bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II acts at AT1receptors in the nucleus of the solitary tract to attenuate the baroreceptor reflex
Authors: Matsumura Kiyoshi , Averill David B. , Ferrario Carlos M.
Published: December 2017

The object of the current study was to determine if ANG II acts at type 1 (AT1) or type 2 (AT2) receptors in the nucleus of the solitary tract (NTS) to reduce baroreceptor reflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR). Experiments were carried out in urethan-anesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Reflex changes in RSNA and HR were elicited by intravenous infusion of either phenylephrine or sodium nitroprusside before and after bilateral microinjection of CV-11974 (AT1 receptor antagonist, 10 pmol), PD-123319 (AT2 receptor antagonist, 100 pmol), or artificial cerebrospinal fluid (aCSF, 50 nl) in the NTS. Mean arterial pressure (MAP)-RSNA and MAP-HR data were fit to logistic functions to analyze the baroreceptor reflex. Baroreceptor reflex sensitivities for RSNA and HR were attenuated in SHR compared with those in WKY rats. Bilateral injection of CV-11974, PD-123319, or aCSF in the NTS of either strain had no effect on baseline arterial pressure, HR, or RSNA. However, CV-11974 injected in the NTS increased significantly ( P < 0.01) the sensitivities for baroreceptor reflex control of RSNA and HR in SHR and WKY rats. Neither PD-123319 nor aCSF altered baroreceptor reflex control of RSNA and HR in either SHR or WKY rats. These results demonstrate that endogenous ANG II acts at AT1 receptors of the NTS to attenuate the baroreceptor reflex in SHR as well as in WKY rats.
Interleukin-1β-induced fever in young and old Long-Evans rats
Authors: Plata-Salamán Carlos R. , Peloso Elizabeth , Satinoff Evelyn
Published: December 2017

Aging is associated with a blunted or absent fever response to naturally occurring infections or to the peripheral administration of bacterial products and proinflammatory cytokines, including interleukin-1β (IL-1β). Whether old rats also exhibit an attenuated fever response when challenged with direct brain administration of IL-1β is unknown. Here we investigated the fever response of young (3–5 mo) and old (24–26 mo) Long-Evans rats to the intracerebroventricular microinfusion of IL-1β. Core body temperature was monitored by telemetry in freely moving rats. Intracerebroventricularly administered IL-1β induced comparable increases in body temperature in young and old Long-Evans rats. In the two groups, IL-1β-induced fever was similar both in latency to peak fever and maximal fever response, whether the cytokine was administered 2 h after lights on or just before lights off. These data show that old Long-Evans rats are not defective in their capacity to develop a fever in response to brain administration of IL-1β.
Stimulation of rat hypothalamus by microdialysis with K+: increase of ACh release elevates plasma glucose
Authors: Takahashi Akira , Kishi Eiko , Ishimaru Hirohisa , Ikarashi Yasushi , Maruyama Yuji
Published: December 2017

The effects of stimulation of the ventromedial hypothalamus (VMH) or lateral hypothalamus (LH) with potassium chloride through a microdialysis probe were studied. The concentrations of ACh and norepinephrine (NE) in the dialysate obtained from the hypothalamic nuclei and plasma glucose concentration were measured. Stimulation of the hypothalamic nuclei, VMH and LH, with potassium increased the plasma glucose level as well as the extracellular concentrations of ACh and choline. Addition of atropine, a muscarinic ACh receptor antagonist, into the potassium solution reduced the increase in the level of plasma glucose. Cholinergic stimulation of these nuclei with neostigmine increased the extracellular concentrations of ACh and plasma glucose. Stimulation of the nuclei with potassium also increased the release of NE. However, stimulation of the VMH or LH with NE and/or pargyline, a monoamine oxidase inhibitor, through the dialysis probe membrane did not significantly increase the plasma glucose concentration. These results suggest that activation of the muscarinic cholinergic or ACh-receptive neurons in the hypothalamic nuclei, VMH and LH, contribute to the elevation of plasma glucose level.
Renal medullary interstitial infusion ofl-arginine prevents hypertension in Dahl salt-sensitive rats
Authors: Miyata Noriyuki , Zou Ai Ping , Mattson David L. , Cowley Allen W.
Published: December 2017

Studies were designed to examine the effects of renal medullary interstitial infusion of l-arginine (l-Arg) on the development of high-salt-induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The threshold dose of l-Arg (300 μg ⋅ kg−1 ⋅ min−1) that increased the renal medullary blood flow without altering the cortical blood flow was first determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose ofl-Arg on salt-induced hypertension in DS rats. In the absence of chronic medullaryl-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 ± 2 to 167 ± 5 mmHg by day 5 of a high-salt diet (4.0%), with no change observed in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP did not change significantly with medullary infusion ofl-Arg alone in DR rats (control = 104 ± 1 mmHg) or in WKY rats (control = 120 ± 3 mmHg) and was not significantly changed from these levels during the 7 days ofl-Arg infusion combined with high-NaCl diet. The same amount of l-Arg that prevented salt-induced hypertension in DS rats when infused into the renal medulla (300 μg ⋅ kg−1 ⋅ min−1) failed to blunt salt-induced hypertension when administered intravenously to DS rats. DS rats receiving l-Arg (300 μg ⋅ kg−1 ⋅ min−1iv) exhibited an increase in plasma l-Arg from control concentrations of 138 ± 11 to 218 ± 4 μmol/l, while MAP, which averaged 124 ± 3 mmHg during the 3-day control period, rose to 165 ± 5 mmHg by day 5of high salt (4%) intake. These results indicate that the prevention of salt sensitivity in DS rats was due specifically to the action of l-Arg on renal medullary function and that DS rats may have a deficit of medullary substrate availability and NO production.
Canine intrinsic cardiac neurons involved in cardiac regulation possess NK1, NK2, and NK3 receptors
Authors: Thompson G. W. , Hoover D. B. , Ardell J. L. , Armour J. A.
Published: December 2017

