bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased oxidative capacity does not protect skeletal muscle fibers from eccentric contraction-induced injury
Authors: Patel T. J. , Cuizon D. , Mathieu-Costello O. , Fridén J. , Lieber R. L.
Published: December 2017

Isometric electrical stimulation was delivered to rabbit dorsiflexor muscles at 10 Hz for 1 s on and 1 s off over 30 min, 5 days/wk for 3 wk to induce an increase in muscle oxidative capacity. Stimulation-trained muscles as well as untrained muscles were then subjected to a 30-min eccentric exercise bout to test whether increased oxidative capacity provided a protective effect against muscle injury. Electrical stimulation resulted in significant training of both the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, with EDL citrate synthase (CS) activity increasing an average of 67% ( P < 0.0001) and TA CS activity increasing by 27% ( P < 0.05). For all parameters measured, the magnitude of change was much greater for EDL than for TA muscle. Dorsiflexor fatigability decreased significantly during the 3-wk training period ( P < 0.0001), whereas the EDL and TA individually showed strong decreasing trends in fatigability after training. TA and EDL capillary density measured histomorphometrically increased from 839 ± 56 to 1,026 ± 71 mm−2( P = 0.07) and from 589 ± 37 to 792 ± 66 mm−2( P < 0.05), respectively. TA and EDL capillary-to-fiber ratio increased from 1.32 ± 0.10 to 1.55 ± 0.16 ( P > 0.2) and 1.08 ± 0.07 to 1.36 ± 0.14 ( P > 0.1), respectively. Type 2A fiber type percentage increased after stimulation training by 68% ( P < 0.0001) for the EDL and by 32% ( P > 0.1) for the TA at the expense of type 2D fibers. Despite the large training effect for the EDL and the modest training effect for the TA, no differences were observed between stimulation-trained and untrained groups for maximum dorsiflexion torque ( P > 0.3) or maximum tetanic tension ( P > 0.3) after eccentric contraction-induced injury. Additionally, no significant correlation was observed between CS activity and maximum tetanic tension after eccentric contraction-induced injury for either muscle ( P > 0.2). Thus we conclude that increasing muscle oxidative capacity by isometric electrical stimulation training did not protect muscle against eccentric contraction-induced injury.
Effects of daily sodium intake and ANG II on cortical and medullary renal blood flow in conscious rats
Authors: Gross Volkmar , Kurth Theresa M. , Skelton Meredith M. , Mattson David L. , Cowley A. W.
Published: December 2017

Implanted optical fibers and laser-Doppler flow measurement techniques were used for the sequential measurement of regional renal blood flow in conscious rats to determine the effects of an increase of daily NaCl intake on the renal cortical blood flow and blood flow to the outer and inner medulla. Cortical blood flow was increased significantly (32%) by the second day when NaCl intake was increased from 1 to 7 meq/day and was increased further (50%) on the second day after a further elevation of NaCl intake to 13 meq/day. Blood flow to the outer and inner medulla was not changed as NaCl intake was elevated. The increase in renal cortical flow was closely associated with significant reductions in circulating concentrations of ANG II from 31 to 16 pg/ml. Rats given a continuous infusion of nonpressor doses of ANG II (5.0 ng ⋅ kg−1 ⋅ min−1) to maintain constant plasma concentrations of ANG II as sodium intake was increased exhibited no increase of cortical flow. We conclude that reductions of plasma ANG II associated with incremental increases of daily sodium intake result in a rise of renal cortical flow. The elevated blood flow to the renal cortex may enhance sodium excretion and contribute to long-term sodium homeostasis.
Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabeticdb/dbmouse
Authors: Ninomiya Yuzo , Imoto Toshiaki , Yatabe Akira , Kawamura Sanae , Nakashima Kiyohito , Katsukawa Hideo
Published: December 2017

Genetically diabetic db/db mice show greater neural and behavioral responses to sugars than lean control mice. The present study examined chorda tympani responses of db/db mice to nonsugar sweeteners and their inhibition by a sweet response inhibitor, gurmarin. The results showed that responses to sucrose, saccharin, glycine,l-alanine, andd-tryptophan, but not tod-phenylalanine, were ∼1.5 times greater in db/db mice than in control mice. Treatment of the tongue with gurmarin suppressed responses to these sweeteners in db/dband control mice, but the extent of suppression was considerably smaller in db/db mice. The magnitudes of gurmarin-sensitive components of the response to sweeteners in db/db mice were not significantly different from those in control mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice were about twice as large as those in control mice. These results suggest that the enhancement of chorda tympani responses in db/db mice to sucrose and other nonsugar sweeteners may occur through gurmarin-insensitive membrane components.
Cholecystokinin satiety involves CCKA receptors perfused by the superior pancreaticoduodenal artery
Authors: Cox James E.
Published: December 2017

Three experiments compared the potency of the type A cholecystokinin (CCKA)-receptor antagonist devazepide for increasing intake of 30% sucrose when injected into the superior pancreaticoduodenal (SPD) artery (SPD group) or jugular vein (IV group). In experiment 1, 15 min of sucrose intake in adult, male Sprague-Dawley rats after 6 h of food deprivation was increased by devazepide (20 μg/kg) administered into the SPD artery whether given alone or in conjunction with cholecystokinin octapeptide (CCK-8, 2 μg/kg ip). Devazepide had no effect in the IV group. In experiment 2, injection of 8, 20, and 50 μg/kg of devazepide into the SPD artery increased sucrose intake of nondeprived rats. Only the highest dose was effective in the IV group. On subsequent tests, administration of 1 μg/kg of CCK-8 significantly suppressed intake only in the SPD group. In experiment 3, nondeprived rats with SPD artery and jugular vein catheters were tested in a within-subjects design. Devazepide (20 μg/kg) increased sucrose intake after injection into the SPD artery, but not into the jugular vein. In experiment 4, intraduodenal devazepide (8, 20, and 50 μg/kg) had no effect. These results indicate that CCKA receptors within the SPD arterial bed mediate the satiating action of CCK, consistent with local action of duodenal CCK.
Theta values for C16O18O and C18O2related to respective pulmonary diffusing capacities
Authors: Heller Hartmut , Schuster Klaus-Dieter
Published: December 2017

