bluuebunny/crossref_metadata_2025 huggingface dataset:
Amiloride-sensitive signals and NaCl preference and appetite: a lick-rate analysis
Authors: Brot Michelle D. , Watson Chae H. , Bernstein Ilene L.
Published: December 2017

Rats prefer hypotonic and isotonic NaCl solutions to water in long-access drinking paradigms. To focus on the role of taste signals in NaCl preference, licking patterns of rats with 30-s exposure to NaCl solutions (0–0.5 M) were examined when they were either water deprived, sodium depleted, or not deprived (NaCl mixed in dilute sucrose). In all three conditions, rats displayed a preference for NaCl. The addition of 100 μM amiloride, a sodium channel blocker, to NaCl did not change rats' licking when they were sodium replete but dramatically reduced licking when they were deplete. Transection of the chorda tympani (CT) nerve, an afferent pathway for amiloride-sensitive Na+ signals, had no effect on NaCl preference in nondeprived rats and only a modest effect on those that were Na+ deplete. Amiloride was found to exert significant suppression of NaCl intake in Na+-depleted rats with transection of the CT, supporting the existence of other afferent pathways for transmission of amiloride-sensitive Na+signalling. Together, these studies argue for the involvement of different neural signalling mechanisms in NaCl preference in the presence and absence of explicit Na+ need.
Detection of apical Na+/H+exchanger activity inhibition in proximal tubules induced by acute hypertension
Authors: Yip Kay-Pong , Wagner Anthony J. , Marsh Donald J.
Published: December 2017

We previously showed that acute arterial hypertension induces an inhibition of fluid and NaCl reabsorption in proximal tubules of Sprague-Dawley rats, which is associated with a rapid reversible internalization of apical Na+/H+ exchanger in brush border. To determine whether there is a corresponding inhibition of apical Na+/H+ exchanger activity in proximal tubules to account for the reduced tubular reabsorption, an instrument capable of measuring intracellular pH (pHi) ratiometrically and repeatedly on the surface of kidney with high temporal resolution is required. We report the design and validation of such a fluorimetric system based on two ultraviolet nitrogen-pulsed lasers and a photomultiplier. pHi of proximal tubules in situ was measured with pH-sensitive fluorescence dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein at 5 Hz. Using the initial rate of change of pHi(dpHi/d t) during luminal Na+ removal as an index of apical Na+/H+ exchanger activity, the exchanger activity was found to be reduced by 52 ± 11% (n = 14, P < 0.05) compared with the baseline after 20 min of induced acute hypertension. The inhibition of Na+/H+ exchange activity was alleviated when the blood pressure was returned to prehypertensive level. These observations indicate that acute changes in arterial pressure can reversibly inhibit apical Na+/H+ exchanger activity, which might contribute to pressure natriuresis in proximal tubule.
Baroreflex modulation of peripheral vasoconstriction during progressive hypothermia in anesthetized humans
Authors: Nakajima Yasufumi , Mizobe Toshiki , Takamata Akira , Tanaka Yoshifumi
Published: December 2017

Mild hypothermia is a major concomitant of surgery under general anesthesia. We examined the hypothesis that baroreceptor loading/unloading modifies thermoregulatory peripheral vasoconstriction and, consequently, body core temperature in subjects undergoing lower abdominal surgery with general anesthesia. Thirty-six patients were divided into four groups: control group (C), applied positive end-expiratory pressure (PEEP; 10 cmH2O) group (P), applied leg-up position group (L), and a group of leg-up position patients with PEEP starting 90 min after induction of anesthesia (L + P). The esophageal temperature (Tes) and the forearm-fingertip temperature gradient, as an index of peripheral vasoconstriction, were monitored for 3 h after induction of anesthesia. Mean arterial pressure and pulse pressure did not change during the study in any group. The change in right atrial transmural pressure from the baseline value was 0.3 ± 0.1 mmHg in C, −3.0 ± 0.5 mmHg in P, and 2.3 ± 0.4 mmHg in L ( P < 0.01). The change in Tes at the end of the study was −1.7 ± 0.1 (35.1 ± 0.1)°C in C, −1.1 ± 0.1 (35.7 ± 0.1)°C in P, and −2.7 ± 0.1 (34.1 ± 0.1)°C in L, showing significant differences ( P < 0.01). The Tes threshold for thermal peripheral vasoconstriction was 35.6 ± 0.1°C in C, 36.2 ± 0.2°C in P, and 34.8 ± 0.2°C in L ( P < 0.01). Excessive Tes decrease in the leg-up-position operation was attenuated by applying PEEP (L + P group; P < 0.05). Our data indicate that baroreceptor loading augments and unloading prevents perioperative hypothermia in anesthetized and paralyzed subjects by reducing and increasing the body temperature threshold for peripheral vasoconstriction, respectively.
Muscle pain perception and sympathetic nerve activity to exercise during opioid modulation
Authors: Cook Dane B. , O'Connor Patrick J. , Ray Chester A.
Published: December 2017

