bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of hexose uptake by the small and large intestine of the chicken
Authors: Amat C. , Planas J. M. , Moreto M.
Published: December 2017

The kinetic parameters of hexose uptake by the small and large intestine of the chicken have been determined in vitro. Rates of initial influx of alpha-methyl-D-glucoside and L-glucose were measured in everted sleeves of the duodenum, jejunum, ileum, proximal cecum, and rectum. Results show the following. 1) Maximal transport capacity values for alpha-methyl-D-glucoside show that the jejunum is the segment that is best suited for Na(+)-mediated uptake. 2) The calculated apparent Michaelis constant values were (in mmol/l) 11.6 for duodenum, 7.8 for jejunum, 3.5 for ileum, 2.4 for proximal cecum, and 7.1 for rectum. This suggests that, with the exception of the rectum, the affinity of the carrier for alpha-methyl-D-glucoside progressively increases in the distal direction. 3) Diffusion constant values indicate that influx of hexoses by a passive mechanism in the duodenum and proximal cecum is significantly higher than in the other segments. 4) The sum of passive and mediated mechanisms confers to the duodenum and jejunum a high capacity to absorb hexoses. The ileum, proximal cecum, and rectum have a quantitatively minor role, albeit significant, in completing the absorptive function.
Renin-angiotensin system modulates renal bradykinin production
Authors: Siragy H. M. , Jaffa A. A. , Margolius H. S. , Carey R. M.
Published: December 2017

Previous studies have shown that sodium depletion is associated with an increase in renal kallikrein-kinin system activity. This system may play an important role in counterbalancing the renal effects of the renin-angiotensin system. In this study, we examined whether the renal renin-angiotensin system participates in the regulation of renal bradykinin (BK) levels during sodium depletion. We measured changes in renal excretory and hemodynamic function, renal interstitial fluid (RIF) BK, and RIF and urinary guanosine 3',5'-cyclic monophosphate (cGMP) and prostaglandin E2 (PGE2) in conscious uninephrectomized dogs (n = 5) in sodium metabolic balance (10 meq/day) in response to intrarenal arterial administration of the renin inhibitor ACRIP (0.2 microgram.kg-1.min-1) or angiotensin II AT1-receptor blocker losartan (100 ng.kg-1.min-1). ACRIP and losartan increased urine flow rate from 0.75 +/- 0.06 to 1.6 +/- 0.03 and 1.5 +/- 0.05 ml/min, respectively (each P < 0.001), and urine sodium excretion from 5.4 +/- 0.7 to 18.3 +/- 1.3 and 15.9 +/- 1.2 meq/min, respectively (each P < 0.001). Glomerular filtration rate and renal plasma flow increased only during losartan administration (P < 0.05). ACRIP decreased RIF BK by 48%, from 33.1 +/- 3.8 to 17.4 +/- 4.1 pg/min (P < 0.01). ACRIP decreased RIF cGMP by 38%, from 0.69 +/- 0.08 to 0.43 +/- 0.1 pmol/min (P < 0.01); urinary cGMP by 16%, from 0.63 +/- 0.05 to 0.53 +/- 0.02 pmol/min (P < 0.05); and RIF PGE2 by 46%, from 10.5 +/- 1.1 to 5.7 +/- 1.1 pg/min (P < 0.01). Urinary PGE2 was unchanged by ACRIP. Losartan decreased RIF PGE2 by 71%, from 10.8 +/- 0.6 to 3.1 +/- 0.6 pg/min (P < 0.01) but failed to change RIF BK, RIF cGMP, urinary cGMP, or urinary PGE2. These data suggest that the renin-angiotensin system tonically stimulates renal BK production and cGMP formation via a non-AT1 angiotensin receptor and renal PGE2 production via the AT1 receptor.
VIP decelerates non-REM-REM cycles and modulates hormone secretion during sleep in men
Authors: Murck H. , Guldner J. , Colla-Muller M. , Frieboes R. M. , Schier T. , Wiedemann K. , Holsboer F. , Steiger A.
Published: December 2017

Centrally administered vasoactive intestinal polypeptide (VIP) promotes rapid eye movement (REM) sleep in rats, rabbits, and cats. We studied the effect of 4 x 10 micrograms VIP (expt 1, n = 7) and 4 x 50 micrograms VIP (expt 2, n = 10) administered hourly as intravenous boluses between 2200 and 0100 on sleep electroencephalogram and secretion of plasma adreno corticotropic hormone, cortisol, growth hormone, and prolactin in humans. In experiment 2, the sleep cycles were decelerated during the first three cycles because of increased duration of both REM and non-REM sleep periods, and there was a tendency to increased REM-to-non-REM ratios. With a low VIP dose, prolactin levels were decreased during the whole night, whereas, with a high dose, they were increased during the first half of the night. In experiment 2, the cortisol nadir was advanced, after midnight the serum cortisol levels were enhanced, and the growth hormone peak was blunted. It appears that VIP may have a phase-advancing effect on sleep cycles and cortisol secretion, possibly through actions that involve the suprachiasmatic nucleus.
Chronic central nervous system exposure to interleukin-1 beta causes catabolism in the rat
Authors: Hill A. G. , Jacobson L. , Gonzalez J. , Rounds J. , Majzoub J. A. , Wilmore D. W.
Published: December 2017