To determine whether intrinsic cardiac neurons involved in cardiac regulation possess neurokinin (NK) receptor subtypes, we administered selective NK receptor agonists individually (100 μM; 0.1 ml) into the coronary arterial blood supply of right atrial intrinsic cardiac neurons of 18 anesthetized dogs. The selective NK1 receptor agonist [Sar9,Met(O2)11]-substance P depressed the spontaneous activity of right atrial neurons (26.7 ± 6.7 to 13.0 ± 4.0 impulses/min; P < 0.05) in 11 dogs and augmented such activity in the other 5 dogs (8.0 ± 3.1 to 27.8 ± 8.7 impulses/min; P < 0.05). Local administration of the selective NK2 receptor agonist [β-Ala8]-NKA-(4—10) depressed right atrial neuronal activity (27.3 ± 6.4 to 14.7 ± 3.8 impulses/min; P < 0.05), whereas the selective NK3 receptor agonist senktide augmented such activity (18.9 ± 6.4 to 53.1 ± 12.0 impulses/min; P < 0.05). Left ventricular chamber pressure fell when selective NK1 and NK2 receptor agonists were administered. Increases in heart rate and right ventricular intramyocardial systolic pressure occurred when the selective NK3 receptor agonist was studied. Administration of a selective NK1or NK2 receptor antagonist altered neuronal activity, with no subsequent change in activity occurring after administration of its respective receptor agonist. Receptor autoradiography demonstrated tachykinin receptors associated with ventral right atrial intrinsic cardiac neurons. It is concluded that intrinsic cardiac neurons involved in cardiac regulation possess NK1, NK2, and NK3 receptors and that some intrinsic cardiac neurons receive tonic input via endogenously released NKs.
β-Endorphin and natural killer cell cytolytic activity during prolonged exercise. Is there a connection?
Authors: Gannon G. A. , Rhind S. G. , Suzui M. , Zamecnik J. , Sabiston B. H. , Shek P. N. , Shephard R. J.
Published: December 2017

This study was designed to test whether a single 50-mg dose of the opioid antagonist naltrexone hydrochloride, ingested 60 min before 2 h of moderate-intensity exercise (i.e., 65% peak O2consumption), influenced the exercise-induced augmentation of peripheral blood natural killer cell cytolytic activity (NKCA). Ten healthy male subjects were tested on four occasions separated by intervals of at least 14 days. A rested-state control trial was followed by three double-blind exercise trials [placebo (P), naltrexone (N), and indomethacin] arranged according to a random block design. The indomethacin exercise trial is discussed elsewhere (S. G. Rhind, G. A. Gannon, P. N. Shek, and R. J. Shepherd. Med. Sci. Sports Exerc. 30: S20, 1998). For both the P and N trials, plasma levels of β-endorphin were increased ( P < 0.05) at 90 and 120 min of exercise but returned to resting (preexercise) levels 2 h postexercise. CD3−CD16+CD56+NK cell counts and NKCA were significantly ( P < 0.05) elevated at each 30-min interval of exercise compared with correspondingly timed resting control values. However, there were no differences in NK cell counts or NKCA between P and N trials at any time point during the two trials. Changes in NKCA reflected mainly changes in NK cell count ( r = 0.72; P < 0.001). The results do not support the hypothesis that the enhancement of NKCA during prolonged submaximal aerobic exercise is mediated by β-endorphin.
Afferent renal inputs to paraventricular nucleus vasopressin and oxytocin neurosecretory neurons
Authors: Ciriello John
Published: December 2017

Extracellular single-unit recording experiments were done in pentobarbital sodium-anesthetized rats to investigate the effects of electrical stimulation of afferent renal nerves (ARN) and renal vein (RVO) or artery (RAO) occlusion on the discharge rate of putative arginine vasopressin (AVP) and oxytocin (Oxy) neurons in the paraventricular nucleus of the hypothalamus (PVH). PVH neurons antidromically activated by electrical stimulation of the neurohypophysis were classified as either AVP or Oxy secreting on the basis of their spontaneous discharge patterns and response to activation of arterial baroreceptors. Ninety-eight putative neurosecretory neurons in the PVH were tested for their response to electrical stimulation of ARN: 44 were classified as putative AVP and 54 as putative Oxy neurons. Of the 44 AVP neurons, 52% were excited, 7% were inhibited, and 41% were nonresponsive to ARN stimulation. Of the 54 Oxy neurons, 43% were excited, 6% inhibited, and 51% were not affected by ARN. An additional 45 neurosecretory neurons (29 AVP and 16 Oxy neurons) were tested for their responses to RVO and/or RAO. RVO inhibited 42% of the putative AVP neurons and 13% of the putative Oxy neurons. On the other hand, RAO excited 33% of the AVP and 9% of the Oxy neurons. No AVP or Oxy neurons were found to be excited by RVO or inhibited by RAO. These data indicate that sensory information originating in renal receptors alters the activity of AVP and Oxy neurons in the PVH and suggest that these renal receptors contribute to the hypothalamic control of AVP and Oxy release into the circulation.
Sleep deprivation increases rat hypothalamic growth hormone-releasing hormone mRNA
Authors: Zhang Jianyi , Chen Zutang , Taishi Ping , Obál Ferenc , Fang Jidong , Krueger James M.
Published: December 2017

