bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical response properties of avian lagena type II hair cells: a model system for vestibular filtering
Authors: Ricci Anthony J. , Correia Manning J.
Published: December 2017

Data presented represent the first electrical recordings from avian lagena type II hair cells. The perforated-patch variant of the whole cell recording technique was used to investigate how the macroscopic currents shaped the voltage response of the hair cells. Voltage-clamp data separated cells into two broad classes on the basis of differences in activation rates, rates and degree of inactivation, and pharmacological sensitivity. Current-clamp recordings revealed low-quality membrane voltage oscillations (Qc < 1) during pulse current injections. Oscillation frequency correlated with activation rate of the macroscopic currents. The quality of membrane oscillations (Qc) varied linearly with frequency for cells with little inactivation. For cells with rapid inactivation, no relationship was found between Qc and frequency. Rapid inactivation may serve to extend the bandwidth of vestibular hair cells. The frequency measured from voltage responses to pulsed currents may reflect the corner frequency of the cell. The filtering properties of avian lagena hair cells are like those found in all other vestibular end organs, suggesting that the electrical membrane properties of these cells are not responsible for specializing them to a particular stimulus modality.
Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state
Authors: Adams G. R. , McCue S. A. , Zeng M. , Baldwin K. M.
Published: December 2017

During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.
Correlation of ventricular mechanosensory neurite activity with myocardial sensory field deformation
Authors: Foreman R. D. , Blair R. W. , Holmes H. R. , Armour J. A.
Published: December 2017

The mechanosensory activity generated by ventricular epicardial sensory neurites associated with afferent axons in thoracic sympathetic nerves was correlated with sensory field deformation (long axis, short axis, and transmural dimension changes), regional intramyocardial pressure, and ventricular chamber pressure in anesthetized dogs. Ventricular mechanosensory neurites generated activity that correlated best with strain developed along either the long or short axis of their epicardial sensory fields in most instances. Activity did not correlate normally to local wall thickness or to regional wall or chamber pressure development in most cases. During premature ventricular contractions, the activity generated by these sensory neurites correlated best with maximum strain developed along at least one sensory field epicardial vector. Identified sensory neurites were also activated by local application of the chemical bradykinin (10 μM) or by local ischemia. These data indicate that the activity generated by most ischemia-sensitive ventricular epicardial sensory neurites associated with afferent axons in sympathetic nerves is dependent on not only their local chemical milieu but on local mechanical deformation along at least one epicardial vector of their sensory fields.
Mechano- and chemoreceptor modulation of renal sympathetic nerve activity at birth in fetal sheep
Authors: Segar Jeffrey L. , Smith Oliva J. , Holley Aaron T.
Published: December 2017

Physiological responses at birth include increases in heart rate (HR), blood pressure, sympathetic nerve activity, and circulating vasoactive peptides. The factors mediating these responses are not known. To test the hypothesis that afferent input from peripheral mechanoreceptors (arterial and cardiopulmonary baroreceptors) and chemoreceptors contribute to the sympathoexcitatory and hormonal responses at birth, we studied the effects of sinoaortic denervation (SAD) and SAD with vagotomy (Vx) on changes in HR, mean arterial blood pressure (MABP), renal sympathetic nerve activity (RSNA), and catecholamine, arginine vasopressin (AVP), and ANG II levels at birth in term sheep. One hour after delivery by cesarean section, RSNA increased by 168 ± 49 and 192 ± 32% (relative to fetal values) in SAD and SAD-Vx animals, respectively. Significant increases in HR (18 ± 5 and 20 ± 6%) and MABP (24 ± 4 and 20 ± 5%) were also observed 1 h after delivery in SAD and SAD-Vx lambs, respectively. These responses are similar to those seen in intact sheep delivered at the same gestational age. AVP levels markedly increased after birth (19.8 ± 6.7 to 136.1 ± 75.9 pg/ml) in SAD-Vx lambs, whereas SAD animals displayed no change in AVP concentrations. Plasma ANG II also did not change after birth in either group, although levels were consistently higher ( P < 0.01) in SAD compared with SAD-Vx animals. In the presence of SAD, Vx resulted in significantly greater plasma levels of norepinephrine, although levels did not change after birth in either group. The epinephrine responses at birth were similar in both groups of animals. The present data suggest that afferent input from peripheral chemoreceptors and mechanoreceptors contributes little to the hemodynamic and sympathetic responses after delivery by cesarean section. On the other hand, these peripheral mechanisms appear to be involved in modulating endocrine responses at birth.
Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion
Authors: Shah N. , Evans W. S. , Veldhuis J. D.
Published: December 2017

