bluuebunny/crossref_metadata_2025 huggingface dataset:
NG-monomethyl-L-arginine and nitroarginine potentiate pressor responsiveness of vasoconstrictors in conscious rats
Authors: Conrad K. P. , Whittemore S. L.
Published: December 2017

NG-monomethyl-L-arginine (NMA) and nitroarginine have been reported to be competitive inhibitors of the production of endothelium-derived relaxing factor (EDRF). In chronically instrumented conscious rats, we observed that the pressor response of NMA was attenuated by pretreatment with L-arginine but not by pretreatment with D-arginine, phentolamine, or meclofenamate. Inhibitors of the renin-angiotensin system, captopril and [Sar1,Ile5,Thr8]angiotensin II, did not significantly affect the pressor response of NMA, either. Ten to fifteen minutes after bolus administration of 7-15 mg/kg NMA, when baseline blood pressure was virtually restored, the pressor responses of angiotensin II (ANG II), norepinephrine, and arginine vasopressin were significantly potentiated by approximately 30-40% compared with control values. This potentiation was prevented by pretreatment with L- but not D-arginine. It was also observed in conscious rats subjected to ganglionic blockade. Likewise, the pressor responses of ANG II were significantly increased during infusions of 2 and 5 micrograms/min nitroarginine methyl ester (NAME), dosages that raised baseline blood pressure by 6 +/- 2 and 15 +/- 3 mmHg, respectively. During administration of 5 and 50 micrograms/min NAME, hypotensive responses of methacholine and histamine were only modestly attenuated compared with the responses recorded during infusions of phenylephrine, which raised resting blood pressure to comparable levels. Finally, in freshly isolated rat aorta, NMA inhibited basal and stimulated production of guanosine 3',5'-cyclic monophosphate in a manner comparable to reduced hemoglobin, a known inhibitor of EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure
Authors: Chapleau M. W. , Hajduczok G. , Abboud F. M.
Published: December 2017

Endothelin is a potent vasoconstrictor peptide released from endothelial cells capable of producing marked and prolonged increases in arterial pressure. The purpose of this study was to determine whether endothelin alters the sensitivity of arterial baroreceptors. Multifiber baroreceptor activity was recorded from the vascularly isolated, endothelium-denuded carotid sinus in dogs anesthetized with alpha-chloralose. Local exposure of baroreceptors to endothelin at a concentration of 10(-8) M produced vasoconstriction of the carotid sinus as measured with sonomicrometer crystals but did not alter baroreceptor discharge significantly. A higher concentration of endothelin (10(-7) M) markedly suppressed baroreceptor activity, particularly at pressures greater than 100 mmHg (n = 7, P less than 0.05). The magnitude of the decrease in activity was dependent on the duration of exposure to endothelin. Baroreceptor activity measured at carotid pressures of 60, 100, and 200 mmHg averaged 23 +/- 4, 65 +/- 6, and 100 +/- 0% of maximum during control; 38 +/- 12, 61 +/- 9, and 74 +/- 15% after exposure to endothelin (10(-7) M) for 2 min; and 27 +/- 8, 53 +/- 12, and 56 +/- 19% after 12 min, respectively. The suppression of nerve activity with the high dose of endothelin was not accompanied by additional vasoconstriction, suggesting a direct effect of endothelin on nerve endings. We speculate that endothelin released from endothelial cells may act in a paracrine manner to suppress activity of baroreceptors, particularly at high levels of arterial pressure. Such an action would interfere with the buffering capacity of the baroreflex and promote hypertension.
Anticipatory activity and entrainment of circadian rhythms in Syrian hamsters exposed to restricted palatable diets
Authors: Abe H. , Rusak B.
Published: December 2017

Activity rhythms were recorded from hamsters in three conditions: during timed feedings of an attractive diet with free access to regular food, during restriction to 70% of normal food consumption, and during moderate food deprivation with limited temporal access to an attractive diet. An attractive diet given to intact animals did not induce anticipatory activity or entrainment, but damage to the suprachiasmatic nuclei (SCN) led to the development of anticipatory activity. Food restriction to 70% of normal intake led to anticipatory components in some intact animals, without entraining the dominant circadian pacemaker. The combination of a palatable diet and food restriction led to anticipatory activity before the daily feeding times and entrainment of a previously free-running circadian rhythm in some animals. Ablation of the SCN did not eliminate anticipatory activity in experimental animals, but did eliminate the free-running component of the rhythms. These results indicate that hamsters have a mechanism separate from the SCN that can anticipate daily feeding times, as rats do, and that they may show entrainment of the SCN-based pacemaker to such feeding schedules.
Hyperosmolality impairs ammonia-mediated inflammation: implications for the renal medulla
Authors: Clark E. C. , Nath K. A. , Hostetter T. H. , Hostetter M. K.
Published: December 2017