The single-breath diffusing capacities for singly and doubly18O-labeled CO2,[Formula: see text]and[Formula: see text], as well as for NO, were determined in seven anesthetized rabbits to investigate whether the theoretically predicted ratio of specific blood uptake rates of both isotopic CO2species,[Formula: see text]/[Formula: see text]= 2.0, can be derived from the measured values of[Formula: see text]and[Formula: see text]. Data of Dl were obtained by inflating the lungs with gas mixtures containing 0.35% C16O18O or 0.8% C18O2or 0.05% NO in nitrogen, with breath-holding periods of 0.05–0.5 s and 2–12 s for the CO2and NO tests, respectively.[Formula: see text]/[Formula: see text]was calculated by applying the double-reciprocal Roughton-Forster equation to Dl values obtained in each animal and by assuming that NO diffusing capacity represents the gas conductance of the alveolar-capillary membrane. The measured ratio was[Formula: see text]/[Formula: see text]= 1.9 ± 0.2 (mean ± SD), thus comparing reasonably with the predicted one. Therefore, our findings provide evidence that the greater value of[Formula: see text]is mainly due to the twofold higher probability (or theta value) for C18O2than for C16O18O to disappear within red blood cells via isotopic exchange reactions.
A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats
Authors: Ishihara A. , Tanaka T. , Kanatani A. , Fukami T. , Ihara M. , Fukuroda T.
Published: December 2017

Neuropeptide Y (NPY) is one of the most potent orexigenic substances known. 1229U91 was found to be a potent and selective NPY antagonist. To elucidate a physiological role of NPY in hyperphagia in obese animals, we studied the effect of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food intake of Zucker rats was suppressed by intracerebroventricular administration of 1229U91 more potently in obese than in lean animals without abnormal behavior (31.7 and 67.3% inhibition at doses of 10 and 30 μg, respectively, in Zucker fatty rats and 22.2% inhibition at 30 μg in lean rats). This compound markedly suppressed NPY-induced food intake at 30 μg but did not affect galanin-induced food intake, suggesting that the feeding suppression seen in Zucker fatty and lean rats is pharmacologically and behaviorally specific. These results suggest that NPY is involved in feeding behavior in Zucker fatty rats and that NPY contributes to feeding to a greater degree in Zucker fatty than in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal overactivation of the NPYergic system.
Central mechanisms for the hypertensive effects of preproadrenomedullin-derived peptides in conscious rats
Authors: Samson Willis K. , Murphy Tonya C. , Resch Zachary T.
Published: December 2017

Peptides derived from postranslational processing of preproadrenomedullin exert potent hypotensive effects in the periphery. One of those peptides, adrenomedullin (AM) also has been demonstrated to act centrally in conscious rats to inhibit water drinking and salt appetite and, in anesthetized rats, surprisingly to increase blood pressure. We examined the effects of AM and the other postranslational product, proadrenomedullin NH2-terminal 20 peptide (PAMP), on blood pressure in conscious rats. Both AM and PAMP elicited dose-related increases in mean arterial pressure after cerebroventricular administration. The hypertensive effects of both AM and PAMP and of ANG II were blocked by peripheral administration of phentolamine, indicating actions of the peptides in brain to stimulate sympathetic nervous system function. Blockade of central ANG II receptors with saralasin prevented the hypertensive effects of both ANG II and PAMP, suggesting recruitment of endogenous angiotensinergic systems by central PAMP. The structural homolog of AM, calcitonin gene-related peptide (CGRP), at similar doses did not significantly affect blood pressure. Furthermore, the hypertensive effects of ANG II, AM, and PAMP were not abrogated by prior administration of the CGRP antagonist. We hypothesize that AM and PAMP exert cardioprotective effects in brain, which may counterbalance the volume-unloading actions of the peptides in the periphery.
A role for NMDA receptors in posthypoxic frequency decline in the rat
Authors: Coles Sharon K. , Ernsberger Paul , Dick Thomas E.
Published: December 2017

Posthypoxic frequency decline (PHFD) refers to the undershoot in respiratory frequency that follows brief hypoxic exposures. Lateral pontine neurons are required for PHFD. The neurotransmitters involved in the circuit that activate and/or are released by these pontine neurons regulating PHFD are unknown. We hypothesized that N-methyl-d-aspartate (NMDA) receptors are required for PHFD, because of the similarity in respiratory pattern after blocking lateral pontine activity or NMDA receptors. Furthermore, we hypothesized that the location of these NMDA receptors could be visualized by optimizing binding affinity with spermidine. In vagotomized, anesthetized rats ( n = 16), cardiorespiratory responses to hypoxia (8% O2, 30–90 s) were recorded before and after dizocilpine (10 μg-1 mg/kg iv), and NMDA receptors were mapped with [3H]dizocilpine ( n = 6). Dizocilpine elicited a dose-related effect on PHFD, blocking PHFD at high doses. Resting arterial blood pressure and breathing frequency decreased with high doses of dizocilpine, but the respiratory response to hypoxia remained intact. Our novel anatomical data indicate that NMDA receptors were widespread but distributed differentially in the brain stem. We conclude that NMDA receptors are located in pontine and medullary respiratory-related regions and that PHFD requires NMDA-receptor activation.
Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the old rat
Authors: Robert Alain , Tran Nguyen N. P. , Giummelly Philippe , Atkinson Jeffrey , Capdeville-Atkinson Christine
Published: December 2017