The neuroendocrine mechanisms by which estradiol drives growth hormone (GH) secretion in the human are poorly defined. Here we investigate estrogen’s specific regulation of the 24-h pulsatile, nyctohemeral, and entropic modes of GH secretion in healthy postmenopausal women. Volunteers ( n = 9) received randomly ordered placebo versus estradiol-17β (1 mg micronized steroid twice daily orally) treatment for 7–10 days and underwent blood sampling at 10-min intervals for 24 h to capture GH release profiles quantitated in a high-sensitivity chemiluminescence assay. Pulsatile GH secretion was appraised via deconvolution analysis, nyctohemeral GH rhythms by cosinor analysis, and the orderliness of GH release patterns via the approximate entropy statistic. Mean (±SE) 24-h serum GH concentrations approximately doubled on estrogen treatment (viz., from 0.31 ± 0.03 to 0.51 ± 0.07 μg/l; P = 0.033). Concomitantly, serum insulin-like growth factor-I (IGF-I), luteinizing hormone, and follicle-stimulating hormone concentrations fell, whereas thyroid-stimulating hormone and prolactin levels rose ( P < 0.01). The specific neuroendocrine action of estradiol included 1) a twofold amplified mass of GH secreted per burst, with no significant changes in basal GH release, half-life, pulse frequency, or duration; 2) an augmented amplitude and mesor of the 24-h rhythm in GH release, with no alteration in acrophase; and 3) greater disorderliness of GH release (higher approximate entropy). These distinctive and dynamic reactions to estrogen are consistent with partial withdrawal of IGF-I’s negative feedback and/or accentuated central drive to GH secretion.
Phenotypic variation in sensorimotor performance among eleven inbred rat strains
Authors: Biesiadecki Brandon J. , Brand Paul H. , Koch Lauren G. , Metting Patricia J. , Britton Steven L.
Published: December 2017

As a first step toward identifying the genes that determine sensorimotor ability (motor coordination) we subjected 11 inbred strains of rats to three different tests for this trait. Rats were tested at 13 wk of age to determine how long they could remain on 1) a rotating cylinder as the velocity of rotation increased every 5 s (1-direction rotation test), 2) a rotating cylinder that reversed direction every 5 s and increased velocity every 10 s (2-direction rotation test), and 3) a platform that was tilted 2° every 5 s from 22 to 47° (tilt test). On all three tests, rats of the PVG strain demonstrated the greatest sensorimotor ability. In contrast, rats of the MNS strain were most often represented among the group of strains that demonstrated the lowest performance on all tests. Considering all three tests, there was a 3- to 13-fold range in sensorimotor performance between the highest and lowest strains. This large divergence between the highest and lowest strains provides a genetic model that can be used to identify intermediate phenotypes and quantitative trait loci that contribute to sensorimotor ability.
Light-induced uncoupling of multioscillatory circadian system in a diurnal rodent, Asian chipmunk
Authors: Honma Sato , Honma Ken-Ichi
Published: December 2017

Responses of the circadian locomotor rhythm to a single light pulse were examined in a diurnal rodent, Asian chipmunk, by exposing it to a 1-h light pulse of 2,000 lx under constant conditions. A light pulse given at the beginning and end of the subjective night produced a phase delay and advance shifts, respectively. When pulsed around the midpoint of the subjective night, the circadian rhythm was shifted as much as 12 h in most animals or became arrhythmic in some. In the latter case, an additional light pulse restored the circadian rhythm. Some animals were unresponsive to light. The phase response curve is categorized as type 0. A large phase-shift was sometimes followed by splitting of an activity band into two components. These results are best explained by an assumption that the chipmunk circadian system is composed of two mutually coupled major oscillators, each of which is constituted by multiple oscillators. Our results suggest that light affects the oscillatory coupling not only of the major oscillators but also of constitutional oscillators.
Abated cardiovascular responses to chronic oral lisinopril treatment in conscious elderly rats
Authors: Buñag Ruben , Mellick Jennifer , Allen Brandy
Published: December 2017

To determine whether the cardiovascular effects of chronic treatment with lisinopril are age related, we compared baroreflex sensitivity and pressor responsiveness in 4-mo- and 21-mo-old male rats that had been given oral lisinopril daily for 4 wk. Reflex bradycardia elicited by elevating blood pressure with phenylephrine was stronger in 4-mo-old rats than it was in 21-mo-old rats and also stronger in lisinopril-treated rats than it was in untreated rats of the same age. Pressor responses to angiotensin or norepinephrine were recorded after combined cholinergic and β-adrenergic blockade and then analyzed not only as absolute but also as percent increases in mean pressure. Although pressor responses seemed to be slightly reduced by lisinopril when expressed as absolute increases in mean pressure, corresponding percent increases were always larger in 4-mo-old rats than they were in 21-mo-old rats and were clearly enhanced by lisinopril more in younger rats. The stronger overall enhancement of pressor responsiveness and reflex bradycardia in younger rats suggests that the cardiovascular effects of lisinopril diminish with advancing age.
Atrial, B-type, and C-type natriuretic peptides cause mesenteric vasoconstriction in conscious dogs
Authors: Woods Robyn L. , Jones Marcus J. M.
Published: December 2017

Cardiovascular responses were compared with equimolar infusions of B-type (BNP) and C-type (CNP) with atrial natriuretic peptide (ANP) in conscious, instrumented dogs. On separate days, each natriuretic peptide or vehicle was infused (intravenously) at step-up doses of 2, 5, 10, and 20 pmol ⋅ kg−1 ⋅ min−1(20 min each dose) to increase circulating levels of the infused peptide from ∼2- to 20-fold. Like ANP, infusions of BNP caused dose-related increases ( P < 0.05) in mesenteric vascular resistance, urine flow, natriuresis, and hematocrit (changes at highest doses were 60 ± 9, 334 ± 113, 313 ± 173, and 12 ± 2%, respectively). BNP also lowered ( P < 0.05) plasma renin activity (−43 ± 11%) and arterial pressure (−10 ± 3%). Effects of BNP were independent of reflex sympathetic activation, since autonomic ganglion blockade did not attenuate the responses. CNP infusions had little effect except to increase ( P < 0.05) mesenteric vascular resistance (27 ± 10%) and plasma ANP (41 ± 7%). Cardiovascular actions of BNP, like those of ANP, counteract the renin-ANG system and may protect the heart by lowering cardiac preload (venous return) and afterload (arterial pressure) while maintaining blood flow to extrasplanchnic regions.
Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist
Authors: Smagin Gennady N. , Howell Leigh Anne , Redmann Stephen , Ryan Donna H. , Harris Ruth B. S.
Published: December 2017

