bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of kinin release in isolated rat hindquarters
Authors: Sakakibara Tohru , Hintze Thomas H. , Nasjletti Alberto
Published: December 2017

We studied the determinants of kinin release into the venous effluent of rat hindquarters perfused with Krebs bicarbonate buffer. Kinin release in preparations perfused with control media (14.6 ± 2.5–20.7 ± 6.7 pg/15 min) was surpassed by that in preparations perfused with media containing kininase inhibitors (243 ± 53 to 276 ± 78 pg/15 min). Kinin release increased when purified kininogen (from 242 ± 43 to 3,365 ± 725 pg/15 min) or kallikrein (from 270 ± 49 to 30,649 ± 8,040 pg/15 min) was added to the perfusate. Conversely, kinin release fell when the kallikrein inhibitor aprotinin (from 272 ± 58 to 122 ± 27 pg/15 min) or soybean trypsin inhibitor (from 273 ± 52 to 195 ± 25 pg/15 min) was added. Both basal and kininogen-induced kinin release were attenuated in preparations perfused with media containing cycloheximide, a protein synthesis inhibitor, but kallikrein-induced kinin release was not. These data suggest that kinin release from perfused rat hindquarters reflects the activity of both the kinin-degrading and kinin-generating pathways and that the latter is sustained by a kallikrein manufactured de novo and by preexistent kininogen(s).
The proinflammatory cytokine network: interactions in the CNS and blood of rhesus monkeys
Authors: Reyes Teresa M. , Coe Christopher L.
Published: December 2017

Proinflammatory cytokines [interleukin (IL)-1 and -6 and tumor necrosis factor-α] function within a complex network, stimulating the release of one another, as well as other cytokine agonists and antagonists. These interactions have not been as widely studied in vivo. Therefore, the following studies measured cytokines in blood and cerebrospinal fluid (CSF) from juvenile rhesus monkeys after intravenous administration of cytokines. IL-1α and IL-1β were equally effective in elevating blood levels of IL-6. In contrast, IL-1β was the only cytokine that significantly elevated IL-6 levels in the CSF. Interestingly, both IL-1 and IL-6 increased levels of IL-1 receptor antagonist in the blood and comparably stimulated the release of cortisol. A second study confirmed that the IL-1-induced IL-6 in CSF was brain derived and not a result of diffusion from blood. This research extends studies of the cytokine cascade to the central nervous system (CNS), highlighting the brain response to peripheral activation.
Cafeteria diet-induced sleep is blocked by subdiaphragmatic vagotomy in rats
Authors: Hansen Michael K. , Kapás Levente , Fang Jidong , Krueger James M.
Published: December 2017

Feeding rats a cafeteria diet results in increased food intake and excess sleep. Furthermore, vagal afferent activity is altered by a variety of gastrointestinal factors, and vagal stimulation can induce sleep. We investigated, therefore, the hypothesis that the vagal nerve plays a critical role in mediating the sleep-inducing effects of cafeteria feeding. We examined the effects of a cafeteria diet on sleep, electroencephalographic (EEG) slow-wave activity (SWA), and brain temperature (Tbr) in control and vagotomized rats. EEG, electromyogram, and Tbrwere recorded for 7 consecutive days. Day 1 was considered a baseline day; normal rat chow was available ad libitum. On days 2- 4, the animals were fed, in addition to normal chow, a mixed, energy-rich diet (cafeteria diet). On days 5- 7, the rats were again fed only normal rat chow. In control rats, the cafeteria diet resulted in an increase in non-rapid eye movement sleep (NREMS), which was the result of a significant lengthening of the NREMS episodes. In contrast, feeding vagotomized rats the cafeteria diet resulted in a decrease in NREMS. Cafeteria feeding decreased REMS and EEG SWA and increased Tbrin both control and vagotomized rats. These results suggest that an intact vagus plays a key role in the NREMS-inducing effects of the cafeteria diet.
CO2asphyxia increases plasma norepinephrine in rats via sympathetic nerves
Authors: Borovsky Vicky , Herman Mike , Dunphy Gail , Caplea Ann , Ely Daniel
Published: December 2017

The objective of this study was to determine whether the plasma norepinephrine (NE) increase in rats exposed to CO2asphyxia was due to adrenal gland release or sympathetic nerve ending (SNS) release. Plasma NE was measured by high-performance liquid chromatography in hypertensive and normotensive rats using the following protocol: control session, CO2exposure, N2exposure, reserpine + CO2, and adrenalectomy + CO2. Four strains of male and female rats were used: spontaneously hypertensive rats, Wistar-Kyoto rats, and two congenic strains with different Y chromosomes. The same rats were used throughout the experiment ( n = 80). Blood pressure measured by aortic telemetry increased ∼50–60 mmHg in response to CO2in all strains. CO2increased NE 6–10× in all strains and both genders. N2produced a significant increase in NE (73% of CO2response). Reserpine significantly decreased (67%) plasma NE after CO2. Adrenalectomy did not significantly reduce the NE response to CO2. In conclusion, the increase in plasma NE after CO2was associated with SNS release and not adrenal medullary release, was mainly due to hypoxia, and was not a specific response to CO2.
Calcium intake by rats: influence of parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D
Authors: Tordoff Michael G. , Hughes Rebecca L. , Pilchak Diane M.
Published: December 2017