Although ammonia modifies the third component of complement (C3) and activates the alternative pathway, inflammation is not seen in the renal medulla where ammonia concentrations are normally elevated. We examined the effect of the unique hyperosmolar milieu of the renal medulla on the interaction of ammonia with C3 and the capacity of ammonia-modified C3 (NH3.C3) to induce cytolytic injury and stimulate neutrophils (PMN). Incubation of purified human C3 with ammonia in concentrations found in urine results in significant disruption of the C3 thiolester bond compared with ammonia-free controls. Coincubation with urinary osmolytes and hyperosmolar NaCl and urea does not impair thiolester disruption over a range of ammonia concentrations. However, hyperosmolar NaCl and urea virtually abolish cytolytic injury mediated by the alternative pathway. Coincubation with the organic osmolytes betaine, sorbitol, and inositol fails to reverse this inhibitory effect of hyperosmolar NaCl and urea. Hyperosmolar NaCl and urea also suppress lytic injury mediated by ammonia and complement in MDCK, a cell line derived from canine distal tubular epithelium. Both PMN degranulation and respiratory burst responses to NH3.C3 are significantly blunted in the presence of hyperosmolar NaCl and urea. Hyperosmolality also impairs PMN responses to the formyl peptide N-formyl-Met-Leu-Phe and phorbol 12-myristate 13-acetate (PMA). Therefore, in an in vitro setting of hyperosmolar NaCl and urea, amidation of C3 occurs, but subsequent membrane-directed and receptor-mediated functions of NH3.C3 are markedly impaired.(ABSTRACT TRUNCATED AT 250 WORDS)
Sepsis produces early depression of gut absorptive capacity: restoration with diltiazem treatment
Authors: Singh G. , Chaudry K. I. , Chudler L. C. , Chaudry I. H.
Published: December 2017

Although gut permeability increases and bacterial translocation occurs under certain pathological conditions, it remains unknown whether gut absorptive capacity (GAC) is altered early after the onset of sepsis. The aim of the present study was to investigate this and also to determine whether diltiazem has any effect on GAC in early sepsis. Rats were lightly anesthetized and cecal ligation and puncture (CLP) was performed. A nasogastric tube was inserted, cannulation of various blood vessels was carried out, and the animals were allowed to recover from anesthesia. One hour after CLP, one group of animals received a 1-ml bolus of normal saline intravenously, and another group received diltiazem, 400 micrograms/kg body wt. Sham animals had no CLP performed. GAC was determined by the D-xylose absorption test at 2 and 4 h after CLP. One hour after the administration of D-xylose via the nasogastric tube, its concentration in portal blood was determined colorimetrically. Results show that GAC is significantly depressed at 2 and 4 h after CLP despite the maintenance of normal blood pressure, central venous pressure, and portal pressure. Administration of diltiazem restored GAC to normal levels at 4 h after CLP. Thus diltiazem is a useful adjuvant in the treatment of sepsis because it restores gut absorptive capacity to normal and allows for early enteral nutrition.
Comparing responses when each response is a curve
Authors: Verotta D. , Sheiner L. B.
Published: December 2017

We describe, generalize, and demonstrate the application of a method (W. H. Lawton, A. Sylvestre, and M. S. Maggio, Technometrics 14: 513-532, 1972) that can be used to partially analyze population data. The data from each subject consist of a series of responses observed at distinct values of a predictor variable. The method assumes that all subjects' data originate from a common process but differ because the “units” of predictor and response variables differ among subjects. For example, if the predictor variable is time, time can be “faster” or “slower” from subject to subject. We deal with two different problems. In the first one the response at x for the ith subject is of the form beta 1i + beta 2iG[(x - beta 3i)/beta 4i] + epsilon, where G(x) is a mathematical “shape” function (of the predictor variable x) representing the process and epsilon is observation error. The units of observed and predictor variable are then defined by the values of beta 1i, beta 2i and beta 3i, beta 4i, respectively. In particular beta 1i and beta 3i express shifts and beta 2i, beta 4i express scales of the observed and predictor variables, respectively. In the second problem the response at x for the ith subject is of the form beta 1i + beta 2i integral of x0 G[(s - beta 3i)/beta 4i].Hi(x - s) ds + epsilon, where Hi(x) is a known function. In both problems, the method estimates the common “shape” function G(x) nonparametrically and the parameters beta 1i, beta 2i, beta 3i, and beta 4i for each subject.(ABSTRACT TRUNCATED AT 250 WORDS)
Preferential retention of linoleic acid-enriched triacylglycerols in liver and serum during fasting
Authors: Chen Z. Y. , Cunnane S. C.
Published: December 2017

