bluuebunny/crossref_metadata_2025 huggingface dataset:
Pontine cholinergic reticular mechanisms cause state-dependent changes in the discharge of parabrachial neurons
Authors: Gilbert K. A. , Lydic R.
Published: December 2017

The present study examined the hypothesis that cholinoceptive reticular mechanisms in the gigantocellular tegmental field (FTG) of the medial pontine reticular formation cause state-dependent changes in the discharge of parabrachial neurons. In chronically implanted, unanesthetized cats, extracellular recordings were made from nonrespiratory and respiratory neurons in the parabrachial nuclear complex (PBNC) during the natural sleep-wake cycle and during the rapid eye movement (REM) sleeplike state caused by FTG microinjection of carbachol or neostigmine. PBNC cells that increased discharge during natural REM sleep (REM-on cells) revealed similar increased discharge during the carbachol-induced REM sleeplike state (DCarb). Cells that decreased discharge in natural REM sleep (REM-off cells) displayed decreased discharge during both DCarb and the neostigmine-induced REM sleeplike states. The limited sample of parabrachial respiratory neurons revealed significantly diminished discharge during the cholinergically induced REM sleeplike state. Thus cholinoceptive mechanisms localized to specific regions of the pontine reticular formation can cause state-dependent changes in the firing rates of respiratory and nonrespiratory neurons in the PBNC.
Validation in sheep of the doubly labeled water method for estimating CO2 production
Authors: Midwood A. J. , Haggarty P. , McGaw B. A. , Mollison G. S. , Milne E. , Duncan G. J.
Published: December 2017

Carbon dioxide production (rCO2) was estimated in four sheep over a period of 10 days using doubly labeled water (2H and 18O) and was compared with simultaneous respiration chamber measurements of CO2. The excess 2H and 18O measurements were corrected for the empirically determined effects of isotope rebreathing within the confines of the chambers. A weighted monoexponential curve was then fitted to the data from which isotope flux rates and ultimately rCO2 and water turnover (rH2O) estimates were made. The curve fits were weighted assuming a Poisson model. Selection of this weighting policy did not bias the results, and curvature in the data also appeared to have little effect on the rCO2 estimates. Fractionated evaporative water loss expressed as a fraction of rH2O (X) was estimated from water balance and breath water production estimates; the mean X was 0.145 and ranged from 0.108 to 0.183. Corrections for 2H loss in fecal solids reduced the mean rH2O (4,746 g/day) by 35.5 g/day and increased the mean rCO2 (332.3 l/day) by 21.2 l/day. Further corrections to account for 2H loss in methane (mean production rate 27.2 l/day) reduced rH2O by 33.8 g/day and increased rCO2 by 20.3 l/day. The final isotopic estimates of rH2O were 14.6 +/- 6.59% (n = 4) lower than direct measurements and the mean rCO2 was 3.5 +/- 14.48% (n = 4) lower than the chamber measured rCO2. However, in one of the animals studied the rCO2 deviated markedly from the chamber-derived value, and this discrepancy has yet to be explained. When this animal was excluded from the comparisons, the standard deviation was greatly reduced (+/- 3.6, n = 3) and the mean overall error on rCO2 was +3.6%.
Adenosine mediates hypoxic release of arginine vasopressin in fetal sheep
Authors: Koos B. J. , Mason B. A. , Ervin M. G.
Published: December 2017

The effects of adenosine on plasma arginine vasopressin (AVP) concentrations were determined in chronically catheterized fetal sheep (> 0.8 term). Infusion of adenosine [0.35 +/- 0.01 (SE) mg.min-1.kg-1] into the inferior vena cava of six fetuses caused a transient fall in arterial PO2 (by approximately 3 Torr), a slight reduction in arterial pH, and a 5- to 6-mmHg decrease in diastolic pressure without significantly affecting systolic or mean arterial values. A lower rate of infusion (0.19 +/- 0.01 mg.min-1 x kg-1) in five fetuses had virtually no effect on arterial blood gases, pH, or arterial pressures. Both the low- and high-dose adenosine infusions significantly increased fetal plasma AVP concentrations (1.7 +/- 0.2 to 25 +/- 7 pg/ml and 1.6 +/- 0.1 to 54 +/- 8 pg/ml, respectively). Intravenous infusion of papaverine lowered fetal diastolic and mean arterial pressures by approximately 8 mmHg but had no significant effect on plasma levels of AVP. During an hour of isocapnic hypoxia (arterial PO2 12-13 Torr), fetal plasma AVP levels increased from 1.7 +/- 0.2 to 40 +/- 6 pg/ml. Intra-arterial infusion of the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline significantly blunted the hypoxia-induced rise in plasma AVP concentrations to a maximum mean level of 11 +/- 6 pg/ml. These results indicate that 1) adenosine causes a dose-dependent increase in plasma AVP concentrations and 2) a hypoxia-induced rise in fetal adenosine levels triggers vasopressin release.
Pontine reticular neurons provide tonic excitation to neurons in rostral ventrolateral medulla in rats
Authors: Hayes K. , Calaresu F. R. , Weaver L. C.
Published: December 2017

To determine whether the pontine reticular formation (PRF) is a source of tonic activity for cardiovascular neurons in the rostral ventrolateral medulla (RVLM), the discharge of PRF neurons was inhibited by unilateral microinjections of glycine (1.0 M; 60 nl) while recording the discharge of single neurons in the RVLM in 14 Saffan-anesthetized rats. RVLM units were characterized as cardiovascular if their spontaneous activity was changed by baroreceptor activation and was synchronized to the cardiac cycle. Glycine injection into the ipsilateral PRF eliminated the ongoing activity of six cardiovascular units and reduced the activity of four (mean decrease -91 +/- 4%). Inhibition of these units lasted 20-115 s (mean 59 +/- 9 s). Glycine injection into the PRF had no effect on the discharge of five cardiovascular units. Activity of six noncardiovascular units did not respond to PRF blockade. Glycine injection into the PRF caused decreases in arterial pressure (-28 +/- 5 mmHg), heart rate (-23 +/- 3 beats/min), and renal nerve activity (-42 +/- 7%) that also returned to control values between 25 and 120 s (mean 55 +/- 5 s). These results indicate that PRF neurons provide tonic excitatory drive to some cardiovascular neurons located in the RVLM.
High-fat diet reduces glucose transporter responses to both insulin and exercise
Authors: Rosholt M. N. , King P. A. , Horton E. S.
Published: December 2017