Much evidence indicates that growth hormone-releasing hormone (GHRH) is involved in sleep regulation. We hypothesized that GHRH mRNA would increase and somatostatin (SRIH) mRNA would decrease during sleep deprivation. With the use of RT-PCR and truncated internal standards, rat hypothalamic GHRH mRNA and SRIH mRNA levels were evaluated after sleep deprivation. After 8 or 12 h of sleep deprivation there was a significant increase in rat hypothalamic GHRH mRNA expression compared with time-matched control samples. Hypothalamic GHRH mRNA levels were not significantly different from control values after 1 or 2 h of recovery after 8 h of sleep deprivation or after 2 h of recovery after 12 h of sleep deprivation. In control animals, variations in hypothalamic GHRH mRNA levels were observed. GHRH mRNA expression was significantly higher in the afternoon than at dark onset or during the dark period. SRIH mRNA levels were significantly suppressed at the termination of an 8-h sleep deprivation period and were significantly higher after dark onset than in the morning. The alterations in GHRH and SRIH mRNA expressions after sleep deprivation and recovery support the notion that GHRH plays an important role in sleep homeostasis and suggest that these neuropeptides may interact reciprocally in modulating sleep as they do in the control of growth hormone secretion.
PGE2 receptor subtype EP1 antagonist may inhibit central interleukin-1β-induced fever in rats
Authors: Oka Kae , Oka Takakazu , Hori Tetsuro
Published: December 2017

We have previously reported that central injection of PGE2 induces hyperthermia through its actions on EP1 receptors in rats. Because the increase in local synthesis of PGE2 is assumed to be a necessary process in a fever caused by central injection of interleukin-1β (IL-1β), an EP1 receptor antagonist (SC-19220) should inhibit the IL-1β-induced fever. To test this hypothesis, we observed the effect of SC-19220 on the fever produced by injection of recombinant human IL-1β (rhIL-1β) into the lateral cerebroventricle (LCV) in conscious rats. Administration of SC-19220 (100 μg) into the LCV 15 min before LCV injection of rhIL-1β (4 ng) suppressed an initial rise in colonic temperature for 30 min, producing a fever with a longer latency to onset and a longer time to peak elevation. SC-19220, given 60 min after the central administration of rhIL-1β, also suppressed the rhIL-1β-induced fever 15–60 min after its injection. These findings suggest that the central IL-1β-induced fever in rats is mediated, at least partly, by activation of EP1 receptors by PGE2.
Respiratory and metabolic functions of carbonic anhydrase in exercised white muscle of trout
Authors: Wang Yuxiang , Henry Raymond P. , Wright Pamela M. , Heigenhauser George J. F. , Wood Chris M.
Published: December 2017

Electrical stimulation of a trout saline-perfused trunk preparation resulted in metabolic and respiratory responses comparable to those occurring after exhaustive exercise in vivo. Recovery of intracellular acid-base status and glycogen resynthesis were faster than in vivo. Intracellular carbonic anhydrase (ICF CA) blockade elevated intracellular[Formula: see text] relative to untreated postexercise controls, whereas extracellular CA (ECF CA) blockade did not, in contrast to previous work with muscle at rest. ECF CA blockade had only a transient effect on postexercise CO2and ammonia efflux. The relatively small pool of membrane-associated CA appears to be overwhelmed by exercise-induced CO2production in muscle. Transmembrane ammonia efflux appears to shift from diffusion primarily as NH3at rest, which is facilitated by ECF CA, to movement predominantly as[Formula: see text] after exercise, which is independent of CA. The postponed recovery of intracellular pH caused by either or both ECF and ICF CA inhibition was consistent with reduced metabolic acid and lactate excretion from muscle. Creatine phosphate resynthesis was delayed by CA inhibition, whereas ATP replenishment was not affected. Delayed glycogen recovery indicates that[Formula: see text]-dependent pathway(s) may be involved in glyconeogenesis.
Sex steroids and the initiation of puberty in male African catfish (Clarias gariepinus)
Authors: Cavaco J. Eduardo B. , Vilrokx Cécile , Trudeau Vance L. , Schulz Rüdiger W. , Goos Henk J. T.
Published: December 2017

The effects of sex steroids on spermatogenesis and testicular androgen secretion were studied in juvenile (spermatogonia present in testes) African catfish. Fish were implanted with Silastic pellets containing 11-ketotestosterone (KT), 11β-hydroxyandrostenedione (OHA), androstenetrione (OA), androstenedione (A), testosterone (T), 5α-dihydrotestosterone (DHT), or estradiol-17β (E2). Control groups received steroid-free pellets. Two weeks later, testis tissue fragments were incubated with African catfish luteinizing hormone (LH) and the amount of OHA secreted in vitro (the main androgen produced by African catfish testes) was quantified. Tissue fragments were then fixed for histological analysis of spermatogenesis. Treatment with KT, OHA, and OA stimulated testicular growth and spermatogenesis (spermatocytes and spermatids were found), whereas T, DHT, A, or E2 had no such effects. All steroids, except for DHT and E2, reduced OHA secretion in the absence and presence of LH to ∼10% of the control values. Previous studies have shown that KT, OHA, and OA have little effect on circulating LH levels in juvenile male African catfish, so that these androgens probably had direct effects on the testis. Inasmuch as OHA, OA, and KT have largely similar effects and because OHA and OA are converted to KT in vivo, we suggest that KT is physiologically the most relevant androgen for the initiation of spermatogenesis in African catfish.
The area postrema modulates hypothalamic Fos responses to intragastric hypertonic saline in conscious rats
Authors: Carlson Scott H. , Collister John P. , Osborn John W.
Published: December 2017

