bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal platelet Ca2+handling accompanied by increased cytosolic free Mg2+in essential hypertension
Authors: Hiraga Hiroyuki , Oshima Tetsuya , Yoshimura Mitsuisa , Matsuura Hideo , Kajiyama Goro
Published: December 2017

To test the hypothesis that abnormal platelet Ca2+handling in essential hypertension results from cellular Mg2+deficiency, cytosolic free Mg2+concentration ([Mg2+]i) and Ca2+metabolism were studied in mag-fura 2 and fura 2-loaded platelets from 30 essential hypertensive patients and 30 sex- and age-matched normotensive controls. Basal cytosolic free Ca2+concentration ([Ca2+]i) and intracellular Ca2+discharge capacity were higher in hypertensives than in normotensives (22 ± 5 vs. 18 ± 5 nM, P < 0.05; 743 ± 250 vs. 624 ± 144 nM, P < 0.05, respectively). The thrombin (0.03–1.0 U/ml)-evoked [Ca2+]iresponse was also enhanced in platelets from hypertensives in both the absence and presence of extracellular Ca2+. However, basal [Mg2+]iwas higher in hypertensives than in normotensives (437 ± 110 vs. 353 ± 85 μM, P < 0.05), whereas serum Mg2+was similar in the two groups. These results oppose the Mg2+deficiency hypothesis in platelets in essential hypertension.
Coupling effect of locomotor activity on the rat’s circadian system
Authors: Lax Pedro , Zamora Salvador , Madrid Juan A.
Published: December 2017

Exercise is recognized to affect circadian rhythmicity in a variety of ways. It masks the expression of other behavioral and physiological rhythms, entrains the master pacemaker, and influences the free-running period of other rhythms. In this paper we study the influence of exercise on the organization of the timing system by analyzing the effect of voluntary locomotor activity on the circadian feeding behavior of rats subjected to different lighting conditions. The availability of wheel running prevented loss of feeding circadian rhythmicity under constant bright light (LL) but did not elicit any circadian pattern in rats showing a previous arrhythmic pattern. Under dim red light (DR), the rhythm was more pronounced in exercising than in sedentary rats, while wheel-running availability accelerated the emergence of circadian rhythmicity in arrhythmic animals that were moved from LL to DR. These results can be explained by the existence of a positive feedback loop between physical exercise and its pacemaker and also suggest that exercise changes the functioning of the circadian system to facilitate the emergence of circadian rhythms in previously arrhythmic animals.
Platelet-activating factor modulates cardiorespiratory responses in the conscious rat
Authors: Gozal David , Holt Gregory A. , Graff Gavin R. , Torres José E.
Published: December 2017

Platelet-activating factor receptor (PAFR) activation is associated with increases in neuronal excitability. We hypothesized that PAF may play a role in cardiorespiratory control. Ventilatory responses to microinjection of a long-acting PAF analog ( mc-PAF, 1 μg in 1 μl) within the dorsocaudal brain stem were measured in unrestrained adult rats. mc-PAF elicited significant minute ventilation (V˙e) enhancements that were primarily due to tidal volume increases and were accompanied by respiratory alkalosis, heart rate increase, and reduction of arterial blood pressure. Such cardiovascular and respiratory effects did not occur after administration of either vehicle or the inactive analog lyso-PAF. The effect was blocked when animals were coadministered the presynaptic PAFR antagonist BN-52021 or recombinant PAF acetyl hydrolase. To determine the relative contribution of PAF to hypercapnic and hypoxic ventilation, microinjections were performed in additional animals with either vehicle (CO, 1 μl) or with 5 μg in 1 μl of BN-52021. Hypercapnic challenges with 5% CO2were unaffected by BN-52021. In contrast, although 10% O2breathing increased V˙e from 120.4 ± 7.5 to 204.6 ± 11.4 ml/min in CO, after BN-52021, V˙e increased only from 118.7 ± 6.9 to 137.3 ± 8.9 ml/min (CO vs. BN-52021, P < 0.001). We conclude that PAFR activation in the dorsocaudal brain stem exerts significant cardioventilatory effects during normoxia and appears to play an important modulatory role in the V˙eresponse to hypoxia in conscious rats.
ANG II AT1 receptors induce depolarization and inward current in rat median preoptic neurons in vitro
Authors: Bai Donglin , Renaud Leo P.
Published: December 2017

To examine ANG II receptors in rat median preoptic (MnPO) neurons, we used patch-clamp whole cell recordings in a parasagittal brain slice preparation. Lucifer yellow-filled neurons displayed a simple morphology with two to three aspiny dendrites. Bath-applied ANG II (1–2,000 nM for 30 s) induced a response in 37 of 70 cells. In current-clamp recordings, cells displayed a prolonged (10- to 30-min) depolarizing plateau with action potential discharges and an associated reduction in postburst afterhyperpolarization and spike frequency adaptation. In voltage-clamp recordings (holding potential −65 mV), cells displayed tetrodotoxin-resistant inward currents of 7.6 ± 1.9 ( n = 5), 9.9 ± 1.9 ( n = 9), and 9.2 ± 2.2 pA ( n = 6) at 10, 200, and 2,000 nM, respectively. Responses were blockable by pretreatment with losartan (2 μM; n = 6) but not by PD-123177 (20 μM; n = 3). Net ANG II-induced current revealed a 7.8 ± 0.9% reduction in membrane conductance, decreasing but not reversing at hyperpolarized levels. Neurons expressing a strong hyperpolarization-activated, time-independent inward rectification were more likely to respond to ANG II. There was no correlation between the response of a neuron to ANG II and its response to norepinephrine.
Increased in vitro fatty acid supply and cellular transport capacities in cold-acclimated ducklings (Cairina moschata)
Authors: Bénistant Christophe , Duchamp Claude , Cohen-Adad Frédérique , Rouanet Jean-Louis , Barré Hervé
Published: December 2017