Fasting has been reported to quantitatively increase linoleic and arachidonic acids in liver triacylglycerols, but the origin and mechanism of this change are unknown. The changes in long-chain fatty acids and triacylglycerol species of liver, serum, adipose tissue, and heart were therefore examined during a period of 24- or 48-h fasting in the rat. In liver and serum triacylglycerols, fasting resulted in a quantitative increase in arachidonic, stearic, linoleic, alpha-linolenic, and docosahexaenoic acids but a decrease in oleic, palmitic, and palmitoleic acids. After fasting, oleic acid was depleted the most from liver and serum triacylglycerols followed by palmitoleic and palmitic acids. Triacylglycerol species containing palmitic, palmitoleic, and oleic acids were depleted the most from liver and serum during fasting. Linoleic acid-enriched triacylglycerol species were proportionally and, in some cases, quantitatively increased in liver and serum triacylglycerols during fasting. Net retention of triacylglycerol species with a total acyl carbon number of 56 or 58 in the liver and 60 in serum was also observed during fasting. Selective retention of triacylglycerol species did not occur in the heart or perirenal or epididymal adipose tissue during fasting. Tissue phospholipid fatty acids were largely unaffected by fasting. Our data suggest that during fasting, long-chain fatty acids released from adipose tissue are differentially utilized and hepatic triacylglycerol species are remodeled, permitting optimal tissue composition of essential fatty acids, particularly linoleic acid.
Relationship between blood O2 content and catecholamine levels during hypoxia in rainbow trout and American eel
Authors: Perry S. F. , Reid S. D.
Published: December 2017

Plasma catecholamine levels and arterial blood respiratory variables were monitored in rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata) acutely exposed (30 min) to graded levels of external hypoxia [water PO2 (PWO2) 20-90 Torr]. The experiments were designed to evaluate the factors controlling catecholamine mobilization in hypoxic fish and to elucidate the basis of marked interspecific differences. In trout, plasma catecholamine levels were unchanged when PWO2 remained above 50 Torr but increased markedly when PWO2 was lowered below this value; the predominant catecholamine released into the circulation was epinephrine. In eel, there was no such obvious PWO2 threshold for catecholamine release although plasma levels were consistently elevated above baseline only at PWO2 less than 35 Torr. The magnitude of the catecholamine release in eel was approximately an order of magnitude less than in trout. Unlike in trout, there was no increase in the plasma epinephrine-to-norepinephrine concentration ratio. During hypoxia, the relationship between arterial blood PO2 (PaO2) and PWO2 was similar in both species and thus could not explain the differences in the PWO2 thresholds for catecholamine release. In trout, the calculated PaO2 thresholds for catecholamine release were 25.3 (epinephrine) and 20.5 Torr (norepinephrine) whereas in eel the corresponding values were 12.5 and 11.6 Torr, respectively. These PaO2 thresholds were in good agreement with the in vivo values for PaO2 at half-maximal hemoglobin (Hb)-O2 saturation (P50) for trout and eel blood of 22.9 and 11.1 Torr, respectively. Thus both species displayed essentially equivalent catecholamine release thresholds when expressed in terms of arterial blood O2 content corresponding to approximately 45-60% Hb-O2 saturation.
Effects of atrial natriuretic peptides on metabolism of arginine vasopressin by isolated perfused rat kidney
Authors: Lebowitz M. R. , Moses A. M. , Scheinman S. J.
Published: December 2017

Atrial natriuretic peptide (ANP) antagonizes the release and action of arginine vasopressin (AVP) both in vivo and in vitro. We have reported that ANP increases the urinary and metabolic clearances of AVP in normal subjects (A. M. Moses et al. J. Clin. Endocrinol. Metab. 70: 222-229, 1990). To clarify this effect, we perfused isolated rat kidneys in vitro and measured the clearances of AVP for 30 min after the addition of rat ANP [rANP-(1-28), 10(-7) M]. In the perfused kidney, rANP increased the urinary clearance of AVP (UCAVP) from 321 +/- 19 to 417 +/- 20 microliters/min (P less than 0.01) and increased the glomerular filtration rate (GFR) from 558 +/- 28 to 696 +/- 28 microliters/min (P less than 0.01). Fractional excretion of AVP was unchanged. Rates of AVP reabsorption were directly related to filtered AVP, and this relationship was not altered by ANP. ANP did not affect the total organ clearance or the renal metabolic clearance of AVP. The increase in GFR was associated with increases in renal vascular resistance (P less than 0.05), filtration fraction (P less than 0.01), and sodium excretion (P less than 0.001). UCAVP also increased when GFR was raised without ANP by perfusing at higher pressures. The rat ANP clearance receptor agonist [cANP- (4-23), 10(-7) M] did not change GFR or UCAVP. ANP increases UCAVP in the isolated perfused rat kidney. This appears to be a hemodynamic effect of ANP, acting through its biological receptor and not the clearance receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial natriuretic peptide inhibits amiloride-sensitive sodium uptake in rat brain
Authors: Kanda F. , Sarnacki P. , Arieff A. I.
Published: December 2017