The purpose of this experiment was to examine the effects of the endogenous opioid system on forearm muscle pain and muscle sympathetic nerve activity (MSNA) during dynamic fatiguing exercise. Twelve college-age men (24 ± 4 yr) performed graded (1-min stages; 30 contractions/min) handgrip to fatigue 1 h after the ingestion of either 60 mg codeine, 50 mg naltrexone, or placebo. Pain (0–10 scale) and exertion (0–10 and 6–20 scales) intensities were measured during the last 15 s of each minute of exercise and every 15 s during recovery. MSNA was measured continuously from the peroneal nerve in the left leg. Pain threshold occurred earlier [1.8 ± 1, 2.2 ± 1, 2.2 ± 1 J: codeine, naltrexone, and placebo, respectively] and was associated with a lower rating of perceived exertion (RPE) (2.7 ± 2, 3.6 ± 2, 3.8 ± 2: codeine, naltrexone, and placebo, respectively) in the codeine condition compared with either the naltrexone or placebo conditions. There were no main effects (i.e., drugs) or interaction (i.e., drugs × time) for either forearm muscle pain or RPE during exercise [pain: F (2, 22) = 0.69, P = 0.51]. There was no effect of drug on MSNA, heart rate, or blood pressure during baseline, exercise, or recovery. Peak exercise MSNA responses were 21 ± 1, 21 ± 2.0, and 21 ± 2.0 bursts/30 s for codeine, naltrexone, and placebo conditions, respectively. Peak mean arterial pressure responses were 135 ± 4, 131 ± 3, and 132 ± 4 mmHg for codeine, naltrexone, and placebo conditions, respectively. It is concluded that neither 60 mg codeine nor 50 mg naltrexone has an effect on forearm muscle pain, exertion, or MSNA during high- intensity handgrip to fatigue.
Dynamic resetting of the human circadian pacemaker by intermittent bright light
Authors: Rimmer David W. , Boivin Diane B. , Shanahan Theresa L. , Kronauer Richard E. , Duffy Jeanne F. , Czeisler Charles A.
Published: December 2017

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.
An ether stressor increases REM sleep in rats: possible role of prolactin
Authors: Bodosi B. , Obál F. , Gardi J. , Komlódi J. , Fang J. , Krueger J. M.
Published: December 2017

Sleep alterations after a 1-min exposure to ether vapor were studied in rats to determine if this stressor increases rapid eye-movement (REM) sleep as does an immobilization stressor. Ether exposure before light onset or dark onset was followed by significant increases in REM sleep starting ∼3–4 h later and lasting for several hours. Non-REM (NREM) sleep and electroencephalographic slow-wave activity during NREM sleep were not altered. Exposure to ether vapor elicited prolactin (Prl) secretion. REM sleep was not promoted after ether exposure in hypophysectomized rats. If the hypophysectomy was partial and the rats secreted Prl after ether exposure, then increases in REM sleep were observed. Intracerebroventricular administration of an antiserum to Prl decreased spontaneous REM sleep and inhibited ether exposure-induced REM sleep. The results indicate that a brief exposure to ether vapor is followed by increases in REM sleep if the Prl response associated with stress is unimpaired. This suggests that Prl, which is a previously documented REM sleep-promoting hormone, may contribute to the stimulation of REM sleep after ether exposure.
Temperature-dependent development of cardiac activity in unrestrained larvae of the minnowPhoxinus phoxinus
Authors: Schönweger G. , Schwerte T. , Pelster B.
Published: December 2017

The minnow ( Phoxinus phoxinus) was raised up to the stage of swim bladder inflation at temperatures between 10°C and 25°C, and the time of development significantly decreased at higher temperatures. Accordingly, initiation of cardiac activity was observed at day 2 in 25°C animals and at day 4 in 12.5°C animals. Only a minor increase in body mass was observed during the incubation period, and, at the end of the incubation period, animals raised at 25°C did not have a significantly lower body mass compared with animals raised at 15°C. Metabolic activity, determined as the rate of oxygen consumption of a larva, increased from 3.3 to 19.5 nmol/h during development at 15°C and from 5.6 to 47.6 nmol/h during development at 25°C. Heart rate showed a clear correlation to developmental stage as well as to developmental temperature, but at the onset of cardiac activity, diastolic ventricular volume and also stroke volume were higher at the lower temperatures. Furthermore, stroke volume increased with development, except for the group incubated at 12.5°C, in which stroke volume decreased with development. Initial cardiac output showed no correlation to incubation temperature. Although metabolic activity increased severalfold during development from egg to the stage of swim bladder inflation at 15°C and at 25°C, weight-specific cardiac output increased only by ∼40% with proceeding development. At 12.5°C, cardiac output remained almost constant until opening of the swim bladder. The data support the notion that oxygen transport is not the major function of the circulatory system at this stage of development. The changes in heart rate with temperature appear to be due to the intrinsic properties of the pacemaker; there was no indication for a regulated response.
Increased ganglionic responses to substance P in hypertensive rats due to upregulation of NK1receptors
Authors: Schoborg Robert V. , Hoover Donald B. , Tompkins John D. , Hancock John C.
Published: December 2017