In cold-acclimated (CA) birds, lipids play a crucial role in regulatory thermogenesis by acting both as substrates for and activators of thermogenic processes. The capacity to supply lipids to thermogenic tissues, which could limit cold thermogenesis, was assessed in CA ducklings (5 wk old, 4°C) and compared with thermoneutral controls (TN, 25°C). In CA ducklings, basal lipolytic activity of adipose tissue fragments was higher (202 ± 9 vs. 130 ± 14 nmol glycerol released ⋅ 100 mg tissue−1⋅ h−1, +55%) than in TN controls, while glucagon had a much higher stimulatory effect (+140 to +500% depending on dose). This was consistent with increased plasma levels of nonesterified fatty acids (FA, +57%) and glycerol (+31%) in vivo. In vitro endothelial lipase activity per organ was higher in CA than in TN ducklings in red gastrocnemius muscle (6.3 ± 0.6 vs. 3.5 ± 0.3 μeq nonesterified FA released per hour, +80%) and liver (+55%). The intracellular FA-binding capacity of (12–18 kDa) proteins was higher in gastrocnemius muscle (+43%) and liver (+74%) from CA ducklings. In gastrocnemius, it was linked to a higher content (21 ± 2 vs. 15 ± 2 μg/mg protein, +37%) of an intracellular 15.4-kDa FA-binding protein. These in vitro results indicate that coordinated increases in FA supply from adipose tissue, cellular uptake of lipoprotein-derived FA, and intracellular FA transport capacity occur in CA ducklings endowed with higher thermogenic capacity and cold endurance.
The thromboxane A2 mimetic U-46619 inhibits somatomotor activity via a vagal reflex from the lung
Authors: Pickar Joel G.
Published: December 2017

Vagal reflexes from the heart and lungs elicit autonomic as well as somatomotor responses. The purpose of the present investigation was to determine whether the inflammatory mediator thromboxane A2 inhibits the knee-jerk reflex via a vagally mediated reflex from either the heart or the lung. The thromboxane A2 mimetic U-46619 (0.8 ± 0.08 μg/kg) was injected through a catheter placed near the right atrium ( n = 11), near the aortic arch ( n = 7), or into the pericardial sac ( n = 4) in 11 chloralose-anesthetized cats. The knee-jerk reflex, elicited by striking the patellar tendon with a solenoid-driven hammer, was used to evaluate somatomotor activity. The mean maximum tension produced by the knee-jerk reflex was 306 ± 21 g (range 154–471 g). Intravenous U-46619 injection inhibited the knee-jerk reflex by 25 ± 6% and increased peak systolic pressure 53 ± 7 mmHg on average. Bilateral cervical vagotomy abolished the somatomotor inhibition but did not reduce the pressor response. Intra-arterial U-46619 injection inhibited the knee-jerk reflex in two of seven cats and increased peak systolic pressure by 41 ± 11 mmHg. Vagotomy abolished the inhibition in one of the two cats but did not reduce the pressor response. Intrapericardial U-46619 injection did not affect the knee-jerk reflex nor blood pressure. The results indicate that U-46619 inhibited the knee-jerk reflex via a vagal reflex from the lung because the inhibition predominated after intravenous injection and was abolished by vagotomy. Speculation is made that the inflammatory mediator thromboxane A2 may contribute via a vagal reflex to the depression of motor activity associated with sickness behavior.
Effects of maturation, artery size, and chronic hypoxia on 5-HT receptor type in ovine cranial arteries
Authors: Teng Guo Qi , Williams James , Zhang Lubo , Purdy Ralph , Pearce William J.
Published: December 2017

To test the hypothesis that variations in cerebrovascular reactivity to 5-HT among arteries of different size or type, during maturation, or during acclimatization to high altitude involve differences in serotonergic receptor subtype, we determined relative agonist potency orders and antagonist affinities in common carotid (Com), main branch middle cerebral (Main), and second branch middle cerebral (2BR) arteries from term fetal lambs and nonpregnant adult sheep acclimatized at sea level or at an altitude of 3,820 m for ≈110 days. In normoxic adult Com segments, agonist potency order was 5-hydroxytryptamine (5-HT) > 5-carboxamidotryptamine (5-CT) ≥ 8-hydroxy-2(di- n-propylamino)tetraline (8-OH-DPAT); sumatriptan (Suma) produced no contractile response; and antagonist dissociation constant (pKb) values were 9.4 and 9.5 for ketanserin against 5-HT and 5-CT, 7.5 for GR-127935 against 5-HT, and 7.2 for SB-206553 against 5-HT. In normoxic adult Main segments, agonist potency order was 5-HT > 5-CT ≥ Suma ≥ DPAT, and pKb values were 9.1 and 9.2 for ketanserin against 5-HT and 5-CT and 7.4 and 8.5 for GR-127935 against 5-HT and Suma, respectively. In the 2BR segments from normoxic adults, agonist potency order was 5-CT > 5-HT > Suma > DPAT and pKb values were 7.4 and 7.2 for ketanserin against 5-HT and 5-CT and 10.0 and 8.7 for GR-127935 against 5-HT and Suma, respectively. Compared with normoxic adults, none of these values were significantly different in hypoxic adults and in fetuses only the pKb values for ketanserin against 5-HT in the 2BR segments (8.8) were greater. From these results we propose that the ratio of 5-HT2 to 5-HT1 receptors is greatest in the Com and decreases progressively to its smallest values in 2BR or smaller segments. Because this gradient appears stable and relatively resistant to the effects of maturation and chronic hypoxia, changes in reactivity associated with these perturbations may involve alterations in receptor density and/or coupling efficiency for 5-HT in ovine cranial arteries.
Regional and functional differences in the distribution of vestibulosympathetic reflexes
Authors: Kerman I. A. , Yates B. J.
Published: December 2017