High-fat diet (HFD) induces skeletal muscle insulin resistance. To investigate associated changes in the plasma membrane glucose transporter, male Sprague-Dawley rats were fed either chow [high-carbohydrate diet (HCD)] or HFD for 3 wk. Plasma membrane vesicles were prepared from hindlimb muscle of control, insulin-stimulated (Ins), and acutely exercised (Ex) rats. Maximal vesicle glucose transport activity (Vmax) increased threefold with Ins and Ex treatment compared with controls in HCD rats; in HFD rats, increases were less than twofold. Transporter numbers (measured by cytochalasin B binding, CB) approximately doubled with Ins and Ex in both diet groups. Intrinsic activity (carrier turnover, Vmax/CB) increased significantly with stimulation in HCD but not HFD rats. Therefore, vesicles from HFD rats showed resistance to both exercise and insulin stimulation of muscle glucose transport. Transporter number increased normally, but intrinsic activity in HFD rats did not respond. Two conclusions are discussed: 1) translocation and activation are distinct, separable steps in transporter stimulation and 2) HFD produces effects that resemble the insulin resistance of starvation.
Biphasic brown fat temperature responses to hypothalamic stimulation in rats
Authors: Woods A. J. , Stock M. J.
Published: December 2017

Low-level electrical stimulation (monophasic square-wave pulses: 15 Hz, 7.0 microA, 0.5 ms) of the ventromedial hypothalamus (VMH) in anesthetized rats produced a decrease (phase 1) in interscapular brown adipose tissue (IBAT) temperature that was sustained for as long as the stimulus was applied (2-45 min). A rise in IBAT temperature (phase 2) occurred only after the stimulation had stopped. VMH stimulations ipsilateral and contralateral to a lateral hypothalamic (LH) lesion indicated that the phase 1 response required an intact LH, and denervation of IBAT showed that both phases required an intact sympathetic innervation. Central intracerebroventricular injections of amphetamine and dopamine produced decreases in IBAT temperature similar in magnitude to the phase 1 response to electrical stimulation of the VMH. This, as well as the observation that pimozide blocked phase 1, suggested that dopaminergic pathways were responsible for mediating the phase 1 decrease in IBAT temperature. The peripheral mechanisms responsible for phase 1 are unknown, but a vascular component might explain the unexpected decrease in IBAT temperature seen during sustained VMH stimulation.
Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle
Authors: Powers S. K. , Criswell D. , Lawler J. , Ji L. L. , Martin D. , Herb R. A. , Dudley G.
Published: December 2017

These experiments examined the influence of exercise intensity and duration on antioxidant enzyme activity in locomotor muscles differing in fiber type composition. Nine groups of female Sprague-Dawley rats (age 120 days) exercised 4 days/wk on a motor-driven treadmill for 10 wk. The impact of three levels of exercise intensity (low, moderate, and high: approximately 55, approximately 65, and approximately 75% of maximal oxygen consumption, respectively) and exercise duration (30, 60, and 90 min/day) was assessed. Sedentary animals served as controls. Oxidative capacity in the soleus and white and red gastrocnemius was assessed by measurement of citrate synthase (CS) activity, and antioxidant capacity was evaluated by assay of total superoxide dismutase, catalase, and total glutathione peroxidase (GPX) activities. In all muscles, CS activity increased as a function of exercise duration. Furthermore, in the soleus and white gastrocnemius, the magnitude of the training-induced increase in CS activity was directly related to exercise intensity. In contrast, the peak increase in CS activity in the red gastrocnemius was relatively independent of exercise intensity. Catalase activity was not increased (P > 0.05) in any muscle with training. Training-induced changes in superoxide dismutase and GPX activities were muscle specific; specifically, exercise training significantly (P < 0.05) increased superoxide dismutase activity in the soleus as a function of exercise duration up to 60 min/day. Conversely, training-induced significant (P < 0.05) increases in GPX activity occurred in red gastrocnemius only; the magnitude of the GPX increase was directly related to exercise duration but relatively independent of intensity. These data demonstrate that exercise training-induced changes in muscle antioxidant enzymes are muscle specific.
Cold acclimation increases carnitine palmitoyltransferase I activity in oxidative muscle of striped bass
Authors: Rodnick K. J. , Sidell B. D.
Published: December 2017