Intravenous injection of substance P (SP) increases renal nerve firing and heart rate in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) by stimulating sympathetic ganglia. Blood pressure is increased in SHRs but lowered in WKYs. This study assesses the role of neurokinin-1 (NK1) receptors in mediating the ganglion actions of SP. Rats for functional studies were anesthetized and then treated with chlorisondamine. Renal nerve, blood pressure, and heart rate responses to intravenous injection of the NK1receptor agonist GR-73632 were similar but less than those to equimolar doses of SP in SHRs. GR-73632 only slightly increased renal nerve firing and heart rate and lowered blood pressure in WKYs. The NK1receptor antagonist GR-82334 (200 nmol/kg iv) blocked the ganglionic actions of GR-73632 and the pressor response to SP in SHRs. It reduced the renal nerve and heart rate responses by 52 and 35%. This suggests that the pressor response to SP is mediated by ganglionic NK1receptors and that NK1receptors also have a prominent role in mediating the renal nerve and heart rate responses to SP. Quantitative autoradiography showed that NK1receptors are more abundant in the superior cervical ganglia of SHRs. RT-PCR showed increased abundance of NK1receptor mRNA in SHRs as well. These observations suggest that the greater ganglionic stimulation caused by SP in SHRs is due to upregulation of NK1receptors.
Endothelin and ETAreceptors in long-term arterial pressure homeostasis in conscious nonhuman primates
Authors: Reinhart Glenn A. , Preusser Lee C. , Opgenorth Terry J. , Wegner Craig D. , Cox Bryan F.
Published: December 2017

This study was designed to quantify the long-term contribution of endogenous endothelin-1 (ET-1) and ETAreceptors to the regulation of arterial pressure under normal conditions in nonhuman primates. Therefore, mean arterial pressure (MAP) and heart rate were measured 24 h/day with the use of telemetry techniques in conscious cynomolgus monkeys under control conditions, during administration of an ETAselective receptor antagonist (ABT-627; 5 mg/kg, 2 times a day by mouth, 4 days), and a 6-day posttreatment period. Systemic ETAblockade reduced MAP (24 h) from 89 ± 3 to 82 ± 2 and 79 ± 2 mmHg on days 1 and 4, respectively. Subsequently, MAP remained suppressed for 3 days posttreatment. Heart rate increased from 111 ± 5 to 122 ± 4 and 128 ± 6 beats/min on days 1and 4 of ABT-627, respectively, and remained above control for 3 days posttreatment. Plasma ET-1 concentration increased from 1.0 ± 0.3 to 1.9 ± 0.4 pg/ml in response to ABT-627 ( day 4) but decreased to control values 4 days posttreatment. These data demonstrate a physiologically important role for endogenous ET-1 and ETAreceptors in the long-term regulation of arterial pressure and plasma ET-1 levels in the conscious nonhuman primate.
Effects of neonatal handling on sympathoadrenal activity and body composition in adult male rats
Authors: Young James B.
Published: December 2017

Neonatal handling permanently alters the hypothalamic-pituitary-adrenal (HPA) response to stress. Because the sympathetic nervous system (SNS) and adrenal medulla also participate in stress responses, the impact of daily handling between birth and weaning on SNS and adrenal medullary function was examined in adult rats using techniques of [3H]norepinephrine ([3H]NE) turnover and urinary catecholamine excretion. Handled animals exhibited a 23% reduction in [3H]NE turnover in heart and a 53% decrease in spleen. [3H]NE turnover in brown adipose tissue, stomach, and kidney did not differ between handled and nonhandled animals. In contrast, urinary epinephrine (Epi) excretion was significantly greater in handled rats in response to a 3-day fast than in nonhandled animals. Although body weight, weight gain in response to dietary enrichment with sucrose or lard, or body fat content did not differ in handled and nonhandled animals, handled rats displayed heavier abdominal fat depots than nonhandled animals, implying a difference in body fat distribution. Neonatal handling thus leads to decreased sympathetic activity within specific subdivisions of the SNS and, by contrast, to increased adrenal medullary responsiveness.
Chronic hypoxia increases the NO contribution of acetylcholine vasodilation of the fetal guinea pig heart
Authors: Thompson Loren P. , Aguan Kripamoy , Pinkas Gerard , Weiner Carl P.
Published: December 2017

To investigate the effect of chronic hypoxia (HPX) on vasodilation of the fetal heart, we exposed pregnant guinea pigs to room air or 12% O2for 4, 7, or 10 days. We excised hearts from anesthetized fetuses (60 ± 3 days; 65-day gestation = term) and measured changes in both the coronary artery pressure of the isolated constant-flow preparation and endothelial nitric oxide synthase (eNOS) mRNA of fetal ventricles. Dilator responses to cumulative addition (10−9–10−5M) of acetylcholine and sodium nitroprusside in prostaglandin F2α(5 × 10−6M)-constricted hearts were similar among normoxia (NMX), 4-, 7-, and 10-day HPX (control). Nitro-l-arginine (l-NA, 10−4M), a NOS inhibitor, inhibited maximal acetylcholine dilation of hearts exposed to 10-day HPX greater than NMX, 4-, and 7-day HPX. Hypoxia (after 7 and 10 days) increased eNOS mRNA of fetal ventricles compared with NMX and 4-day HPX. 4-Aminopyridine (3 mM), a voltage-dependent K+-channel inhibitor, inhibited acetylcholine- but not sodium nitroprusside-induced dilation of NMX and 10-day HPX hearts to a similar magnitude. Glibenclamide (10−5M), an ATP-sensitive K+-channel inhibitor, had no effect on vasodilation. We conclude that chronic HPX increases the contribution of NO but does not alter K+-channel activation in response to acetylcholine-stimulated coronary dilation. Thus increases in NO production via upregulation of eNOS gene expression may be an adaptive response to chronic HPX in the fetal coronary circulation.
Hemodynamic responses to static and dynamic muscle contractions at equivalent workloads
Authors: Daniels Jason W. , Stebbins Charles L. , Longhurst John C.
Published: December 2017