We examined the contribution of the primary hormones of calcium homeostasis to the control of calcium intake in the rat. Male Sprague-Dawley rats with 50 mM CaCl2 solution as their only source of calcium received subcutaneous hormone infusions for 13 days. Parathyroid hormone (PTH; 40, 80, or 160 ng/h) produced sustained dose-related decreases in CaCl2intake. High doses of calcitonin (CT; 32 or 64 ng/h) increased CaCl2 intake transiently, and low doses (4, 8, or 16 ng/h) had no effect. 1,25-Dihydroxyvitamin D [1,25(OH)2D] in doses >1 ng/h initially increased CaCl2 intake, but the effects of moderate doses (2 or 4 ng/h) tended to dissipate, and the sustained effect of high doses (8 or 16 ng/h) was to reduce CaCl2 intake. Infusions of combinations of the hormones had effects consistent with their individual actions: there was no evidence for synergy. Based on changes in plasma hormone concentrations, it appeared that most of the infusions had effects within the physiological range. Consistent with hypotheses that calcium appetite is mediated by circulating calcium, PTH and CT infusions produced reciprocal changes in plasma calcium concentrations and CaCl2 intake. However, the finding that 1,25(OH)2D elevated both plasma calcium concentrations and CaCl2intake raises the possibility that one or more of the hormones may mediate calcium appetite directly.
Mesolimbic expression of neurotensin and neurotensin receptor during stress-induced gastric mucosal injury
Authors: Xing Lianping , Karinch Anne M. , Kauffman Gordon L.
Published: December 2017

Neurotensin is a neurotransmitter present in the brain and gastrointestinal tract. Intracerebroventricular injection of neurotensin protects rats from gastric mucosal injury caused by cold water restraint (CWR). Direct injection of neurotensin into the nucleus accumbens (NACB), part of the mesolimbic dopamine system, reduces gastric mucosal injury, suggesting that neurotensin confers protection on the mucosa through interaction with the mesolimbic system. The hypothesis is that the concentration of neurotensin in the mesolimbic system decreases during CWR, affecting the expression of neurotensin and the neurotensin receptor. After 1 h of CWR, neurotensin concentration significantly decreased 41% in the NACB and returned toward control concentrations after 2 h of CWR. The concentration of neurotensin mRNA significantly decreased 46% after 1 h CWR and returned toward control after 2 h. In contrast, neurotensin binding sites in the NACB increased from 159 to 228 fmol/mg protein after 1 h of CWR and increased significantly to 280 fmol/mg protein after 2 h CWR, whereas the level of neurotensin receptor mRNA significantly decreased 51 and 50% at 1 and 2 h, respectively. These studies show that neurotensin concentration within the mesolimbic system is transiently reduced by CWR stress and that the number of neurotensin binding sites increases, presumably in response to the decrease in neurotensin.
Influences of melatonin administration on the circulation of women
Authors: Cagnacci Angelo , Arangino Serenella , Angiolucci Marco , Maschio Elisabetta , Melis Gian Benedetto
Published: December 2017

The cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared with those of placebo in 17 young, healthy, early follicular-phase women. Compared with placebo, the administration of melatonin modified, within 90 min, the pulsatility index (PI), evaluated by color Doppler ultrasound, of the internal carotid artery, abdominal aorta, and axillary artery. The effect was linearly related to baseline PI, higher baseline PI being associated with greater PI declines. Melatonin administration significantly decreased mean PI of internal carotid artery ( P < 0.02), systolic and diastolic blood pressure ( P < 0.01), and norepinephrine levels evaluated after 5 min of standing position ( P < 0.02). Heart rate and supine catecholamine levels were not modified. These data indicate that in young, healthy women the administration of 1 mg of melatonin greatly influences artery blood flow, decreases blood pressure, and blunts noradrenergic activation. Clinical implications of present data are worthy to be fully explored.
Vagotomy attenuates but does not prevent the somnogenic and febrile effects of lipopolysaccharide in rats
Authors: Kapás Levente , Hansen Michael K. , Chang Hee-Yoon , Krueger James M.
Published: December 2017

The role of the vagus nerve in the somnogenic and pyrogenic effects of lipopolysaccharide (LPS) was studied in rats. Control rats ( n= 8) and rats subjected to bilateral subdiaphragmal vagotomy (VX; n = 9) were injected with 100 μg/kg ip LPS at the beginning of the dark period. Sleep and brain temperature (Tbr) were recorded for 23 h after the injections. LPS caused increases in non-rapid eye movement sleep (NREMS) for 12 h after the injection in control rats. Sleep intensity, as indicated by the slow-wave activity (SWA) of the electroencephalogram during NREMS, was suppressed. LPS elicited biphasic Tbr responses: an initial hypothermia was followed by increases in Tbr that lasted for ∼20 h. In vagotomized rats, the NREMS responses to LPS were blunted. The magnitude of the LPS-induced NREMS increases was about one-half of that seen in control rats, and these sleep responses lasted only for 6 h. LPS did not affect SWA in VX animals. VX completely abolished the hypothermic responses to LPS and shortened the duration of the hyperthermia. The results suggest that the subdiaphragmal vagi play an important, but not exclusive, role in the somnogenic and pyrogenic actions of intraperitoneally injected LPS.
Electroneutral Na+/H+exchange in brush-border membrane vesicles fromPenaeus japonicushepatopancreas
Authors: Vilella Sebastiano , Zonno Vincenzo , Ingrosso Laura , Verri Tiziano , Storelli Carlo
Published: December 2017