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play a role in mediating weight loss, net protein catabolism, anorexia, and fever after infection or injury. Because IL-1 and IL-6 can be synthesized in the brain and have been shown to be increased in central nervous system (CNS) infections, we investigated the metabolic consequences of prolonged CNS exposure to these cytokines. At equivalent doses, intracerebroventricular infusion of IL-1, but not IL-6, caused negative nitrogen balance, weight loss, and anorexia. Intracerebroventricular infusion of IL-1 also caused adrenocortical activation, as indicated by increased adrenal weight and plasma corticosterone, and decreased thymus weight. However, clamping plasma glucocorticoids at low levels by adrenalectomy and corticosterone pellet replacement did not attenuate IL-1-induced losses of body weight and nitrogen. We conclude that centrally produced IL-1 could play an important role in the metabolic alterations associated with CNS injury or infection and that these effects may not be solely attributable to increased secretion of glucocorticoids.
Thyrotropin-releasing hormone stimulates perinatal rat respiration in vitro
Authors: Greer J. J. , al-Zubaidy Z. , Carter J. E.
Published: December 2017

In the present study, we test whether thyrotropin-releasing hormone (TRH) stimulates respiratory frequency in perinatal rats by acting at regions of the medulla responsible for respiratory rhythmogenesis, the pre-Botzinger complex. We also test whether TRH stimulates respiration in the fetal rat at a time shortly after the inception of respiratory rhythmogenesis [embryonic days (E) 17-18]. Two in vitro experimental models were utilized: the isolated brain stem-spinal cord preparation from fetal (E17-E18) and neonatal [postnatal days (P) 0-2] rats and the medullary slice preparation isolated from neonatal rats (P1-P2). Bath application of TRH caused a dose-dependent, reversible increase (maximum increase approximately 60%) in the frequency of respiratory rhythmic neural discharge generated by brain stem-spinal cord [half-maximal effective concentration (EC50) approximately 9 nM] and medullary slice (EC50 approximately 2.5 nM) neonatal rat preparations. Pressure injection of TRH unilaterally into the region of the pre-Botzinger complex of the neonatal medullary slice caused an approximately 28% increase in the frequency of respiratory discharge. Application of TRH to the medium bathing fetal rat brain stem-spinal cord preparations caused an approximately threefold increase in respiratory discharge frequency. We conclude that TRH stimulates respiratory discharge frequency from the time near inception of respiratory motor discharge and acts directly at the pre-Botzinger complex.
Angiotensin II and bladder obstruction in the rat: influence on hypertrophic growth and contractility
Authors: Persson K. , Pandita R. K. , Waldeck K. , Andersson K. E.
Published: December 2017

The mechanisms and mediators of hypertrophic growth secondary to infravesical urinary outflow obstruction are unknown. The renin-angiotensin system has been implicated in vascular and cardiac hypertrophy, but the involvement of angiotensin II (ANG II) as a trophic factor in the lower urinary tract has not been investigated. In this study, the ANG II subtype AT1 receptor antagonist losartan (DuP 753) was administered perorally (15 mg.kg-1.day-1) for 28 days to rats subjected to partial urethral obstruction or sham surgery. Partial urethral obstruction caused a 3.5-fold increase in bladder weight and a 3-fold increase in bladder protein content compared with sham rats. However, no difference was observed in bladder weight or bladder protein content between losartan-treated rats and rats receiving no drug. Cystometric evaluation of bladder function revealed significant increases in micturition volume, bladder capacity, bladder compliance, and spontaneous contractile activity in rats subjected to partial urethral obstruction compared with sham rats. However, bladder function in rats treated with losartan was not different from bladder function in rats receiving no drug. In vitro studies of isolated bladder tissue showed a weak contractile response to ANG II (1 microM) that amounted to 4.4 +/- 1.0% of the response to K+ (124 mM). The ANG II-induced contraction was abolished by losartan (10 microM) and indomethacin (10 microM). The contractile response to ANG II (1 microM), K+ (124 mM), and transmural nerve stimulation (2 Hz) was reduced in bladder strips from obstructed rats. In conclusion, no evidence was found for involvement of ANG II in development of bladder hypertrophy. The effect of ANG II on bladder smooth muscle tone was minor but was mediated by stimulation of the AT1 subtype receptor.
Role of excitatory amino acid receptors in cardiorespiratory coupling in ventrolateral medulla
Authors: Miyawaki T. , Minson J. , Arnolda L. , Chalmers J. , Llewellyn-Smith I. , Pilowsky P.
Published: December 2017

The role of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-kainate and N-methyl-D-aspartate (NMDA) receptors in the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) on the central respiratory drive (CRD)-related activity of splanchnic sympathetic nerve activity (SNA) was examined in rats. SNA increased during inspiration (I peak) and postinspiration (PI peak). Bilateral microinjections of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; AMPA-kainate antagonist) or DL-2-amino-5-phosphonovaleric acid (APV; NMDA antagonist) into RVLM abolished the PI, but not the I, peak. Blockade of all excitatory amino acid receptors in RVLM with kynurenate, or mixtures of APV and CNQX, also failed to eliminate the I peak. Somatosympathetic responses were abolished by CNQX injection into RVLM, but were unaffected by APV. CNQX, but not APV, injection into CVLM increased the PI peak of SNA. Our findings suggest the following. 1) Both NMDA and AMPA-kainate receptors in RVLM are involved in the coupling between the sympathetic nervous system and CRD, which generates the PI peak seen in SNA. 2) The I peak of SNA is independent of excitatory amino acid transmission within RVLM. 3) There are different relative amounts of NMDA and AMPA-kainate receptors at synapses where respiratory and somatic inputs converge onto RVLM neurons. 4) Glutamatergic inputs to CVLM neurons modulate the coupling between SNA and CRD in RVLM.
Influence of elevated muscle temperature on metabolism during intense, dynamic exercise
Authors: Febbraio M. A. , Carey M. F. , Snow R. J. , Stathis C. G. , Hargreaves M.
Published: December 2017