We tested the hypothesis that static contraction causes greater reflex cardiovascular responses than dynamic contraction at equivalent workloads [i.e., same tension-time index (TTI), holding either contraction time or peak tension constant] in chloralose-anesthetized cats. When time was held constant and tension was allowed to vary, dynamic contraction of the hindlimb muscles evoked greater increases (means ± SE) in mean arterial pressure (MAP; 50 ± 7 vs. 30 ± 5 mmHg), popliteal blood velocity (15 ± 3 vs. 5 ± 1 cm/s), popliteal venous Pco 2 (15 ± 3 vs. 3 ± 1 mmHg), and a greater decrease in popliteal venous pH (0.07 ± 0.01 vs. 0.03 ± 0.01), suggesting greater metabolic stimulation during dynamic contraction. Similarly, when peak tension was held constant and time was allowed to vary, dynamic contraction evoked a greater increase in blood velocity (13 ± 1 vs. −1 ± 1 cm/s) without causing any differences in other variables. To investigate the reflex contribution of mechanoreceptors, we stretched the hindlimb dynamically and statically at the same TTI. A larger reflex increase in MAP during dynamic stretch (32 ± 8 vs. 24 ± 6 mmHg) was observed when time was held constant, indicating greater mechanoreceptor stimulation. However, when peak tension was held constant, there were no differences in the reflex cardiovascular response to static and dynamic stretch. In conclusion, at comparable TTI, when peak tension is variable, dynamic muscle contraction causes larger cardiovascular responses than static contraction because of greater chemical and mechanical stimulation. However, when peak tensions are equivalent, static and dynamic contraction or stretch produce similar cardiovascular responses.
Aging and baroreflex control of RSNA and heart rate in rats
Authors: Irigoyen M. C. , Moreira E. D. , Werner A. , Ida F. , Pires M. D. , Cestari I. A. , Krieger E. M.
Published: December 2017

Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 ± 5 vs. 410 ± 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 ± 3 vs. 113 ± 5 mmHg) or HR (344 ± 9 vs. 347 ± 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (−0.63 ± 0.18 vs. −1.84 ± 0.4 bars · cycle−1 · mmHg−1 · s−1). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.
Human skeletal muscle exercise metabolism following an expedition to Mount Denali
Authors: Green Howard , Roy B. , Grant S. , Otto C. , Pipe A. , McKenzie D. , Johnson M.
Published: December 2017

Chronic exposure to high altitude is known to result in changes in the mechanisms regulating O2delivery to the contracting muscle. However, the effects of acclimatization on metabolism in the contracting muscle cell remain unclear. In this study, we have investigated the hypothesis that acclimatization would result in a closer coupling between ATP utilization and ATP production and that the improved energy state would be accompanied by a reorganization of the metabolic pathways consisting of an increased oxidative and decreased glycolytic potential. Five men, mean age of 28 ± 2 (SE) yr, performed a standardized, two-stage submaximal cycling task in normoxia for 20 min at each of 59 and 74% peak O2consumption before and 3–4 days after returning from a 21-day expedition to Mount Denali (6,194 m). Acclimatization was without effect in altering the resting values of the adenine nucleotides (ATP, ADP, AMP), inosine monophosphate (IMP), or phosphocreatine (PCr) in the vastus lateralis. During exercise (40 min) after acclimatization compared with preacclimatization, PCr was not as depressed (33.2 ± 7.1 vs. 40.6 ± 5.4 mmol/kg dry wt) and IMP (0.289 ± 0.11 vs. 0.131 ± 0.03 mmol/kg dry wt) and lactate (26.1 ± 6.2 vs. 18.6 ± 8.8 mmol/kg dry wt) in contracting muscle were not as elevated ( P < 0.05). Although no effect of acclimatization was observed for the maximal activity (mol · kg protein−1· h−1) of citrate synthase (4.76 ± 0.44 vs. 4.94 ± 0.45), lactate dehydrogenase was increased by 13% (36.5 ± 2.6 vs. 41.2 ± 3.1, P < 0.05). It is concluded that acclimatization results in an improved energy state in the contracting muscle when tested under normoxic conditions; however, these effects are not associated with a higher oxidative potential or a lower glycolytic potential as hypothesized.
Carotid and aortic baroreflexes of the rat: I. Open-loop steady-state properties and blood pressure variability
Authors: Dworkin Barry R. , Dworkin Susan , Tang Xiaorui
Published: December 2017

To characterize the baroreflex in central nervous system-intact neuromuscular-blocked rats, we measured the vascular and cardiac responses and compared direct stimulation of the aortic depressor nerve (ADN) with a capacitance electrode (differentially activating either A or A + C fibers) to carotid sinus pressure with a micro-balloon (SINUS). One-thousand-two-hundred-ninety-seven open-loop measurements of systolic blood pressure (SBP), heart rate, venous pressure (VBP), and mesenteric (msBF), femoral (fmBF), and skin (skBF) blood flow were completed; the linear range of the effects was determined for each response and stimulus mode. The rats were sinoaortic denervated (SAD). The open-loop stimulation effect was very stable; e.g., the mean effect of 790 ADN stimulations during >7 days was −9.8 mmHg, with an average drift of +0.001 mmHg/h. In contrast, there was large variability of the SBP baseline (e.g., SD = ±10.9), which was due to SAD (±6.3 to ±16.3 mmHg, t = −13.9, df = 4, P < 0.0002) and was reversed by ganglionic block (±10.8 to ± 2.9 mmHg, t = −12.9, df = 3, P < 0.001). The ADN stimuli produced larger depressor responses than sinus stimuli (−66 vs. −45 mmHg); all component responses paralleled the magnitude of the SBP effect, except interbeat interval (IBI), for which the ADN ΔIBI was ≈10 times that of SINUS. For all stimuli, fmBF increased and msBF did not. Mesenteric and femoral vascular conductance both increased, whereas VBP decreased and skBF followed SBP. We found that for all baroreflex response components, with the exception of SINUS-elicited ΔIBI, there was an orderly, substantially linear, relationship between stimulus strength and response magnitude.
Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB
Authors: Grindstaff Ryan J. , Grindstaff Regina R. , Cunningham J. Thomas
Published: December 2017