An electroneutral Na+/H+exchange mechanism (dimethylamiloride inhibitable, Li+sensitive, and Ca2+insensitive) was identified in brush-border membrane vesicles (BBMV) from Kuruma prawn hepatopancreas by monitoring Na+-dependent H+fluxes with the pH-sensitive dye acridine orange and measuring22Na+uptake. Kinetic parameters measured under short-circuited conditions were the Na+concentration that yielded one-half of the maximal dissipation rate ( Fmax) of the preset transmembrane ΔpH ( KNa) = 15 ± 2 mM and Fmax= 3,626 ± 197 Δ F ⋅ min−1⋅ mg protein−1, with a Hill coefficient for Na+of ∼1. In addition, the inhibitory constant for dimethylamiloride was found to be ∼1 μM. The electroneutral nature of the antiporter was assessed in that an inside-negative transmembrane electrical potential neither affected kinetic parameters nor stimulated pH-dependent (intracellular pH > extracellular pH)22Na+uptake. In contrast, electrogenic pH-dependent22Na+uptake was observed in lobster hepatopancreatic BBMV. Substitution of chloride with gluconate resulted in increasing KNaand decreasing Δ Fmax, which suggests a possible role of chloride in the operational mechanism of the antiporter. These results indicate that a Na+/H+exchanger, resembling the electroneutral Na+/H+antiporter model, is present in hepatopancreatic BBMV from the Kuruma prawn Penaeus japonicus.
Acute exercise and gender alter cardiac autonomic tonus differently in hypertensive and normotensive rats
Authors: Chandler Margaret P. , Dicarlo Stephen E.
Published: December 2017

Arterial pressure (AP), heart rate (HR), cardiac sympathetic tonus (ST), and parasympathetic tonus (PT) were determined in spontaneously hypertensive rats (SHR, 8 male and 8 female) and Wistar-Kyoto normotensive rats (WKY, 8 male and 12 female) before and after acute exercise. Before exercise, hypertensive rats (regardless of gender) had an increased ST (+15 beats/min), increased resting HR (+12 beats/min), and decreased PT (−11 beats/min). Similarly, female rats (regardless of strain) also had an increased ST (+15 beats/min), increased resting HR (+39 beats/min), and decreased PT (−14 beats/min). Hypertensive rats had a significant reduction in AP (−17 ± 3 mmHg), ST (−26 beats/min), PT (−7 beats/min), and HR (−14 beats/min) after exercise. In contrast, AP was not reduced in normotensive rats and ST (+18 beats/min) and HR (+42 beats/min) were increased in female normotensive rats after exercise. However, male normotensive rats had a postexercise reduction in ST (−14 beats/min) and HR (−19 beats/min). In summary, AP, ST, and resting HR were higher whereas PT was lower in hypertensive vs. normotensive rats. Furthermore, females had a higher resting HR, intrinsic HR, and ST and lower PT than male rats. These data demonstrate that gender and the resting level of AP influence cardiac autonomic regulation.
Increased cytosolic free Mg2+and Ca2+in platelets of patients with vasospastic angina
Authors: Yoshimura Mitsuisa , Oshima Tetsuya , Hiraga Hiroyuki , Nakano Yukiko , Matsuura Hideo , Yamagata Togo , Shiode Nobuo , Kato Masaya , Kambe Masayuki , Kajiyama Goro
Published: December 2017

This study was designed to test the hypothesis that the cellular metabolism of Ca2+and Mg2+, which is important in platelet function, is abnormal in the platelets of patients with vasospastic angina. Cytosolic free Mg2+concentration ([Mg2+]i) and Ca2+handling were determined in the platelets of 24 patients with vasospastic angina and 24 control subjects by use of mag-fura 2 and fura 2. Platelet aggregation was also examined. Basal [Mg2+]iand cytosolic free Ca2+concentration ([Ca2+]i) in platelets were significantly higher in patients with vasospastic angina than in control subjects. The amplitude of the [Ca2+]itransient induced by thrombin (0.03–1.0 U/ml) was significantly increased in the presence, but not in the absence, of extracellular Ca2+in patients with vasospastic angina, as compared with controls. Therefore, the influx of Ca2+across the plasma membrane may be accelerated in vasospastic angina. Thrombin (0.1–1.0 U/ml)-induced maximum aggregation response was significantly greater in patients with vasospastic angina than in controls. Results suggest that increased [Mg2+]iand altered Ca2+handling by platelets may be associated with coronary vasospasm.
Elevation of brain 5-HT activity, POMC expression, and plasma cortisol in socially subordinate rainbow trout
Authors: Winberg Svante , Lepage Olivier
Published: December 2017