The effect of thermal acclimation on the activity of carnitine palmitoyltransferase I (CPT I), the rate-limiting enzyme for beta-oxidation of long-chain fatty acids, was determined in oxidative red muscle of striped bass (Morone saxatilis) acclimated at 5 or 25 degrees C. As observed in mammalian tissues, malonyl-CoA potently inhibited CPT I activity of mitochondria. Inhibition by malonyl-CoA required inclusions of both bovine serum albumin (BSA) and palmitoyl-CoA in the reaction media. Because BSA binds long-chain fatty acyl-CoAs, this observation suggests that free fatty acyl-CoAs may disrupt mitochondrial membranes and affect the CPT I protein. Cold acclimation increased citrate synthase activity 1.6-fold and total CPT activity 2-fold in homogenates of red muscle; free carnitine increased 62%, and specific activity of CPT I in mitochondria increased 2-fold. No differences were observed between cold- and warm-acclimated fish in substrate-binding properties of CPT I at an assay temperature of 15 degrees C, as judged by the Michaelis constant (Km) for carnitine (0.11 +/- 0.02 vs. 0.13 +/- 0.02 mM) or inhibition of CPT I, as determined by the half-maximal inhibition concentration (IC50) for malonyl-CoA (0.14 +/- 0.05 vs. 0.09 +/- 0.03 microM). Thermal sensitivity of CPT I (Q10 = 2.91 +/- 0.12 vs. 3.02 +/- 0.20) and preference of CPT I for different long-chain fatty acyl-CoA substrates (16:1-CoA = 16:0-CoA > 18:1-CoA) were not altered by thermal acclimation.(ABSTRACT TRUNCATED AT 250 WORDS)
Reflex control of renal sympathetic nerve activity during furosemide diuresis in rats
Authors: Petersen J. S. , DiBona G. F.
Published: December 2017

To examine the relative role of cardiopulmonary and sinoaortic baroreceptor afferents in reflex changes in efferent renal sympathetic nerve activity (ERSNA) during furosemide diuresis, ERSNA was measured before and after administration of a maximal diuretic dose of furosemide (300 mg/kg iv) in four groups (n = 8 each) of pentobarbital sodium-anesthetized rats: animals with intact baroreflexes, sinoaortic denervation (SAD), bilateral vagotomy, or SAD plus bilateral vagotomy. In addition, measurements of left ventricular end-diastolic pressure (LVEDP), mean arterial pressure (MAP), heart rate, and afferent vagal nerve activity were performed. Furosemide administration produced an early increase in MAP (+40 mmHg) and ERSNA (+50%) that was maintained in rats with SAD plus vagotomy, suggesting that this effect is not of sinoaortic or cardiopulmonary baroreflex origin. The early pressor response was due to the vehicle, 2% ethanolamine, whereas the early renal sympathoexcitation was due to furosemide. Whereas MAP remained unchanged in rats with intact arterial baroreflexes, MAP gradually decreased along with a reduction in LVEDP during progressive diuresis-related volume depletion in animals with SAD. With progressive diuresis-related volume depletion and falling LVEDP, ERSNA increased in intact animals (delta ERSNA/delta LVEDP = 46.0 +/- 1.5%/mmHg). This late increase in ERSNA was inhibited by bilateral vagotomy or SAD, suggesting that vagal and sinoaortic baroreceptor afferents are both essential for expressing the reflex increase in ERSNA observed during furosemide-induced volume depletion. There were no significant differences among furosemide groups in urinary flow rate and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Selective enhancement in SHR of hypotension and bradycardia caused by NTS-injected serotonin
Authors: Okada M. , Bunag R. D.
Published: December 2017

To examine whether serotonergic mechanisms in the nucleus tractus solitarius (NTS) become altered by hypertension, responses to serotonin (5-HT) or L-glutamate injected into the NTS were compared in anesthetized rats. Because isotonic saline had appreciable effects whereas artificial cerebrospinal fluid did not, artificial cerebrospinal fluid was routinely used as the vehicle. Microinjections of 5-HT or L-glutamate always reduced mean pressure, heart rate, and renal nerve activity. Depressor and bradycardic responses to 5-HT were consistently more pronounced in spontaneously hypertensive rats than in either regular Wistar or Wistar-Kyoto rats, but similar responses elicited with L-glutamate did not differ between rat groups. By contrast, attendant inhibition of renal nerve activity was the same in all rats, thereby suggesting that it either is not a good indicator of sympathetic activity or does not contribute to the hypotensive effects of 5-HT. Our results are compatible with the interpretation that hypotensive responses to 5-HT were enhanced because serotonergic mechanisms for cardiovascular regulation in the NTS were sensitized in spontaneously hypertensive rats.
1H-NMR measurement of fractional dissociation of imidazole in intact animals
Authors: Hitzig B. M. , Perng W. C. , Burt T. , Okunieff P. , Johnson D. C.
Published: December 2017

The alphastat hypothesis states that intracellular acid-base status is regulated to maintain constancy of the fractional dissociation of intracellular protein and enzyme imidazole-histidine (alpha-imidazole). A major drawback of this theory has been the lack of a means to directly measure alpha-imidazole in intact animals. We developed a method for directly measuring alpha-imidazole in intact unanesthetized animals using 1H-nuclear magnetic resonance spectroscopy (NMR). We measured carnosine alpha-imidazole of white skeletal muscle from intact unanesthetized newts at three body temperatures (10, 20, and 30 degrees C). alpha-Imidazole remained constant, approximately 0.56, with alterations in body temperature, whereas intracellular pH (pHi) changed significantly (-0.015 U/degrees C), affirming the validity of the imidazole alphastat hypothesis for this tissue. This method was also used to determine the pK values of the imidazole moiety of carnosine and the imidazole moiety alone over a temperature (T) range 4-40 degrees C. The pK values of carnosine differed from those of imidazole, but the delta pK/delta T was the same. pHi was also determined using 31P-NMR and found to be the same as that calculated from carnosine alpha-imidazole values. Therefore Pi and carnosine share a similar pHi environment. We describe a novel technique to directly measure alpha-imidazole in intact tissue.
Effects of acute and chronic cocaine on breathing and chemosensitivity in awake rats
Authors: Trippenbach T. , Kelly G.
Published: December 2017