We have recently reported that an acute intragastric hypertonic saline load increases Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We have also shown that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and vagal afferent projections. However, it is unclear whether the primary projections of peripheral osmoreceptors terminate in the NTS or the AP, both of which project to the SON and PVN. This study tested the hypothesis that efferent projections from the AP were necessary for the Fos responses in the SON, PVN, and LPBN. We examined the effect of AP lesion on the response of central Fos immunoreactivity to intragastric hypertonic saline infusion in conscious rats. Compared with sham-lesioned rats ( n = 5), Fos expression in AP-lesioned rats ( n = 6) was similar in the SON following the intragastric sodium load. However, in contrast to the sham group, Fos expression was significantly reduced in the PVN of AP-lesioned rats. Fos levels observed in the NTS and LPBN were similar in both groups. These results suggest that the PVN response to intragastric hypertonic saline is dependent on efferent projections from the AP. In contrast, Fos responses to this stimulus in the NTS, SON, and LPBN are independent of the activity of the AP.
Compositional correlates of metabolic depression in the mitochondrial membranes of estivating snails
Authors: Stuart J. A. , Gillis T. E. , Ballantyne J. S.
Published: December 2017

The phospholipid and protein compositions of mitochondrial membranes from hepatopancreas of active and estivating terrestrial snails ( Cepaea nemoralis) were compared. Mitochondria from estivating snails contained 82.7% less cardiolipin, and this was associated with an 83.9% reduction in cytochrome- c oxidase activity. Substantial changes also occurred in the proportional amounts of other individual phospholipid classes and their constituent fatty acids, including a 72% loss of total mitochondrial phospholipids, a 37% increase in monoenes, and 49% fewer n–3 fatty acids in membranes of estivating snails. These changes are consistent with those correlated with lowered metabolic rate and lower rates of proton leak in other animal models. Estivating snail hepatopancreas showed no change in total phospholipid content, indicating that the phospholipids lost from mitochondrial membranes may be sequestered elsewhere within the cell. We suggest that estivating snails remodel mitochondrial membranes as part of a coordinated, reversible suppression of mitochondrial membrane-associated processes, which may include a concomitant reduction in rates of proton pumping and leaking.
ATP-sensitive K+channel activation provides transient protection to the anoxic turtle brain
Authors: Pék-Scott Marta , Lutz Peter L.
Published: December 2017

There is wide speculation that ATP-sensitive K+(KATP) channels serve a protective function in the mammalian brain, being activated during periods of energy failure. The aim of the present study was to determine if KATPchannels also have a protective role in the anoxia-tolerant turtle brain. After ouabain administration, rates of change in extracellular K+were measured in the telencephalon of normoxic and anoxic turtles ( Trachemys scripta). The rate of K+efflux was reduced by 50% within 1 h of anoxia and by 70% at 2 h of anoxia, and no further decrease was seen at 4 h of anoxia. The addition of the KATPchannel blocker glibenclamide or 2,3-butanedione monoxime prevented the anoxia-induced decrease in K+efflux during the first hour of anoxia, but the effect of these blockers was diminished at 2 h of anoxia and was not seen after 4 h of anoxia. This pattern of change in KATPchannel blocker sensitivity can be related to a previously established temporary fall and subsequent recovery of tissue ATP during early anoxia. We suggest that activated KATPchannels are involved in the downregulation of membrane ion permeability (channel arrest) during the initial energy crisis period but are switched off when the full anoxic state is established and tissue ATP levels have been restored. We also found that, in contrast to those in mammals, KATPchannels are not a major route for K+efflux in the energy-depleted turtle brain.
Dynamic exercise shifts the operating point and reduces the gain of the arterial baroreflex in rats
Authors: Burger Heather R. , Chandler Margaret P. , Rodenbaugh David W. , DiCarlo Stephen E.
Published: December 2017

We tested the hypothesis that dynamic exercise resets the operating point and attenuates the gain of the arterial baroreflex regulation of heart rate (HR) in rats. Seven adult female spontaneously hypertensive rats (SHR) were chronically instrumented with left carotid arterial catheters. After the rats recovered, arterial baroreflex function was examined by recording reflex changes in HR in response to spontaneous changes in arterial pressure (AP) during a preexercise condition and during steady-state treadmill running at 6 and 18 m/min. Dynamic exercise at 6 and 18 m/min, respectively, reduced the spontaneous range (by 55 and 70%) and spontaneous gain (by 64 and 82%) of the arterial baroreflex control of HR. Dynamic exercise at 6 and 18 m/min, respectively, also increased the pressure at the midpoint of the spontaneous pressure range (by 7 and 12%), the spontaneous minimum HR response (by 35 and 59%), the HR at the midpoint of the spontaneous HR range (by 31 and 52%), and the spontaneous maximum HR response (by 27 and 46%). Sinoaortic denervation eliminated the relationship between AP and HR by reducing the spontaneous gain 95%. These results demonstrate that dynamic exercise shifted the operating point of the arterial baroreflex to a higher pressure and reduced the spontaneous gain in female SHR.
Volume-evoked micturition reflex is mediated by the ventrolateral periaqueductal gray in anesthetized rats
Authors: Matsuura Shinobu , Allen Gary V. , Downie John W.
Published: December 2017