Both atrial natriuretic peptide (ANP) and its receptors are present in the central nervous system, but effects of ANP on brain are unclear. In the present study, we evaluated both the effects of ANP on sodium uptake, and a possible effector mechanism, the putative intracellular second messenger guanosine 3',5'-cyclic monophosphate (cGMP), in rat brain synaptosomes. In the presence of ANP (10(-7) M), the basal level of sodium uptake in synaptosomes was reduced (n = 6) from the control value of 1.90 +/- 0.06 to 1.73 +/- 0.04 (SE) nmol/mg protein at 5 min, P less than 0.05. The observed reduction of sodium uptake by ANP was not influenced by blockade of the other important pathways for sodium uptake. Addition of either a sodium channel blocker (tetrodotoxin) or an inhibitor of Na(+)-K(+)-adenosinetriphosphatase (ATPase) (ouabain) did not affect sodium uptake in the presence of ANP. However, the reduction of sodium uptake was completely blocked by addition of amiloride. These findings suggest that ANP reduced sodium uptake via inhibition of an amiloride-sensitive pathway for sodium uptake. cGMP is a major intracellular second messenger for ANP in other tissues. We found that after stimulation with 10(-7) M ANP, synaptosomal cGMP increased significantly from 58.0 +/- 9.5 to 73.5 +/- 10.6 fmol/mg protein (P less than 0.01). When an analogue of cGMP, 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP), was added to synaptosomes, amiloride-sensitive sodium uptake was again inhibited, by a similar amount as occurred with ANP. It appears that in rat brain, ANP inhibits amiloride-sensitive sodium uptake via a pathway involving intracellular production of cGMP.
Chemoreceptor and baroreceptor responses of A1 area neurons projecting to supraoptic nucleus
Authors: Li Y. W. , Gieroba Z. J. , Blessing W. W.
Published: December 2017

Extracellular recordings were made from 127 neurons, identified by antidromic activation from the supraoptic nucleus, in the A1 area of urethan-anesthetized rabbits. The median axonal conduction velocity was 0.7 m/s, and the median discharge rate was 3.9 spikes/s. Raising arterial pressure decreased the discharge rate in 94 of 101 neurons tested. Lowering arterial pressure increased the discharge rate in 50 of 64 neurons tested. Of 70 neurons inhibited by baroreceptor activation, 40 were excited and 25 inhibited by hypercapnic hypoxia. Of 23 neurons excited by hypercapnic hypoxia, all were excited by hypoxia but only 2 were affected by hypercapnia. Of 16 neurons inhibited by hypercapnic hypoxia, 15 were inhibited by hypoxia and 1 was inhibited by hypercapnia. Of 14 neurons excited by hypoxia, 13 were excited by injection of sodium cyanide into the common carotid artery. Of five neurons inhibited by hypoxia, four were inhibited by sodium cyanide. Our results provide electrophysiological evidence that neurons projecting from the A1 area to the supraoptic nucleus increase their discharge rate in response to baroreceptor unloading and decrease their discharge rate in response to baroreceptor activation. These neurons may form part of the central pathway mediating secretion of vasopressin in response to hemorrhage. A high proportion of the neurons also receive peripheral chemoreceptor inputs, and these A1 cells may also be part of the central pathway whereby chemoreceptor stimulation modifies the secretion of vasopressin.
Carotid baroreflexes and plasma vasopressin in humans during head-up tilt
Authors: Kamegai M. , Kristensen M. S. , Warberg J. , Norsk P.
Published: December 2017

To investigate the influence of carotid baroreflexes on plasma arginine vasopressin (AVP) in humans, eight healthy males underwent two sessions of passive head-up tilt to 60 degrees for 15 min each. During one of the sessions (sequence randomized), carotid baroreflexes were simultaneously stimulated by static neck suction of 23 +/- 1 mmHg during the whole period of head-up tilt. Only subjects who did not develop presyncopal symptoms during head-up tilt were included. Head-up tilt increased AVP significantly from 1.0 +/- 0.3 to 4.2 +/- 1.3 pg/ml (P less than 0.05). In contrast to this, AVP did not at any point in time increase significantly during head-up tilt when neck suction was applied. Plasma renin activity and heart rate were unaffected by neck suction, whereas mean arterial pressure and central venous pressure decreased. We conclude that the moderate but significant increase in plasma AVP during nonhypotensive head-up tilt is in part mediated by deloading of carotid baroreceptors induced by the acute fall in hydrostatic pressure at the level of the carotid sinus.
Maintenance of intestinal nutrient transport during hibernation
Authors: Carey H. V. , Sills N. S.
Published: December 2017