In male Wistar rats, the in vitro vasoconstrictor response of the perfused tail artery elicited by norepinephrine or serotonin decreased with age (24 mo old vs. 3 mo old), whereas the fluorescent signal (fura 2) produced by intracellular calcium ([Formula: see text]) mobilization increased. Both vasoconstriction and the increase in intracellular calcium concentration elicited by a high-K+, depolarizing solution were unaffected by aging. Pertussis toxin, a G protein inhibitor, had no effect on vasoconstriction induced by high K+but diminished vasoconstrictor responses to norepinephrine in 3- and 12-mo-old animals but not in 24-mo-old animals. Pertussis toxin had no effect on[Formula: see text] mobilization. The sensitivity of receptor activation to pertussis toxin in tail arteries from 24-mo-old animals was restored by pretreatment with the α-adrenoceptor antagonist nicergoline. Nicergoline had no effect on vasoconstriction induced by high K+. Plasma norepinephrine concentration rose with age; nicergoline had no effect on this rise. We suggest that aging leads to a decrease in the intracellular G protein-modulated amplification of vasoconstriction produced by receptor activation and that this could be linked to the hyperadrenergic state. Ca2+sensitivity can be restored by chronic treatment with an α-adrenoceptor antagonist.
Odor structure-activity relationships of carboxylic acids correspond between squirrel monkeys and humans
Authors: Laska Matthias , Teubner Peter
Published: December 2017

With use of a conditioning paradigm, the ability of four squirrel monkeys to distinguish n-valeric acid from n-forms and isoforms of other carboxylic acids (acetic acid to octanoic acid) was investigated. All four animals were clearly able to discriminate between all odor pairs tested and showed a significant negative correlation between discrimination performance and structural similarity of odorants in terms of differences in carbon chain length of the carboxylic acids. Branching of the carbon chain was also found to affect odorant quality because all animals performed better in discriminating n-valeric acid from isoforms of other carboxylic acids compared with the corresponding n-forms of these substances. With use of a triple forced-choice procedure, 10 human subjects were tested on the same tasks in parallel and showed a very similar pattern of discrimination performance compared with the squirrel monkeys. Thus the results of this study provide evidence of well-developed olfactory discrimination ability in squirrel monkeys for carboxylic acids and support the assumption that human and nonhuman primates may share common principles of odor quality perception.
Effect of calcitonin on the activity of ANG II-responsive neurons in the rat subfornical organ
Authors: Schmid Herbert A. , Rauch Matthias , Koch Julia
Published: December 2017

In addition to the well-documented ability of calcitonin to lower blood calcium levels, blood-borne calcitonin may also affect neurons located outside the blood-brain barrier, e.g., in the subfornical organ (SFO), where numerous receptors for this peptide have been described. In an in vitro preparation of the rat SFO, calcitonin activated 61% of 36 neurons, only 1 neuron was inhibited, and the remainder were unresponsive. All but two of the neurons excited by 10−7 M calcitonin were also stimulated by 10−7 M ANG II. The threshold concentration for the excitatory effects of calcitonin was 10−9 M and was thus similar to ANG II. Like ANG II, subcutaneous injection of calcitonin stimulated water intake, although to a lower extent. These results suggest that blood-borne calcitonin could stimulate drinking by its excitatory effect on neurons in the SFO. Calcitonin, which is released during food intake, might be involved in prandial drinking, which is presently considered an acquired behavior.
Role of taste in the microstructure of quinine ingestion by rats
Authors: Spector Alan C. , St. John Steven J.
Published: December 2017

The microstructure of the licking behavior of water-deprived rats presented with either water or quinine during 45-min single-bottle tests was analyzed. The chorda tympani (CT) and glossopharyngeal (GL) nerves, which innervate the taste buds of the tongue, were transected in deeply anesthetized rats to discern their contribution to the behavioral pattern of quinine drinking. Rats were presurgically habituated to the testing protocol and postsurgically tested first with water and then novel 0.2 mM quinine-HCl in a subsequent session. The substantial decrease in intake observed in sham-operated controls ( n = 16) when quinine was the stimulus was entirely a function of a decrease in lick volume and burst size (a run of licks with interlick intervals <1 s). Contrary to the intake-suppressing effects of quinine, pause duration decreased and burst number increased. Combined transection of the CT and GL ( n = 6) strikingly opposed all of these quinine-induced behavioral changes, whereas CT transection ( n = 7) was without effect and GL transection ( n = 8) had an intermediate influence. These results suggest that taste acts more on neural circuits governing burst termination as opposed to burst initiation, which, in turn, appears to be more sensitive to signals related to physiological state. These findings are discussed in terms of other known nerve transection effects on quinine responsiveness, and the implications of the microstructural results are considered with respect to probabilistic as opposed to deterministic control of licking behavior.
Inhibition of gastric emptying in response to intestinal lipid is dependent on chylomicron formation
Authors: Raybould Helen E. , Meyer James H. , Tabrizi Yuri , Liddle Rodger A. , Tso Patrick
Published: December 2017

