates partially separate neural pathways for satiety signals generated by duodenal nutrients and gastric mechanoreceptors.
Entrainment in calorie-restricted mice: conflicting zeitgebers and free-running conditions
Authors: Challet Etienne , Solberg Leah C. , Turek Fred W.
Published: December 2017

Phase-shifting effects of timed calorie restriction were investigated in mice during exposure to a 12:12-h light-dark cycle. Food-anticipatory activity (FAA), the output of a food-entrainable pacemaker, was expressed before the time of feeding whether mice received daily hypocaloric food (3.3 g of chow/day) or normocaloric food (5 g of chow/day) at zeitgeber time (ZT) 2 (ZT12 = lights off). Subsequently, mice were placed in constant darkness and fed ad libitum. The onset of the nocturnal period of locomotor activity was phase advanced by 1 h in calorie-restricted mice compared with normocalorie-fed controls. The phase advance still occurred when FAA was prevented by restraining calorie-restricted mice. Giving hypocaloric food at ZT2, ZT10, ZT14, or ZT22 phase advanced the nocturnal pattern of activity by 1, 3, 1, and 1 h, respectively. After transfer to constant darkness, FAA free ran in parallel with the normal nocturnal period of locomotor activity. A light pulse during the early subjective night phase delayed both components. These results indicate that 1) timed calorie restriction under a light-dark cycle can phase advance the light-entrainable pacemaker with a phase-dependent magnitude, 2) FAA feedback is not crucial for the observed phase advance, and 3) the light-entrainable pacemaker may control the period of the food-entrainable pacemaker in mice fed ad libitum.
ACTH responses to CRF and AVP in pregnant and nonpregnant ewes
Authors: Keller-Wood Maureen
Published: December 2017

During both ovine and human pregnancy plasma cortisol is increased. In human pregnancy the placenta secretes corticotropin-releasing factor (CRF), but pituitary responses to CRF are decreased. However, in ovine pregnancy there is no measurable placental secretion of CRF. This study tests for changes in pituitary responsiveness to CRF or AVP. Pregnant and nonpregnant ewes were infused with saline or CRF at three doses (3, 9, 45 μg/h), with or without coinfusion of AVP (9 μg/h). AVP infusion increased plasma AVP to ∼250 pg/ml. CRF infusions increased plasma CRF from ∼25 to 50, 150, and 850 pg/ml. ACTH was significantly increased by the infusion of AVP and by all infusions of CRF. Within-animal comparisons revealed a potentiation of the ACTH response to CRF in the presence of AVP. The ACTH responses to AVP and/or CRF were not different between pregnant and nonpregnant ewes. The results suggest that there is no change in pituitary responsiveness to CRF or AVP during ovine pregnancy.
Effect of leptin on energy balance does not require the presence of intact adrenals
Authors: Arvaniti Konstantinia , Deshaies Yves , Richard Denis
Published: December 2017

The present study was conducted to assess the effects of leptin on food intake and energy balance in the presence or absence of corticosterone. Three cohorts of C57BL/6 mice differing in their corticosterone status [nonadrenalectomized (intact), adrenalectomized (ADX), and ADX with corticosterone replacement] were infused with either saline or leptin at a dose of 150 μg ⋅ kg−1 ⋅ day−1. Throughout the study, mice had free access to both a high-starch and a high-fat diet. At the end of the experimental period, mice were decapitated and their carcasses were processed for the determination of energy, protein, and lipid contents. Leptin significantly reduced body gains in weight, fat, and energy, whereas corticosterone therapy significantly promoted all of these gains. Leptin and ADX significantly reduced food intake and gross energetic efficiency, whereas corticosterone therapy significantly increased these variables. The effects of leptin, ADX, and corticosterone on food intake were accounted for by changes in the intake of the high-fat diet. Leptin also attenuated the preference for fat that developed quickly in mice simultaneously exposed to the high-starch and high-fat regimen. Altogether, the results of this study 1) emphasize the abilities of leptin and corticosterone to, respectively, decrease and increase energy deposition and ingestion of fat, 2) do not substantiate any leptin-corticosterone interaction in the regulation of energy balance, and 3) demonstrate that leptin can produce its effect on energy and fat gains in the absence of an intact hypothalamic-pituitary-adrenal axis.
A physiological strain index to evaluate heat stress
Authors: Moran Daniel S. , Shitzer Avraham , Pandolf Kent B.
Published: December 2017

A physiological strain index (PSI), based on rectal temperature (Tre) and heart rate (HR), capable of indicating heat strain online and analyzing existing databases, has been developed. The index rates the physiological strain on a universal scale of 0–10. It was assumed that the maximal Tre and HR rise during exposure to exercise heat stress from normothermia to hyperthermia was 3°C (36.5–39.5°C) and 120 beats/min (60–180 beats/min), respectively. Tre and HR were assigned the same weight functions as follows: PSI = 5(Tre t − Tre0) ⋅ (39.5 − Tre0)−1+ 5(HR t − HR0) ⋅ (180 − HR0)−1, where Tre t and HR t are simultaneous measurements taken at any time during the exposure and Tre0 and HR0 are the initial measurements. PSI was applied to data obtained from 100 men performing exercise in the heat (40°C, 40% relative humidity; 1.34 m/s at a 2% grade) for 120 min. A separate database representing seven men wearing protective clothing and exercising in hot-dry and hot-wet environmental conditions was applied to test the validity of the present index. PSI differentiated significantly ( P < 0.05) between the two climates. This index has the potential to be widely accepted and to serve universally after extending its validity to women and other age groups.
Chronic lymph flow responses to hyperproteinemia
Authors: Manning R. Davis
Published: December 2017

The long-term responses of lymph flow, lymph protein transport, and the permeability-surface area (PS) product to hyperproteinemia have been studied in conscious dogs. Plasma protein concentration (PPC) was increased by daily intravenous infusion of previously collected autologous plasma for 9 days. Lymph flow was determined by collecting lymph chronically from a lymphatic afferent to the popliteal node in the hind leg. Compared with the average value during the normal-PPC period, the following changes occurred during 10 days of high PPC: lymph flow decreased from 12.3 ± 1.1 to 3.8 ± 0.6 μl/min, lymph protein transport decreased from 241 ± 24 to 141 ± 21 μg/min, PS product decreased from 4.7 ± 0.5 to 3.0 ± 0.5 μl/min, PPC increased from 7.1 ± 0.1 to 8.8 ± 0.4 g/dl, lymph protein concentration increased from 1.9 ± 0.1 to 3.8 ± 0.1 g/dl, plasma colloid osmotic pressure increased from 18.6 ± 0.8 to 24.2 ± 2.1 mmHg, and lymph colloid osmotic pressure increased from 4.8 ± 0.2 to 10.4 ± 0.7 mmHg. In conclusion, long-term hyperproteinemia in dogs resulted in chronic decreases in lymph flow, lymph protein transport, and the PS product and chronic increases in lymph protein concentration and lymph colloid osmotic pressure. The marked decrease in lymph flow during hyperproteinemia decreased lymph protein transport and thus contributed to the increase in lymph protein concentration. In addition, the decreases in PS product and lymph protein transport suggest that transcapillary protein flux decreases during hyperproteinemia.