This study examined the effects of elevated muscle temperature on muscle metabolism during exercise. Seven active but untrained men completed two cycle ergometer trials for 2 min at a workload estimated to require 115% maximal oxygen uptake (VO2) either without pretreatment (CT) or after having their thigh wrapped in a heating blanket for 60 min before exercise (HT). HT increased (P < 0.01) muscle temperature (Tm) and resulted in a difference in Tm between the two trials before (delta = 1.9 +/- 0.1 degrees C, P < 0.01) and after exercise (delta = 0.6 +/- 0.2 degree C, P < 0.05). HT did not affect rectal temperature or plasma catecholamines. In addition, these parameters were not different between CT and HT either before or after exercise. No differences in resting intramuscular concentrations of the adenine nucleotides (ATP, ADP, AMP) or their degradation products (inosine 5'-monophosphate, ammonia), lactate, glycogen, creatine phosphate, or creatine were observed between HT and CT. During exercise, the magnitude of ATP degradation and inosine 5'-monophosphate and ammonia accumulation was higher (P < 0.05) in HT compared with CT. Although preexercise concentrations of glycogen and lactate were not different between the two trials, postexercise lactate concentration was higher (P < 0.05) and glycogen lower (P < 0.05) in HT compared with CT. In addition, net muscle glycogen use was higher (P < 0.05) in HT. It is concluded that an elevated Tm per se increases muscle glycogenolysis, glycolysis, and high-energy phosphate degradation during exercise. These alterations may be the result of an increased rate of ATP turnover associated with the exercise and/or changes in the anaerobic/aerobic contribution to ATP resynthesis.
Enhanced thermogenesis during recovery from diet-induced weight gain in the rat
Authors: Almeida N. G. , Levitsky D. A. , Strupp B.
Published: December 2017

The present study examined the contribution of energy expenditure to the recovery of body weight after a period of overfeeding. Three groups of 2-mo-old female rats (n = 24) were fed, respectively, a 10% (wt/wt)-fat diet (control), a 35% (wt/wt)-fat diet (high fat) or were force fed 130% of the control diet (tube fed). After 30 days, all groups received the control diet for 18 days of recovery. Both overfeeding protocols significantly increased weight above control levels. This difference disappeared after 7 days of recovery. Increases in resting oxygen consumption, serum 3,5,3'-triiodothyronine (T3) levels, and the thermogenic response to norepinephrine were observed at the end of overfeeding. Serum T3 and resting oxygen consumption returned to control levels by day 3 of recovery from overfeeding, whereas the thermogenic response to norepinephrine required 9 days to recover. Whereas total energy expenditure was not significantly elevated during overfeeding, significant increases of 9.6 and 13.9% were observed in the formerly high-fat and tube-fed animals, respectively, during recovery. These data indicate that changes in energy expenditure play an important role in maintaining the stability of body weight.
Functional response to graded increases in renal nerve activity during hypoxia in conscious rabbits
Authors: Malpas S. C. , Shweta A. , Anderson W. P. , Head G. A.
Published: December 2017

Changes in renal sympathetic nerve activity (SNA) are postulated to influence renal function in selective ways, such that different levels of activation produce particular renal responses, initially in renin release, then sodium excretion, with changes in renal hemodynamics occurring only with much greater stimulus intensities. The aim of this study was to determine the renal hemodynamic and excretory responses to graded physiological increases in renal SNA induced by breathing different hypoxic gas mixtures. Experiments were performed in seven conscious rabbits subjected to four gas mixtures (14% O2, 10% O2, 10% O2 + 3% CO2, and 10% O2 + 5% CO2) and instrumented for recording of renal nerve activity. After a 30-min control period, rabbits were subjected to one of the four gas mixtures for 30 min, and then room air was resumed for a further 30 min. The four gas mixtures increased renal SNA by 14, 38, 49, and 165% respectively, but arterial pressure (thus renal perfusion pressure) was not altered by any of the gas mixtures. The greatest level of sympathetic activation produced significant falls in glomerular filtration rate (GFR), renal blood flow, sodium and fluid excretion, and significant increases in plasma renin activity. These returned to levels not significantly different from control conditions in the 30-min period after the gas mixture. When the changes to the various gas mixtures were analyzed within each rabbit, a significant linear relationship was found with all variables to the increase in SNA. Renal denervation in a separate group of seven rabbits completely abolished all of the above responses to the different gas mixtures. Thus graded activation of renal nerves induced by changes in inspired gas mixtures resulted in graded decreases in renal blood flow, GFR, and sodium excretion and graded increases in renin activity, with the changes occurring across a similar range of nerve activities; there was no evidence for a selective change in any renal variable.
Measurement of tissue volume during non-steady state high-intensity muscle contraction
Authors: Ward D. S. , Hamilton M. T. , Watson P. D.
Published: December 2017