Although considerable evidence suggests that the vestibular system regulates sympathetic outflow during movement and changes in posture, little is known about relative vestibular influences on activity of different sympathetic nerves and sympathetic efferents with different functions. In the present study, we demonstrated that electrical stimulation of the vestibular nerve in the cat elicited responses in sympathetic nerves innervating the head and abdominal viscera. This observation suggests that activity of sympathetic efferents innervating multiple body regions is affected by vestibular signals. These responses were attenuated by >80% when blood pressure was increased to >160 mmHg. Because raising blood pressure decreases the responsiveness of vasoconstrictor fibers, the simplest explanation for these data is that the vestibular system provides particularly strong inputs to components of the sympathetic nervous system that regulate peripheral vascular resistance. Furthermore, the relative magnitude of vestibulosympathetic reflexes was over four times larger in one sympathetic nerve composed mainly of vasoconstrictor efferents (renal nerve) than another nerve (external carotid nerve) containing similar types of fibers. Collectively, these data indicate that the vestibular system has selective influences on sympathetic outflow to particular tissues and body regions.
Evaluation of different levels of hydration using a new physiological strain index
Authors: Moran Daniel S. , Montain Scott J. , Pandolf Kent B.
Published: December 2017

A physiological strain index (PSI), based on rectal temperature (Tre) and heart rate (HR), was recently suggested for evaluating heat stress. The purpose of this study was to evaluate the PSI for different combinations of hydration level and exercise intensity. This index was applied to two databases. The first database was obtained from eight endurance-trained men dehydrated to four different levels (1.1, 2.3, 3.4, and 4.2% of body wt) during 120 min of cycling at a power output of 62–67% maximum O2consumption (V˙o2 max) in the heat [33°C and 50% relative humidity (RH)]. The second database was obtained from nine men performing exercise in the heat (30°C and 50% RH) for 50 min. These subjects completed a matrix of nine trials of exercise on a treadmill at three exercise intensities (25, 45, and 65%V˙o2 max) and three hydration levels (euhydration and hypohydration at 3 and 5% of body wt). Tre, HR, esophageal temperature (Tes), and local sweating rate were measured. PSI (obtained from either Treor Tes) significantly ( P < 0.05) differentiated among all exposures in both databases categorized by exercise intensity and hydration level, and we assessed the strain on a scale ranging from 0 to 10. Therefore, PSI applicability was extended for heat strain associated with hypohydration and continues to provide the potential to be universally accepted.
Preventing hemodilution abolishes natriuresis of water immersion in humans
Authors: Johansen Lars Bo , Pump Bettina , Warberg Jørgen , Christensen Niels Juel , Norsk Peter
Published: December 2017

The hypothesis was tested that hemodilution is one of the determinants of the water immersion (WI)-induced natriuresis. Eight males were subjected to 3 h of 1) WI to the midchest (Chest), 2) WI to the neck combined with thigh cuff-induced (80 mmHg) venous stasis (Neck + stasis), and 3) a seated time control ( n = 6). Central venous pressure and left atrial diameter increased to the same extent during Chest and Neck + stasis ( P < 0.05), whereas renal sodium excretion only increased during Chest from 77 ± 7 to 225 ± 13 μmol/min ( P < 0.05). During Chest, plasma colloid osmotic pressure (COP) decreased from 27.7 ± 0.7 to 25.1 ± 0.7 mmHg ( P< 0.05), and plasma volume (PV) increased from 3,263 ± 129 to 3,581 ± 159 ml ( P < 0.05), whereas these variables remained unchanged during Neck + stasis. Plasma norepinephrine concentration decreased similarly during Chest and Neck + stasis by 45 ± 7 and 34 ± 4%, respectively ( P < 0.05), whereas plasma renin activity decreased only during Chest ( P < 0.05). In conclusion, during WI in humans 1) hemodilution (decrease in COP and increase in PV) is a pivotal stimulus for the natriuresis and 2) central blood volume expansion without hemodilution does not augment renal sodium output.
Ontogenetic and regional changes in α-methyl-d-glucoside andl-proline intestinal transport in guinea pig
Authors: Juan M. Emília , Turmo M. Carmen , Planas Joana M.
Published: December 2017

Regional brush-border uptakes of α-methyl-d-glucose andl-proline as well as morphometric parameters were studied from birth until adulthood in guinea pig small intestine. Intestinal weight, length, and area were fitted to two-segmented straight lines: from birth until the 2nd wk there was a sharp rise, whereas from day 14 to the adult stage the increase was slower. In everted sleeves, total uptakes of α-methyl-d-glucoside were higher on day 1 in duodenum, jejunum, and ileum, diminishing with increasing age. The initial fluxes ofl-proline were higher during the 1st wk, diminishing to values that kept constant thereafter. Total uptakes of l-proline relative to α-methyl-d-glucoside showed a peak in the 1st wk in the three segments studied, reflecting the high demand for protein during the postnatal period. Regional ratios ofl-proline to α-methyl-d-glucoside indicated that the ileum is the segment best suited to transporting this amino acid during the first 3 wk. Changes observed in the present study indicated a different pattern between hexose and amino acid transport during development and along the small intestine of guinea pig.
Isoform expression of Na+-K+-ATPase α-subunit in gills of the teleostOreochromis mossambicus
Authors: Lee Tsung-Han , Tsai Jong-Chang , Fang Mei-Jane , Yu Ming-Jiun , Hwang Pung-Pung
Published: December 2017