We previously reported that rats exposed to repeated restraint (3 h/day for 3 days) experience temporary hypophagia and a sustained reduction in body weight compared with nonrestrained controls. Studies described here determined the involvement of central corticotropin-releasing factor (CRF) receptors in the initiation of this chronic response to acute stress. In experiment 1, Sprague-Dawley rats were fitted with cannulas in the lateral ventricle and infused with 50 μg of αhCRF-(9—41) or saline immediately before restraint on each of the 3 days of restraint. The receptor antagonist inhibited hypophagia and weight loss on day 1 of restraint but not on days 2 and 3. In experiment 2, 10 μg of αhCRF-(9—41) or saline were infused into the third ventricle immediately before each restraint. The receptor antagonist totally blocked stress-induced hypophagia and weight loss. These results demonstrate that CRF receptors located in or near the hypothalamus mediate the acute responses to stress that lead to a permanent change in the hormonal or metabolic processes that determine body weight and body composition.
Cardiovascular response to group I metabotropic glutamate receptor activation in NTS
Authors: Foley C. Michael , Vogl Helen W. , Mueller Patrick J. , Hay Meredith , Hasser Eileen M.
Published: December 2017

Glutamate is the proposed neurotransmitter of baroreceptor afferents at the level of the nucleus tractus solitarius (NTS). Exogenous glutamate in the NTS activates neurons through ionotropic and metabotropic glutamate receptors (mGluRs). This study tested the hypothesis that group I mGluRs in the NTS produce depressor, bradycardic, and sympathoinhibitory responses. In urethan-anesthetized rats, unilateral 30-nl microinjections of the group I-selective mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. The dose of drug that produced 50% of the maximal response (ED50) was 50–100 μM. The response to microinjection of equal concentrations of DHPG or the general mGluR agonist 1-aminocyclopentane-1 S,3 R-dicarboxylic acid (ACPD) produced similar cardiovascular effects. The cardiovascular response to injection of DHPG or ACPD was abolished by NTS blockade of mGluRs with α-methyl-4-carboxyphenylglycine (MCPG). Blockade of ionotropic glutamate receptors with kynurenic acid did not attenuate the response to DHPG or ACPD injection. These data suggest that DHPG and ACPD activate mGluRs in the NTS and do not require ionotropic glutamate receptors to produce their cardiovascular response. In the NTS the group I mGluRs produce responses that are consistent with excitation of neurons involved in reducing sympathetic outflow, heart rate, and arterial pressure.
Effect of hyposmotic challenge on microvillous membrane potential in isolated human placental villi
Authors: Birdsey T. J. , Boyd R. D. H. , Sibley C. P. , Greenwood S. L.
Published: December 2017

This study examined the effect of hyposmotic solutions on the syncytiotrophoblast microvillous membrane potential ( E m) in mature intermediate villi isolated from term human placentas. When villi were exposed to a control solution (280 mosmol/kgH2O; 116 mM NaCl) and then to either a 138-hyposmotic (138 mosmol/kgH2O; 37 mM NaCl) or 170-hyposmotic (170 mosmol/kgH2O; 55 mM NaCl) solution, there was a significant hyperpolarization of E m (−5.1 ± 1.5 mV, P < 0.01 and −5.0 ± 0.5 mV, P < 0.001, respectively; n = 10), which was reversible on removal of the hyposmotic stimulus. Low-NaCl (37 and 55 mM) solutions made isosmotic with control (i.e., 280 mosmol/kgH2O) by addition of raffinose did not significantly alter E m, suggesting that reducing NaCl concentration per se had no effect on E m. Exposure to 170-hyposmotic solution in the presence of 5 mM BaCl2 depolarized E m by +4.1 ± 0.7 mV ( P < 0.001, n = 6); BaCl2 similarly depolarized E m when added in control solution (+5.6 ± 1.1 mV, n= 5). Exposure to 170-hyposmotic solution containing 1 mM DIDS hyperpolarized E mby −9.0 ± 1.7 mV ( P < 0.001, n = 5). This degree of hyperpolarization was significantly greater than that observed in hyposmotic solution alone ( P < 0.01) but was not different from the hyperpolarization when DIDS was added to control solution (−7.4 ± 0.2 mV, n = 6). We conclude 1) that Ba2+-sensitive K+ conductances and DIDS-sensitive anion conductances contribute to the resting potential of the syncytiotrophoblast microvillous membrane and 2) that the syncytiotrophoblast microvillous membrane responds to a hyposmotic stimulus by activating both Ba2+-sensitive K+ and DIDS-sensitive anion conductances.
Glycogen depletion rather than glucose 6-Pincrements controls early glycogen recovery in human cultured muscle
Authors: Montell Eulàlia , Arias Alexandra , Gómez-Foix Anna M.
Published: December 2017