To investigate the pressures driving water into stimulated muscle, water distribution during and after muscle stimulation was studied in isolated cat muscles perfused by recirculating diluted blood. 51Cr-labeled EDTA (51Cr-EDTA) and Evans blue-labeled albumin were used to determine extracellular volume and plasma volume (PV), respectively. Change in tissue volume was calculated as -PV. Interstitial volume (IFV) was determined from the ratio of interstitial solute (51Cr-EDTA and sodium) mass and interstitial concentration. Interstitial mass was determined by mass balance, and interstitial concentration was determined from solute flux and Fick's Law. One group was stimulated at 4 Hz for 2 min, and a second was stimulated by 80-Hz trains (1 train/s, 0.1 s duration). Four Hertz stimulation increased total tissue volume by approximately 3 ml/100 g and decreased IFV by 1 ml/100 g. Train stimulation increased total tissue volume by 6 ml/100 g and decreased IFV by 4. These data indicate that water moves into cells faster than the simultaneous transcapillary flow, suggesting that intracellular osmoles provide the primary driving pressure in stimulation-induced swelling.
Upregulation of endothelial and neuronal constitutive nitric oxide synthase in pregnant rats
Authors: Xu D. L. , Martin P. Y. , St John J. , Tsai P. , Summer S. N. , Ohara M. , Kim J. K. , Schrier R. W.
Published: December 2017

Pregnancy is characterized by hemodynamic and body fluid alterations. Increased nitric oxide (NO) production has been suggested to play a role in the hemodynamic alterations of pregnancy and has also been reported to increase arginine vasopressin (AVP) release. We therefore hypothesized that gestation could increase both NO synthase (NOS) constitutive isoforms, neuronal NOS and endothelial NOS, and thereby contribute to the hyposmolality and peripheral arterial vasodilation of pregnancy, respectively. The present study was therefore undertaken to examine the constitutive NOS isoforms in aortas, mesenteric arteries, and hypothalami of pregnant rats on day 20 of gestation compared with age-matched nonpregnant rats. Plasma AVP was determined by radioimmunoassay and hypothalamic mRNA AVP by solution hybridization assay. Hypothalamic neuronal NOS was assessed by Northern blot and Western blot; endothelial NOS was assessed by Western blot in arteries and hypothalamus. The results demonstrated that 1) plasma AVP and hypothalamic AVP mRNA are increased in pregnant rats (n = 8), 2) neuronal NOS protein and mRNA are increased in hypothalamus of pregnant rats (n = 4), and 3) endothelial NOS expression, as assessed by Western blot analysis, is increased in both conductance (aorta) as well as resistance (mesenteric) arteries of pregnant rats (n = 4). We conclude that both of the constitutive NOS isoforms are increased in pregnant rats, suggesting that the peripheral arterial vasodilation and hyposmolality of pregnancy could be mediated by these isoforms.
Cardiac hypertrophy and telemetered blood pressure 6 wk after baroreceptor denervation in normotensive rats
Authors: Van Vliet B. N. , Hu L. , Scott T. , Chafe L. , Montani J. P.
Published: December 2017

We investigated cardiac morphometry 6 wk after sinoaortic baroreceptor denervation (SAD) in Long-Evans rats. SAD (n = 19) was associated with an 11% increase in the weight of the left ventricle (LV) plus septum (P < 0.001) and a 39% increase in that of the right ventricular (RV) free wall (P < 0.001), relative to sham-operated rats (n = 18). RV wall thickness was significantly increased in SAD animals, but there was no difference in the LV wall thickness and volumes of the RV and LV between groups. Constrictor responses to methoxamine and dilation responses to acetylcholine were assessed in an in vitro perfused mesenteric circulation preparation, but neither response was affected by SAD. Baroreceptor denervation was associated with marked and significant increases in the variability (2.8-fold) and daily peak (39 mmHg) levels of telemetered mean arterial pressure (MAP) and small (5%) but significant increases in the daily mean MAP level. Our results are consistent with an effect of increased MAP variability on ventricular weight but cannot rule out possible contributions from other mechanisms.
Potassium-induced aldosterone secretion involves a Cl(-)-dependent mechanism
Authors: Wang W. , Schneider E. G.
Published: December 2017

Stimulation of aldosterone secretion by increases in extracellular potassium concentration is associated with increases in the volume of the adrenal glomerulosa cell. Because increases in cell volume have been associated with increases in aldosterone secretion, the effect of preventing the potassium-induced increase in cell volume by removal of chloride from the medium on the response of dispersed bovine glomerulosa cells grown in primary culture was determined. Totally replacing the chloride ion with the methylsulfate ion prevented the increase in cell volume and significantly suppressed the increase in aldosterone secretion normally associated with increasing [K] to 10 mM. In the absence of Cl-, the increase in cytosolic calcium concentration ([Ca2+]c) normally induced by increasing the [K] to 10 mM was also significantly suppressed. The replacement of 10 mM methylsulfate by Cl- restored the potassium-induced increase in both cell volume and aldosterone secretion to values not different from those found in the presence of 108 mM Cl-. The potassium-induced increase in cell volume was dependent also on the presence of extracellular calcium. Thus a component of the glomerulosa cell response to an increase in [K] may be caused by a chloride-dependent increase in cell volume that is triggered by the initial depolarization-induced increase in [Ca2+]c. The increase in cell volume enhances the increase in [Ca2+]c and amplifies the increase in aldosterone secretion.
Osmoregulation of the magnocellular neuroendocrine system during lactation
Authors: Summy-Long J. Y. , Gestl S. , Terrell M. L. , Wolz G. , Kadekaro M.
Published: December 2017