We studied nutrient absorption across the brush-border membrane in jejunal tissues from active 13-lined ground squirrels and in hibernating squirrels that had not eaten for at least 6 wk. Body weights and jejunal wet weights per centimeter were significantly reduced in the hibernators. Rates of total and carrier-mediated uptake of 3-O-methylglucose (3-OMG) per centimeter intestinal length were greater in the active squirrels, but 3-OMG uptakes per milligram intestinal weight were greater in the hibernators, due to a significantly greater maximum rate of uptake (Jmax) per milligram with no differences in apparent Michaelis constant (Km). Passive permeabilities to L-glucose were similar in both groups. Total uptake of L-proline per centimeter was greater in active squirrels, but total proline uptake per milligram was greater in the hibernators due to a significantly greater Jmax per milligram with no difference in apparent Km. Na(+)-independent proline uptake accounted for a greater proportion of total proline uptake in active compared with hibernating squirrels. As a consequence, Na(+)-dependent proline uptake was greater in the hibernators when uptake was normalized either to intestinal length or intestinal weight. Thus hibernation is associated with an increase in the Jmax per milligram for 3-OMG and proline transport, as well as a shift in the Na+ dependency of proline uptake. We conclude that nutrient absorption is selectively retained in mammalian hibernators to maintain transport function after the extended winter fast.
Forced oscillations in sympathetic nerve discharge
Authors: Huang Z. S. , Gebber G. L. , Zhong S. , Barman S. M.
Published: December 2017

Periodic electrical stimulation of the medullary raphe or lateral tegmental field in baroreceptor-denervated cats was used to force the central systems responsible for the 10-Hz and 2- to 6-Hz rhythms in post-ganglionic sympathetic nerve discharge (SND). The 10-Hz rhythm in SND could be entrained either to the frequency of medullary stimulation or to harmonics of the stimulus frequency. The harmonic of the stimulus frequency to which the 10-Hz rhythm was entrained in one postganglionic nerve could be different from that in another nerve. On this basis, we propose that the circuits responsible for the 10-Hz rhythms in SND may be modeled as a system of coupled nonlinear oscillators, each of which either influences one postganglionic nerve or nonuniformly affects different postganglionic nerves. The relatively wide band 2- to 6-Hz component in SND could be forced into a stable oscillatory state by medullary stimulation at frequencies between 3 and 5 Hz. This observation is consistent with the view that the 2- to 6-Hz component reflects the complex behavior of a nonlinear oscillator rather than the output of a physiological noise generator.
Placental glucose transport in heat-induced fetal growth retardation
Authors: Thureen P. J. , Trembler K. A. , Meschia G. , Makowski E. L. , Wilkening R. B.
Published: December 2017

In six ewes heat stressed from 39 to 125 days gestation and studied in a normothermic environment at 135 days, fetal and placental masses were less than in control sheep (1,645 vs. 3,112 and 149 vs. 356 g, respectively, P less than 0.01). Umbilical glucose uptakes (Rf,UP) were measured keeping maternal arterial plasma glucose at 70 mg/dl at spontaneously occurring fetal plasma glucose values (state A) and at two additional fetal glucose levels, to determine the transplacental glucose difference (delta) vs. Rf,UP relation. At normal delta of 49.2 mg/dl, Rf,UP was less in the experimental group (3.2 vs. 5.6 mg.min-1.kg fetus-1, P less than 0.05). Differences in placental perfusion and glucose consumption could not account for this result, thus indicating a reduced placental glucose transport capacity. In state A, fetal hypoglycemia enlarged significantly (P less than 0.01) the delta to 56.7 mg/dl and increased Rf,UP approximately 50% over the Rf,UP at a normal delta. In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity.
Effects of CGRP on baroreflex control of heart rate and renal sympathetic nerve activity in rabbits
Authors: Okamoto H. , Hoka S. , Kawasaki T. , Sato M. , Yoshitake J.
Published: December 2017

We examined the effects of intravenous infusion of calcitonin gene-related peptide (CGRP) and sodium nitroprusside (SNP) on baroreceptor afferent nerve activity, renal sympathetic efferent nerve activity (RSNA), and heart rate in alpha-chloralose-anesthetized rabbits. Baroreceptor afferent nerve activity was measured from aortic nerves during CGRP- and SNP-induced hypotension. Decreases in aortic nerve activity in response to decreases in mean arterial pressure were not different during CGRP and SNP infusion. Progressive infusion of CGRP (12-120 pmol.kg-1.min-1) increased RNSA by 83 +/- 14 (mean +/- SE), 175 +/- 26, 246 +/- 36, and 343 +/- 41%, and heart rate by 8 +/- 2, 24 +/- 3, 37 +/- 4, and 47 +/- 6 beats/min during falls of blood pressure of 5, 10, 15, and 20 mmHg, respectively. These increases in RSNA and heart rate produced by CGRP were significantly greater than those produced by SNP. The alterations in heart rate and RSNA with CGRP were reversed by restoring blood pressure with phenylephrine HCl. In rabbits with sinoaortic and vagal deafferentation, the responses of heart rate and RSNA to a fall of blood pressure were abolished during both CGRP and SNP infusion. Therefore, it is suggested that the facilitated responses of heart rate and RSNA during CGRP infusion occurred by way of the arterial baroreflex arc.
Elevated muscle acidity and energy production during exhaustive exercise in humans
Authors: Bangsbo J. , Graham T. , Johansen L. , Strange S. , Christensen C. , Saltin B.
Published: December 2017