In glycogen-containing muscle, glycogenesis appears to be controlled by glucose 6-phosphate (6- P) provision, but after glycogen depletion, an autoinhibitory control of glycogen could be a determinant. We analyzed in cultured human muscle the contribution of glycogen depletion versus glucose 6- P in the control of glycogen recovery. Acute deglycogenation was achieved by engineering cells to overexpress glycogen phosphorylase (GP). Cells treated with AdCMV-MGP adenovirus to express 10 times higher active GP showed unaltered glycogen relative to controls at 25 mM glucose, but responded to 6-h glucose deprivation with more extensive glycogen depletion. Glycogen synthase (GS) activity ratio was double in glucose-deprived AdCMV-MGP cells compared with controls, despite identical glucose 6- P. The GS activation peak (30 min) induced by glucose reincubation dose dependently correlated with glucose 6- P concentration, which reached similar steady-state levels in both cell types. GS activation was significantly blunted in AdCMV-MGP cells, whereas it strongly correlated, with an inverse relationship, with glycogen content. An initial (0–1 h) rapid insulin-independent glycogen resynthesis was observed only in AdCMV-MGP cells, which progressed up to glycogen levels ∼150 μg glucose/mg protein; control cells, which did not deplete glycogen below this concentration, showed a 1-h lag time for recovery. In summary, acute deglycogenation, as achieved by GP overexpression, caused the activation of GS, which inversely correlated with glycogen replenishment independent of glucose 6- P. During glycogen recovery, the activation promoted by acute deglycogenation rendered GS effective for controlling glycogenesis, whereas the transient activation of GS induced by the glucose 6- P rise had no impact on the resynthesis rate. We conclude that the early insulin-independent glycogen resynthesis is dependent on the activation of GS due to GP-mediated exhaustion of glycogen rather than glucose 6- P provision.
Indomethacin inhibits circulating PGE2and reverses postexercise suppression of natural killer cell activity
Authors: Rhind Shawn G. , Gannon Greg A. , Suzui Masatoshi , Shephard Roy J. , Shek Pang N.
Published: December 2017

Natural killer (NK) cells are important in combating viral infections and cancer. NK cytolytic activity (NKCA) is often depressed during recovery from strenuous exercise. Lymphocyte subset redistribution and/or inhibition of NK cells via soluble mediators, such as prostaglandin (PG) E2and cortisol, are suggested as mechanisms. Ten untrained (peak O2consumption = 44.0 ± 3.5 ml ⋅ kg−1⋅ min−1) men completed at 2-wk intervals a resting control session and three randomized double-blind exercise trials after the oral administration of a placebo, the PG inhibitor indomethacin (75 mg/day for 5 days), or naltrexone (reported elsewhere). Circulating CD3−CD16+/56+NK cell counts, PGE2, cortisol, and NKCA were measured before, at 0.5-h intervals during, and at 2 and 24 h after a 2-h bout of cycle ergometer exercise (65% peak O2consumption). During placebo and indomethacin conditions, exercise induced significant ( P < 0.0001) elevations of NKCA (>100%) and circulating NK cell counts (>350%) compared with corresponding control values. With placebo treatment, total NKCA was suppressed (28%; P < 0.05) 2 h after exercise, and a postexercise elevation (36%; P = 0.02) of circulating PGE2was negatively correlated ( r = 0.475, P = 0.03) with K-562 tumor cell lysis. NK counts were unchanged in the postexercise period, but at this stage CD14+monocyte numbers were elevated ( P < 0.0001). Indomethacin treatment eliminated the postexercise increase in PGE2concentration and completely reversed the suppression of total and per CD16+56+NKCA 2 h after exercise. These data support the hypothesis that the postexercise reduction in NKCA reflects changes in circulating PGE2rather than a differential lymphocyte redistribution.
Brain adaptation to acute hyponatremia in young rats
Authors: Silver Stephen M. , Schroeder Barbara M. , Bernstein Paul , Sterns Richard H.
Published: December 2017

Brain swelling after acute hyponatremia in prepubescent rats, in contrast to adults, has recently been associated with an increase in brain sodium and a high mortality that could be prevented by preadministration of testosterone. To reexamine the effect of acute hyponatremia in young brain, we measured brain water and solute content in prepubescent rats after induction of hyponatremia over 4 h with water and arginine vasopressin. An 18% decrease in plasma sodium was associated with a 13% increase in brain water and a decrease in brain sodium and glutamate contents. No animals died. To assess the effect of sex hormones on brain adaptation, prepubescent rats were pretreated with estrogen or testosterone before acute hyponatremia. Brain sodium and potassium contents were significantly reduced in comparison to normonatremia in testosterone-pretreated but not estrogen-pretreated animals. However, there was no difference between estrogen-pretreated and testosterone-pretreated groups in mortality or in brain contents of water, electrolytes, or major organic osmolytes. In conclusion, we found that brain adaptation to acute hyponatremia in prepubescent rats is similar to that observed in adults.
Gut vagal afferent lesions increase meal size but do not block gastric preload-induced feeding suppression
Authors: Schwartz Gary J. , Salorio Cynthia F. , Skoglund Chris , Moran Timothy H.
Published: December 2017