The barometric method was used to study effects of acute (AC) and chronic cocaine (CC) on breathing and chemosensitivity in awake rats. Effects of AC were evaluated 15 min after daily intraperitoneal injections, and effects of CC were measured at each week of the 4-wk treatment. Sham rats (group 1, n = 10) were injected with NaCl (0.2 ml). Cocaine HCl was given daily in groups 2 (20 mg/kg, n = 5) and 3 (40 mg/kg, n = 10). Effects of AC on the respiratory responses to 10% O2 in N2 and 5% CO2 in 21% O2 were studied 15 min after the first injection of cocaine. Effects of CC on chemosensitivity were studied at weekly intervals. NaCl had no effects on the breathing pattern or chemosensitivity. During normoxia, AC caused an increase in respiratory rate in group 2 and rapid and shallow respiration in group 3. The effects were similar from the first to the last injection at week 4. Haloperidol, a dopamine (DA) receptor blocker, abolished (group 4, n = 8) or prevented (group 5, n = 9) effects of AC. CC had no effects in all normoxic rats. During exposure to either low O2 or high CO2 the AC-induced polypnea was replaced by deep and slow respiration. CC had no effects on CO2 response in all rats. In contrast, 10% O2 response of tidal volume in group 2 and minute ventilation in group 3 were attenuated at weeks 3 and 4 compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)
Reflex control of glucoregulatory exercise responses by group III and IV muscle afferents
Authors: Vissing J. , Iwamoto G. A. , Fuchs I. E. , Galbo H. , Mitchell J. H.
Published: December 2017

Group III and IV muscle afferents are active during exercise and relay information from mechano- and metaboreceptors in muscle. We hypothesized that these afferents participate in the regulation of endocrine and metabolic adjustments to exercise. Muscle branches of the femoral nerves were electrically stimulated in 10 anesthetized and paralyzed cats at 3, 20, and 140 times motor threshold, for 10 min at each intensity, recruiting group III afferents at 20 times motor threshold and group III and IV afferents at 140 times motor threshold. Six cats were not stimulated but were otherwise treated as stimulated cats. [3-3H]glucose was infused intravenously, and arterial blood was sampled for analysis of substrates and hormones. Three times motor threshold stimulation induced no changes in measured metabolic parameters. Twenty times motor threshold stimulation elicited increases (P < 0.05 vs. control) in glucose production (8.2 +/- 1.8 mumol.min-1.kg-1) and plasma glucose (0.29 +/- 0.07 mmol/l) and adrenocorticotropic hormone (ACTH; 35 +/- 12 pg/ml). Stimulation at 140 times motor threshold elicited increases (P < 0.05 vs. control) in glucose production (10.2 +/- 5.4 mumol.min-1.kg-1), plasma glucose (0.53 +/- 0.10 mmol/l), ACTH (94 +/- 28 pg/ml), beta-endorphin (17 +/- 6 pg/ml), and Met-enkephalin (15 +/- 2 pg/ml) and decreases (P < 0.05 vs. control) in insulin (0.65 +/- 0.14 microU/ml). Glycerol and glucagon did not change with stimulations. The findings provide evidence for a reflex control from muscle of hormone secretion and mobilization of glucose during exercise.
Linkage of stress-induced hypocalcemia, gastric lesions, and emotional behavior in Wistar-Kyoto rats
Authors: Ma J. , Aou S. , Hori T. , Ding J.
Published: December 2017

The effects of water-restraint stress on blood calcium levels and gastric pathology and their behavioral relevance were examined in Wistar-Kyoto (WKY) and Wistar rats. The stress induced more severe hypocalcemia (0.32 mM decrease) and gastric lesions (34.6 mm in mean length) in WKY rats than in Wistar rats (0.19 mM and 17.7 mm, respectively). The magnitude of hypocalcemia correlated positively with that of gastric lesions in both strains (WKY, r = 0.59; Wistar, r = 0.69). In the forced-swimming test, WKY rats exhibited a longer immobility time (6.53 min) and a shorter struggling time (0.54 min) than Wistar rats (3.33 and 1.90 min, respectively). The severity of hypocalcemia and gastric lesions correlated positively (r = 0.59 and 0.69, respectively) with the length of immobility time in the WKY rats, while it correlated negatively (r = -0.70 and -0.61, respectively) with the length of struggling time in the Wistar rats. These results suggest that stress-induced hypocalcemia and gastric lesions are closely related and are also influenced by behavioral responsiveness in a strain-dependent manner.
Effect of maternal glucocorticoid treatment on fetal fluids in sheep at 0.4 gestation
Authors: Wintour E. M. , Alcorn D. , McFarlane A. , Moritz K. , Potocnik S. J. , Tangalakis K.
Published: December 2017

Treatment of nine pregnant Merino ewes (64.0 +/- 0.4 days of gestation) with dexamethasone (D; 0.76 mg/h for 48 h) resulted in significant alterations in fetal fluids compared with eight saline-infused control animals (S; 63.0 +/- 0.9 days). There was a substantial increase in allantoic fluid volume (177 +/- 18 ml, D vs. 31 +/- 6, S) but no change in amniotic fluid volume (248 +/- 12 ml, D; 305 +/- 24, S). For allantoic fluid there was a significant decrease in osmolality (213 +/- 4 mosmol/kg water, D; 230 +/- 5, S) and alterations in composition. Amniotic fluid osmolality was unchanged (292 +/- 2 mosmol/kg water, D; 293 +/- 1, S), but amniotic fluid composition was affected. In four fetuses in which bladder and amniotic cannulas were inserted at gestational age 68-75 days, fetal urine flow rate increased from a mean of 4.1 +/- 1.1 to 13.8 +/- 2.6 ml/h after 24 h and 11.8 +/- 3.0 ml/h at 48 h for a similar maternal D infusion, whereas no such increase occurred in four control fetuses. All the fetal urine voided during a 3.5- to 4-h infusion of 51Cr-labeled EDTA into the fetal bladder was directed to the allantois. The results suggest that the increase in allantoic fluid volume resulted from increased fetal urine output into the allantoic compartment, although the composition of the excess allantoic fluid differed substantially from that of fetal urine. There was a greater incidence of abnormal cotyledons in the D-infused ewes.(ABSTRACT TRUNCATED AT 250 WORDS)
Naloxone augments sympathetic outflow induced by centrally administered endothelin in conscious rabbits
Authors: Matsumura K. , Abe I. , Fukuhara M. , Tominaga M. , Tsuchihashi T. , Kobayashi K. , Fujishima M.
Published: December 2017