Agonistic behavior, brain concentrations of serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA, the main 5-HT metabolite), plasma cortisol levels, and the pituitary expression of pro-opiomelanocortin (POMC) A and B mRNA were determined in socially dominant and subordinate rainbow trout after 1 or 7 days of social interaction. Telencephalic and brain stem 5-HIAA/5-HT ratios, plasma cortisol levels, and pituitary POMC mRNA concentrations were elevated in fish being subordinate for 1 day. Furthermore, neither telencephalic 5-HIAA/5-HT ratios nor pituitary POMC A or POMC B mRNA expression showed any decline after 7 days of social interaction. By contrast, plasma cortisol concentrations of subordinate fish declined after 7 days but were still significantly higher than in dominant fish. Furthermore, in subordinate fish, hypothalamic 5-HIAA/5-HT ratios and plasma cortisol levels were highly correlated, suggesting an important role of hypothalamic 5-HT in the regulation of the teleost hypothalamic-pituitary-interrenal (HPI) axis. The number of aggressive acts received and plasma cortisol levels were highly correlated in 1-day subordinates, a relationship not seen in fish subjected to 1 wk of subordination. Thus the chronic stress experienced by subordinates in established dominance hierarchies appears to be more closely related to the threat imposed by the presence of the dominant fish than to actual aggressive encounters. The sustained elevation of pituitary POMC mRNA expression, an effect mainly related to an increase of melanotropic POMC expression, in subordinates could be a mechanism serving to maintain HPI axis excitability and promote acclimation in these individuals.
Circadian rhythms in diving behavior and ventilatory response to asphyxia in canvasback ducks
Authors: Woodin Melanie , Stephenson Richard
Published: December 2017

Underwater feeding behavior was measured in 10 captive canvasback ducks ( Aythya valisineria) for 12 days under a 12:12-h light-dark photoperiod. Feeding activity exhibited a daily rhythm, with 76% of dives occurring at night. In separate experiments on six of these ducks, a circadian rhythm was observed in the duration of voluntary dives. Dives at night (14.7 ± 0.7 s) were significantly longer than those during the day (10.7 ± 0.7 s). These day-night differences in diving behavior were accompanied by day-night differences in respiratory responses to progressive asphyxia. In the same six ducks, ventilation increased exponentially as a function of inspired CO2concentration during rebreathing in a closed-circuit barometric plethysmograph. The exponential rate constant for inspired ventilation was significantly smaller at night (0.23 ± 0.02) than during the day (0.26 ± 0.01). We suggest that intermittent apneic exercise is facilitated by reduced respiratory chemosensitivity and that the respiratory and behavioral control systems are synchronized by the circadian timing system in diving ducks.
Respiratory, metabolic, and acid-base correlates of aerobic metabolic rate reduction in overwintering frogs
Authors: Donohoe Paul H. , West Timothy G. , Boutilier Robert G.
Published: December 2017

Aerobic metabolic rates (M˙o2) and respiratory quotients (RQ = CO2production/M˙o2) were measured contemporaneously in hibernating frogs Rana temporaria (L.), submerged for 90 days at 3°C. After 3 mo of submergence in fully aerated water,M˙o2levels were 61% of those seen at the same temperature before hibernation. Over the first 40 days of hibernation, RQ values (≤0.82) favored a lipid-based metabolism that progressively shifted to an exclusively carbohydrate metabolism (RQ = 1.01) by 90 days of hibernation. Liver glycogen concentrations fell by 68% during the first 8 wk of submergence, thereafter exhibiting a less rapid rate of utilization. Conversely, muscle glycogen concentrations remained stable over the first 2 mo of the experiment before falling by 33% over the course of the remaining 2 mo, indicating that the frog was recruiting muscle glycogen reserves to fuel metabolism. Submerged frogs exhibited an extracellular acidosis during the first week of submergence, but over the course of the next 15 wk “extracellular pH” values were not significantly different from the values obtained from the control air-breathing animals. The initial extracellular acidosis was not mirrored in the intracellular compartment, and the acid-base state was not significantly different from the control values for the first 8 wk. However, over the subsequent 8- to 16-wk period, the acid-base status shifted to a lower intracellular pH-[Formula: see text] concentration set point, indicative of a metabolic acidosis. Even so, there was no indication that the acidosis could be attributed to anaerobic metabolism, as both plasma and muscle lactate levels remained low and stable. Muscle adenylate energy charge and lactate-to-pyruvate and creatine-to-phosphocreatine ratios also remained unchanged throughout hibernation. The capacity for profound metabolic rate suppression together with the ability to match substrate use to shifts in aerobic metabolic demands and the ability to fix new acid-base homeostatic set points are highly adaptive, both in terms of survival and reproductive success, to an animal that is often forced to overwinter under the cover of ice.
Brain type I but not type II IL-1 receptors mediate the effects of IL-1β on behavior in mice
Authors: Cremona Sandrine , Goujon Emmanuelle , Kelley Keith W. , Dantzer Robert , Parnet Patricia
Published: December 2017

In the immune system, interleukin (IL)-1β effects are mediated by the type I IL-1 receptors (IL-1RI), whereas the type II IL-1 receptors (IL-1RII) act as inhibitory receptors. IL-1RI and IL-1RII are also present in the brain. To study their functionality in the brain, mice were centrally treated with neutralizing monoclonal antibody (MAb) directed against IL-1RI (35F5, 1 μg) or against IL-1RII (4E2, 2 μg) and were centrally injected with recombinant rat IL-1β at a dose (2 ng) that decreased social exploration. Only 35F5 was effective in abrogating the behavioral effect of IL-1β. Moreover, 4E2 (1 μg icv) did not potentiate the behavioral response to a subthreshold dose of IL-1β (1 ng icv). To examine the ability of brain IL-1RI to mediate the effects of endogenous IL-1β, mice were centrally treated with 35F5 (4 μg) and peripherally injected with IL-1β (1 μg). Like IL-1 receptor antagonist (4 μg icv), 35F5 abrogated the effects of IL-1β. These results suggest that brain IL-1RI mediates the behavioral effects of IL-1β in mice.
Estradiol phase shifts circannual body mass rhythms of male ground squirrels
Authors: Hiebert Sara M. , Lee Theresa M. , Licht Paul , Zucker Irving
Published: December 2017