Subdiaphragmatic vagal afferent (SVA) signals arising from gut sites may provide critical feedback for the control of food intake within a meal. To evaluate the role of SVAs in both spontaneous and scheduled meals, food intake was assessed in two paradigms in male Sprague-Dawley rats. In the first study, control (Con) rats ( n = 6) and rats with subdiaphragmatic vagal deafferentation (SDA) ( n = 7) had 12-h nightly access to Ensure liquid diet (1 kcal/ml). SDA rats had larger and fewer meals and maintained initial rapid rates of licking, yet total numbers of licks were unaffected. In the second study, Con ( n = 8) and SDA ( n = 7) rats had scheduled access to 12.5% liquid glucose after overnight food deprivation. Glucose intake was assessed after 5-ml gastric preloads of 0.9% saline or glucose, peptone, and Intralipid solutions at three concentrations (0.5, 1, and 2 kcal/ml). Glucose and peptone preloads suppressed intake similarly in Con and SDA rats, whereas Intralipid was ineffective. These results suggest that meal-related SVA signals 1) are not critical in determining preload-induced feeding suppression after deprivation, yet 2) contribute to satiety during spontaneous meals.
Exposure to febrile temperature upregulates expression of pyrogenic cytokines in endotoxin-challenged mice
Authors: Jiang Qingqi , Detolla Louis , Singh Ishwar S. , Gatdula Lisa , Fitzgerald Bridget , van Rooijen Nico , Cross Alan S. , Hasday Jeffrey D.
Published: December 2017

Fever is a phylogenetically ancient response that is associated with improved survival in acute infections. In endothermic animals, fever is induced by a set of pyrogenic cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6] that are also essential for survival in acute infections. We studied the influence of core temperature on cytokine expression using an anesthetized mouse model in which core temperature was adjusted by immersion in water baths. We showed that raising core temperature from basal (36.5–37.5°C) to febrile (39.5–40°C) levels increased peak plasma TNF-α and IL-6 levels by 4.1- and 2.7-fold, respectively, and changed the kinetics of IL-1β expression in response to lipopolysaccharide challenge. TNF-α levels were increased predominantly in liver, IL-1β levels were higher in lung, and IL-6 levels were widely increased in multiple organs in the warmer mice. This demonstrates that the thermal component of fever may directly contribute to shaping the host response by regulating the timing, magnitude, and tissue distribution of cytokine generation during the acute-phase response.
Role of cholecystokinin in the anorexia produced by duodenal delivery of peptone in rats
Authors: Woltman Todd , Reidelberger Roger
Published: December 2017

We used the cholecystokinin receptor antagonist devazepide to assess the importance of CCK in mediating the anorexia produced by 2-h duodenal infusions of peptone, a protein digest, at dark onset in nonfasted rats. Peptone alone (0.14–2.24 g/h) suppressed food intake dose dependently by 18–96%, with an approximate half-maximal dose of 1 g/h. Peptone-induced reductions in caloric ingestion were comparable to the caloric loads infused. Devazepide alone (30–1,000 μg/kg) stimulated food intake dose dependently by 30–73%, with a minimal effective dose of 100 μg/kg. Devazepide appeared to reverse the anorexic response to peptone (1.1 g/h) dose dependently by 29–65%, with a minimal effective dose of 30 μg/kg. The magnitudes of these devazepide-induced effects were similar to, and in some cases were larger than, those produced when the same doses of devazepide were administered alone. Coadministration of devazepide (1,000 μg/kg) and a lower peptone dose (0.8 g/h) produced similar results. These results suggest that an essential CCK mechanism plays a significant role in mediating the satiety response to duodenal delivery of protein.
Amiloride-sensitive sodium signals and salt appetite: multiple gustatory pathways
Authors: Roitman Mitchell F. , Bernstein Ilene L.
Published: December 2017

In the rat, the ionic specificity of Na+ appetite is thought to rely on amiloride-sensitive Na+ signals conveyed by the chorda tympani (CT) nerve. We evaluated whether robust Na+ appetite relies exclusively on CT-mediated amiloride-sensitive Na+ signals. Amiloride dramatically reduced sham drinking of NaCl (41.9 ± 9.0 vs. 6.9 ± 3.7 ml, 0.1 M NaCl without vs. with 100 μM amiloride), which resulted in intake that was not different from intake of a non-Na+ salt solution (8.8 ± 2.3 ml, 0.15 M KCl). In addition, intake of 0.1 M NaCl in CT-transected (CTX) rats was reduced (35.8 ± 13.3 vs. 8.67 ± 3.4 ml, sham-operated vs. CTX rats), but the addition of amiloride (100 μM) further reduced intake in CTX rats (0.5 ± 0.29 ml). These data support the idea that amiloride-sensitive Na+ channels are the critical gustatory substrate for Na+identification during Na+ appetite in the rat. However, the data indicate that these amiloride-sensitive signals are not conveyed exclusively by the CT nerve but by an additional afferent pathway.
Identification of barosensitive neurons in the mediobasal forebrain using juxtacellular labeling
Authors: Kirouac Gilbert J. , Pittman Quentin J.
Published: December 2017

Previous investigations suggest a possible role in cardiovascular regulation for neurons of the mediobasal forebrain. The present study was designed to determine the location and morphology of basal forebrain neurons that respond to acute changes in arterial blood pressure. Extracellular recordings of single units were done in α-chloralose- or urethan-anesthetized rats. The effect of cardiovascular pressor (phenylephrine, 1–2 μg/kg iv) and depressor (sodium nitroprusside, 0.5–1 μg/kg iv) events on the discharge rates of units was determined. Some of the neurons tested were subsequently filled with biocytin using the juxtacellular method. Brain sections were processed using the avidin-biotin complex reaction to reveal a Golgi-like appearance of the neuron. Of 32 neurons located in the horizontal limb of the diagonal band of Broca (hDB), 13 (41%) were found to be excited by depressor events. Barosensitive biocytin-labeled cells were located in all regions of the hDB and had small- to medium-sized cell bodies with sparse and simple dendritic morphology. Only 2 of 47 neurons tested in the region of the olfactory tubercle, islands of Calleja (IC), and ventral pallidum responded to changes in arterial blood pressure. The results of the present investigation suggest a role in the regulation of cardiovascular function for neurons of the hDB. The findings also suggest that most neurons in the olfactory tubercle, including the IC complex, do not respond to acute changes in arterial blood pressure.
Effect of dorsomedial hypothalamic nuclei knife cuts on ingestive behavior
Authors: Bellinger Larry L. , Bernardis Lee L.
Published: December 2017