The central pathway of the micturition reflex in the rat was investigated functionally by acute blockade of synaptic neurotransmission using microinjection of cobalt chloride into the periaqueductal gray or pontine tegmental region. In 27 urethan-anesthetized (1.2 g/kg ip) rats, the bladder pressure response to continuous infusion of the bladder with saline (0.1–0.25 ml/min) was assessed. Electromyographic activity of external urethral sphincter and arterial blood pressure were also monitored. Bladder contractions and external urethral sphincter activity were reversibly attenuated after unilateral or bilateral stereotaxic injections of 10 mM cobalt chloride into the caudal (bregma −7.80 to −8.80) ventrolateral periaqueductal gray as well as into Barrington’s nucleus. Blood pressure was not affected by injection into either area. The results demonstrate that the caudal ventrolateral periaqueductal gray, in addition to Barrington’s nucleus, is a critical part of the long-routed micturition reflex circuitry in the anesthetized rat.
Nonstationarity and 1/f noise characteristics in heart rate
Authors: Pilgram Berndt , Kaplan Daniel T.
Published: December 2017

The power spectrum of human heart rate (HR) measured over 24 h exhibits “power-law” 1/ f α-type spectral behavior with α ≈ 1. We investigate possible nonstationarity in time of the exponent α using maximum likelihood estimation, which allows relatively short data segments to be used. Examination of 24-h HR records from ambulatory normal and congestive heart failure (CHF) subjects indicates that the power-law structure of HR is nonstationary. In addition, α varies with time scale and is different for normal (α ≈ 1) and CHF (α ≈ 1.5) subjects. Simulations suggest that a possible mechanism underlying the observed power-law spectrum may be a switching between values of α near zero (white noise) and near two (Brownian motion). This mechanism generates power-law forms quantitatively similar to CHF subjects when the switching occurs very rapidly and similar to normal subjects when the switching is less rapid.
Short- and long-term enalapril affect renal medullary hemodynamics in the spontaneously hypertensive rat
Authors: Dukacz Stephen A. W. , Adams Michael A. , Kline Robert L.
Published: December 2017

Long-term angiotensin-converting enzyme (ACE) inhibition in the spontaneously hypertensive rat (SHR) resets pressure natriuresis and shifts the relationship between renal arterial pressure (RAP) and renal interstitial hydrostatic pressure (RIHP) to lower levels of arterial pressure. These effects persist after withdrawal of treatment. The purpose of this study was to determine the effect of short- and long-term ACE inhibition on medullary blood flow (MBF). Enalapril (25 mg ⋅ kg−1 ⋅ day−1in drinking water) was given to male SHR from 4 to 14 wk of age. Four weeks after stopping treatment, we measured MBF over a wide range of RAP using laser-Doppler flowmetry in anesthetized rats. Additional rats, either untreated or previously treated for 10 wk, received 3-day enalapril treatment just before the experiment. MAP (mmHg ± SE) was 178 ± 6 ( n = 8), 134 ± 6 ( n = 8), 138 ± 5 ( n = 9), and 111 ± 6 mmHg ( n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. Total renal blood flow for the groups receiving 3-day treatment was significantly higher when compared with that in rats with an intact renin-angiotensin system. Three-day treatment had no effect on the relationship between RAP and RIHP, whereas that in rats receiving 10-wk treatment was shifted to lower levels of RAP by ∼30 mmHg. Both 10-wk and 3-day treatment independently increased the slope of the RAP versus MBF relationship at values of RAP > 100 mmHg. The slopes in perfusion units/mmHg were 0.12 ± 0.01 ( n = 8), 0.26 ± 0.01 ( n = 8), 0.27 ± 0.01 ( n = 9), and 0.30 ± 0.02 ( n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. These results indicate that the effect of short-term and the persistent effect of long-term enalapril alter renal medullary hemodynamics in a way that may contribute to the resetting of the pressure-natriuresis relationship in treated rats.
Neural substrate for an integrated metabolic control of feeding behavior
Authors: Horn Charles C. , Addis Aleymayehu , Friedman Mark I.
Published: December 2017

Evidence indicates that feeding behavior in rats is controlled by a mechanism that integrates information about different aspects of fuel metabolism. We investigated the neural substrate for this integrated control by measuring the effect of metabolic inhibitors given alone and in combination on food intake and neuronal activity as reflected by the expression of c-Fos protein. Combined administration of methyl palmoxirate (5 mg/kg po), an inhibitor of fatty acid oxidation, and 2,5-anhydro-d-mannitol (150 mg/kg ip), which decreases liver ATP content, increased feeding in rats more than expected on the basis of eating responses after treatment with either inhibitor given alone. Combined treatment also produced a synergistic increase in Fos-like immunoreactivity in several brain areas, including the nucleus of the solitary tract, area postrema, and parvocellular portion of the hypothalamic paraventricular nucleus. These findings provide strong evidence for the involvement of selected brain regions in the metabolic control of food intake and suggest that metabolic information used to control feeding behavior is integrated in the periphery or at the level of the brain stem.
Modulation of adrenal catecholamine release by PACAP in vivo
Authors: Lamouche Stéphane , Martineau Daniel , Yamaguchi Nobuharu
Published: December 2017