Gonadectomized male golden-mantled ground squirrels ( Spermophilus lateralis) were implanted with estradiol benzoate (EB)-filled or empty capsules. Body mass was monitored before, during, and for at least 1 yr after hormone treatment. EB treatment during the mass-gain phase of the annual cycle significantly decelerated increases in body mass; the period of the circannual rhythm (CAR) of body mass was 54 days longer in EB- than blank-treated squirrels. Hormone treatment during the mass-loss phase accelerated mass loss; although this effect only approached statistical significance, some phase markers of the CAR were significantly advanced in subsequent cycles. We conclude that, as in females, estradiol affects the waveform of the CAR of males differently at different phases of the circannual cycle. Sexual differentiation does not eliminate responsiveness of CARs of squirrels to estradiol; sex differences, if any, are subtle rather than absolute and, in this respect, differ from circadian rhythms.
Thyroid hormone-induced upregulation of Na+channels and Na+-K+pumps: implications for contractility
Authors: Harrison A. P. , Clausen T.
Published: December 2017

We have previously observed in rat soleus muscle that endurance is a function of the ratio between the concentration of Na+channels and Na+-K+pumps [Harrison, A. P., O. B. Nielsen, and T. Clausen. Am. J. Physiol. 272 ( Regulatory Integrative Comp. Physiol.41): R1402–R1408, 1997]. In this study we explore this relationship further by comparing the changes in Na+channel and Na+-K+pump concentrations induced by injections of 3,5,3′-triiodothyronine (T3) with endurance. T3induced upregulation of the concentration of Na+channels and Na+-K+pumps, which was associated with a progressive loss of contractile endurance. The increase in Na+channels preceded that of the Na+-K+pumps and amounted to 49 and 52% (both P < 0.01) after 48 and 72 h of T3treatment, respectively. Concomitantly, during 90-Hz stimulation, the initial rate of force decline increased by 42 and 45% after 48 and 72 h of T3treatment, respectively (both P < 0.001). These observations are important for an understanding of the fatigue associated with hyperthyroidism and add further support to the hypothesis that muscle endurance depends on the leak-to-pump ratio for Na+.
Seasonality and role of SCN in entrainment of lizard circadian rhythms to daily melatonin injections
Authors: Bertolucci Cristiano , Foà Augusto
Published: December 2017

To establish whether the capability of daily melatonin injections to entrain circadian rhythms varies with season, we examined in constant conditions the locomotor behavior of lizards Podarcis sicula collected and subjected to daily melatonin injections at different times of the year. Although in summer locomotor rhythms of both pineal-intact and pinealectomized lizards became entrained to the 24-h injection period, in the other seasons their rhythms did not entrain to the injection period. To establish whether the suprachiasmatic nuclei (SCN) mediate summer entrainment of locomotor rhythms to melatonin, we examined the behavioral effects of daily melatonin injections in lizards subjected to either bilateral (SCN-X) or unilateral (USCN-X) ablation of the SCN. SCN-X lizards became behaviorally arrhythmic, and daily melatonin injections did not restore rhythmicity. USCN-X lizards remained rhythmic, and their locomotor rhythms did entrain to the injections. Besides demonstrating for the first time in a vertebrate that daily melatonin injections are capable of entraining circadian rhythmicity in only one season (summer), the present results support the view that the SCN (and not the pineal gland) are the primary target sites of melatonin in the circadian system of P. sicula.
Contribution of α2-adrenoceptors in caudal ventrolateral medulla to cardiovascular regulation in rat
Authors: Sesoko Shogo , Muratani Hiromi , Yamazato Masanobu , Teruya Hiroshi , Takishita Shuichi , Fukiyama Koshiro
Published: December 2017