Lipid in the intestine initiates feedback inhibition of proximal gastrointestinal function and food intake. In rats and humans, inhibition of gastric emptying is mediated, at least in part, by cholecystokinin (CCK)-A receptors, and in rats there is evidence for involvement of an intestinal vagal afferent pathway. The mechanism by which luminal lipid acts to release CCK or activate vagal afferent nerve terminals is unclear. The role of chylomicron formation in this sensory transduction pathway has been investigated using the hydrophobic surfactant Pluronic L-81 that inhibits chylomicron formation. Gastric emptying of liquids was measured in awake rats fitted with a Thomas gastric fistula and a duodenal cannula. Intestinal perfusion of lipid induced a dose-dependent inhibition of gastric emptying (6, 12, and 39% inhibition for 25, 50, and 100 mg lipid, respectively). Perfusion of lipid with Pluronic L-81 (2.8% wt/vol) reversed the lipid-induced inhibition of gastric emptying. Pluronic L-63, a chemically similar surfactant that has no effect on chylomicron formation, had no effect on lipid-induced inhibition of gastric emptying. Perfusion of the intestine with lipid (100 mg) increased plasma levels of CCK from 1.9 ± 0.8 to 6.5 ± 1 pM. This increase was blocked by Pluronic L-81 but unaffected by L-63. These results provide evidence that chylomicron formation is important in the signaling of lipid in the intestinal lumen to CCK endocrine cells and to producing feedback inhibition of gastric emptying.
Respiratory responses to selective blockade of carotid sinus baroreceptors in the dog
Authors: Hopp Francis A. , Seagard Jeanne L.
Published: December 2017

Activation of carotid sinus (CS) baroreceptors has been shown to increase inspiratory time (Ti) and expiratory time (Te) and to have a varied effect on tidal volume. The contribution of two functionally different types of baroreceptors to changes in respiratory function were examined in the current study. The techniques of DC anodal block and bupivacaine anesthetic block were used to selectively block fibers, from largest (type I) to smallest (type II) and smallest to largest, respectively, in the CS nerve (CSN) from an isolated CS in an anesthetized, paralyzed, vagotomized, artificially ventilated dog. Anodal blocking currents from 25 to 60 μA, which blocked primarily large A fibers, produced significant decreases in Ti and Te and increased the slope of the average phrenic neurogram [PNG( t)], with no change in peak PNG( t). Further increases in blocking current to levels that also blocked small C fibers did not result in additional changes. Bupivacaine blockade using concentrations that blocked primarily C fibers did not block changes in Ti and Te to step CS pressure changes. Increasing bupivacaine concentration to 20 mg/100 ml blocked all CSN conduction, and respiratory responses were eliminated. Therefore respiratory responses arising from CS baroreceptors appear to originate from the larger type I baroreceptors.
β2-Agonist ritodrine, unlike natural catecholamines, activates thermogenesis prematurely in fetal sheep
Authors: Bassett John M. , Symonds Michael E.
Published: December 2017

Prolonged administration of the β2-adrenergic agonist ritodrine to fetal sheep increases nonesterified fatty acid mobilization. To investigate whether changes in fetal growth or functional development of brown adipose tissue (BAT) also occur, ritodrine was infused at 5 μg/min iv into eight fetal sheep (6 twins and 2 singletons at 125–128 days of gestation) for 5 days and then at twice this rate for a further 7–11 days. Fetal growth was reduced significantly ( P < 0.02) during ritodrine infusion relative to controls (5.8 ± 17.5 vs. 79.7 ± 10.3 g/day), with growth of skeletal muscles ceasing. Ritodrine reduced perirenal BAT weight by 50% from 18.6 ± 1.89 to 9.3 ± 0.60 g ( P < 0.01) and its lipid content by >70% from 6.5 ± 0.96 to 1.9 ± 0.45 g ( P < 0.01). Mitochondrial protein in BAT was also less ( P < 0.002), but GDP binding to uncoupling protein increased ( P < 0.05). In similar experiments, epinephrine and norepinephrine increased plasma nonesterified fatty acid initially, but neither altered perirenal BAT composition. The β2-adrenergic agonist ritodrine appears able to promote lipid mobilization and thermogenesis in utero.
Active renin, prorenin, and renin gene expression after reduced renal perfusion pressure in term ovine fetuses
Authors: Rosnes Jon S. , Valego Nancy , Wang Jinjuan , Zehnder Timothy , Rose James C.
Published: December 2017

We studied the pattern of plasma active renin concentration (ARC), prorenin concentration (PRC), renal renin concentration, and the renin mRNA levels in ovine fetuses subjected for 24 h to reduced renal perfusion pressure (RPP). The results obtained in five animals (133.8 ± 1.4 days of gestation) in which RPP was reduced by 10 mmHg were compared with those in seven control fetuses (130.3 ± 0.8 days of gestation) without pressure reduction. Plasma samples were obtained before and at intervals of 24 h after initiating reduced RPP. The plasma ARC increased within 60 min of reduced RPP, reaching a maximum (13.0 ± 4.7 vs. 115.7 ± 23.8, P < 0.01) at 3 h. The ARC then declined toward control values. In contrast, plasma PRC did not increase consistently until 4 h into reduced RPP, with maximal levels at 24 h (8.2 ± 2.4 vs. 87.7 ± 21.9, P = 0.016). Within the kidney PRC, but not ARC, increased significantly, by 2.5-fold. Reduced RPP also increased renal renin mRNA levels ( P = 0.004). We conclude that a chronic reduction in RPP in the near-term ovine fetus increases renal PRC and is associated with increased plasma prorenin levels. The data suggest that the conversion of prorenin to active renin is an important regulation point of the renin ANG system during development.
Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm
Authors: Kopin Irwin J. , Rundqvist Bengt , Friberg Peter , Lenders Jacques , Goldstein David S. , Eisenhofer Graeme
Published: December 2017