Previous studies suggest that cholinergic neurons in the diagonal band of Broca (DBB) participate in the baroreceptor-mediated inhibition of phasic vasopressin neurons in the supraoptic nucleus (SON). To test this hypothesis, extracellular recordings were obtained from putative vasopressin SON neurons of anesthetized rats injected with the cholinergic immunotoxin 192 IgG-saporin (0.8 μg/μl) in the DBB. Baroreceptor sensitivity of neurons was tested with brief phenylephrine-induced (10 μg/10 μl iv) increases in blood pressure of at least 40 mmHg. In rats injected with vehicle or unconjugated saporin, 19 of 21 and 18 of 20 phasic neurons, respectively, were inhibited by increased blood pressure. In rats injected with 192 IgG-saporin, which significantly reduced the number of choline acetyltransferase (ChAT)-positive DBB neurons, 33 of 36 phasic neurons were inhibited. Normal rats and rats with DBB saporin injections received rhodamine bead injections into the perinuclear zone (PNZ) to retrogradely label DBB neurons, and their brains were stained for ChAT. ChAT-positive DBB neurons were not retrogradely labeled from the PNZ. Together, these results indicate that the pathway relaying baroreceptor information to the SON involves noncholinergic DBB neurons.
Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine
Authors: Owen Medge D. , Unal Can B. , Callahan Michael F. , Trivedi Kavita , York Catherine , Millington William R.
Published: December 2017

Glycyl-glutamine (Gly-Gln; β-endorphin30–31) is an endogenous dipeptide that is synthesized through the posttranslational processing of β-endorphin in brain stem regions that control respiration and autonomic function. This study tested the hypothesis that Gly-Gln administration to conscious rats will prevent the respiratory depression caused by morphine without affecting morphine antinociception. Rats were administered Gly-Gln (1–100 nmol) or saline (10 μl) intracerebroventricularly followed, 5 min later, by morphine (40 nmol icv). Arterial blood gases and pH were measured immediately before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatment inhibited morphine-induced hypercapnia, hypoxia, and acidosis significantly. The response was dose dependent and significant at Gly-Gln doses as low as 1 nmol. In contrast, Gly-Gln (1–300 nmol) had no effect on morphine-evoked antinociception in the paw withdrawal test. When given alone to otherwise untreated animals, Gly-Gln did not affect nociceptive latencies or blood gas values. These data indicate that Gly-Gln inhibits morphine-induced respiratory depression without compromising morphine antinociception.
Endothelial expression of selectins during endotoxin preconditioning
Authors: Bauer Philippe , Welbourne Tomas , Shigematsu Takeharu , Russell Janice , Granger D. Neil
Published: December 2017

Although bacterial endotoxins [lipopolysaccharide (LPS)] can confer tissue resistance to subsequent inflammatory insults, the mechanisms that underlie this LPS-preconditioning (LPS-PC) response remain poorly defined. The dual-radiolabeled monoclonal antibody technique was used to examine whether LPS-PC alters the upregulation (protein) of E- and P-selectins after subsequent LPS challenge. In the gut of wild-type (C57BL/6J) mice, LPS-PC was associated with a reduction in E- (66%) and P-selectin (33%) expression. A similar reduction in E-selectin expression was observed in mutant mice that were genetically deficient in either the endothelial or inducible isoform of nitric oxide synthase or that overexpressed the human gene for Cu/Zn superoxide dismutase. Severe combined immunodeficient mice, genetically devoid of lymphocytes, did exhibit partial inhibition of the LPS-PC response. We conclude that 1) LPS-PC can be demonstrated for E- and P-selectins in some vascular beds (e.g., gut), 2) the mechanism(s) underlying this blunted selectin response does not include a major role for either nitric oxide and superoxide, and 3) circulating lymphocytes may contribute to the LPS-PC response.
Anticipatory changes in liver metabolism and entrainment of insulin, glucagon, and corticosterone in food-restricted rats
Authors: Díaz-Muñoz Mauricio , Vázquez-Martínez Olivia , Aguilar-Roblero Raúl , Escobar Carolina
Published: December 2017

Restricted feeding schedules entrain behavioral and physiological circadian rhythms, which depend on a food-entrainable oscillator (FEO). The mechanism of the FEO might depend on digestive and endocrine processes regulating energy balance. The present study characterizes the dynamics of circulating corticosterone, insulin, and glucagon and regulatory parameters of liver metabolism in rats under restricted feeding schedules. With respect to ad libitum controls, food-restricted rats showed 1) an increase in corticosterone and glucagon and a decrease in insulin before food access, indicating a predominant catabolic state; and 2) a reduction in lactate-to-pyruvate and β-hydroxybutyrate-to-acetoacetate ratios, indicating an oxidized cytoplasmic and mitochondrial redox state in the liver metabolism. All these changes were reversed after feeding. Moreover, liver energy charge in food-restricted rats did not show a significant modification before feeding, despite an increase in adenine nucleotides, but showed an important decrease after food intake. Variations detected in the liver of food-restricted rats are different from those prevailing under 24-h fasting. These observations suggest “anticipatory activity” of the liver metabolism to optimize the processing of nutrients to daily feeding. Data also suggest a possible relationship of the liver and endocrine signals with the FEO.
Spectrum of myelinated pulmonary afferents
Authors: Yu Jerry
Published: December 2017