Three isoform-specific antibodies, 6F against the α1-isoform of the avian sodium pump, HERED against the rat α2-isoform, and Ax2 against the rat α3-isoform, were used to detect the expression of Na+-K+-ATPase α-subunits in gills of a teleost, the tilapia ( Oreochromis mossambicus). Tilapia gill tissue showed positive reactions to antibodies specific for α1- and α3-isoforms. The results of immunoblots were converted to numerical values (relative intensities) by image analysis for comparisons. Relative amounts of α1-like isoform alone and consequently the ratio of α1-like to α3-like isoforms were higher in gills of seawater-adapted tilapia than in those of freshwater-adapted ones, indicating that the two isoforms respond differently to environmental salinities. In the subsequent immunocytochemical experiments, gill mitochondria-rich cells were demonstrated to immunoreact with antibodies specific for α1- and α3-isoforms. α1-like and α3-like isoforms of gill Na+-K+-ATPase are suggested to be involved in the ion- and osmoregulation mechanisms in tilapia. Moreover, differential expressions of two isoforms may be associated with different functions, secretion and uptake of ions and acid-base regulation, in gills of seawater- and freshwater-adapted tilapia.
Role of endothelial carbon monoxide in attenuated vasoreactivity following chronic hypoxia
Authors: Caudill Timothy K. , Resta Thomas C. , Kanagy Nancy L. , Walker Benjimen R.
Published: December 2017

Chronic hypoxic exposure has been previously demonstrated to attenuate systemic vasoconstrictor activity to a variety of agents. This attenuated responsiveness is observed not only in conscious animals but in isolated vascular preparations as well. Because hypoxia has been documented to increase heme oxygenase (HO) levels and the subsequent production of the vasodilator CO in vitro, we hypothesized that the blunted reactivity observed with chronic hypoxia (CH) may be in part due to increased HO activity. In thoracic aortic rings from CH rats, cumulative dose-response curves to phenylephrine (PE) in the presence of the nitric oxide (NO) synthase inhibitor N ω-nitro-l-arginine (l-NNA) and the HO inhibitor zinc protoporphyrin 9 (ZnPPIX) elicited increased contractility compared with CH rings treated with onlyl-NNA. Similar results were observed in rings incubated overnight with the HO-inducing agent sodium m-arsenite. In contrast, contractile responses in rings from control rats were unaffected by the HO inhibitor. Furthermore, endothelium-denuded rings from either control or CH rats did not exhibit an increase in reactivity to PE following ZnPPIX incubation. ZnPPIX had no effect on relaxant responses to the NO donor S-nitroso- N-penicillamine, suggesting that its actions were specific to HO inhibition. Finally, aortic rings exhibited dose-dependent relaxant responses to exogenous CO that were endothelium independent and blocked by an inhibitor of soluble guanylyl cyclase. The other products of HO enzyme activity, iron and biliverdin, were without effect on vasoreactivity. Thus we conclude that the attenuated vasoreactivity to PE following CH is likely to involve the induction of endothelial HO and the subsequent enhanced production of CO.
Mechanism of suppressed neutrophil mobilization in a mouse model for binge drinking: role of glucocorticoids
Authors: Vinson Robert B. , Carroll Jennifer L. , Pruett Stephen B.
Published: December 2017

The goals of this study were to determine if suppression of neutrophil accumulation and TNF-α production in the peritoneal cavity occurs in mice exposed to a chemical stressor [ethanol (EtOH)], to evaluate the role of EtOH-induced increases in endogenous glucocorticoids in any such suppression, and to determine if decreased tumor necrosis factor-α (TNF-α) production is responsible for decreases in neutrophil accumulation in EtOH-treated mice. An inflammatory response induced in the peritoneal cavity of mice by administration of heat-killed Propionibacterium acnes ( P. acnes) was suppressed by a single dose of EtOH given 1 h before administration of the bacteria, as indicated by decreased accumulation of neutrophils in the peritoneal cavity. The concentration of TNF-α in the peritoneal cavity was also decreased by EtOH, but exogenous TNF-α did not prevent the suppression of neutrophil accumulation. The glucocorticoid antagonist RU-486 did not prevent the suppression of neutrophil accumulation in mice treated with EtOH, but RU-486 did block suppression of neutrophil accumulation caused by administration of exogenous corticosterone. The suppression of neutrophil accumulation caused by exogenous corticosterone was less than produced by EtOH. These observations suggest that the increase in endogenous corticosterone induced by EtOH may explain some of the suppression of neutrophil accumulation, but other neuroendocrine mediators (or EtOH per se) are sufficient to cause the full suppressive effect when the action of corticosterone is blocked by RU-486. The results also demonstrate that EtOH decreases TNF-α production, but this is not the mechanism by which neutrophil accumulation is decreased in this model.
Alteration of renal function of rats following spaceflight
Authors: Wade Charles E. , Morey-Holton Emily
Published: December 2017