Spillover of norepinephrine (NE) into plasma is used frequently as an index of NE release and therefore of sympathetic nerve activity. An important limitation of NE spillover is that it reflects not only release but also uptake processes that intervene before the transmitter reaches the circulation. To overcome this limitation, we developed a method for estimating NE release based on measurements of the specific activities of [3H]NE in plasma and interstitial fluid during intravenous infusion of [3H]NE. We applied this method to examine relationships among NE release, tissue uptake, and spillover in the human heart, kidneys, and forearm. The sum of uptake and spillover of released NE provided an estimate of NE release into the interstitial fluid. In the kidneys, NE release averaged three times NE spillover, in skeletal muscle, 12 times NE spillover, and in the heart, >20 times NE spillover. Thus NE release greatly and variably exceeds NE spillover from these organs, so that assessing regional sympathetic function requires an understanding of the relationship of NE spillover to NE release.
Characterization of a primary cell culture model of the avian renal proximal tubule
Authors: Sutterlin Gayle Gocek , Laverty Gary
Published: December 2017

Methods have been developed for producing functional, transporting monolayers of avian proximal tubule (PT) cells. A highly homogenous fraction of PT fragments was prepared by enzymatic digestion (collagenase + Dispase) of chick (3- to 5-day-old) kidneys, followed by Percoll gradient centrifugation. The PT fraction was enriched in glucose-6-phosphatase, a proximal enzyme marker, and reduced in specific activity of hexokinase, a distal marker. PT fragments were grown to confluence in serum-free media on collagen-coated permeable filter supports. Electron microscopy of confluent monolayers revealed numerous microvilli and mitochondria, central cilia, and tight junctions, all characteristic of PT cells. γ-Glutamyltranspeptidase, a proximal brush-border enzyme, showed threefold higher activity on apical than on basolateral sides of the monolayer. The electrophysiological characteristics of monolayers were investigated by voltage-clamp techniques. Monolayers displayed low transepithelial resistances (40–60 Ω ⋅ cm2), lumen-negative potentials, and baseline currents of 6–12 μA/cm2(with or without 5 mM glucose). Both α-methyl-d-glucose (2 mM), a nonmetabolizable hexose, and phenylalanine (2 mM) significantly stimulated short-circuit current when added to the mucosal side of glucose-free monolayers. Phloridzin, a specific inhibitor of Na+-coupled glucose transport, significantly inhibited short-circuit current, as did 10−5M amiloride. Monolayers also expressed net secretory transport of urate. This cell culture preparation may provide a useful working model for the study of avian PT transport.
Central angiotensin AT1 and muscarinic receptors in ITF expression on intracerebroventricular NaCl
Authors: Moellenhoff E. , Lebrun C. J. , Blume A. , Culman J. , Herdegen T. , Unger T.
Published: December 2017

In the present study, we investigated the expression pattern of the inducible transcription factors (ITF) c-Fos, c-Jun, JunB, JunD, and Krox-24 following intracerebroventricular injections of hyperosmolar saline (0.2, 0.3, and 0.6 M NaCl) and its mediation via angiotensin and/or muscarinic receptors. c-Fos, c-Jun, and Krox-24 were differentially expressed in organum vasculosum laminae terminalis, median preoptic area, subfornical organ (SFO), and paraventricular and supraoptic nuclei. Expression of c-Fos and c-Jun was inhibited by pretreatment with the angiotensin AT1 receptor antagonist losartan (10 and 20 nmol icv) following 0.20 and 0.30 M saline. Pretreatment with atropine (15 nmol icv) inhibited the 0.30 and 0.60 M NaCl-induced expression of c-Fos, c-Jun, and Krox-24 in all areas except the SFO. Coexpression of the ITF with vasopressin and oxytocin, the major effector peptides in osmoregulation, was demonstrated, implying the corresponding genes as putative target genes of the ITF. The results show a highly differentiated ITF expression pattern in the brain mediated by angiotensinergic and muscarinergic pathways, suggesting a finely tuned regulation of target genes.
Medullary c-Fos activation in rats after ingestion of a satiating meal
Authors: Rinaman L. , Baker E. A. , Hoffman G. E. , Stricker E. M. , Verbalis J. G.
Published: December 2017

The distribution and chemical phenotypes of hindbrain neurons that are activated in rats after food ingestion were examined. Rats were anesthetized and perfused with fixative 30 min after the end of 1-h meals of an unrestricted or rationed amount of food, or after no meal. Brain sections were processed for localization of the immediate-early gene product c-Fos, a marker of stimulus-induced neural activation. Hindbrain c-Fos expression was low in rats that ate a rationed meal or no meal. Conversely, c-Fos was prominent in the medial nucleus of the solitary tract (NST) and area postrema in rats that ate to satiety. There was a significant positive correlation between postmortem weight of gastric contents and the proportion of NST catecholaminergic neurons expressing c-Fos. Cells in the ventrolateral medulla (VLM) were not activated in rats after food ingestion, in contrast with previous findings that stimulation of gastric vagal afferents with anorexigenic doses of cholecystokinin activates c-Fos expression in both NST and VLM catecholaminergic cells. These findings indicate that anatomically distinct subsets of hindbrain catecholaminergic neurons are activated in rats after food ingestion and that activation of these cells is quantitatively related to the magnitude of feeding-induced gastric distension.
Role of plasma osmolality in the delayed onset of thermal cutaneous vasodilation during exercise in humans
Authors: Takamata Akira , Nagashima Kei , Nose Hiroshi , Morimoto Taketoshi
Published: December 2017