The aim of the present study was to investigate whether pituitary adenylate cyclase-activating polypeptide-(1—27) (PACAP27) can modulate the adrenal catecholamine (CA) secretion induced by splanchnic nerve stimulation (SNS) and by exogenous acetylcholine (ACh) in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were quantified by a high-performance liquid chromatography coupled with electrochemical detection. Adrenal venous blood flow was measured by gravimetry. Local infusion of PACAP27 (0.5, 5, and 50 ng) to the left adrenal gland via the adrenolumbar artery resulted in an increase in CA output, reaching a significant level at the highest dose tested. Either direct SNS (2 Hz) or local infusion of ACh (0.5 μg) to the left adrenal gland produced significant increases in CA output to an extent similar to that obtained with 50 ng of PACAP27 alone. In the presence of PACAP27 (50 ng), CA responses to either SNS or exogenous ACh were significantly potentiated by approximately four- and sixfold, respectively, compared with those obtained in response to each stimulus alone. However, the enhanced CA responses to ACh were not significantly different from those to SNS. The results indicate that the increase in adrenal CA secretion, induced by either direct SNS or exogenous ACh, is synergistically enhanced by PACAP27. The study suggests that the enhanced CA secretion may result from the activation of a PACAP-mediated facilitatory mechanism(s) localized presumably at the postsynaptic level in the canine adrenal medulla in vivo, although the possible involvement of presynaptic mechanisms cannot completely be ruled out in the present study.
IgG-coated erythrocytes augment the lipopolysaccharidestimulated increase in serum tumor necrosis factor-α
Authors: Richard Craig A. H. , Gudewicz Paul W. , Loegering Daniel J.
Published: December 2017

Previous studies have shown that the injection of IgG-coated erythrocytes (EIgG) caused an increase in the mortality rate due to bacterial lipopolysaccharide (LPS). This observation led to the present evaluation of the effect of EIgG on the LPS-stimulated increase in serum tumor necrosis factor-α (TNF-α) levels and TNF-α secretion by macrophages. The prior injection of EIgG augmented the increase in LPS-stimulated serum TNF-α levels ninefold at 1 h after LPS. Serum TNF-α levels were augmented when LPS was injected 2 or 6 h after EIgG but not at 0.5 or 12 h after EIgG. Complement activation caused by EIgG may contribute to the priming for TNF-α, because activation of complement with cobra venom factor caused a threefold augmentation of the LPS-stimulated serum TNF-α levels. Isolated macrophages that had ingested EIgG or were adherent to immobilized IgG showed augmented TNF-α secretion in response to LPS. Thus clearance of immune complexes from the blood can augment the LPS-stimulated increase in serum TNF-α levels that is due, in part, to complement activation and signaling via FcγR.
Evaluation of LH secretory dynamics during the rat proestrous LH surge
Authors: Hoeger Kathleen M. , Kolp Lisa A. , Strobl Frank J. , Veldhuis Johannes D.
Published: December 2017

The preovulatory luteinizing hormone (LH) surge results from the integration of complex interactions among gonadal steroids and hypothalamic and pituitary hormones. To evaluate changes in LH secretory dynamics that occur during the rat LH surge, we have 1) obtained frequently sampled serum LH concentration time series, 2) used both waveform-dependent and waveform-independent convolution analyses, and 3) independently assessed proestrous LH half-life and basal non-gonadotropin-releasing hormone (GnRH)-dependent LH secretion during the LH surge. Waveform-independent pulse analysis revealed a 24-fold increase in the maximal pulsatile LH secretory rate attained during late proestrus compared with early proestrus. A 15-fold increase was quantified for the mean LH secretory rate. In complementary analyses, we applied a measured LH half-life of 17 ± 2.7 min and a median basal LH secretion rate of 0.0046 μg ⋅ l−1 ⋅ min−1 for convolution analysis, revealing a 16-fold increase in the mass of LH released/burst and more than sixfold rise in the amplitude of the secretory peaks. Evaluation of the approximate entropy of the LH surge profiles was performed, showing an increase in the orderliness of the LH release process during the surge. We conclude that both quantitative (mass/burst) and qualitative (approximate entropy) features of LH release are regulated during the proestrous LH surge.
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise
Authors: Turinsky Jiri , Damrau-Abney Alice
Published: December 2017

Activities of Akt1, Akt2, and Akt3 kinases and glucose uptake in hindlimb muscles of the rat in vivo were investigated. The rats were studied either after intravenous injection of 0.1 U of insulin or during exercise induced by stimulating calf muscles electrically at 1 contraction/s. Akt kinases were immunoprecipitated from supernatants of muscle homogenates. Glucose uptake by muscles in vivo was assessed by cellular accumulation of 2-deoxy-d-[1,2-3H(N)]glucose. Administration of insulin resulted in rapid activation of Akt1 kinase, with peak activity observed 5 min after insulin injection. Soleus muscle, a slow-twitch muscle, and plantaris muscle, a fast-twitch muscle, differed in their content of Akt1 kinase and in their response to insulin. Soleus muscle exhibited a 105% higher abundance of Akt1 kinase, a 101% higher insulin-stimulated activity of Akt1 kinase, and 83% higher insulin-stimulated 2-deoxyglucose uptake compared with plantaris muscle. Additionally, insulin administration increased the activities of Akt1, Akt2, and Akt3 kinases in calf muscles and caused a sevenfold augmentation in 2-deoxyglucose uptake by these muscles. In contrast, the exercised calf muscles exhibited an increase in Akt1 kinase activity at 5, 15, and 25 min of exercise but no change in activities of Akt2 and Akt3 isoforms, and the 2-deoxyglucose uptake by calf muscles exercised for 25 min was 11-fold higher compared with muscles of resting rats. The data demonstrate that 1) there is a close, direct correlation between the magnitude of insulin-stimulated activity of Akt1 kinase and the level of glucose uptake in muscles with different fiber populations, 2) insulin activates three isoforms of Akt kinase in skeletal muscle, and 3) exercise in vivo is associated with activation of Akt1 but not Akt2 and Akt3 kinases in contracting muscles.
Role of skeletal muscle in plasma ion and acid-base regulation after NaHCO3and KHCO3loading in humans
Authors: Lindinger Michael I. , Franklin Thomas W. , Lands Larry C. , Pedersen Preben K. , Welsh Donald G. , Heigenhauser George J. F.
Published: December 2017