Myelinated pulmonary afferents are classified as rapidly adapting receptors (RARs) or slowly adapting receptors (SARs) by their adaptation rate. Behavior of SARs varies greatly, and therefore the present study tries to further categorize SARs according to their mechanical properties. Single-fiber activity of 104 SARs was examined in anesthetized, open-chest, artificially ventilated rabbits. According to the increase or decrease in activity during removal of positive-end-expiratory pressure (PEEP), SARs were divided into two groups. In one group mean activity increased from 31 ± 6 to 46 ± 7 impulses per second (imp/s; n = 11); in another group mean activity decreased from 44 ± 2 to 25 ± 1 imp/s ( n = 93). The first group of SARs has high adaptation indexes (RAR-like), which increased with inflation pressure (36 ± 3, 44 ± 3, and 47 ± 3% for 10, 15, and 20 cmH2O, respectively; P < 0.005). Their peak activity shifted from inflation phase to deflation phase during PEEP removal. The second group of SARs has low-adaptation indexes (typical SARs), which were not affected by inflation pressure (19 ± 1, 18 ± 1, and 17 ± 1% for 10, 15, and 20 cmH2O; P = 0.516). Their peak activity did not shift during PEEP removal. Because there are overlaps in other characteristics, it is proposed that myelinated vagal afferents are viewed as a heterogeneous group; their behaviors are like a spectrum, where typical RARs and SARs represent two extremes of the spectrum. The receptor behavior might be determined by anatomic location and its environment.
Control of fetal insulin secretion
Authors: Jackson Benjamin T. , Piasecki George J. , Cohn Herbert E. , Cohen Wayne R.
Published: December 2017

In this study, we investigated the way in which fetal insulin secretion is influenced by interrelated changes in blood glucose and sympathoadrenal activity. Experiments were conducted in late gestation sheep fetuses prepared with chronic peripheral and adrenal catheters. The fetus mounted a brisk insulin response to hyperglycemia but with only a minimal change in the glucose-to-insulin ratio, indicating a tight coupling between insulin secretion and plasma glucose. In well-oxygenated fetuses, α2-adrenergic blockade by idazoxan effected no change in fetal insulin concentration, indicating the absence of a resting sympathetic inhibitory tone for insulin secretion. With hypoxia, fetal norepinephrine (NE) and epinephrine secretion and plasma NE increased markedly; fetal insulin secretion decreased strikingly with the degree of change related to extant plasma glucose concentration. Idazoxan blocked this effect showing the hypoxic inhibition of insulin secretion to be mediated by a specific α2-adrenergic mechanism. α2-Blockade in the presence of sympathetic activation secondary to hypoxic stress also revealed the presence of a potent β-adrenergic stimulatory effect for insulin secretion. However, based on an analysis of data at the completion of the study, this β-stimulatory mechanism was seen to be absent in all six fetuses that had been subjected to a prior experimentally induced hypoxic stress but in only one of nine fetuses not subjected to this perturbation. We speculate that severe hypoxic stress in the fetus may, at least in the short term, have a residual effect in suppressing the β-adrenergic stimulatory mechanism for insulin secretion.
Cardiorespiratory interactions during resistive load breathing
Authors: Calabrese Pascale , Perrault Helene , Dinh Tuan Pham , Eberhard Andre , Benchetrit Gila
Published: December 2017

The addition to the respiratory system of a resistive load results in breathing pattern changes and in negative intrathoracic pressure increases. The aim of this study was to use resistive load breathing as a stimulus to the cardiorespiratory interaction and to examine the extent of the changes in heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) in relation to the breathing pattern changes. HRV and RSA were studied in seven healthy subjects where four resistive loads were applied in a random order during the breath and 8-min recording made in each condition. The HRV spectral power components were computed from the R-R interval sequences, and the RSA amplitude and phase were computed from the sinusoid fitting the instantaneous heart rate within each breath. Adding resistive loads resulted in 1) increasing respiratory period, 2) unchanging heart rate, and 3) increasing HRV and changing RSA characteristics. HRV and RSA characteristics are linearly correlated to the respiratory period. These modifications appear to be linked to load-induced changes in the respiratory period in each individual, because HRV and RSA characteristics are similar at a respiratory period obtained either by loading or by imposed frequency breathing. The present results are discussed with regard to the importance of the breathing cycle duration in these cardiorespiratory interactions, suggesting that these interactions may depend on the time necessary for activation and dissipation of neurotransmitters involved in RSA.
Autonomic cardiovascular control in conscious mice
Authors: Just Armin , Faulhaber Jörg , Ehmke Heimo
Published: December 2017