Previous findings show that rats with electrolytic or excitotoxic lesions in the dorsomedial hypothalamic nucleus (DMN) are hypophagic and hypodipsic and have reduced ponderal and linear growth but normal body composition. DMN-lesioned (DMNL) rats also show altered ingestive responses to naloxone. The present study investigated the intrahypothalamic nerve pathways involved in these DMNL effects and the response of the pathways to deprivation challenges by placing knife cuts posterior (Post), lateral (Lat), ventral (Vent), dorsal, or anterior to the DMN or by administering sham operations. One major finding was that rats with Post or Vent were hypophagic ( P < 0.05) and had reduced body weight but responded normally to deprivation challenges. Post and Lat groups were hypodipsic ( P < 0.05), but plasma Na+, K+, and osmolality and 24-h post-water-deprivation drinking responses were similar in all groups. Naloxone did not suppress the intake of Post rats. It appears that the hypophagia and the reduced body weight after DMNL involve fibers entering or leaving the DMN from ventral and posterior directions, and they may be part of an opioid feeding system.
Neonatal rabbit proximal tubule basolateral membrane Na+/H+antiporter and Cl−/base exchange
Authors: Shah Mehul , Quigley Raymond , Baum Michel
Published: December 2017

The present in vitro microperfusion study examined the maturation of Na+/H+antiporter and Cl−/base exchanger on the basolateral membrane of rabbit superficial proximal straight tubules (PST). Intracellular pH (pHi) was measured with the pH-sensitive fluorescent dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in neonatal and adult superficial PST. Na+/H+antiporter activity was examined after basolateral Na+addition in tubules initially perfused and bathed without Na+. Neonatal Na+/H+antiporter activity was ∼40% that of adult segment (9.7 ± 1.5 vs. 23.7 ± 3.2 pmol ⋅ mm−1⋅ min−1; P < 0.001). The effect of bath Cl−removal on pHiwas used to assess the rates of basolateral Cl−/base exchange. In both neonatal and adult PST, the Cl−/base exchange activity was significantly higher in the presence of 25 mM[Formula: see text] than in the absence of[Formula: see text] and was inhibited by cyanide and acetazolamide, consistent with Cl−/[Formula: see text]exchange. The proton flux rates in the presence of bicarbonate in neonatal and adult tubules were 14.1 ± 3.6 and 19.5 ± 3.5 pmol ⋅ mm−1min−1, respectively ( P = NS), consistent with a mature rate of Cl−/[Formula: see text]exchanger activity in neonatal tubules. Basolateral Cl−/base exchange activity in the absence of CO2and[Formula: see text], with luminal and bath cyanide and acetazolamide, was greater in adult than in neonatal PST and inhibited by bath DIDS consistent with a maturational increase in Cl−/OH−exchange. We have previously shown that the rates of the apical membrane Na+/H+antiporter and Cl−/base exchanger were approximately fivefold lower in neonatal compared with adult rabbit superficial PST. These data demonstrate that neonatal PST basolateral membrane Na+/H+antiporter and Cl−/base exchanger activities are relatively more mature than the Na+/H+antiporter and Cl−/base exchangers on the apical membrane.
Role of glucocorticoids in the maturation of renal cortical Na+-K+-ATPase during fetal life in sheep
Authors: Petershack Jean A. , Nagaraja Sudhir C. , Guillery Edward N.
Published: December 2017

Glucocorticoid levels increase greatly at the time of birth in humans and sheep, coinciding with an increased ability of the kidney to reabsorb sodium. Cortisol induces proximal tubule apical membrane Na+/H+exchanger maturation in near-term fetal sheep. Proximal tubule salt transport is ultimately dependent on Na+pump activity, so we studied the effects of cortisol treatment on renal cortical Na+-K+-ATPase. We first looked at six 140 day gestation fetal sheep (term is 145) and compared their renal cortical Na+-K+-ATPase to that of six 1-day-old lambs. Na+-K+-ATPase activity increased 80% after birth. Then nine pairs of twin fetal sheep were chronically instrumented at 127 days gestation. After 72 h recovery, one twin was given a 48-h continuous intraperitoneal infusion of cortisol. Both twins were then killed, and their renal cortices were studied. Na+-K+-ATPase activity increased 122% with cortisol treatment; activity equaled that of 1-day-old lambs. Protein abundance of the α1-subunit of the Na+-K+-ATPase increased 19%; the β1-subunit increased 39% with cortisol treatment. mRNA abundance of the α1-subunit increased 58%; the β1-subunit increased 72%. These results indicate that cortisol matures Na+-K+-ATPase activity.
Cold face test demonstrates parasympathetic cardiac dysfunction in familial dysautonomia
Authors: Hilz M. J. , Stemper B. , Sauer P. , Haertl U. , Singer W. , Axelrod F. B.
Published: December 2017