This paper examines the time course of changes in plasma electrolyte and acid-base composition in response to NaHCO3and KHCO3ingestion. It was hypothesized that skeletal muscle is involved in the correction of the ensuing plasma disturbance by exchanging ions, gasses, and fluids between cells and extracellular fluids. Five male subjects, with catheters in a brachial artery and antecubital vein, ingested 3.57 mmol/kg body mass NaHCO3or KHCO3. While seated, blood samples were taken 30 min before ingestion of the solution, at 10-min intervals during the 60-min ingestion period, and periodically for 210 min after ingestion was complete. Blood was analyzed for gases, hematocrit, plasma ions, and total protein. With NaHCO3, arterial plasma Na+concentration ([Na+]) increased from 143 ± 1 to 147 ± 1 (SE) meq/l, H+concentration ([H+]) decreased by 6 ± 1 neq/l, and [Formula: see text] increased by 5 ± 1 mmHg. There was no detectable net Na+uptake by tissues. An increased plasma strong ion difference ([SID]) accounted fully for the decrease in plasma [H+]. With KHCO3, K+concentration increased from 4.25 ± 0.10 to 7.17 ± 0.13 meq/l, plasma volume decreased by 15.5 ± 2.3%, [H+] decreased by 4 ± 1 neq/l, and there was no change in[Formula: see text]. The decrease in [H+] in the KHCO3trial primarily arose in response to the increased [SID]. Net K+uptake by tissues accounted for 37 ± 5% of the ingested K+. In conclusion, ingestion of NaHCO3and KHCO3produced markedly different fluid and ionic disturbances and associated regulatory responses by skeletal muscle. Accordingly, the physicochemical origins of the acid-base disturbances also differed between treatments. The tissues did not play a role in regulating plasma [Na+] after ingestion of NaHCO3. In contrast, the net influx of K+to tissues played an important role in removing K+from the extracellular compartment after ingestion of KHCO3.
Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice
Authors: Paul Lada , Fraifeld Vadim , Kaplanski Jacob
Published: December 2017

The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-α (TNF-α), hypothalamic LT, and PGE2production. Intraperitoneal injection of LPS (50 μg/mouse) led to a decrease in Tbstarting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-α level in plasma and in LT and PGE2production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-α. MK-886 significantly inhibited LT and enhanced PGE2production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-α bioactivity.
Sympathoexcitatory neurotransmission of the chemoreflex in the NTS of awake rats
Authors: Haibara Andréa S. , Bonagamba Leni G. H. , Machado Benedito H.
Published: December 2017

Cardiovascular responses to chemoreflex activation by potassium cyanide (KCN, 20 μg/rat iv) were analyzed before and after the blockade of ionotropic or metabotropic receptors into the nucleus of the solitary tract (NTS) of awake rats. Microinjection of ionotropic antagonists [6,7-dinitroquinoxaline-2,3-dione or kynurenic acid (Kyn)] into the lateral commissural NTS (NTSlat), the midline commissural NTS (NTSmid), or into both (NTSlat+mid), produced a significant increase in basal mean arterial pressure, and the pressor response to chemoreflex activation was only partially reduced, whereas microinjection of Kyn into the NTSmid produced no changes in the pressor response to the chemoreflex. The bradycardic response to chemoreflex activation was abolished by microinjection of Kyn into the NTSlat or into NTSlat+mid but not by Kyn microinjection into the NTSmid. Microinjection of α-methyl-4-carboxyphenylglycine, a metabotropic receptor antagonist, into the NTSlat or NTSmid produced no changes in baseline mean arterial pressure or heart rate or in the chemoreflex responses. These results indicate that 1) the processing of the parasympathetic component (bradycardia) of the chemoreflex seems to be restricted to the NTSlat and was blocked by ionotropic antagonists and 2) the pressor response of the chemoreflex was only partially reduced by microinjection of ionotropic antagonists and not affected by injection of metabotropic antagonists into the NTSlat or NTSmid or into NTSlat+mid in awake rats.
Influence of photoperiod on immune cell functions in the male Siberian hamster
Authors: Yellon Steven M. , Fagoaga Omar R. , Nehlsen-Cannarella Sandra L.
Published: December 2017