To elucidate the role of increased plasma osmolality (Posmol), which occurs during exercise in the regulation of cutaneous vasodilation (CVD) during exercise, we determined the relationship between the change in esophageal temperature (ΔTes) required to elicit CVD (ΔTes threshold for CVD) and Posmol during light and moderate exercise (30 and 55% of peak oxygen consumption, respectively) and passive body heating. Then we compared the relationship with the data obtained in our previous study [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol.42): R197–R204, 1997], in which we determined the relationships during passive body heating following isotonic (0.9% NaCl) or hypertonic (2 or 3% NaCl) saline infusions in the same subjects. Posmol values at 5 min after the onset of exercise were 287.5 ± 0.9 mosmol/kgH2O during light exercise and 293.0 ± 1.2 mosmol/kgH2O during moderate exercise. Posmol just before passive body heating was 289.9 ± 1.4 mosmol/kgH2O. The ΔTes threshold for CVD was 0.09 ± 0.05°C during light exercise, 0.31 ± 0.09°C during moderate exercise, and 0.10 ± 0.05°C during passive body heating. The relationship between the ΔTes threshold for CVD and Posmol was shown to be on the same regression line both during exercise and during passive body heating with or without infusions [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol.42): R197–R204, 1997]. Our data suggest that the elevated body core temperature threshold for CVD during exercise could be the result of increased Posmol induced by exercise and is not due to reduced plasma volume or the intensity of the exercise itself.
Misty (m) affects growth traits
Authors: Truett Gary E. , Tempelman Robert J. , Walker Jerilyn A. , Wilson J. Krause
Published: December 2017

The misty ( m) coat color mutation is commonly maintained in linkage disequilibrium with the obesity mutation diabetes ( Leprdb) to serve as a marker for Leprdbgenotype. Comparisons among Leprdbgenotypes are made under the untested assumption that m has no effects on traits under investigation. We tested this assumption in a population segregating m in the absence of db. Analysis of growth curves revealed that m/m mice are smaller than M/M mice by the 2nd wk of life and remain smaller through the 5th wk of life. Analysis of variance of three traits measured at 35 days of age revealed that m/m mice are 8% shorter than M/M mice, weigh 15% less, and have 21% less inguinal adipose mass. These results indicate that m affects growth traits. Therefore, when m and Leprdbsegregate in the same cross, interpretation of their effects is confounded by linkage. More accurate estimates of Leprdbgenotype effects can be made by removing m from populations segregating Leprdband using a direct assay to measure Leprdbgenotype.
Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue
Authors: Bamshad Maryam , Aoki Victor T. , Adkison M. Gregory , Warren Wade S. , Bartness Timothy J.
Published: December 2017

White adipose tissue (WAT) is innervated by postganglionic sympathetic nervous system (SNS) neurons, suggesting that lipid mobilization could be regulated by the SNS [T. G. Youngstrom and T. J. Bartness. Am. J. Physiol. 268 ( Regulatory Integrative Comp. Physiol. 37): R744–R751, 1995]. A viral transsynaptic retrograde tract tracer, the pseudorabies virus (PRV), was used to identify the origins of the SNS outflow from the brain to WAT neuroanatomically. PRV was injected into epididymal or inguinal WAT (EWAT and IWAT, respectively) of Siberian hamsters and IWAT of rats. PRV-infected neurons were visualized by immunocytochemistry and found in the spinal cord, brain stem (medulla, nucleus of the solitary tract, caudal raphe nucleus, C1 and A5 regions), midbrain (central gray), and several areas within the forebrain. The general pattern of infection of WAT in both species was more similar than different and resembled that seen after PRV injections into the adrenal medulla in rats (A. M. Strack, W. B. Sawyer, J. H. Hughes, K. B. Platt, and A. D. Loewy. Brain Res. 491: 156–162, 1989). EWAT versus IWAT injected hamsters had relatively less labeling in the suprachiasmatic, dorsomedial, and arcuate nuclei. Overall, it appeared that the SNS innervation of WAT originates from the general SNS outflow of the central nervous system and therefore may play a significant role in lipid mobilization.
Reserve capacities of the small intestine for absorption of energy
Authors: Weber E. , Ehrlein H. J.
Published: December 2017

Previous in vitro studies showed that the small intestine has reserve capacities for absorption of nutrients. However, the size of the reserve capacity is controversial. Therefore, we measured the intestinal capacity for absorption of energy in relation to the postprandial gastric delivery of energy into the gut. In minipigs, a 150-cm length of jejunum was perfused (1–8 kcal/min) with four nutrient solutions containing 60% of energy as carbohydrate, protein, and fat, respectively, or containing 33.3% of each nutrient. In separate experiments, gastric delivery of energy to the jejunum was measured after oral administration of four meals with the same nutrient composition as the perfusion solutions. With all nutrient solutions, intestinal absorption of energy demonstrated saturation kinetics. The jejunal capacity for absorption of energy ranged from 0.66 to 0.94 kcal ⋅ m−1 ⋅ min−1. Despite large differences in nutrient composition of the four meals, equal amounts of energy (1.3 ± 0.41 kcal/min) were delivered from the stomach to the jejunum. The absorption rates of energy after meals ranged from 0.40 to 0.58 kcal ⋅ m−1 ⋅ min−1. Therefore, only 58.8 ± 2.7% of the jejunal capacity for absorption of energy was used. Additionally, the length of small intestine that would have been required for complete absorption was 42.9 ± 3.7% of the total length. Results indicate that the feedback control of gastric emptying provides at least two types of intestinal reserve capacities: a reserve in absorption (1.7 fold) and a reserve in intestinal length (2.4 fold).
Bcl-2 and Bax expression in adult rat hearts after coronary occlusion: age-associated differences
Authors: Liu Lixin , Azhar Gohar , Gao Wei , Zhang Xiaomin , Wei Jeanne Y.
Published: December 2017