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats (∼245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals ( n = 6), flight controls ( n = 6) housed in the flight cages on the ground, and vivarium controls ( n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.
Endothelins inhibit the mineralization of osteoblastic MC3T3-E1 cells through the A-type endothelin receptor
Authors: Hiruma Yoshiharu , Inoue Atsuto , Shiohama Aiko , Otsuka Eri , Hirose Shigehisa , Yamaguchi Akira , Hagiwara Hiromi
Published: December 2017

We examined the effects of various endothelins on the mineralization of mouse clonal preosteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed mRNAs for endothelin (ET)-1 and the A-type receptor for ET (ETA). A pharmacological study also demonstrated the predominant expression of the ETA receptor. Northern blotting analysis revealed that ETs decreased the expression of mRNA for osteocalcin, which is a marker protein for the maturation of osteoblastic cells. ET-1 also decreased in the deposition of calcium by MC3T3-E1 cells in a dose-dependent manner and it had an inhibitory effect even at 10−11 M. The rank order of potency of ETs was ET-1 = ET-2 > ET-3. Brief treatment with 10−7 M ET-1 on days 6– 8 alone suppressed mineralization. ET-1 enhanced the rate of production of inositol 1,4,5-trisphosphate (IP3) in MC3T3-E1 cells, but it had no effect on the rate of production of cAMP. Taken together, our data indicate that ET-1 might inhibit the mineralization of osteoblastic cells via an interaction with the ETA receptor, with generation of IP3 as the intracellular signal.
Dissimilarity of slow-wave activity enhancement by torpor and sleep deprivation in a hibernator
Authors: Strijkstra Arjen M. , Daan Serge
Published: December 2017

Sleep regulation processes have been hypothesized to be involved in function and timing of arousal episodes in hibernating ground squirrels. We investigated the importance of sleep regulation during arousal episodes by sleep deprivation experiments. After sleep deprivation of 4, 12, and 24 h, starting 4 h after onset of euthermy, a duration-dependent enhancement of slow-wave activity (SWA) of the cortical electroencephalogram during non-rapid eye movement sleep was found, as expected for normal sleep regulation. When sleep deprivation was applied during the initial phase of the arousal episode, in which effects of prior torpor were present in undisturbed recordings, no subsequent recurrence of SWA was found. In addition, prior torpor induced a reduction in the spectral activity of the sigma frequency range (7–14 Hz), which was not observed after sleep deprivation. The effects of torpor and sleep deprivation on subsequent SWA appear qualitatively different. This indicates that effects of deep torpor on sleep are dissimilar to normal sleep regulation.
Contrasting cardiovascular effects following central and peripheral injections of trout galanin in trout
Authors: Le Mével Jean-Claude , Mabin Dominique , Hanley Ann M. , Conlon J. Michael
Published: December 2017

Little is known about the role of galanin (Gal) in fish. In the present study, cardiovascular effects of central and peripheral administrations of a synthetic replicate of trout Gal (tGal) were investigated in the unanesthetized trout. Intracerebroventricular injection of 0.1, 0.5, 1.0, and 3.0 nmol/kg body mass of the peptide demonstrated that the two highest doses tested produced a significant ( P < 0.001) and equivalent increase in mean dorsal aortic blood pressure (PDA) without changing heart rate (HR). At a dose of 1.0 nmol/kg, the systemic vascular resistance ( Rs) increased, but no change was detected in cardiac output compared with that produced by intracerebroventricular injection of vehicle only. In contrast, intra-arterial injections of 0.1, 0.5, and 1.0 nmol/kg body mass of tGal produced a dose-dependent decrease in PDAwith a threshold dose for significant effects observed at a dose of 0.5 nmol/kg. None of the doses tested changed HR. At a dose of 1 nmol/kg, a significant decrease in Rs( P < 0.001) was the factor responsible for the fall in PDA. Intra-arterial injection of porcine Gal (1 nmol/kg) produced a change in PDAsimilar to that of the same dose of tGal, but HR increased slightly. Pretreatments of trout with the cyclooxygenase inhibitors indomethacin and meclofenamate did not inhibit the vasodepressor effects of tGal. However, after intra-arterial injection of NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase, the hypotensive action of Gal was reduced threefold, suggesting the possible involvement of the nitric oxide system in mediating the vasodilatory effect of Gal. In conclusion, our results have shown that tGal may have contrasting cardiovascular regulatory functions in trout depending on whether its site of action is the brain or the peripheral circulation.
Genetic variation in EEG activity during sleep in inbred mice
Authors: Franken Paul , Malafosse Alain , Tafti Mehdi
Published: December 2017

The genetic variation in spontaneous rhythmic electroencephalographic (EEG) activity was assessed by the quantitative analysis of the EEG in six inbred mice strains. Mean spectral EEG profiles (0–25 Hz) over 24 h were obtained for paradoxical sleep (PS), slow-wave sleep (SWS), and wakefulness. A highly significant genotype-specific variation was found for theta peak frequency during both PS and SWS, which strongly suggests the presence of a gene with a major effect. The strain distribution of theta peak frequency during exploratory behavior differed from that during sleep. In SWS, the relative contributions of delta (1–4 Hz) and sigma (11–15) power to the EEG varied with genotype and power in both frequency bands was negatively correlated. In addition, the EEG dynamics at state transitions were analyzed with a 4-s resolution. The onset of PS, but not that of wakefulness, was preceded by a pronounced peak in high-frequency (>11 Hz) power. These findings are discussed in terms of the neurophysiological mechanisms underlying rhythm generation and their control and modulation by the brain stem reticular-activating system.
Intracellular pH regulation in neurons from chemosensitive and nonchemosensitive areas of the medulla
Authors: Ritucci Nick A. , Chambers-Kersh Laura , Dean Jay B. , Putnam Robert W.
Published: December 2017