In familial dysautonomia (FD), i.e., Riley-Day syndrome, parasympathetic dysfunction has not been sufficiently evaluated. The cold face test is a noninvasive method of activating trigeminal brain stem cardiovagal and sympathetic pathways and can be performed in patients with limited cooperation. We performed cold face tests in 11 FD patients and 15 controls. For 60 s, cold compresses (0–1°C) were applied to the cheeks and forehead while we monitored heart rate, respiration, beat-to-beat radial artery blood pressure, and laser-Doppler skin blood flow at the first toe pulp. From these measurements heart rate variability parameters were calculated: root mean square of successive differences (RMSSD), coefficient of variation (CV), low- and high-frequency (LF and HF, respectively) power spectra of the electrocardiogram, and the LF transfer function gain between blood pressure and heart rate. All patients perceived cold stimulation and acknowledged discomfort. In controls, heart rate and skin blood flow decreased significantly during cold face test; in patients, both parameters decreased only briefly and not significantly. In controls, blood pressure, RMSSD, CV, and heart rate HF-power spectra increased but remained unchanged in patients. Respiration, as well as heart rate LF power spectra, did not change in either group. In controls, LF transfer function gain between blood pressure and heart rate indicated that bradycardia was not secondary to blood pressure increase. We conclude that the cold face test demonstrated that patients with FD have a reduced cardiac parasympathetic response, which implies efferent parasympathetic dysfunction.
Mitochondrial protein and HSP70 signaling after ischemia in hypothermic-adapted hearts augmented with glucose
Authors: Ning Xue-Han , Xu Cheng-Su , Portman Michael A.
Published: December 2017

Hypothermia improves resistance to subsequent ischemia in the cardioplegic-arrested heart (CAH). This adaptive process produces mRNA elevation for heat shock protein (HSP) 70–1 and mitochondrial proteins, adenine nucleotide translocator (ANT1), and β-F1-ATPase. Glucose in cardioplegia also enhances myocardial protection. These processes might be linked to reduced ATP depletion. To assess for synergism between these protective processes, isolated rabbit hearts ( n = 91) were perfused at 37°C and exposed to ischemic cardioplegic arrest for 2 h. Hearts were in four groups: control (C), hypothermia adapted (H) perfused to 31°C 20 min before ischemia, 22 mM glucose (G) in cardioplegia, and hypothermic adaptation and glucose (HG). Developed pressure (DP), dP/d tmax, and pressure-rate product (PRP) improved ( P < 0.05) in G, H, and HG compared with C during reperfusion. DP and PRP were elevated in HG over H and G. ATP was higher in G, H, and HG, although no additional increase in HG over H was found. Lactate and CO2production were elevated in G only. The mRNA expression for HSP70–1, ANT1, and β-F1-ATPase was elevated severalfold in H and HG, but not G over C during reperfusion. In conclusion, glucose provides additional functional improvement in H. Additionally, neither ATP levels nor anaerobic metabolism are linked to mRNA expression for HSP70, ANT1, or β-F1-ATPase in CAH.
Molecular and functional evidence for Na+-K+-2Cl−cotransporter expression in rat skeletal muscle
Authors: Wong Jennifer A. , Fu Liusong , Schneider Edward G. , Thomason Donald B.
Published: December 2017

Doubt has been raised about the expression of a functional Na+-K+-2Cl−cotransporter in rat skeletal muscle. In this study we present molecular and functional evidence for expression of a protein having the characteristics of a cotransporter. RT-PCR of RNA isolated from rat soleus muscle with primers to a conserved putative membrane-spanning domain resulted in a single product of predicted size. Sequencing of the product showed that it bears >90% homology with known rodent NKCC1 (BSC2) cotransporters. RNase protection assay of RNA isolated from the rat soleus muscle also identified this sequence. Immunologic detection of the cotransporter with two different antibodies indicated the presence of cotransporter protein, perhaps more than one, in blots of total muscle protein. Immunohistochemical detection by confocal microscopy localized the majority of expression of the protein to the muscle fibers. Functional studies of cotransport activity also indicate the appropriate sensitivity to inhibitors and ion dependence. Taken together, these data support the presence and function of Na+-K+-2Cl−cotransporter activity in the soleus muscle of the rat.
Mechanisms of inhibition of vasopressin release during moderate antiorthostatic posture change in humans
Authors: Pump Bettina , Gabrielsen Anders , Christensen Niels Juel , Bie Peter , Bestle Morten , Norsk Peter
Published: December 2017

The hypothesis was tested that the carotid baroreceptor stimulation caused by a posture change from upright seated with legs horizontal (Seat) to supine (Sup) participates in the suppression of arginine vasopressin (AVP) release. Ten healthy males underwent this posture change for 30 min without or with simultaneous application of lower body negative pressure (LBNP) adjusted to maintain left atrial diameter (LAD) at the Seat level. Throughout Sup, mean arterial pressure and heart rate decreased from 98 ± 2 to 91 ± 2 mmHg and from 63 ± 2 to 55 ± 2 beats/min ( P < 0.05), respectively, whereas the corresponding decreases during Sup + LBNP were attenuated and of shorter duration (98 ± 2 to 93 ± 2 mmHg and 62 ± 2 to 58 ± 3 beats/min, P < 0.05). During Sup, LAD increased from 30 ± 1 to 33 ± 1 mm, and arterial pulse pressure (PP) increased from 40 ± 2 to 47 ± 2 mmHg, whereas plasma AVP decreased from 0.9 ± 0.2 to 0.5 ± 0.1 pg/ml ( P < 0.05), and plasma norepinephrine (NE) decreased from 176 ± 20 to 125 ± 16 pg/ml ( P < 0.05). During Sup + LBNP, there were no changes in LAD, PP, plasma AVP, or NE. In conclusion, vasopressin secretion is suppressed during an antiorthostatic posture change, which increases carotid sinus pressure, PP, and LAD. The suppression is absent when PP and LAD are prevented from increasing and is thus critically dependent on at least one of these stimuli.
Heterologous acclimation: a novel approach to the study of thermal acclimation in the crabCancer pagurus
Authors: Pearson Timothy , Hyde David , Bowler Ken
Published: December 2017