Glucose utilization and Fos expression were used to compare responses of cerebral structures involved in osmoregulation in virgin and lactating rats given 0.15, 0.85, or 1.5 M NaCl subcutaneously. In virgin animals, glucose utilization increased (P < 0.05) in the supraoptic nuclei (SON), paraventricular nuclei (PVN), and neural lobe (NL) proportionally to the osmotic stimulus (0.15 M NaCl < 0.85 M NaCl < 1.5 M NaCl), whereas metabolism in the median preoptic nucleus (MPO) and median eminence (ME) increased only after 1.5 M NaCl. In lactating rats, enhanced utilization of glucose in response to osmotic stimulation was absent in the PVN (0.85 M NaCl), MPO, and ME or significantly (P < 0.01) reduced (SON, PVN, NL) compared with virgin animals. Glucose utilization in each structure correlated linearly with plasma osmolality but with a lower slope (P < 0.05) in lactating animals. Magnocellular neurons expressing Fos in the SON increased linearly with plasma osmolality and were more numerous (P < 0.05) in control lactating animals but increased less (P < 0.05) than in virgin rats after 0.85 M NaCl. The attenuated magnocellular response during lactation results from reduced afferent activation from osmosensitive forebrain sites.
Pituitary and adrenals are required for hyperglycemic reflex initiated by stimulation of CBR with cyanide
Authors: Alvarez-Buylla R. , Alvarez-Buylla E. , Mendoza H. , Montero S. A. , Alvarez-Buylla A.
Published: December 2017

We have previously shown that stimulation of carotid body receptors (CBR) with sodium cyanide (NaCN) elicits a rapid hyperglycemic reflex. Here we explore whether the pituitary and adrenals, two glands involved in glucose homeostasis, are necessary for this reflex. Experiments were performed on anesthetized rats that were artificially ventilated. Measurements of hepatic venous-arterial glucose difference indicated that CBR stimulation with a bolus of 5 micrograms/100 g NaCN produced an immediate increase in the output of glucose by the liver. The same dose of NaCN failed to increase hepatic output of glucose in rats with bilateral adrenalectomy or in rats 1 wk after surgical removal of neurohypophysis. Reflex glucose output by the liver was maintained after adenohypophysectomy or in adrenalectomized rats after adrenal autotransplantation to epiploon. Measurements of epinephrine in plasma and in the grafted adrenal tissue showed that the adrenal autograft can store and secrete catecholamines Immunocytochemical observations indicated that the grafted adrenals retain medullary cells. These results indicate that neurohypophysis and adrenals are necessary for the hyperglycemic reflex initiated by CBR stimulation with NaCN and that the participation of these two organs in this reflex is probably humoral.
Transplantation of fetal suprachiasmatic nuclei into middle-aged rats restores diurnal Fos expression in host
Authors: Cai A. , Lehman M. N. , Lloyd J. M. , Wise P. M.
Published: December 2017

In young animals, the suprachiasmatic nuclei (SCN) of the hypothalamus, which are critical circadian pacemakers, exhibit a light-induced diurnal rhythm in Fos expression. The expression of this immediate-early gene has been used as an index of the activity of the SCN and their ability to respond to external cues that entrain them, such as light. In the present study, we show that by the time rats reach middle age baseline Fos expression increases prematurely during the dark and that light-induced Fos expression is blunted and delayed. We also demonstrate that transplantation of fetal tissue containing the SCN into the third cerebral ventricle of middle-aged rats enables aged hosts to regain the ability to exhibit diurnal patterns of Fos expression that are strikingly similar to those observed in young animals. Our findings lead to the following conclusions: 1) the diurnal pattern of activity of SCN cells is blunted in middle-aged rats, and 2) SCN transplants provide unique signals that enable the cellular systems of the host to regain rhythmic functional capabilities. These results provide new insights into the critical active role that the host plays in restoration of function evoked by the presence of a transplant.
Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice
Authors: Leon L. R. , Kozak W. , Peschon J. , Kluger M. J.
Published: December 2017

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.
A hypercaloric load induces thermogenesis but inhibits stress responses in the SNS and HPA system
Authors: Strack A. M. , Akana S. F. , Horsley C. J. , Dallman M. F.
Published: December 2017