Autonomic cardiovascular control was characterized in conscious, chronically catheterized mice by spectral analysis of arterial pressure (AP) and heart rate (HR) during autonomic blockade or baroreflex modulation of autonomic tone. Both spectra were similar to those obtained in humans, but at ∼10× higher frequencies. The 1/ f relation of the AP spectrum changed to a more shallow slope below 0.1–0.2 Hz. Coherence between AP and HR reached 0.5 or higher below 0.3–0.4 Hz and also above 2.5 Hz. Muscarinic blockade (atropine) or β-adrenergic blockade (atenolol) did not significantly affect the AP spectrum. Atropine reduced HR variability at all frequencies, but this effect waned above 1 Hz. β-Adrenergic blockade (atenolol) slightly enhanced the HR variability only above 1 Hz. α-Adrenergic blockade (prazosin) reduced AP variability between 0.05 and 3 Hz, most prominently at 0.15–0.7 Hz. A shift of the autonomic nervous tone by a hypertensive stimulus (phenylephrine) enhanced, whereas a hypotensive stimulus (nitroprusside) depressed AP variability at 1–3 Hz; other frequency ranges of the AP spectrum were not affected except for a reduction below 0.4 Hz after nitroprusside. Variability of HR was enhanced after phenylephrine at all frequencies and reduced after nitroprusside. As with atropine, the reduction with nitroprusside waned above 1 Hz. In conclusion, in mice HR variability is dominated by parasympathetic tone at all frequencies, during both blockade and physiological modulation of autonomic tone. There is a limitation for further reduction but not for augmentation of HR variability from the resting state above 1 Hz. The impact of HR on AP variability in mice is confined to frequencies higher than 1 Hz. Limits between frequency ranges are proposed as 0.15 Hz between VLF (very low frequency range) and LF (low frequency range) and 1.5 Hz between LF and HF (high frequency range).
Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats
Authors: Levin Barry E. , Dunn-Meynell Ambrose A.
Published: December 2017

Chronic administration of sibutramine lowers body weight, presumably by altering brain monoamine metabolism. Here the effect of sibutramine on sympathoadrenal function (24-h urine norepinephrine and epinephrine levels) and arcuate nucleus (ARC) neuropeptide Y (NPY) and proopiomelanocortin (POMC) expression was assessed in diet-induced obese rats fed a low-fat diet. Chronic (10 wk) sibutramine [5 mg · kg−1· day−1ip; rats fed ad libitum and injected with sibutramine (AS)] lowered body weight by 15% but only transiently (3–4 wk) reduced intake compared with vehicle-treated controls [rats fed chow ad libitum and injected with vehicle daily (AV)]. Other rats food restricted (RS) to 90% of the weight of AS rats and then given sibutramine restored their body weights to the level of AS rats when allowed libitum food intake. After reequilibration, RS rats were again energy restricted to reduce their weight to 90% of AS rats, and additional vehicle-treated rats (RV) were restricted to keep their body weights at the level of AS rats for 3 wk more. Terminally, total adipose depot weights and leptin levels paralleled body weights (AV > AS = RV > RS), although AS rats had heavier abdominal and lighter peripheral depots than RV rats of comparable body weights. Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats. Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis.
Muscle recruitment patterns regulate physiological responses during exercise of the same intensity
Authors: Deschenes Michael R. , Kraemer William J. , McCoy Raymond W. , Volek Jeff S. , Turner Benjamin M. , Weinlein John C.
Published: December 2017

On different days, 10 men performed 30-min sessions of cycling at 50–55% of their peak oxygen uptake (V˙o 2); one at 40 rpm and another at 80 rpm. Rectal temperature, heart rate (HR), mean arterial pressure (MAP), plasma lactate, glucose, insulin, and cortisol were measured before exercise, during the 15th and 30th min of exercise, and at 5 and 10 min postexercise. Rating of perceived exertion (RPE) was assessed 15 and 30 min into exercise. Electromyography established cadence-specific different intensities of quadriceps activation during cycling. At minute 30 of exercise and 5 min postexercise, HR was significantly ( P < 0.05) greater at 40 rpm than at 80 rpm. MAP remained elevated longer after the 40-rpm than after the 80-rpm bout. Similarly, exercise-induced increases in plasma lactate persisted longer after the 40-rpm bout. Cortisol levels were elevated only at 40 rpm. RPE was higher during the slower cadence. These data indicated that the more pronounced muscle activation pattern associated with pedaling at 40 rpm resulted in greater physiological and psychophysiological stress than that observed at 80 rpm even thoughV˙o 2 was the same.
Hemodilution mediates hemodynamic changes during acute expansion in unanesthetized rats
Authors: Inoue Rosana Y. , Gontijo José A. R. , Franchini Kleber G.
Published: December 2017

Studies were carried out to determine the relative importance of volume and hemodilution on hemodynamic adjustments to acute volume expansion. Systemic and renal hemodynamics were monitored in unanesthetized and unrestrained rats during progressive and equivalent blood volume expansion with saline (Sal; 1, 2, and 4% body wt), 7% BSA solution (0.35, 0.7, and 1.4% body wt), and reconstituted whole blood from donor rats (WBL; 0.35, 0.7, and 1.4% body wt). Mean arterial pressure remained unchanged in Sal and BSA but increased progressively in WBL-expanded rats (from 92 to 106 mmHg after maximal expansion). In Sal and BSA-expanded rats, cardiac output (CO) and renal blood flow (RBF) increased (CO: Sal from 19 to 20, 22, and 25; BSA from 21 to 23, 27, and 31; RBF: Sal from 1.6 to 1.8, 2.2, and 2.5; BSA from 2 to 2.4, 2.7, and 3.1 ml · min−1 · 100 g body wt−1), whereas total peripheral (TPR) and renal vascular (RVR) resistance decreased in parallel with the expansions. After expansion with WBL, CO increased progressively but less extensively than in cell-free expanded rats (21 to 22, 24, and 26 ml · min−1 · 100 g body wt−1), whereas TPR and RVR remained unchanged. Systemic hematocrit (Hct) decreased approximately the same after expansion with Sal or BSA solutions but remained unchanged after expansion with WBL. Isovolemic hemodilution to Hct levels comparable to those seen after maximal expansion with cell-free solutions also reduced SVR and RVR, although less extensively. These findings suggest that in unanesthetized rats hemodilution plays a major role in the systemic and renal hemodynamics during expansion.
Spontaneous c-Fos rhythm in the rat suprachiasmatic nucleus: location and effect of photoperiod
Authors: Sumová Alena , Trávníčková Zdeňka , Illnerová Helena
Published: December 2017