Intracellular pH (pHi) regulation was studied in neurons from two chemosensitive [nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM)] and two nonchemosensitive [hypoglossal (Hyp) and inferior olive (IO)] areas of the medulla oblongata. Intrinsic buffering power (βint) was the same in neurons from all regions (46 mM/pH U). Na+/H+exchange mediated recovery from acidification in all neurons [Ritucci, N. A., J. B. Dean, and R. W. Putnam. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol.42): R433–R441, 1997]. Cl−/[Formula: see text]exchange mediated recovery from alkalinization in VLM, Hyp, and IO neurons but was absent from most NTS neurons. The Na+/H+exchanger from NTS and VLM neurons was fully inhibited when extracellular pH (pHo) <7.0, whereas the exchanger from Hyp and IO neurons was fully inhibited only when pHo <6.7. The Cl−/[Formula: see text]exchanger from VLM, but not Hyp and IO neurons, was inhibited by pHo of 7.9. These pH regulatory properties resulted in steeper pHi-pHorelationships in neurons from chemosensitive regions compared with those from nonchemosensitive regions. These differences are consistent with a role for changes of pHi as the proximate signal in central chemoreception and changes of pHo in modulating pHi changes.
Differential catecholamine responses to protein intake in healthy and hypertensive subjects
Authors: Kuchel Otto
Published: December 2017

Protein intake-induced natriuresis previously related to increased urinary dopamine excretion was reexamined in an extensive controlled study comparing healthy and hypertensive subjects. In healthy subjects, ingestion of 1 g/kg wt tuna induced natriuresis that was associated, between postprandial hours 1 and 2, with increased plasma tyrosine [191 ± 13% (mean ± SE); P < 0.01], 3,4-dihydroxyphenylalanine (104 ± 12%, P < 0.05 in plasma; 162 ± 20%, P < 0.05 in urine), plasma free dopamine (156 ± 32%; P < 0.05), and dopamine sulfate (191 ± 11%, P < 0.001 in plasma; 199 ± 15%, P < 0.01 in urine) but affected urinary free dopamine excretion only at limits of significance. Hypertensive subjects had less ( P < 0.02) natriuresis and, despite comparable plasma tyrosine and dopamine sulfate increases, no increase in plasma and urinary 3,4-dihydroxyphenylalanine and plasma free dopamine. Their plasma and urinary free epinephrine responses were less ( P < 0.05) than the borderline increases in control subjects. Compared with control subjects, they significantly increased plasma 3,4-dihydroxyphenylalanine sulfate ( P < 0.05), epinephrine sulfate ( P < 0.05), and the dopamine sulfate-to-free dopamine ratio ( P < 0.02). Postprotein natriuresis is thus associated with nutritional priming-induced plasma but not urinary free dopamine increase. Hypertensive subjects have attenuated natriuretic and plasma free dopamine responses and less free epinephrine increase. This may partly result from higher circulating 3,4-dihydroxyphenylalanine, dopamine, and epinephrine sulfoconjugates leaving fewer free amines for biological actions.
Interleukin-4 inhibits spontaneous sleep in rabbits
Authors: Kushikata Tetsuya , Fang Jidong , Wang Ying , Krueger James M.
Published: December 2017

Proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α, are involved in sleep regulation. IL-4 is an antiinflammatory cytokine that inhibits proinflammatory cytokine production. The hypothesis that IL-4 should attenuate sleep was studied by determining the effects of IL-4 on rabbit spontaneous sleep. Thirty-six rabbits were used. Four doses of IL-4 (0.25, 2.5, 25, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-4 (25 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were done in the same rabbits on different days. The three highest doses of IL-4 significantly inhibited spontaneous non-rapid eye movement sleep if IL-4 was given during the light cycle. The highest dose of IL-4 (250 ng) also significantly decreased rapid eye movement sleep. On the other hand, IL-4 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-4 provide additional evidence for the hypothesis that a brain cytokine network is involved in the regulation of physiological sleep.
Effects of 17β-estradiol on sympathetic activity and pressor response to phenylephrine in ovariectomized rats
Authors: He Xiao-Rui , Wang Weihua , Crofton Joan T. , Share Leonard
Published: December 2017

The effects of 17β-estradiol (E2) on sympathetic activity were examined in conscious unrestrained ovariectomized rats, instrumented under methohexital anesthesia to record mean arterial pressure (MABP), heart rate (HR), renal nerve activity (RNA), and splanchnic nerve activity (SNA) 1 day before the experiment. Injection of E2 (150 μg/kg iv) caused reductions ( P < 0.01) in RNA (29 ± 6%), SNA (25 ± 2%), and HR (26 ± 5 beats/min) within 20 min, but MABP remained unchanged. Ninety minutes after intravenous injection of E2 or vehicle, intravenous infusion of phenylephrine (PE; 6.2 μg ⋅ min−1 ⋅ kg−1) induced similar increases in MABP and decreases in HR, RNA, and SNA in both groups. By contrast, in rats chronically treated with E2, the pressor response to PE was smaller ( P < 0.01; 22 ± 5 mmHg) than in vehicle-treated rats (40 ± 4 mmHg). The changes in HR, RNA, and SNA were similar in both groups, but the ratios of changes in HR and SNA to MABP, an index of baroreflex sensitivity, were greater in the E2-treated rats. These findings suggest that E2 can act centrally to modulate sympathetic function and thereby participate in cardiovascular regulation.
Heterogeneous neurochemical responses to different stressors: a test of Selye’s doctrine of nonspecificity
Authors: Pacak Karel , Palkovits Miklos , Yadid Gal , Kvetnansky Richard , Kopin Irwin J. , Goldstein David S.
Published: December 2017