This study examined the effect of previous intense exercise on energy production during exhaustive exercise. Subjects (n = 6) performed dynamic knee extensor exercise to exhaustion twice (Ex1 and Ex2) separated by 16 min of recovery consisting of 10 min of rest, 3.5 min of very high-intensity intermittent exercise, and a further 2.5 min of rest. This resulted in an elevated muscle lactate concentration of 13.1 mmol/kg wet wt before Ex2. Muscle lactate concentration was the same at end of Ex1 and Ex2, but the accumulation of lactate and net lactate release during Ex2 was reduced (P < 0.05) by 67 and 38%, respectively. The time to exhaustion was 3.73 and 2.98 min, respectively, and the mean rate of net lactate production for Ex2 was lower (P < 0.05) than for Ex1 (4.6 +/- 1.2 and 9.6 +/- 1.7 mmol.min-1.kg wet wt-1, respectively). Leg O2 uptake was the same for Ex1 and Ex2. Muscle pH (6.85) was lowered (P < 0.05) before Ex2, but at the end of Ex2 (6.77) it tended (P < 0.1) to be higher compared with that at the end of Ex1 (6.73). In summary, the net lactate production rate is reduced but the aerobic energy production is not significantly altered when intense exercise is repeated. Fatigue and the lowered glycolysis do not appear to be caused by the elevated acidity per se before exercise.
Potentiation of thermoregulatory responses to isoproterenol by beta-adrenergic antagonists
Authors: Carlisle H. J. , Stock M. J.
Published: December 2017

The thermoregulatory effects of isothermogenic doses of isoproterenol (Iso) and a novel beta-agonist (BRL 35135) were tested in rats at 22 degrees C and in rats trained to bar press for radiant heat at -8 degrees C. BRL 35135 produced hyperthermia at 22 degrees C and reduced operant responding for heat at -8 degrees C, whereas Iso reduced body temperature and increased operant responding. In both situations, the negative effects of Iso on thermal balance were abolished by propranolol at doses that did not inhibit heat production. In anesthetized rats, propranolol potentiated the Iso-induced rise in brown adipose tissue and colonic temperature. The potentiation was more marked with the beta 2-selective antagonist ICI 118,551, whereas treatment with the beta 1-selective antagonist atenolol resulted in a profound Iso-induced reduction in temperature. The two selective antagonists also produced divergent responses in operant behavior in Iso-treated rats at -8 degrees C. These experiments demonstrate the extent to which responses to a nonselective agonist can be manipulated using appropriately low doses of selective antagonists and indicate that the effects of Iso on thermal balance are due to its beta 2 activity.
Iron uptake in relation to transferrin degradation in brain and other tissues of rats
Authors: Strahan M. E. , Crowe A. , Morgan E. H.
Published: December 2017

The possibility that iron uptake by the brain involves transcytosis of the iron-transferrin complex across the brain capillaries, followed by degradation of the transferrin (Tf) within the brain, was investigated using diferric 125I-[59Fe]Tf and [59Fe]Tf coupled to 125I-tyramine cellobiose (TC). The radiolabeled catabolic products of proteins labeled with 125I-TC remain in the cells where degradation occurs. The TCTf complex behaved normally with respect to its ability to donate iron to rat reticulocytes in vitro or to the brain, liver, kidneys, and femurs in vivo. In the brain there was little difference in the uptake of 125I derived from Tf and TCTf, and the amounts were equivalent to only a small fraction of the 59Fe uptake. Hence, the rate of Tf catabolism in the brain was insufficient to account for the rate of accumulation of iron from plasma Tf. It was concluded that Tf recycles to the plasma after delivering its iron to the brain. The uptake of 125I from TCTf by the liver and kidneys accounted for 40-50% of the total rate of Tf catabolism. This indicated that they were important but not the only sites of degradation of this protein.
Duodenal preabsorptive origin of gustatory alliesthesia in rats
Authors: Cabanac M. , Lafrance L.
Published: December 2017