We examined the role of endogenous opioids in cardiovascular and neurohormonal responses to intracerebroventricular (icv) endothelin-1 (ET-1) in conscious rabbits. With or without pretreatment with intravenous naloxone (1 mg/kg), the effects of icv ET-1 (25 pmol/kg) on cardiovascular and neurohormonal responses were examined. ET-1 (icv) caused significant increases in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), plasma catecholamines, and vasopressin levels. Naloxone pretreatment significantly augmented the increases in MAP and RSNA induced by icv ET-1. To clarify the mechanism of these effects, we also examined the effects of naloxone and naloxone methobromide, which does not cross the blood-brain barrier, on baroreceptor reflex. Intravenous naloxone (1 mg/kg) attenuated the baroreflex sensitivity assessed by RSNA (Smax: -9.9 +/- 1.7 vs. -6.9 +/- 1.2, P < 0.01); however, intravenous naloxone methobromide failed to alter the baroreflex sensitivity. Furthermore, in sinoaortic-denervated rabbits, naloxone pretreatment did not affect the increase in MAP induced by (icv) ET-1. These results suggest that intravenous naloxone acts in the central nervous system to attenuate the baroreflex sensitivity, which might augment the increases in MAP and RSNA induced by icv ET-1 in conscious rabbits.
Adaptation of muscle glucose transport with caloric restriction in adult, middle-aged, and old rats
Authors: Cartee G. D. , Kietzke E. W. , Briggs-Tung C.
Published: December 2017

The effects of prolonged caloric restriction (60% of ad libitum intake initiated at 14 wk of age) on glucose transport activity in isolated epitrochlearis muscles were studied in female Fischer 344 rats aged 8, 18, and 23 mo. Basal 3-O-methylglucose transport (3-MG) rate (without insulin) was not significantly altered by caloric restriction. With a submaximally effective insulin concentration (75 microU/ml), 3-MG transport was enhanced in the caloric-restricted groups by 59, 59, and 105% at 8, 18, and 23 mo of age, respectively. With a maximally effective insulin concentration (20,000 microU/ml), 3-MG transport was increased after caloric restriction, despite no change in muscle GLUT4 glucose transporter protein content. These results indicate that chronic caloric restriction enhances insulin stimulation of the glucose transport system independent of changes in basal glucose transport or muscle GLUT4 levels, and insulin-stimulated glucose transport is enhanced in rats with chronic caloric restriction at least until 23 mo of age.
Renin release in rats during blockade of nitric oxide synthesis
Authors: Johnson R. A. , Freeman R. H.
Published: December 2017

The influence of renal perfusion pressure on renin release was examined in rats administered the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Compared with the control plasma renin of 6.0 +/- 0.7 ng angiotensin I (ANG I).ml-1.h-1, plasma renin activity was suppressed (1.8 +/- 0.2 ng ANG I.ml-1.h-1, P < 0.05) in L-NAME-treated animals in which the renal perfusion pressure was permitted to increase and reached 141 +/- 8 mmHg. Plasma renin activity also was suppressed (2.5 +/- 0.4 ng ANG I.ml-1.h-1, P < 0.05) in a second L-NAME-treated group in which the renal perfusion pressure was controlled to a level of 105 +/- 5 mmHg via tightening of a suprarenal aortic snare. Plasma renin activity was increased (12.0 +/- 1.4 ng ANG I.ml-1.h-1, P < 0.05) in a third L-NAME-treated group in which renal perfusion pressure was reduced to 59 +/- 1 mmHg. Overall, these findings suggest that the intrarenal pressure-sensing mechanism for renin release does not stringently require nitric oxide synthesis. In a second experimental series, bilaterally renal-denervated rats were administered L-NAME, and again plasma renin activity was suppressed significantly whether renal perfusion pressure was permitted to increase or was controlled. Thus L-NAME also suppressed plasma renin activity independently of reflex reductions in renal neuroadrenergic activity even when renal perfusion pressure was controlled. Infusions of sodium nitroprusside completely inhibited L-NAME-induced suppression of plasma renin activity in these renal-denervated rats. Nitric oxide may function as a paracrine stimulatory mechanism for the local regulation of renin release.
Photoperiodic time measurement in Djungarian hamsters evaluated from T-cycle studies
Authors: Puchalski W. , Lynch G. R.
Published: December 2017

We investigated the photoperiodic response to T-cycles (0.5 h of light at intervals ranging from 23.0 h to 25.3 h) of two phenotypes of Djungarian hamsters that either exhibit or lack physiological short-day adjustments under a photoperiod of 9 h light:15 h darkness. Illumination of the same circadian time caused a similar photoperiodic response in both phenotypes. Thus hamsters found to be insensitive under a full short-day photoperiod can exhibit short-day adjustments after exposure to certain T-cycles. Given these results we conclude that the absence of photoperiodic adjustments normally found in short-day-insensitive hamsters results from their atypical entrainment under a full short-day photoperiod. We further suggest that the photoperiodic phenomena seen in Djungarian hamsters cannot be adequately explained by an external coincidence model of photoperiodic time measurement. As a more suitable model, we propose one form of internal coincidence where duration of daily motor activity reflects the phasing of multiple, endogenous oscillators. This conclusion is supported by the close relationship between duration of activity and the photoperiodic response as well as by the observation that a light pulse modulates duration of activity in a phase-dependent manner.
Hypothalamic network for thermoregulatory shivering
Authors: Kanosue K. , Zhang Y. H. , Yanase-Fujiwara M. , Hosono T.
Published: December 2017