Selye defined stress as the nonspecific response of the body to any demand. Stressors elicit both pituitary-adrenocortical and sympathoadrenomedullary responses. One can test Selye’s concept by comparing magnitudes of responses at different stress intensities and assuming that the magnitudes vary with stress intensity, with the prediction that, at different stress intensities, ratios of increments neuroendocrine responses should be the same. We measured arterial plasma ACTH, norepinephrine, and epinephrine in conscious rats after hemorrhage, intravenous insulin, subctaneous formaldehyde solution, cold, or immobilization. Relative to ACTH increments, cold evoked large norepinephrine responses, insulin large epinephrine responses, and hemorrhage small norepinephrine and epinephrine responses, whereas immobilization elicited large increases in levels of all three compounds. The ACTH response to 25% hemorrhage exceeded five times that to 10%, and the epinephrine response to 25% hemorrhage was two times that to 10%. The ACTH response to 4% formaldehyde solution was two times that to 1%, and the epinephrine response to 4% formaldehyde solution exceeded four times that to 1%. These results are inconsistent with Selye’s doctrine of nonspecificity and the existence of a unitary “stress syndrome,” and they are more consistent with the concept that each stressor has its own central neurochemical and peripheral neuroendocrine “signature.”
Role of small intestine in caloric compensations to oil premeals in rats
Authors: Meyer J. H. , Hlinka M. , Khatibi A. , Raybould H. E. , Tso P.
Published: December 2017

We postulated that dose-responsive satiety after oil premeals varies with the number of gut sensors stimulated by lipolytic products along intestine. These experiments in fasted rats on satiety after oil premeals were performed to 1) determine whether satiety was induced by lipolytic products but not triglycerides; 2) confirm that oil empties from the stomach at rates that vary with oil loads; 3) ascertain that increasing rates of oil entry into duodenum extend the length of gut contacted by lipolytic products; and 4) judge whether length of gut contacted correlated with dose-responsive satieties to dietary oils. 5) Using specific antagonists, we attempted to define how satiety was signalled by gut sensors. Timing and degrees of satiety did not correlate with timing and extent of gastric distensions but, rather, with the timing and extent of spread of lipolytic products along small bowel. Satiety after the highest premeal load of oil was blocked by Pluronic L-81, an inhibitor of intestinal secretion of apolipoprotein A-IV, but was unaffected by MK-329 (a specific antagonist of cholecystokinin) or by capsaicin blockade of chemosensory nerves.
Spinal and peripheral mechanisms contributing to hyperactive voiding in spontaneously hypertensive rats
Authors: Persson Katarina , Pandita Raj K. , Spitsbergen John M. , Steers William D. , Tuttle Jeremy B. , Andersson Karl-Erik
Published: December 2017

The influence of noradrenergic mechanisms involved in micturition in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was investigated using continuous cystometry in in vivo and in vitro studies on isolated bladder and urethral tissues. Compared with WKY rats, SHR had a significantly lower bladder capacity (SHR: 0.7 ± 0.05 ml; WKY rats: 1.3 ± 0.06 ml; P < 0.001), micturition volume (SHR: 0.4 ± 0.04 ml, WKY rats: 1.2 ± 0.05 ml; P < 0.001), and an increased amplitude of nonvoiding (unstable) bladder contractions. The effects of intrathecal and intra-arterial doxazosin on cystometric parameters were more pronounced in SHR than in WKY rats. There was a marked reduction in nonvoiding contractions after intrathecal (but not intra-arterial) doxazosin in SHR. Norepinephrine (0.1 μM–1 mM) failed to evoke contractions in bladder strips from WKY rats, in contrast to a weak contractile response in SHR. The response to electrical field stimulation was significantly less in bladder strips from SHR than from WKY rats. In WKY rats, norepinephrine produced concentration-dependent inhibition (87 ± 5%, n = 6) of nerve-evoked bladder contractions. Almost no inhibition (11 ± 8%, n = 6) was found in SHR. Alterations in bladder function of SHR appear to be associated with changes in the noradrenergic control of the micturition reflex, in addition to an increased smooth muscle and decreased neuronal responsiveness to norepinephrine. The marked reduction in nonvoiding contractions after intrathecal doxazosin suggests that the bladder hyperactivity in SHR has at least part of its origin in supraspinal and/or spinal structures.
Role of nitric oxide in systemic vasopressin-induced hypothermia
Authors: Steiner Alexandre A. , Carnio Evelin C. , Antunes-Rodrigues José , Branco Luiz G. S.
Published: December 2017

It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or N G-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 ± 0.08°C. We observed a significant ( P < 0.05) reduction in Tb to 35.44 ± 0.19°C after intravenous injection of AVP (2 μg/kg) and to 35.74 ± 0.10°C after intravenous injection ofl-NAME (30 mg/kg). The systemic injection of the AVP blocker [β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Et-Tyr2,Val4,Arg8]vasopressin (10 μg/kg) caused a significant increase in Tb to 37.33 ± 0.23°C, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and l-NAME were combined, systemically injected l-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose ofl-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection ofl-NAME caused an increase in Tb, but when intracerebroventricular l-NAME was combined with systemic AVP injection (2 μg/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.
Effects of costimulation of dopamine D1- and D2-like receptors on renal function
Authors: Jose Pedro A. , Asico Laureano D. , Eisner Gilbert M. , Pocchiari Felice , Semeraro Claudio , Felder Robin A.
Published: December 2017