Facial consummatory responses reflecting ingestive and aversive perceptions were studied and quantified in rats chronically implanted with gastric, duodenal, and oral catheters. A gustatory stimulus of 50 microliters of 1.75 mol/l sucrose was injected into the mouth every 5 min for 65 min. At time 0, 0.5 ml containing 0.3 g glucose was injected into the stomach or into the duodenum. Typical ingestive facial consummatory responses were observed in response to sweet stimuli prior to the load. Aversive consummatory responses were observed in response to sweet stimuli after the glucose duodenal load (negative alliesthesia). The gastric load of glucose was not followed by negative alliesthesia in response to sweet oral stimuli. In the last part of the experiment the rats were vagotomized. When the rats were subjected again to the same gustatory sessions, the duodenal load was followed by weak and delayed negative alliesthesia in response to sweet stimuli. These results in rats parallel results obtained in human subjects and reinforce the hypothesis of the existence of a duodenal preabsorptive signal for alimentary alliesthesia. They also suggest that the vagus nerve plays a part in the perception of satiety.
Kinetic heterogeneity of Na-D-glucose cotransport in teleost gastrointestinal tract
Authors: Ahearn G. A. , Behnke R. D. , Zonno V. , Storelli C.
Published: December 2017

D-[3H]glucose transport properties of brush-border membrane vesicles (BBMV) of upper intestine and pyloric ceca of the Pacific copper rockfish (Sebastes caurinus) were characterized and compared. Vesicles from both organs exhibited Na-dependent, phloridzin-sensitive, carrier-mediated transport systems. Kinetic constants for D-[3H]glucose influx across vesicle membranes were as follows: upper intestine, apparent affinity of glucose (Kt) = 0.14 +/- 0.02 mM, maximal glucose influx (JM) = 1,649 +/- 57 pmol.mg protein-1.10 s-1; pyloric ceca, Kt = 0.58 +/- 0.12 mM, JM = 2,439 +/- 178 pmol.mg protein-1.10 s-1. A hyperbolic relationship, following Michaelis-Menten kinetics, occurred between D-glucose influx and external Na concentration for pyloric ceca, while a sigmoidal function, following Hill cooperativity kinetics (n = 1.71 +/- 0.31), was disclosed between the variables for the intestine. External phloridzin, D-glucose, methyl alpha-D-glucopyranoside, and D-galactose were the most potent inhibitors of D-[3H]glucose influx in each organ. Other compounds were generally more inhibitory in vesicles from the pyloric cecum than those of the intestine except for D-mannose which was considerably more potent in the intestine. Results suggest that there may be proximal-to-distal hexose- and Na-binding gradients in the teleost gut for optimizing sugar absorption during passage of food through the gastrointestinal tract.
Cardiovascular responses to nasal water flow in rats are unaffected by chemoreceptor drive
Authors: McCulloch P. F. , West N. H.
Published: December 2017

Peripheral chemoreceptors generally play a limited role in the initial development of diving bradycardia in mammals. However, T.F. Huang and Y.I. Peng (Jpn. J. Physiol. 26: 395-401, 1976) reported that peripheral chemoreceptors are very important for manifestation of the diving response in conscious rats. The objectives of this study were to reinvestigate those findings and determine whether the cardiovascular responses to simulated diving in the rat were potentiated during preexisting hypoxia or hypercapnia. Responses to simulated diving were elicited by nasal water flow with concurrent apnea in paralyzed, artificially ventilated Sprague-Dawley rats anesthetized with Innovar. The experiments show that nasal stimulation in the rat results in rapid bradycardia and hypotension and that these responses are not due to laryngeal stimulation. The data also suggest that chemoreceptors do not play a role in the initiation of the responses to simulated diving in rats and that preexisting chemoreceptor drive does not alter the cardiovascular responses. Additionally, we found that concomitant expiratory apnea is necessary to sustain the profound initial cardiovascular changes induced by nasal water flow.
Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation
Authors: Obal F. , Payne L. , Opp M. , Alfoldi P. , Kapas L. , Krueger J. M.
Published: December 2017

Previous reports suggest that the hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep, especially non-rapid-eye-movement sleep (NREMS). To evaluate the role of endogenous GHRH in sleep regulation, the effects of antibodies to rat GHRH (GHRH-ab) were studied on normal sleep, brain temperature (Tbr), and GH secretion in experiment I and on enhanced sleep after sleep deprivation in experiment II. In experiment I, affinity-purified GHRH-ab (50 and 200 micrograms) raised in goats and a control goat immunoglobulin G (IgG) preparation were injected intracerebroventricularly (icv) in rats 1 h before the onset of the light cycle, and sleep-wake activity and Tbr were recorded for the next 12 or 23 h. Both doses of GHRH-ab suppressed NREMS and REMS throughout the light cycle. Sleep durations at night were normal. Electroencephalographic (EEG) slow-wave activity, characterized by EEG slow-wave amplitudes, was reduced after GHRH-ab during both the light and the dark cycles. Plasma GH concentrations measured 6-12 h after injection of GHRH-ab (200 micrograms) were diminished. Both the control IgG and GHRH-ab elicited fever. In experiment II, the sleep-wake activity and Tbr of rats were recorded for 24 h in three experimental conditions: base-line with icv injection of IgG, 3-h sleep deprivation with icv IgG injection, and 3-h sleep deprivation with icv GHRH-ab (200 micrograms). After sleep deprivation (+IgG), a prompt increase in EEG slow-wave activity (power density analysis) and late increases in NREMS and REMS durations were found.(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise-induced cellular alterations in the diaphragm
Authors: Powers S. K. , Criswell D. , Lieu F. K. , Dodd S. , Silverman H.
Published: December 2017