Warming one side of a rat's preoptic area and anterior hypothalamus (POAH) suppresses shivering on both sides of the body, and the present study evaluated the extent to which signals mediating this suppression cross the midline within and below the POAH. Hind paw shivering during unilateral POAH thermal stimulation was measured for rats in which the POAH had been midsagittally transected and for rats in which one side of the hypothalamus had been coronally transected just caudal to the POAH. In midsagittally transected rats, unilateral warming on either side of the POAH suppressed shivering equally on both sides of the body. In unilaterally transected rats, POAH warming on the transected side did not affect shivering, but warming the intact side suppressed shivering equally on both sides of the body. When a unilateral transection of only the lateral part of the hypothalamus included the medial forebrain bundle, the effect was the same as that of a unilateral transection of the whole hypothalamus. These results indicate that no information controlling shivering is exchanged between the left and right POAH and that efferent signals from the POAH, descending through the medial forebrain bundle, cross the midline somewhere below the hypothalamus to innervate both sides of the body equally.
EP1-receptor mediation of prostaglandin E2-induced hyperthermia in rats
Authors: Oka T. , Hori T.
Published: December 2017

To investigate what type of prostanoid receptors are involved in the development of fever induced by brain prostaglandin E2 (PGE2), PGE2 and its analogues were injected into a lateral cerebroventricle (LCV) of rats, and the changes in colonic temperature (Tco) were observed in a 23 +/- 1 degrees C environment. 17-Phenyl-omega-trinor-PGE2 (an EP1 agonist; 0.01-10 nmol) produced a rapid and dose-dependent rise in Tco. Even though the EP1 agonist was 10 times less potent than PGE2 on a molar basis, the time course of this hyperthermia was quite similar to that of the PGE2-induced one. No fever was elicited by an LCV injection of butaprost (an EP2 agonist; 0.1-100 nmol), 11-deoxy-PGE1 (an EP2 agonist; 0.1-1.0 nmol). The PGE2 (0.3 nmol)-induced hyperthermia was blocked by LCV pretreatment with SC-19220 (150 nmol), an EP1 antagonist. The results suggest that the PGE2-induced hyperthermia in the rat is mediated predominantly through EP1 receptors in the brain.
Hypothalamic linkage in stress-induced hypocalcemia, gastric damage, and emotional behavior in rats
Authors: Aou S. , Ma J. , Hori T. , Tashiro N.
Published: December 2017

The effects of hypothalamic lesions on stress-induced hypocalcemia, gastric damage, and swim test-evoked behavior were examined in rats. Bilateral lesions of the ventromedial nucleus in the hypothalamus (VMH) eliminated water-restraint stress-induced hypocalcemia and attenuated any gastric damage compared with those in the sham-operated rats. In contrast, lesions in the paraventricular nucleus (PVN) exacerbated both the stress-induced hypocalcemia and gastric lesions in comparison with those in the control rats. In a forced-swimming test, the VMH-lesioned rats showed a significantly shorter time of immobility as well as a longer duration of struggling than the control rats, respectively, while the PVN-lesioned animals spent a longer time in immobility and a shorter period struggling than the control rats. These results suggest that the VMH has an accelerative action in stress-induced hypocalcemia, gastric lesions, and behavioral despair, while the PVN has an opposite effect.
Glucocorticoid negative feedback in sheep corticotrophs: a comparison with AtT-20 corticotroph tumor cells
Authors: Clark T. P. , Kemppainen R. J.
Published: December 2017

Early glucocorticoid feedback in sheep anterior pituitary (AP) cells was compared and contrasted with that in mouse pituitary tumor AtT-20 cells. Dexamethasone (DEX) inhibited corticotropin-releasing hormone (CRH)-stimulated adrenocorticotropin (ACTH) release in a concentration- and time-dependent manner with similar potency amongst cell types. This inhibition was mediated through type II glucocorticoid receptors and required the synthesis of new protein. However, stimulation of protein kinase C with phorbol 12-myristate 13-acetate (PMA) resulted in greater ACTH release and greater inhibition by DEX in sheep AP cells. In contrast to sheep AP cells, AtT-20 cells were insensitive to glucocorticoids when secretion was stimulated by KCl depolarization or the voltage-dependent calcium channel agonist, maitotoxin (MTX). In both cell types, CRH-, KCl-, and MTX-stimulated ACTH release was inhibited by the calcium channel blocker, nifedipine (NIF). Whereas NIF also inhibited PMA-induced ACTH secretion in AtT-20 cells, it did not in sheep AP cells. These data demonstrate that early glucocorticoid feedback is operative in sheep corticotrophs and that AtT-20 cells appear to serve as an appropriate mechanistic model for aspects of negative feedback when the CRH-protein kinase A pathway is activated but may not be appropriate when ACTH secretion is activated via other intracellular signaling pathways.
Regulation of central vascular blood flow in the turtle
Authors: Comeau S. G. , Hicks J. W.
Published: December 2017

The purpose of this study was to determine the effects of vagal nerve stimulation on the pulmonary and systemic circulations in the turtle Pseudemys scripta. The heart rate (HR), systemic vascular resistance (Rsys), pulmonary vascular resistance (Rpul), total pulmonary blood flow (Qpul), and total systemic blood flow (Qsys) were measured during electrical stimulation of the vagal efferent and the vagal afferent nerves. Vagal efferent nerve stimulation resulted in a bradycardia, increased Rsys and Rpul, and a 60% reduction in the Qpul and Qsys. These cardiovascular changes were eliminated after an intravenous injection of atropine. In contrast, vagal afferent nerve stimulation resulted in a tachycardia, a twofold increase in Rsys, a reduction in Rpul, and an 85% increase in Qpul. These changes were eliminated after pretreating the animals with bretylium tosylate (10 mg/kg). An intravenous infusion of epinephrine (0.1 micrograms/kg) produced cardiovascular changes similar to vagal afferent stimulation. The cardiovascular changes resulting from afferent and efferent nerve stimulation were similar to the cardiovascular adjustments often associated with intermittent lung ventilation in reptiles. The results of our study suggest that such cardiovascular changes are under cholinergic and adrenergic control.
Circadian rhythm of heat production, heart rate, and skin and core temperature under unmasking conditions in men
Authors: Krauchi K. , Wirz-Justice A.
Published: December 2017