A recently reported circadian rhythm in the spontaneous c-Fos immunoreactivity in the rat suprachiasmatic nucleus (SCN) is expressed mostly in the dorsomedial (dm) SCN, where vasopressinergic cells are located. The aim of the present study is to find out whether day length, i.e., photoperiod, affects the dm-SCN rhythm and, if so, how the rhythm adjusts to a change from a long to a short photoperiod. In addition, a question of whether the spontaneous c-Fos production is localized in vasopressin- producing cells or in other cells is also studied to characterize further the dm-SCN rhythmicity. Combined immunostaining for c-Fos and arginine vasopressin (AVP) revealed that most of c-Fos immunopositive cells were devoid of AVP; the results suggest that c-Fos-producing cells in the dm-SCN are mostly not identical with those producing AVP. In rats maintained under a long photoperiod with 16:8-h light-dark cycle (LD 16:8) daily and then released into darkness, the time of the afternoon and evening decline of the spontaneous c-Fos immunoreactivity in the dm-SCN differed just slightly from the time in rats maintained originally under a short LD 8:16 photoperiod; however, the morning c-Fos rise occurred about 4 h earlier under the long than under the short photoperiod. After a change from a long to a short photoperiod, a rough but not yet a fine adjustment of the morning c-Fos rise to the change was accomplished within 3–6 days. The results show that similar to the recently reported ventrolateral SCN rhythmicity, the intrinsic dm-SCN rhythmicity is also affected by the photoperiod and suggest that the whole SCN state is photoperiod dependent.
c-Fos rhythm in subdivisions of the rat suprachiasmatic nucleus under artificial and natural photoperiods
Authors: Jáč Martin , Sumová Alena , Illnerová Helena
Published: December 2017

Recent studies have shown that the waveform of the rhythm of c-Fos photoinduction in the ventrolateral (vl) part of the suprachiasmatic nucleus (SCN) and that of the rhythm in the spontaneous c-Fos production in the dorsomedial (dm) part of the SCN in rats released into constant darkness depend on the photoperiod under which the animals were previously maintained. The aim of the present study was to find out how the rhythms of c-Fos immunoreactivity in both SCN subdivisions are affected by actual light-dark (LD) cycles with various photoperiods, either artificial or natural ones, that animals may usually experience. Rats were maintained under artificial LD cycles, with either a long (16-h photoperiod) or a short (8-h photoperiod) or under natural daylight. In the latter case, c-Fos rhythms were followed in the summer when the photoperiod lasted about 16 h or in winter when it lasted only 8 h. The rhythms of c-Fos immunoreactivity under natural daylight did not differ significantly from those under corresponding artificial photoperiods. Under a long photoperiod, the morning c-Fos rise in the dm- as well as in the vl-SCN occurred about 4 h earlier than under a short one. In both SCN subdivisions, the interval when the nighttime c-Fos immunoreactivity was low, was shorter under a long than under a short photoperiod by roughly 6 h. The morning c-Fos rise in the dm-SCN always preceded that in the vl-SCN. Whereas in the former one the rise was due to the endogenous dm-SCN rhythmicity, in the latter one the rise was induced by the morning light onset. The results show that whereas c-Fos rhythmicity under actual LD cycles is affected by the photoperiod in both SCN subdivisions, mechanism of c-Fos induction in the dm-SCN differs from that in the vl-SCN.
Circumventricular organs and ANG II-induced salt appetite: blood pressure and connectivity
Authors: Fitts Douglas A. , Starbuck Elizabeth M. , Ruhf Alexandra
Published: December 2017

A lesion of the subfornical organ (SFO) may reduce sodium depletion-induced salt appetite, which is largely dependent on ANG II, and yet ANG II infusions directly into SFO do not provoke salt appetite. Two experiments were designed to address this apparent contradiction. In experiment 1 sustained infusions of ANG II into SFO did not produce a sustained elevation of blood pressure, and neither a reduction of blood pressure alone with minoxidil and captopril nor a reduction of both blood pressure and volume with furosemide and captopril enhanced salt appetite. Infusions of ANG II in the organum vasculosum laminae terminalis (OVLT) did evoke salt appetite without raising blood pressure. In experiment 2 knife cuts of the afferent and efferent fibers of the rostroventral pole of the SFO abolished water intake during an infusion of ANG II into the femoral vein but failed to reduce salt appetite during an infusion of ANG II into the OVLT. We conclude that 1) hypertension does not account for the failure of infusions of ANG II in the SFO to generate salt appetite and 2) the OVLT does not depend on its connectivity with the SFO to generate salt appetite during ANG II infusions.