The inhibitory action of α2-agonists on the cardiovascular neurons has been elucidated in the rostral ventrolateral medulla (RVLM) but not in the caudal ventrolateral medulla (CVLM). Our study aimed to clarify whether microinjection of clonidine into the CVLM elicits any cardiovascular effect and whether endogenous α2-adrenoceptor-mediated mechanisms contribute to the tonic activity of the CVLM neurons. In male Sprague-Dawley rats (7–9 wk old, 270–320 g) anesthetized with urethan, unilateral microinjection of 8 nmol of clonidine into the CVLM ( n = 10) increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) by 12.1 ± 1.8 mmHg (mean ± SE, P < 0.01) and 25.8 ± 4.8% ( P < 0.01), while heart rate (HR) remained unaltered. Unilateral microinjection of 2 nmol of SKF-86466, a selective blocker of the α2-adrenoceptors, into the CVLM ( n = 10) decreased MAP, HR, and RSNA (−11.6 ± 2.6 mmHg, −26 ± 7 beats/min, and −15.3 ± 1.7%, respectively, P < 0.01 for each). Artificial cerebrospinal fluid caused neither a cardiovascular effect nor a sympathetic response. Prior injection of SKF-86466 into the ipsilateral CVLM attenuated the effects of clonidine. Bilateral microinjection of muscimol into the RVLM abolished the effects of both clonidine and SKF-86466 injected into the CVLM. The pressor and sympathoexcitatory effects of clonidine injected into the CVLM suggest a neuroinhibitory action of the drug on the CVLM neurons. In addition,the depressor and sympathoinhibitory effects of SKF-86466 injected into the CVLM indicated that activation of α2-adrenoceptors by endogenous ligand inhibits CVLM neurons. The effects of clonidine and the α2-adrenoceptor antagonist in the CVLM require the integrity of the RVLM.
Selective REM sleep deprivation in humans: effects on sleep and sleep EEG
Authors: Endo Takuro , Roth Corinne , Landolt Hans-Peter , Werth Esther , Aeschbach Daniel , Achermann Peter , Borbély Alexander A.
Published: December 2017

To investigate rapid eye movement (REM) sleep regulation, eight healthy young men were deprived of REM sleep for three consecutive nights. In a three-night control sleep deprivation (CD) session 2 wk later, the subjects were repeatedly awakened from non-REM sleep in an attempt to match the awakenings during the REM sleep deprivation (RD) nights. During the RD nights the number of sleep interruptions required to prevent REM sleep increased within and across consecutive nights. REM sleep was reduced to 9.2% of baseline (CD nights: 80.7%) and rose to 140.1% in the first recovery night. RD gave rise to changes in the EEG power spectra of REM sleep. Power in the 8.25- to 11-Hz range was reduced in the first recovery night, an effect that gradually subsided but was still present in the third recovery night. The rising REM sleep propensity, as reflected by the increase of interventions within and across RD nights, and the moderate REM sleep rebound during recovery can be accounted for by a compensatory response that serves REM sleep homeostasis. The changes in the electroencephalogram power spectra, which were observed during enhanced REM sleep propensity, may be a sign of an altered quality of REM sleep.
Catecholaminergic regulation of venous function in the rainbow trout
Authors: Zhang Yutong , Weaver Leroy , Ibeawuchi Andrew , Olson Kenneth R.
Published: December 2017

The significance of the sympathetic nervous system (SNS) in regulating peripheral vascular resistance and cardiac function in fish has been well established, whereas its effect on venous function in vivo is unknown. Two protocols were employed in the present study to evaluate SNS effects on the venous system in intact, unanesthetized trout. In the first, trout were instrumented with pressure cannulas in the ventral (PVA) and dorsal (PDA) aortas and ductus Cuvier (PVEN), and cardiac output (CO) was measured with a flow probe around the ventral aorta. Heart rate, stroke volume, and gill and systemic resistances were calculated from the measured parameters. In the second group, vascular capacitance curves were obtained by monitoring mean circulatory filling pressure (PVEN) during transient interruption of CO and while blood volume was adjusted between 80 and 120% of normal. Unstressed blood volume (USBV) and vascular compliance (C) were derived from the capacitance curves. Infusion of epinephrine (Epi; 3.3 nmol ⋅ min−1⋅ kg body wt−1) increased PVA, PDA, and PVEN, whereas norepinephrine (NE) infusion (3.3 nmol ⋅ min−1⋅ kg body wt−1) increased PVAand PDAbut did not affect PVEN. Epi (1.0 nmol ⋅ min−1⋅ kg body wt−1), but not NE (2.6 or 10.4 nmol ⋅ min−1⋅ kg body wt−1), displaced the capacitance curve to the right and significantly decreased USBV. Inhibition of α1-adrenoceptors with prazosin, or ganglionic nicotinic receptor blockade with hexamethonium, produced a left shift in the capacitance curve, and both treatments increased USBV and C. Conversely, the α-adrenoceptor antagonist phentolamine did not effect vascular capacitance. These results show that Epi has potent effects on trout veins in vivo and that it mobilizes blood from the unstressed into the stressed vascular compartment and augments central venous pressure by decreasing venous compliance. These results also show that the SNS is an active effector of venous tone and compliance in trout; this is the first demonstration of tonic regulation of vascular capacitance in any fish.
Effects of increased fat availability on fat-carbohydrate interaction during prolonged exercise in men
Authors: Odland L. Maureen , Heigenhauser George J. F. , Wong Denis , Hollidge-Horvat Melanie G. , Spriet Lawrence L.
Published: December 2017