Seven healthy men were studied in a 34-h constant routine protocol to investigate whether the daily rhythm of heat production and heat loss has an endogenous circadian component. Under these unmasking conditions (constant bed rest, no sleep allowed, regular food and fluid intake), a significant circadian rhythm could be demonstrated for heat production, heart rate, and skin temperatures but not for the respiratory quotient. Heat production and heart rate were phase locked with a maximum at 1100-1200 h. Proximal skin temperatures (infraclavicular region, thigh, and forehead) followed the same circadian rhythm as rectal temperature, whereas distal skin temperatures (hands and feet) were opposite in phase. These physiological circadian rhythm parameters, as well as biochemical parameters (urinary sodium, potassium, urea, and urine flow), were phase advanced by 25-180 min with respect to the circadian rhythm in rectal temperature. Our findings under unmasking conditions show that the circadian variation in rectal temperature is a consequence of endogenous circadian rhythms in both heat production and heat loss.
Effects of glucose and fructose solutions on food intake and gastric emptying in nonobese women
Authors: Guss J. L. , Kissileff H. R. , Pi-Sunyer F. X.
Published: December 2017

The differential effects of fructose and glucose on food intake were studied by giving two concentrations (1 and 10%) of glucose and fructose solutions (500 ml) to one group of women 30 min, and to another 135 min, before a meal of macaroni and beef. The 1% solutions of each sugar were sweetened to match 10% fructose by selective additions of aspartame. Gastric emptying of the 10% solutions and water was measured for 90 min. Under the 30-min delay, subjects ate a mean of 75.8 g more (P < 0.05) after the 1% solutions than after water, and 52.2 g (P > 0.05) less after the 10% solutions than after water, but there were no differences in intake between types of sugar under either delay nor between concentrations at the 135-min delay. However, 10% fructose and 1% glucose sweetened to match it reduced intake significantly compared with water. Glucose (10%) emptied significantly slower (t1/2 = 93.61 min) than water (t1/2 = 29.77 min), while fructose (10%) was intermediate (t1/2 = 65.45 min). Therefore, gastric emptying differences did not account for these results. We conclude that sweetener-enhanced dilute sugar solutions may increase subsequent intake at 30 min, but dilute glucose solutions may have potential for substantial energy savings if consumed 135 min before a meal.
Central actions of parathyroid hormone on blood calcium and hypothalamic neuronal activity in the rat
Authors: Matsui H. , Aou S. , Ma J. , Hori T.
Published: December 2017

The central actions of parathyroid hormone (PTH) on the blood ionized calcium level in anesthetized rats and the neuronal activity of the ventromedial nucleus of the hypothalamus (VMH) in vitro were investigated. An intracerebroventricular injection of PTH (0.01, 0.1, and 1 microgram) prevented urethan-induced hypocalcemia in a dose-dependent manner, whereas either an intravenous or an intracisternal injection of PTH (1 microgram) was ineffective. Eighty-three of 177 VMH neurons responded to a bath application of PTH (10(-7) or 3 x 10(-7) M): a majority (72, 83%) of the responsive cells decreased, whereas 11 increased their activity. This inhibitory effect of PTH on neuronal activity still persisted after synaptic blocking in a Ca(2+)-free/high-Mg2+ medium. A PTH receptor antagonist, [Tyr34]bPTH-(7-34)-NH2, suppressed the effect of PTH on the neuronal activity. These findings thus suggest that brain PTH has a calciotropic function and that one of the possible target sites is the VMH, where PTH inhibits its neuronal activity through a postsynaptic mechanism mediated by PTH receptors.
Tissue-specific HSP70 response in animals undergoing heat stress
Authors: Flanagan S. W. , Ryan A. J. , Gisolfi C. V. , Moseley P. L.
Published: December 2017

Heatstroke is a multisystem disorder that can result in death. Activities that increase the rate of heat storage predispose an organism to thermal injury. Using a 72-kDa heat shock protein (HSP72) as a marker of thermal injury, we determined 1) which organs synthesize HSP in animals after hyperthermia and 2) whether a high heating rate (HHR) resulted in more HSP72 than a low heating rate (LHR). Rats were assigned to either control, HHR (0.166 degrees C/min), or LHR (0.045 degrees C/min) groups. Heat exposure ended when colonic temperature (Tc) reached 42 degrees C. Total time in the heat and thermal load (measured as the time an animal maintained a Tc > 40.4 degrees C) were significantly lower in HHR compared with LHR animals. Hyperthermia resulted in a tissue-specific increase in HSP72 in the liver, small intestine, and kidney, but not in the brain or quadriceps muscles. In addition, HHR animals showed significantly greater accumulation of HSP72 in the liver compared with animals in the LHR group. Thus HSP72 synthesis is tissue specific at high physiological temperatures and may identify a critical target tissue susceptible to early thermal damage.
Plasma proteins as biomarkers of the aging process
Authors: Vranckx R. , Savu L. , Lambert N. , de Conchard G. V. , Grosse R. , Mourey M. S. , Corman B.
Published: December 2017