Caloric overingestion generates a sympathetic nervous system (SNS)-mediated increase in brown adipose tissue (BAT) thermogenesis; its effect on the hypothalamo-pituitary-adrenal (HPA) axis is unknown. To determine whether metabolic activation affects the HPA axis, male rats were provided palatable sucrose ad libitum. After 5 or 10 days of sucrose ingestion, BAT and basal and restraint-induced HPA variables were measured. Some rats were instrumented with temperature probes. BAT temperature and HPA axis responses to restraint were measured. Although caloric intake increased > or = 18%, body weight gain did not change after sucrose ingestion; DNA, protein, and uncoupling protein increased in BAT depots, and white adipose tissues were heavier after both 5 and 10 days. During days 5-10, the BAT-core temperature difference was +0.30 degrees C in sucrose rats and -0.46 degrees C in controls (P < 0.05); this, together with the biochemical changes, shows persistent activation of BAT by excess calories. Basal HPA measures were not altered. The sucrose group exhibited smaller BAT temperature and HPA responses to restraint on day 10; there was no HPA difference on day 5. We conclude that calorically mediated increases in BAT thermogenesis are independent of basal HPA activity; however, both systems respond concordantly to restraint stress. The diminished response to restraint in both systems in sucrose-fed rats may result from signals indicating increased energy stores.
Neurocardiac response to esophageal electric stimulation in humans: effects of varying stimulation frequencies
Authors: Bajwa A. , Hollerbach S. , Kamath M. V. , Upton A. R. , Fitzpatrick D. , Fallen E. L. , Tougas G.
Published: December 2017

The purpose of this study was to determine if the cardioautonomic responses to esophageal electric stimulation were mediated entirely through modulation of respiratory frequency or a direct vagal effect. We performed electric stimulation of the esophagus in 13 healthy male controls (24 +/- 6 yr) using a manometric catheter to which a stainless steel electrode was attached. Stimulation frequencies ranged from 0.1 to 1 Hz and were applied in random fashion. We computed the power spectra of the heart rate variability and respiratory frequency as measures of autonomic function. Electric stimulation of the esophagus produced significant increases in the high-frequency power of the heart rate autospectrum at all stimulation frequencies (maximal at 0.2 Hz). However, regardless of the frequency of esophageal stimulation, the respiratory rate was not changed from baseline. These studies indicate that enhancement of cardiac vagal modulation observed in response to esophageal electric stimulation is not primarily due to changes in respiratory frequency, but rather occurs through a direct, vagally mediated action through sensory neural pathways involving vagal esophageal afferents.
Spinal Fos labeling and penile erection elicited by stimulation of dorsal nerve of the rat penis
Authors: Rampin O. , Gougis S. , Giuliano F. , Rousseau J. P.
Published: December 2017

Penile afferents present in the dorsal nerve of the penis (DNP) convey sensory information from the penis to the spinal cord and represent the afferent limb of reflexive erections. Immunocytochemical staining of Fos was used to identify spinal neurons that receive excitatory inputs from the DNP in anesthetized rats. Intracavernous pressure (ICP) was recorded as an index of erection. Dissection as well as stimulation of the DNP elicited a comparable increase in Fos staining. Labeling was present in the dorsal horn, the dorsal gray commissure, and the sacral parasympathetic nucleus, supporting the hypothesis of direct or indirect afferent projection from the penis and penile sheath in these areas. No change in ICP was observed in these rats. Stimulation of the DNP elicited both increased Fos labeling and ICP after spinalization, demonstrating the presence of a supraspinal inhibitory control exerted on the polysynaptic intraspinal circuitry responsible for reflexive penile erection.
beta-MHC transgene expression in suspended and mechanically overloaded/suspended soleus muscle of transgenic mice
Authors: McCarthy J. J. , Fox A. M. , Tsika G. L. , Gao L. , Tsika R. W.
Published: December 2017

Non-weight-bearing (NWB) activity [space flight and hindlimb suspension (HS)] results in the loss of soleus muscle mass, a slow-to-fast fiber-type conversion, and decreased beta-myosin heavy chain (beta-MHC) protein and mRNA expression. To identify beta-MHC promoter sequences required for decreased beta-MHC expression in response to HS, we have modified an existing noninvasive hindlimb unweighting model to accommodate the use of (transgenic) mice. After 2 wk of HS, body and muscle (soleus > gastrocnemius > plantaris) weights were decreased as was the proportion of histochemically classified type I fibers in HS soleus muscle. Northern blot analysis revealed decreases in endogenous mRNA representing beta-MHC, slow myosin light chain 1 and 2, and cardiac/slow troponin C, whereas those representing skeletal troponin C, muscle creatine kinase, and glyceraldehyde-3-phosphate dehydrogenase increased. Protein extracts prepared from HS soleus (SS) muscle of mice harboring transgenes comprised of 5.6 or 0.6 kilobase of wild type (wt) mouse beta-MHC promoter (beta 5.6 wt, beta 0.6wt) and those carrying the simultaneous mutation (mut) of the MCAT, C-rich, and beta e3 subregions (beta 5.6mut3, beta 0.6mut3) revealed decreases in chloramphenicol acetyltransferase (CAT) specific activity relative to respective controls. Decreased CAT mRNA was observed for transgene beta 5.6mut3, line 85. Two weeks of the simultaneous imposition of mechanical overload (synergist ablation) and HS (MOV/HS) countermanded the loss in absolute and normalized SS weight but did not decrease beta 0.6wt transgene expression. These transgenic results demonstrate that regulatory sequences within a 600-base pair beta-MHC promoter are sufficient to direct decreased transcription of beta-MHC transgenes after 2 wk of HS.
Vasopressin V2 receptor mRNA expression and cAMP accumulation in aging rat kidney
Authors: Klingler C. , Preisser L. , Barrault M. B. , Lluel P. , Horgen L. , Teillet L. , Ancellin N. , Corman B.
Published: December 2017