The present study tested the hypothesis that immune cell function is influenced by ambient photoperiod. The male Siberian hamster served as the experimental model because day length regulates a variety of seasonal adaptations in physiology. Adult hamsters were in long days (16 h of light daily), which sustains gonadal function, or transferred to short days (8 h) for >4 wk to induce testes regression. Blood was drawn from the ocular sinus or splenocytes obtained to assess basal indexes of immune cell function. In hamsters in short days, natural killer cell cytolytic capacity, as well as spontaneous blastogenesis in both whole blood and isolated lymphocytes, were enhanced compared with that in hamsters in long days. By contrast, phagocytosis and oxidative burst activity by both granulocytes and monocytes were suppressed in hamsters by exposure to short days versus long days. Selective changes in immune cell function coincided with short-day-induced gonadal atrophy. These findings raise the hypothesis that photoperiod regulation of physiological adaptations, including distinct immune cell functions, may help individuals anticipate seasonal challenges posed by opportunistic diseases or climate to facilitate survival.
Light masking of circadian rhythms of heat production, heat loss, and body temperature in squirrel monkeys
Authors: Robinson Edward L. , Fuller Charles A.
Published: December 2017

Whole body heat production (HP) and heat loss (HL) were examined to determine their relative contributions to light masking of the circadian rhythm in body temperature (Tb). Squirrel monkey metabolism ( n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of body temperature and activity. Feeding was also measured. Responses to an entraining light-dark (LD) cycle (LD 12:12) and a masking LD cycle (LD 2:2) were compared. HP and HL contributed to both the daily rhythm and the masking changes in Tb. All variables showed phase-dependent masking responses. Masking transients at L or D transitions were generally greater during subjective day; however, L masking resulted in sustained elevation of Tb, HP, and HL during subjective night. Parallel, apparently compensatory, changes of HL and HP suggest action by both the circadian timing system and light masking on Tb set point. Furthermore, transient HL increases during subjective night suggest that gain change may supplement set point regulation of Tb.
Neutralization of TNF does not influence endotoxininduced changes in thyroid hormone metabolism in humans
Authors: van der Poll Tom , Endert Erik , Coyle Susette M. , Agosti Jan M. , Lowry Stephen F.
Published: December 2017

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced changes in plasma thyroid hormone and thyroid-stimulating hormone (TSH) concentrations, 24 healthy postabsorptive humans were studied on a control study day ( n= 6), after infusion of a recombinant TNF receptor IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) after intravenous injection of endotoxin (2 ng/kg; n = 6), or after administration of endotoxin with TNFR:Fc ( n = 6). Administration of TNFR:Fc alone did not affect thyroid hormone or TSH levels when compared with the control day. Endotoxin induced a transient rise in plasma TNF activity (1.5 h: 219 ± 42 pg/ml), which was completely prevented by TNFR:Fc ( P < 0.05). After endotoxin administration, plasmal-thyroxine (T4), free T4, 3,5,3′-triiodothyronine (T3), and TSH were lower and 3,3′,5′-triiodothyronine was higher than on the control day (all P < 0.05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-induced changes. Our results suggest that endogenous TNF does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.
Effect of diet on the response to leptin in the marsupialSminthopsis crassicaudata
Authors: Hope Perdita J. , Chapman Ian , Morley John E. , Horowitz Michael , Wittert Gary A.
Published: December 2017

The aim of this study was to determine in the marsupial Sminthopsis crassicaudata 1) the effect of leptin on food intake, body fat stores, and metabolism and 2) whether leptin can prevent a diet-induced increase in adiposity. In response to 21 days of feeding with mealworms (2.99 kcal/g, 30% fat), body weight ( P < 0.0001) and tail width ( P < 0.0001) increased, compared with control animals fed with laboratory diet (1.01 kcal/g, 20% fat). Subsequently, S. crassicaudata were randomly allocated to receive either laboratory diet or a choice between laboratory diet and mealworms. For 13 days, one-half of the animals in each dietary group received intraperitoneal human leptin (2.5 mg/kg twice daily), while the other one-half received phosphate-buffered saline. In animals receiving laboratory diet alone, leptin induced a decrease in body weight ( P < 0.0001), tail width ( P < 0.0001), and energy intake ( P < 0.01). In animals receiving both laboratory diet and mealworms, leptin had no effect on body weight or tail width, although the proportion of laboratory diet eaten was reduced ( P = 0.0001), and there was a nonsignificant fall in overall energy intake ( P = 0.07). We conclude that in S. crassicaudata, 1) a high-calorie, higher-fat diet induces an increase in adiposity and 2) leptin induces weight loss, but 3) an increase in dietary calories and fat content is associated with resistance to the actions of leptin.
Electrophysiological and behavioral studies on taste effectiveness of alcohols in rats
Authors: Sako Noritaka , Yamamoto Takashi
Published: December 2017

Electrophysiological and behavioral studies were performed in rats to analyze the gustatory effects of alcohols, such as methanol, ethanol, ethylene glycol, 1-propanol, 2-propanol, propylene glycol, 1,3-propandiol, and glycerin. When the whole bundle responses to each of the alcohols at 1.0 M were recorded from the chorda tympani (CT) and glossopharyngeal nerve (Gl), the alcohols with two or three hydroxyl groups elicited larger responses than the other alcohols in both nerves. Single-fiber analyses showed that the responses to alcohols were induced dominantly in sucrose-best fibers and were correlated well with sucrose responses in the CT, whereas the responses to alcohols were induced in quinine-best fibers and were correlated well with quinine responses in the Gl. The rats that acquired conditioned taste aversions to alcohols with two or three hydroxyl groups also avoided sucrose and quinine, although the aversion did not generalize to NaCl or HCl. These results suggest that alcohols have a taste similar to the taste of both sucrose and quinine in the rat.