The study examined the existence and regulation of fat-carbohydrate interaction during low- and moderate-intensity exercise. Eight males cycled for 10 min at 40% and 60 min at 65% maximal O2uptake (V˙o2 max) while infused with either Intralipid and heparin (Int) or saline (Con). Before exercise, plasma arterial free fatty acid (FFA) was 0.69 ± 0.04 mM (Int) vs. 0.25 ± 0.04 mM (Con). Muscle biopsies were taken at rest and at 10, 20, and 70 min of exercise. Arterial and femoral venous blood samples and expired gases were collected simultaneously throughout exercise, and blood flow was estimated from pulmonary O2uptake and the leg arterial-venous O2difference. Respiratory exchange ratio was higher in Con (0.94 ± 0.01) compared with Int (0.91 ± 0.01). Mean net leg FFA uptake was higher in Int (0.16 ± 0.03 vs. 0.04 ± 0.01 mmol/min), and net lactate efflux was reduced (Int, 1.55 ± 0.36 vs. Con, 3.07 ± 0.47 mmol/min). Leg net glucose uptake was unaffected by Int. Muscle glycogen degradation was 23% lower in Int [230 ± 29 vs. 297 ± 36 mmol glucosyl units/kg dry muscle (dm)]. Pyruvate dehydrogenase activity in the a form (PDH a) was lower during Int (1.61 ± 0.17 vs. 2.22 ± 0.24 mmol ⋅ min−1⋅ kg wet muscle−1), and muscle citrate was higher (0.59 ± 0.04 vs. 0.48 ± 0.04 mmol/kg dm). Muscle lactate, phosphocreatine, ATP, acetyl-CoA, acetyl-carnitine, and Piwere unaffected by Int. Calculated free AMP was significantly lower in Int compared with Con at 70 min of exercise (3.3 ± 0.8 vs. 1.5 ± 0.3 μmol/kg dm). The high FFA-induced reduction in glycogenolysis and carbohydrate oxidation at 65% V˙o2 maxappears to be due to regulation at several sites. The reduced flux through phosphorylase and phosphofructokinase during Int may have been due to reduced free AMP accumulation and increased cytoplasmic citrate. The mechanism for reduced PDH transformation to the a form is unknown but suggests reduced flux through PDH.
Neurosteroid modulation of arterial baroreflexsensitive neurons in rat rostral ventrolateral medulla
Authors: Laiprasert J. D. , Rogers R. C. , Heesch C. M.
Published: December 2017

The major metabolite of progesterone, 3α-OH-dihydroprogesterone (3α-OH-DHP), is the most potent endogenous positive modulator of central nervous system GABAA receptors. Acute intravenous administration of 3α-OH-DHP to virgin female rats potentiates arterial baroreflex sympathoinhibitory responses. The current experiments tested the possibility that circulating 3α-OH-DHP potentiates central GABAergic influences in the rostral ventrolateral medulla (RVLM). The unit activity of spontaneously active, spinally projecting, and arterial pressure-sensitive neurons was recorded in the RVLM of urethan-anesthetized rats. Arterial pressure sensitivity of RVLM neurons was tested before (control) and 10 min after bolus injection (44 μl iv) of 3α-OH-DHP (1.12 μg/kg, n = 19) or vehicle (40% β-cyclodextrin, n = 8). Both threshold pressure and saturation pressure for inhibition of RVLM neurons were decreased after acute administration of a physiological dose of 3α-OH-DHP (1.12 μg/kg iv), which produces plasma concentrations similar to those seen during pregnancy (20–30 ng/ml), suggesting potentiated responsiveness to endogenously released GABA. Following suppression by 3α-OH-DHP, high doses of the inactive stereoisomer 3β-OH-DHP (112–224 μg/kg iv; n = 8) restored unit activity, presumably by displacing 3α-OH-DHP from the neurosteroid binding site on GABAA receptors.
Contribution of hypercapnia and trigeminal stimulation to cerebrovascular dilation during simulated diving
Authors: Ollenberger G. P. , West N. H.
Published: December 2017

We investigated the relative contribution of humoral (carbon dioxide) and neural (trigeminal stimulation) inputs in the cerebrovasodilatory response to simulated diving in the rat. The cerebral hemodynamic profile of rats was determined using the brain blood flow tracer N-[14C]isopropyl- p-iodoamphetamine. During a simulated dive response, cerebral vascular resistance (CVR) decreased 63.1%, resulting in a 1.5-fold increase in cerebral blood flow (CBF). To investigate the contribution of hypercapnia to the decrease in CVR during simulated diving, we measured CBF during simulated diving in rats with preexisting hypocapnia. To investigate the contribution of trigeminal input, we measured CBF during periods of trigeminal stimulation alone with continued ventilation. Preexisting hypocapnia abolished the cerebrovasodilatory response to simulated diving. Trigeminal stimulation alone did not produce a significant increase in CBF from control values in any brain region, suggesting that trigeminal input does not contribute to the cerebrovascular response to simulated diving in rats. These results suggest that the cerebrovasodilatory response observed during diving in small mammals is driven primarily by progressive hypercapnia associated with asphyxia.
Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists
Authors: Ni Xi-Ping , Kesterson Robert A. , Sharma Shubh D. , Hruby Victor J. , Cone Roger D. , Wiedemann Eckehart , Humphreys Michael H.
Published: December 2017