It has been reported that programmed cell death (apoptosis) occurs during myocardial infarction. The influence of age on programmed cell death or DNA fragmentation after coronary occlusion has not been extensively characterized. To test the hypothesis that there are age-related differences in susceptibility to DNA fragmentation during ischemia-infarction, we studied DNA fragmentation in young adult and old male F344 rat hearts after acute coronary artery occlusion. Hearts were studied at 1, 3, and 5 h and 1 and 7 days after coronary ligation. The percentage of apoptotic cells was determined by the in situ end-labeling technique, and internucleosomal fragmentation (DNA laddering) pattern was also analyzed. Our results show that 1) DNA fragmentation began earlier and peaked earlier in the old compared with young adult hearts during infarction; 2) there was heightened expression of both Bcl-2 and Bax in the old hearts at baseline; and 3) the Bcl-2-to-Bax ratio was higher in the older heart after coronary ligation. These results suggest that, compared with the young adult heart, the aged heart may be more susceptible to ischemia-induced DNA fragmentation.
Effect of chronic bradykinin administration on insulin action in an animal model of insulin resistance
Authors: Henriksen Erik J. , Jacob Stephan , Fogt Donovan L. , Dietze Guenther J.
Published: December 2017

The nonapeptide bradykinin (BK) has been implicated as the mediator of the beneficial effect of angiotensin-converting enzyme inhibitors on insulin-stimulated glucose transport in insulin-resistant skeletal muscle. In the present study, the effects of chronic in vivo BK treatment of obese Zucker ( fa/ fa) rats, a model of glucose intolerance and severe insulin resistance, on whole body glucose tolerance and skeletal muscle glucose transport activity stimulated by insulin or contractions were investigated. BK was administered subcutaneously (twice daily at 40 μg/kg body wt) for 14 consecutive days. Compared with a saline-treated obese group, the BK-treated obese animals had significantly ( P < 0.05) lower fasting plasma levels of insulin (20%) and free fatty acids (26%), whereas plasma glucose was not different. During a 1 g/kg body wt oral glucose tolerance test, the glucose and insulin responses [incremental areas under the curve (AUC)] were 21 and 29% lower, respectively, in the BK-treated obese group. The glucose-insulin index, the product of the glucose and insulin AUCs and an indirect index of in vivo insulin action, was 52% lower in the BK-treated obese group compared with the obese control group. Moreover, 2-deoxyglucose uptake in the isolated epitrochlearis muscle stimulated by a maximally effective dose of insulin (2 mU/ml) was 52% greater in the BK-treated obese group. Contraction-stimulated (10 tetani) 2-deoxyglucose uptake was also enhanced by 35% as a result of the BK treatment. In conclusion, these findings indicate that in the severely insulin-resistant obese Zucker rat, chronic in vivo treatment with BK can significantly improve whole body glucose tolerance, possibly as a result of the enhanced insulin-stimulated skeletal muscle glucose transport activity observed in these animals.
Endogenous ANG II supports lumbar sympathetic activity in conscious sodium-deprived rats: role of area postrema
Authors: Xu Ling , Collister John P. , Osborn John W. , Brooks Virginia L.
Published: December 2017

This study tests the hypothesis that the area postrema (AP) is necessary for endogenous ANG II to chronically maintain lumbar sympathetic nerve activity (LSNA) and heart rate (HR) in conscious sodium-deprived rats. The effect of the ANG II type 1-receptor antagonist, losartan, on LSNA and HR was determined in rats that were either AP lesioned (APX) or sham lesioned. The sham rats were divided into groups, with (SFR) or without (SAL) food restriction, to control for the decreased food intake of APX rats. Before losartan, basal mean arterial pressure (MAP), HR, and baroreflex control of LSNA and HR were similar between groups, with the exception of lower maximal reflex LSNA and higher maximal gain of the HR-MAP curve in APX rats. In all groups, losartan similarly shifted ( P < 0.01) the LSNA-MAP curve to the left without altering maximal gain. Losartan also decreased ( P < 0.05) minimal LSNA in all groups, and suppressed ( P < 0.01) maximal LSNA (% of control) in SFR (240 ± 13 to 205 ± 15) and SAL (231 ± 21 to 197 ± 26) but not APX (193 ± 10 to 185 ± 8) rats. In general, losartan similarly shifted the HR-MAP curve to a lower MAP in all groups. The results suggest that the AP is not necessary for endogenous ANG II to chronically support LSNA and HR at basal and elevated MAP levels in sodium-deprived rats. However, the AP is required for endogenous ANG II to increase maximal reflex LSNA at low MAP levels.
Rapid brain cooling in diving ducks
Authors: Caputa Michał , Folkow Lars , Blix Arnoldus Schytte
Published: December 2017