This study was designed to characterize the rat serum proteins as biomarkers of the normal aging process. Crossed immunoelectrophoresis or electroimmunodiffusion quantitation of proteins was performed in rats aged 6, 12, 24, and 30 mo. Selection of healthy animals was based on confrontation of crossed immunoelectrophoresis patterns with those of experimentally inflamed young adults and with individual anatomopathological data. Convergence of inflammatory patterns and severe histological lesions was the exclusion criterion. Senescence-induced decrease was demonstrated for eight proteins [negative senescence reactants (SRs-)] and increase for six proteins [positive SRs (SRs+)]. Most SRs belonged to the class of proteins responsive to acute inflammation [acute phase reactants (APRs)]. One SR+, the thyroxine-binding globulin, a high-affinity thyroid hormone binder, emerged as a particularly reliable senescence biomarker, showing the highest aging-related variation (8-fold increase from 6 to 30 mo) and not belonging to the APR class. Chronic treatment with perindopril, an angiotensin I-converting enzyme inhibitor used in heart and renal disease therapy, significantly enhanced thyroxine-binding capacity, possibly by preventing age-related alterations of serum lipids. Serum protein patterns prove valuable both as indexes for selecting aging animals free from superimposed pathologies and as parameters of senescence-induced changes in protein biosynthesis.
Effect of salt and water balance on colonic motility of white leghorn roosters
Authors: Brummermann M. , Braun E. J.
Published: December 2017

The motility of the lower gastrointestinal (GI) tract of white leghorn roosters was observed by radiographic methods. Intracolonic pressure changes were recorded, and the mechanical activity of the colon was quantified using strain gauges that were attached to the serosa. Two types of retrograde contraction waves were observed: small fast peristaltic contractions (15 min-1) and large slow contractions. The small fast contractions are the actual vehicle of the retrograde movement, but they seemed to be linked to respiratory movements in the fashion of coupled oscillators during most of their activity time (94%). This makes them an unlikely target for regulation. The large slow waves (3 min-1) probably reflect contractions of the longitudinal musculature. They are retrograde and may permit or modulate the refluxing of urine. The effects of water deprivation, intravenous volume, and salt loads on colonic motility were analyzed. All manipulations that increased urine flow rates without changing urine osmolality resulted in increased propagation speed of the large contraction waves. All manipulations that increased urine osmolality resulted in decreases in activity time of the large-wave pattern. These results suggest a hydration state-related control of the retrograde colonic motility in birds. Direct stimulation of central osmoreceptors had no such effects, indicating that local volume and osmolality receptors of the cloaca are more important than central receptors for this adjustment of colonic motility.
TNF-alpha, TSH, and aging regulate TGF-beta synthesis and secretion in FRTL-5 rat thyroid cells
Authors: Pekary A. E. , Berg L. , Wang J. , Lee P. , Dubinett S. M. , Hershman J. M.
Published: December 2017

Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by macrophages in response to a variety of pathological conditions, can inhibit thyroid cell function in vitro and in vivo. TNF-alpha induction of transforming growth factor-beta 1 (TGF-beta 1) in rat endothelial cells suggested that TGF-beta, a known mediator of inflammatory effects of TNF-alpha, may be involved in the sensitivity of aged thyroid cells to TNF-alpha (G. Chen, A. E. Pekary, and J. M. Hershman. Endocrinology 131: 863-870, 1992). To determine whether TNF-alpha induces TGF-beta production in FRTL-5 cells, young (< 20 passages) and aged (> 40 passages) FRTL-5 cells were grown to near confluency in medium containing 2 U/l of bovine thyroid-stimulating hormone [TSH; 6-hormone (6H) medium] or no TSH [5-hormone (5H) medium]. TNF-alpha (0-100 ng/ml) was added 0-48 h before total RNA was extracted. Northern blots were hybridized with 32P-TGF-beta 1, -beta 2, and -beta 3 cDNAs. In aged cells TNF-alpha increased their TGF-beta 1 (and -beta 2 and -beta 3) mRNA levels 5.4-fold (and > 10-fold), respectively, while in young cells all TGF-beta mRNAs remained almost undetectable during incubation with TNF-alpha. In contrast, TNF-alpha and TSH had a highly significant stimulatory effect on the secretion rate of TGF-beta precursors in both young and old cells as measured in the mink lung cell bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of loading right atrial and ventricular receptors on stimulated AVP, ACTH, and renin secretion in awake dogs
Authors: Andersen L. J. , Andersen J. L. , Thrasher T. N. , Keil L. C. , Ramsay D. J.
Published: December 2017

The goal of this study was to test the hypothesis that increasing or decreasing the load on baroreceptors in the right heart influenced the secretion of arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and renin during a state of sustained arterial hypotension. The hypothesis was tested in chronically instrumented conscious dogs prepared with inflatable cuffs around the pulmonary artery (PA) and the thoracic inferior vena cava (IVC). In one protocol (n = 5), mean arterial pressure was reduced 10 or 20% below control by constriction of the PA, a maneuver that caused a fall in left atrial pressure (LAP) and an increase in right atrial pressure (RAP). Plasma AVP, ACTH, atrial natriuretic peptide (ANP), and plasma renin activity (PRA) all increased (P < 0.05) in response to constriction of the PA. Reducing RAP to control by constriction of the IVC during maintained constriction of the PA had no effect on MAP, LAP, plasma AVP, ACTH, or PRA, but plasma ANP fell significantly. In a separate protocol (n = 4), constriction of the IVC was used to reduce MAP 10 or 20% below control, and this led to significant decreases in both LAP and RAP and increases in plasma AVP, ACTH, and PRA. RAP was then increased above control by constriction of the PA without altering either MAP or LAP. Raising RAP from a level that was 6.3 +/- 1.3 mmHg below control to 3.5 +/- 1.0 mmHg above control had no effect on plasma AVP, ACTH, or PRA.(ABSTRACT TRUNCATED AT 250 WORDS)