γ-Melanocyte-stimulating hormone (γ-MSH), atrial natriuretic peptide (ANP), and oxytocin have been identified as candidate hormonal mediators of the reflex natriuresis that follows acute unilateral nephrectomy (AUN). Pharmacological characterization of the third melanocortin receptor (MC3-R) indicates that it uniquely responds to physiological concentrations of γ-MSH. We tested the roles of γ-MSH, ANP, and oxytocin in the postnephrectomy natriuresis by carrying out AUN during continuous intrarenal infusion of specific antagonists for their cognate receptors. In anesthetized Sprague-Dawley rats, urinary sodium excretion (UNaV) increased from 0.34 ± 0.04 to 1.12 ± 0.11 μeq/min 90 min after AUN ( P < 0.001). No change in UNaV occurred in rats undergoing a sham AUN procedure. Plasma immunoreactive γ-MSH concentration was 53 ± 8 fmol/ml after sham AUN but 112 ± 17 fmol/ml after AUN ( P < 0.01). SHU-9119 and SHU-9005 are substituted derivatives of α-MSH with potent antagonism at the MC3-R in vitro. Infusion of these compounds at 5 pmol/min completely blocked the natriuretic response to AUN despite a similar elevation in plasma γ-MSH (111 ± 12 vs. 49 ± 8 fmol/ml in sham rats, P < 0.01). Intrarenal infusion of the ANP receptor antagonist A-71915 (5 pmol/min) or the oxytocin receptor antagonist [d(CH2)51, Tyr(Me)2,Orn8] vasotocin (10 pmol/min) effectively inhibited the natriuresis induced by intravenous infusion of ANP or oxytocin (each at 1 pmol/min), respectively, but did not block the natriuresis after AUN. Plasma immunoreactivity of these peptides was not increased after AUN. These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma γ-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R. The data indicate that γ-MSH or a closely related peptide mediates postnephrectomy natriuresis and provide further support for the possibility that γ-MSH may play a wider role in sodium homeostasis.
Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis
Authors: Lang Charles H. , Fan Jie , Wojnar Margaret M. , Vary Thomas C. , Cooney Robert
Published: December 2017

Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1β alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1β can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL-1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1β (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28–36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1β. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30–35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1β is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.
Hemodynamic effect of 17β-estradiol in absence of NO in ovariectomized rats: role of angiotensin II
Authors: Hernández Isabel , Delgado Juan L. , Carbonell Luis F. , Pérez M. Carmen , Quesada Tomas
Published: December 2017

Previous reports correlate plasma levels of estrogen with increased nitric oxide (NO) production. To investigate whether the hemodynamic effects of estrogens are mediated by NO, we compared the hemodynamic changes induced by 17β-estradiol (100 μg/kg) in the absence and presence of the NO synthesis inhibitor N ω-nitro-l-arginine methyl ester (l-NAME). All protocols were performed in ovariectomized, conscious rats. Estradiol alone resulted in no significant changes in cardiac index (CI) or mean arterial pressure (MAP). However, in the presence ofl-NAME, estradiol induced a significant increase in total peripheral resistance (TPR) of 37.3 ± 11.7% and a decrease in CI of 27 ± 4.9%, without changes in MAP. Previous blockade of angiotensin II AT1 receptors with losartan prevented any change in CI and TPR induced by 17β-estradiol in the presence of l-NAME. These observations suggest that NO is necessary to offset a vasoconstrictor action of angiotensin II, which is stimulated by estradiol administration.
Nonphotic entrainment of the human circadian pacemaker
Authors: Klerman Elizabeth B. , Rimmer David W. , Dijk Derk-Jan , Kronauer Richard E. , Rizzo Joseph F. , Czeisler Charles A.
Published: December 2017

In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals “free run” even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.
Lateral parabrachial nucleus modulates baroreflex regulation of sympathetic nerve activity
Authors: Hayward Linda F. , Felder Robert B.
Published: December 2017

Previous studies have demonstrated that the lateral parabrachial nucleus (LPBN) is an important site for descending modulation of baroreflex control of heart rate. In the present study it was hypothesized that the LPBN neurons may also modulate baroreflex control of arterial pressure and sympathetic nerve activity. In urethan-anesthetized rats, electrical or chemical activation of the LPBN produced a significant reduction in the magnitude of the baroreflex inhibition of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) elicited by aortic depressor nerve stimulation. Chemical inactivation of the LPBN resulted in a small increase in baroreflex control of MAP, but baroreflex control of RSNA was not affected. The results suggest that LPBN neurons have little tonic influence over baroreflex control of MAP and RSNA in the anesthetized rat. When the LPBN is activated, however, LPBN neurons may function to reduce the capacity of the baroreflex to regulate sympathetically mediated increases in arterial pressure.
Acclimation to humid heat lowers resting core temperature
Authors: Buono Michael J. , Heaney Jay H. , Canine Katherine M.
Published: December 2017

The purpose of this study was to test the hypothesis that a reduction in resting rectal temperature (Tre) is partially responsible for the attenuation in the rise of core temperature during heat exposure following acclimation to humid heat. Nine male volunteers completed 7 days of acclimation, performing 2 h of exercise per day in a hot, humid environment (35°C, 75% relative humidity). Mean (±SD) ending Tre significantly ( P < 0.05) decreased from 38.9 ± 0.5°C on day 1 to 38.3 ± 0.4°C on day 7. Likewise, mean (±SD) resting Tre significantly ( P < 0.05) decreased from 37.0 ± 0.3 to 36.7 ± 0.4°C. In fact, all nine men showed a decrease in resting Tre from day 1to day 7, ranging from −0.1 to −0.5°C. In addition, resting Tre and ending Tre were significantly correlated ( r = 0.68). However, the mean increases in Tre (ending Tre minus resting Tre) and heat storage that occurred on each of the 7 acclimation days were not significantly different. These results support the hypothesis that a reduction in resting Tre is partially responsible for the attenuation in ending Tre during heat exposure following short-term acclimation to humid heat.