In vitro studies have suggested that dopamine D1- and D2-like receptors interact to inhibit renal sodium transport. We used Z-1046, a dopamine receptor agonist with the rank-order potency D3≥ D4> D2> D5> D1, to test the hypothesis that D1- and D2-like receptors interact to inhibit renal sodium transport in vivo in anesthetized rats. Increasing doses of Z-1046, administered via the right renal artery, increased renal blood flow (RBF), urine flow, and absolute and fractional sodium excretion without affecting glomerular filtration rate. For determination of the dopamine receptor involved in the renal functional effects of Z-1046, another group of rats received Z-1046 at 2 μg ⋅ kg−1⋅ min−1( n = 10) in the presence or absence of the D2-like receptor antagonist domperidone and/or the D1-like antagonist SCH-23390. Domperidone alone had no effect but blocked the Z-1046-mediated increase in urine flow and sodium excretion; it enhanced the increase in RBF after Z-1046. SCH-23390 by itself decreased urine flow and sodium excretion without affecting RBF and blocked the diuretic, natriuretic, and renal vasodilatory effect of Z-1046. We conclude that the renal vasodilatory effect of Z-1046 is D1-like receptor dependent, whereas the diuretic and natriuretic effects are both D1- and D2-like receptor dependent.
Cholecystokinin actions in the parabrachial nucleus: effects on thirst and salt appetite
Authors: Menani Jose Vanderlei , Johnson Alan Kim
Published: December 2017

The present study investigated the effects of bilateral injections of the nonselective CCK receptor antagonist proglumide or CCK-8 into the lateral parabrachial nuclei (LPBN) on the ingestion of 0.3 M NaCl and water induced by intracerebroventricular injection of ANG II or by a combined treatment with subcutaneous furosemide (Furo) + captopril (Cap). Compared with the injection of saline (vehicle), bilateral LPBN injections of proglumide (50 μg ⋅ 200 nl−1⋅ site−1) increased the intake of 0.3 M NaCl induced by intracerebroventricular ANG II (50 ng/1 μl). Bilateral injections of proglumide into the LPBN also increased ANG II-induced water intake when NaCl was simultaneously available, but not when only water was present. Similarly, the ingestion of 0.3 M NaCl and water induced by the treatment with Furo (10 mg/kg) + Cap (5 mg/kg) was increased by bilateral LPBN proglumide pretreatment. Bilateral CCK-8 (0.5 μg ⋅ 200 nl−1⋅ site−1) injections into the LPBN did not change Furo + Cap-induced 0.3 M NaCl intake but reduced water consumption. When only water was available after intracerebroventricular ANG II, bilateral LPBN injections of proglumide or CCK-8 had no effect or significantly reduced water intake compared with LPBN vehicle-treated rats. Taken together, these results suggest that CCK actions in the LPBN play a modulatory role on the control of NaCl and water intake induced by experimental treatments that induce hypovolemia and/or hypotension or that mimic those states.
Heritability of treadmill running endurance in rats
Authors: Koch Lauren Gerard , Meredith Todd A. , Fraker Teigen D. , Metting Patricia J. , Britton Steven Loyal
Published: December 2017

Treadmill running was evaluated as a phenotype for selective breeding for high- and low-endurance performance from a starting population of 18 male and 24 female outbred Sprague-Dawley rats. Each rat was exercised to exhaustion once per day for 5 consecutive days. The treadmill was set at a constant 15° slope, and the initial velocity of 10 m/min was increased by 1 m/min every 2 min. The total distance run on the single best day out of the five trials was taken as the measure of endurance performance. The original population (males and females combined, n = 42) ran on average for 396 m. The two lowest-performing pairs and two highest-performing pairs were selectively bred through three successive generations. After three generations of selection, performance of the offspring from the high selected line averaged 659 ± 36 m ( n = 20), whereas low-performance offspring ( n = 13) averaged 388 ± 28 m. The narrow-sense heritability, calculated as the regression of individual offspring performance on midparental value for each family, was 0.39 across the three generations. This implies that 39% of the variation in running endurance performance between the low and high selected lines was determined by heritable factors.
Membrane and tissue distribution of folate binding protein in pig
Authors: Villanueva Jesus , Ling Erh-Hsin , Chandler Carol J. , Halsted Charles H.
Published: December 2017

Folate binding protein may participate in folate homeostasis by regulating monoglutamyl folate transport across relevant cell membranes. We compared the activity, immunoreactivity, and transcripts of folate binding protein in pig liver, kidney, and jejunal mucosa and their relevant cell membranes. Binding of [3H]folic acid was sixfold greater to pig liver plasma membranes than to kidney brush-border membranes, whereas there was no binding to jejunal brush-border membranes. The IgG fraction of rabbit antibody detected pig recombinant folate binding protein at 30 kDa and stained pig liver plasma membranes and kidney brush-border membranes but did not react with jejunal brush-border membranes. Folate binding protein transcripts were present in threefold greater abundance in pig liver than in kidney. Species comparisons showed folate binding protein transcripts in rat and human kidney but not in liver. Thus folate binding protein participates in folate homeostasis by regulating uptake by renal tubular membranes and uniquely by pig liver plasma membranes, but it is not involved in jejunal folate absorption.