The ability of the kidney to regulate water balance is impaired with age, although the secretion of vasopressin is maintained in senescent animals. This suggests that the cellular response to antidiuretic hormone is reduced in aging kidney. To test this hypothesis, the relationship between the expression of the vasopressin. V2 receptor mRNA and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- and 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old animals (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12, respectively). The concentration of vasopressin corresponding to half-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comparable sensitivity of the renal cells with age. The age-related impaired response to vasopressin of the V2 receptor was specific for females and was not observed in males. Direct stimulation of adenylyl cyclase by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V2 receptor mRNA level in the MTAL was constant between 10 and 30 mo whether the animals were normally hydrated or dehydrated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V2 mRNA or in posttranslational processing mechanisms or in the coupling between the V2 receptor and adenylyl cyclase.
Differentiated norepinephrine spillover in human skeletal muscle
Authors: Karlsson A. K. , Elam M. , Lonnroth P. , Sullivan L. , Friberg P.
Published: December 2017

Most neurophysiological studies have shown similar sympathetic outflow to arm and leg. However, some direct microneurographic recordings indicate differentiated sympathetic outflow to limbs both at rest and during mental stress. Hence, differentiated levels of norepinephrine (NE) spillover could prevail. By steady-state infusion of [3H]NE and body composition determination by dual-energy X-ray absorptiometry-scan, we simultaneously assessed arm and leg NE spillover related to 100 g tissue and total limb weight. NE spillover was lower in leg than arm (0.26 vs. 1.51 pmol.min-1.100 g-1, P < 0.05), and the difference remained when expressed as a function of total limb weight (66 vs. 137 pmol/min, P < 0.05). Fractional extraction of [3H]NE was similar in arm and leg. Neuronal uptake blockade by desipramine was more effective in leg than arm; fractional extraction in leg decreased by 32% (P < 0.05) but was unaltered in arm. Thus a lower NE spillover was observed from leg than arm, possibly reflecting a lower sympathetic outflow and a more neuronally dependent reuptake.
Frequency domain characteristics of muscle sympathetic nerve activity in heart failure and healthy humans
Authors: Ando S. , Dajani H. R. , Floras J. S.
Published: December 2017

The purpose of this study was to characterize oscillations in muscle sympathetic nerve activity (MSNA) in the frequency domain in healthy subjects and patients with congestive heart failure (CHF) and to relate these to blood pressure (BP), heart rate (HR), and breathing frequency. MSNA burst frequency was significantly greater in CHF [52 +/- 21 (n = 12) vs. 35 +/- 11 (n = 19) bursts/min, P < 0.05], whereas breathing frequency and HR were similar. There was no significant difference between CHF and healthy subjects in total power, harmonic power, and nonharmonic power in the MSNA spectrum from 0 to 0.5 Hz, but low frequency power (LF, 0.05-0.15 Hz, P < 0.05) was reduced in heart failure patients. There was less coherence between BP and MSNA in the LF range, but similar spectral power in both groups in the very LF (VLF, 0-0.05 Hz) and high frequency (0.15-0.5 Hz) ranges. The transfer of MSNA oscillations into BP in the VLF (P < 0.05) and LF (P < 0.02) ranges was significantly lower in CHF, but gains in the transfer function and in the coherence between BP and MSNA and in the coherence between respiration and MSNA were similar in the two groups. These observations indicate that modulation of MSNA by the arterial baroreflex and respiration is preserved in CHF. The loss of LF power in the MSNA signal may be due to impaired neuroeffector transduction. The higher sympathetic nerve firing rate in CHF would therefore appear to be caused by factors other than the loss of regulation by these two inhibitory influences.
Acute depressor actions of angiotensin II in the nucleus of the solitary tract are mediated by substance P
Authors: Diz D. I. , Fantz D. L. , Benter I. F. , Bosch S. M.
Published: December 2017

Angiotensin II stimulates release of substance P from medulla oblongata slices, and low doses of substance P or angiotensin II injected into the nucleus of the solitary tract (NTS) decrease heart rate and mean arterial pressure. In this study, angiotensin II (250 fmol in 30 nl) was injected into the NTS of halothane-anesthetized male Sprague-Dawley rats before and after NTS injections of the substance P antagonist [Leu11, psi CH2NH-(10-11)]substance P (600 fmol in 60 nl). The substance P antagonist blocked the angiotensin II-induced hypotension and bradycardia (-16 +/- 3 mmHg and -24 +/- 7 beats/min before versus -0.3 +/- 1 mmHg and -2 +/- 3 beats/min after; P < 0.05). The depressor and bradycardic effects of glutamate were not altered by the substance P antagonist. In vitro receptor autoradiography showed that the substance P antagonist (10 or 100 microM) did not compete for 125I-labeled angiotensin II binding in the dorsal medulla, suggesting that the substance P antagonist does not interact directly with angiotensin II receptors. We conclude that the cardiovascular effects of angiotensin II in the NTS are mediated at least in part by substance P.
Nocturnal melatonin onset is phase locked to the primary sleep gate
Authors: Shochat T. , Luboshitzky R. , Lavie P.
Published: December 2017