The control of the attainment of acclimation in Cancer pagurus has been studied. Homologous (8 or 22°C) and heterologous acclimation [central nervous system (CNS) and periphery of crabs simultaneously held at 8 or 22°C] were used. The dependence of electrophysiological parameters of dactylopodite closer muscles of walking legs on nerve stimulation was determined between 6 and 26°C. Muscle resting potential (RP) hyperpolarized linearly with increasing measurement temperatures and showed a 69% compensation between 8 and 22°C on homologous acclimation. With the CNS temperature constant at 8°C, the leg muscle RP showed a 72% compensation on heterologous acclimation to 8 and 22°C; when CNS temperature was constant at 22°C, leg muscle RP showed a 48% compensation on heterologous acclimation to 8 and 22°C. In homologous acclimation, the shape of the excitatory junction potential vs. temperature relationship was characteristic of acclimation temperature. In heterologous acclimation, the shape of this plot was related to the temperature experienced by the leg and not by the CNS. Thus acclimation was principally dependent on local tissue temperature and was relatively independent of CNS or hormonal influences.
Pseudoaffective cardioautonomic responses to gastric distension in rats
Authors: Tougas Gervais , Wang Lu
Published: December 2017

We examined the heart rate response to gastric distension, the involvement of vagal and sympathetic sensory afferents, adrenergic and cholinergic neural pathways, and the effects of capsaicin on this response in anesthetized rats. Gastric distension volume dependently decreased heart rate by 24.5% (resting rate = 219.87 ± 14.06 beats/min, mean rate during gastric distension with 15 ml = 165.97 ± 17.36 beats/min, P < 0.05). The bradycardic response was significantly decreased after removal of the celiac plexus (9.71 ± 1.77 vs. 38.03 ± 7.06% in controls, P < 0.05) or after bilateral subdiaphragmatic vagotomy (6.38 ± 2.65%, P = 0.05). The response to gastric distension was largely prevented by systemic capsaicin (29.92 ± 4.93% in controls, 2.58 ± 4.19% after systemic capsaicin, P < 0.05) and decreased by perivagal capsaicin (18.72 ± 4.75%, P < 0.05). Atropine almost completely prevented the cardiac response to distension, while propranolol and bretylium partially blocked it, implying the response is primarily mediated by cholinergic efferents but also involves adrenergic pathways. We conclude that unmyelinated, capsaicin-sensitive vagal afferents are essential to the pseudoaffective cardioautonomic response to a noxious gastric stimulus.
Reduced sensitivity to the satiation effect of intestinal oleate in rats adapted to high-fat diet
Authors: Covasa Mihai , Ritter Robert C.
Published: December 2017

When rats are maintained on high-fat diets, digestive processes adapt to provide for more efficient digestion and absorption of this nutrient. Furthermore, rats fed high-fat diets tend to consume more calories and gain more weight than rats on a low-fat diet. We hypothesized that, in addition to adaptation of digestive processes, high-fat maintenance diets might result in reduction of sensitivity to the satiating effects of fat digestion products, which inhibit food intake by activating sensory fibers in the small intestine. To test this hypothesis we measured food intake after intestinal infusion of oleic acid or the oligosaccharide maltotriose in rats maintained on a low-fat diet or one of three high-fat diets. We found that rats fed high-fat diets exhibited diminished sensitivity to satiation by intestinal infusion of oleic acid. Sensitivity to the satiation effect of intestinal maltotriose infusion did not differ between groups maintained on the various diets. Reduced sensitivity to oleate infusion was specifically dependent on fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. These results indicate that diets high in fat reduce the ability of fat to inhibit further food intake. Such changes in sensitivity to intestinal fats might contribute to the increased food intake and obesity that occur with high-fat diet regimens.
Muscle IMP accumulation during fatiguing submaximal exercise in endurance trained and untrained men
Authors: Baldwin Jacinta , Snow Rodney J. , Carey Michael F. , Febbraio Mark A.
Published: December 2017

To examine the effect of training status on muscle metabolism during exercise, seven endurance-trained [peak oxygen uptake (V˙o2 peak) = 65.8 ± 2.4 ml ⋅ kg−1⋅ min−1] and six untrained (V˙o2 peak= 46.2 ± 1.9 ml ⋅ kg−1⋅ min−1) men cycled to fatigue at a work rate calculated to require 70%V˙o2 peak. Time to exhaustion was 36% longer ( P < 0.01) in trained (TR) compared with untrained (UT) men (148 ± 11 vs. 95 ± 8 min). Although intramuscular glycogen content was reduced ( P < 0.05) in both TR and UT at fatigue, IMP, a marker of a mismatch between ATP supply and demand, was only elevated ( P < 0.01) in UT muscle at fatigue and was approximately fourfold higher at this point in UT compared with TR. These data demonstrate that fatiguing submaximal exercise was associated with a similar low level of intramuscular glycogen in both TR and UT men, but a mismatch between ATP supply and demand only occurred in UT individuals.