Hypothermia may limit asphyxic damages to the brain, and many small homeotherms have been shown to use anapyrexic strategies when exposed to asphyxic conditions. Larger homeotherms do not seem to use the same strategy, but could save oxygen and prevent hypoxic brain damage by employing selective brain cooling (SBC) in connection with asphyxia. To test the hypothesis that selective brain cooling may take place in connection with asphyxia, we have recorded brain [hypothalamic (THyp)] and body [colonic (TC)] temperatures and heart rates in four Pekin ducks during 5-min simulated (head submersion) diving in cold water (10°C). Diving resulted in a drop in THyp(3.1 ± 1.4°C) that continued into the recovery period ( P < 0.001). Restricting heat loss from the buccal cavity and eyes during diving compromised brain cooling in an additive manner. TCwas not influenced by diving. Control cooling of the head with crushed ice during a 5-min period of undisturbed breathing had no effect on THyp. Warm water (35°C) markedly reduced brain cooling, and dive capacity was reduced by ∼14% ( P < 0.05) compared with diving in water at 10°C. The data suggest that SBC is used in ducks during diving, and we propose that this mechanism may enable the bird to save oxygen for prolonged aerobic submergence and to protect the brain from asphyxic damages.
Feeding behavior and entrainment limits in the circadian system of the rat
Authors: Madrid J. A. , Sánchez-Vázquez F. J. , Lax P. , Matas P. , Cuenca E. M. , Zamora S.
Published: December 2017

The entrainment limits of the circadian rhythms of feeding activity were studied in Wistar rats exposed to gradually increasing and decreasing or to static light-dark cycles. In the former, the entrainment limits of feeding behavior were 22 h 10 min and 26 h 40 min. In the latter, the upper limit was higher, because rats under zeitgeber period ( t) length = 27 h ( t27) and t28 met the criteria of entrainment. The lower limit, on the other hand, was not modified because none of the t22 animals showed entrained rhythms and one-half of the t23 rats exhibited two components in their circadian feeding rhythms, one with a period of 23 h and the other free running. This 23-h component reflected not only the masking effect of light-dark cycles but also seemed a true light-entrained component. In well-synchronized animals, food intake seemed to depend more on the number of cycles that the animal experienced than on actual time lived; however, other feeding parameters, such as meal frequency and feeding duration, remained constant when expressed per 24 h, irrespective of the t cycle. These results concerning feeding duration, meal frequency, and food intake revealed that the homeostatic and circadian controls interacted to a degree that depended on the type of variable considered. In conclusion, the entrainment limits appeared much more imprecise than they were previously thought to be, because the circadian system can only be partially synchronized near its entrainment limits. The hypothesis that the rat’s circadian system is composed of multiple oscillators with different intrinsic frequencies and varying capacities for light synchronization would explain the partial desynchronization observed near the entrainment limits.
Angiotensin II modulates respiratory and acid-base responses to prolonged hypoxia in conscious dogs
Authors: Heitman Steven J. , Jennings Donald B.
Published: December 2017

We tested the hypothesis that angiotensin II (ANG II) contributes to ventilatory and acid-base adaptations during 3–4 h of hypoxia (partial pressure of O2 in arterial blood ≈ 43 Torr) in the conscious dog. Three protocols were carried out over 3–4 h in five dogs: 1) air control, 2) 12% O2 breathing, and 3) 12% O2 breathing with ANG II receptors blocked by infusion of saralasin (0.5 μg ⋅ kg−1 ⋅ min−1). After 2 h of hypoxia, expired ventilation and alveolar ventilation progressively increased, and the partial pressure of CO2 in arterial blood and the difference between the arterial concentrations of strong cations and strong anions ([SID]) decreased. When the hypoxic chemoreceptor drive to breathe was abolished transiently for 30 s with 100% O2, the resultant central apneic time decreased between 0.5 and 2.5 h of hypoxia. All these adaptive responses to hypoxia were abolished by ANG II receptor block. Because plasma ANG II levels were lower during hypoxia and hypoxic release of arginine vasopressin from the pituitary into the plasma was prevented by ANG II receptor block, the brain renin-angiotensin system was likely involved. It is possible that ANG II mediates ventilatory and acid-base adaptive responses to prolonged hypoxia via alterations in ion transport to decrease [SID] in brain extracellular fluid rather than acting by a direct neural mechanism.
Spinal segments communicating resting sympathetic activity to postganglionic nerves of the stellate ganglion
Authors: Kocsis Bernat , Gyimesi-Pelczer Katalin
Published: December 2017

It has been shown earlier using sympathetic reflexes and anatomic techniques that preganglionic neurons controlling different effectors occupy wide and overlapping ranges of adjacent segments in the spinal cord (cardiac: T1–T7, vertebral: T2–T8). Because, however, the majority of preganglionic neurons are silent at resting states, the present study was designed to estimate the segmental map of subsets of these neurons including only those active at rest using simultaneous recordings from the inferior cardiac and vertebral nerves, under chloralose-urethan or urethan anesthesia. In 22 cats, thoracic white rami T1–T8 were cut in a sequential manner. Three-minute-long data segments were recorded between sectionings and analyzed in the frequency domain using the fast Fourier transform. We found that cardiac and vertebral active maps involved segments T3–T5 and T4–T8, respectively. In individual experiments, however, most of the power of rhythmic activity originated from only one or two segments and the dominant segments for the two nerves never overlapped. Moreover, the separation between dominant segments generating cardiac and vertebral nerve discharges was wider and the distribution of tonically active preganglionic neurons projecting to each nerve was narrower under urethan than chloralose-urethan anesthesia. We conclude that the proportion of active to quiescent preganglionic neurons regulating cardiac and vertebral nerve discharges varies from spinal segment to segment and that active neurons projecting to these nerves are nonoverlapping.