In this study, we used the "ultrashort sleep-wake paradigm" (7/13), which measures sleep propensity three times an hour for 29 h, from 0700 to 1200 the next day, on 6 healthy male subjects concomitantly with melatonin plasma level. Melatonin was measured once an hour during the morning and early afternoon of the first day and three times an hour from 1600 to 1000 the following morning. Rectal temperature was measured continuously for four subjects. Subjects underwent the 7/13 paradigm three times, and in all three sessions consistent phase relationships were found between the nocturnal onset of melatonin secretion and opening of the nocturnal sleep gate; also, there was an inverse relationship between melatonin and core body temperature and an almost perfect out-of-phase relationship between sleep propensity and temperature, with the temperature peak falling precisely in the middle of the "forbidden zone" for sleep, i.e., the early evening nadir in sleepiness. On the basis of these phase relationships and previous findings from our laboratory on the effects of exogenous melatonin on the sleep propensity function, we conclude that melatonin participates in sleep-wake regulation in humans.
Acid stress induces a D1-like dopamine receptor in pituitary MSH cells of Oreochromis mossambicus
Authors: Lamers A. E. , Ter Brugge P. J. , Flik G. , Wendelaar Bonga S. E.
Published: December 2017

A 7-day exposure of tilapia (Oreochromis mossambicus) to water with a pH of 4.5 activates their pituitary melanophore-stimulating hormone (MSH) cells to preferentially release diacetyl alpha-MSH as an important corticotrope (13). We here focus on the control of alpha-MSH release by dopamine in tilapia exposed to water with low pH ("low-pH tilapia"). The MSH cells of low-pH tilapia showed a decreased sensitivity to inhibitory concentrations (10(-7)-10(-5) M) of dopamine compared with controls. Low concentrations (10(-14)-10(-8) M) of dopamine stimulated the release of alpha-MSH in low-pH tilapia but not in controls. Strong pharmacological evidence for a stimulatory dopamine receptor (D1-like) was obtained: the D1-agonists SKF-38393 and 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazep ine hydrobromide (6-chloro APB) had a stimulatory effect on the release of alpha-MSH in low-pH tilapia MSH cells but not in controls. The selective D2-agonists quinpirole and 2-hydroxy apomorphin inhibited the release of alpha-MSH in controls as well as in low-pH tilapia, and there was no difference in the sensitivity of the cells to these agonists. We conclude that only MSH cells of low-pH exposed tilapia exhibit a D1-like receptor activity. A comparable D2-like receptor activity, as demonstrated by specific D2-receptor agonists, is present in both controls and low-pH-adapted fish. The apparent loss of sensitivity of the MSH cells to inhibitory concentrations of dopamine, therefore, must be caused by the activation of the D1-like receptors and not by changes in the activity of the D2-like receptor proper. Stimulatory concentrations of dopamine not only quantitatively but also qualitatively enhanced the corticotropic activity of the released alpha-MSH, as indicated by the elevated ratio of diacetyl and monoacetyl alpha-MSH. This effect was mimicked by the D1-like agonists SKF-38393 and 6-chloro APB, indicating that the D1-like receptor activity is responsible for the enhancement of the di/mono ratio.
Contribution of humoral systems to the short-term variability of blood pressure after severe hemorrhage
Authors: Ponchon P. , Elghozi J. L.
Published: December 2017

The aim of this study was to generate hemorrhage-triggered fluctuations in blood pressure (BP) at low frequency (LF, < 0.2 Hz) in conscious rats and investigate with spectral analysis the relative roles of hemorrhage-activated catecholamines, the renin-angiotensin system (RAS), and arginine vasopressin (AVP) on the generation of these fluctuations. The individual contribution of these factors was assessed using a combination of the selective antagonists, prazosin, losartan, and Manning compound (AVPX). At rest, systolic BP (SBP) LF fluctuations were slightly increased by losartan. The mid-frequency (MF; 0.2-0.6 Hz) oscillations of SBP and diastolic BP (DBP) were decreased by prazosin alone or associated with AVPX or losartan. The high-frequency (HF; respiratory) oscillations of SBP were increased by prazosin, prazosin plus losartan, and prazosin plus AVPX. After severe hemorrhage (20 ml/kg), the spontaneous BP recovery was characterized by the occurrence of slow fluctuations of SBP and DBP, centered approximately 0.065 Hz, and by increases of MF (89%) oscillations of SBP. The HF component of SBP variability tended to be increased by blood loss. The occurrence of the SBP LF fluctuations was prevented when alpha 1-adrenergic activity was blocked by prazosin. These oscillations were always present, despite inhibition of angiotensin II, and were increased after inhibition of the AVP activity. Pretreatment with the specific inhibitors used in these studies favored the amplifying effect of hemorrhage on HF fluctuations while they prevented the postbleeding increase in MF oscillations. In conclusion, the present results show an association between the dependence of the postbleeding blood pressure level on catecholamines and the occurrence of slow fluctuations of BP. The buffering role of AVP suggests the establishment of a hierarchy between humoral systems in the genesis of the LF oscillations of BP, with the slow oscillations being generated by the main pressor system and being dampened by the other systems. The postbleeding rise in the MF component of SBP variability could be considered a reflection of the activations of both the sympathetic vasomotor drive and the RAS. The postbleeding increase in the HF component of BP variability was dampened by the activation of the humoral systems. These effects may reflect the low preload state due to hypovolemia.