Limited data exist concerning the effects of exercise training on cellular oxidative capacity in the diaphragm of senescent animals. In this study we examined the changes in cellular oxidative capacity, muscle cell cross-sectional area (CSA), and capillarity within the costal diaphragm of senescent animals after a 10-wk endurance-training program. Twelve 24-mo-old female Fischer 344 rats were divided into either a sedentary control group (n = 6) or exercise training group (n = 6). The trained animals exercised on a motor-driven treadmill (60 min/day, 5 days/wk) at a work rate equal to approximately 55-65% VO2max. Capillaries were identified histologically and fiber types determined using adenosinetriphosphatase (ATPase) histochemistry. Succinate dehydrogenase (SDH) activity and CSA in individual fibers were measured using a computerized image analysis system. Exercise training did not increase (P > 0.05) the capillary-to-fiber ratio for any fiber type. However, training significantly decreased CSA (P < 0.05) and increased capillary density (capillary number/CSA) (P < 0.05) in type I, type IIa, and type IIb fibers. Furthermore, exercise training resulted in small but significant increase in SDH activity (P < 0.05) in type I and IIa fibers, whereas training did not alter SDH activity (P > 0.05) in type IIb fibers. These data demonstrate that endurance training in senescent animals results in small relative improvements in both oxidative capacity and capillary density in costal diaphragmatic type I and IIa muscle fibers. The increase in both capillary density and fiber SDH activity was largely due to a reduction in fiber CSA.
Modulation of glucose metabolic response to endotoxin by granulocyte colony-stimulating factor
Authors: Lang C. H. , Bagby G. J. , Dobrescu C. , Nelson S. , Spitzer J. J.
Published: December 2017

The present study examines whether in vivo administration of granulocyte colony-stimulating factor (G-CSF) and the resultant neutrophilia alters basal glucose metabolism or modulates the glucose metabolic response to a subsequent endotoxin [lipopolysaccharide (LPS)] challenge. Rats were injected with human recombinant G-CSF (50 micrograms/kg sc) twice daily for 2 days preceding an injection of LPS. Animals treated with G-CSF showed an eightfold increase in blood polymorphonuclear leukocytes (PMNs) but no detectable changes in hemodynamics or glucose metabolism. In control animals, LPS transiently decreased circulating PMN number, but by 4 h neutrophils had returned to control levels. LPS produced a greater reduction in circulating neutrophils in G-CSF-treated animals, which did not return to pretreatment levels by 4 h. G-CSF also produced marked changes in the glucose metabolic response to LPS. Rates of whole body glucose production and utilization in both control and G-CSF-treated rats were rapidly increased by LPS; however, the increment in glucose flux was 55-100% greater in the latter group. The enhanced rate of hepatic glucose production in this group occurred despite lower plasma levels of lactate and glucagon. The elevated rate of whole body glucose utilization was attributable to the G-CSF-enhanced LPS-induced increase in glucose uptake by the ileum, spleen, liver, and lung. Furthermore, LPS increased glucose uptake by skeletal muscle in G-CSF-treated rats but not in control animals. The enhanced glucose disposal in G-CSF-treated rats was not mediated by increases in plasma glucose or insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Sympathoadrenal-circulatory regulation of arterial pressure during orthostatic stress in young and older men
Authors: Taylor J. A. , Hand G. A. , Johnson D. G. , Seals D. R.
Published: December 2017

Our purpose was to test the hypothesis that human aging alters sympathoadrenal-circulatory control of arterial blood pressure during orthostasis. Plasma catecholamine and hemodynamic adjustments to two different forms of orthostatic stress, lower body suction (-10 to -50 mmHg) and standing, were determined in 14 young (26 +/- 1 yr) and 13 older (64 +/- 1) healthy, normally active men. During quiet supine rest, cardiac output tended to be lower and systemic vascular resistance higher in the older men, but no other differences were observed. On average, arterial blood pressure was well maintained during both forms of orthostasis in the two groups; the older men actually demonstrated better maintenance of pressure (P < 0.05) and a lesser incidence of orthostatic hypotension than the young men during lower body suction. Despite a blunted reflex tachycardia during orthostatic stress (P < 0.05), cardiac output tended to decrease less in the older men because of a smaller decline in stroke volume (P < 0.05, suction only), whereas the reflex increases in systemic vascular resistance were not different in the two groups. The whole forearm vasoconstrictor response tended to be attenuated in the older men during lower body suction, but was identical in the two groups with standing. Forearm skin vascular resistance was unaltered during lower body suction in both groups. Orthostasis-evoked increases in antecubital venous plasma norepinephrine concentrations were similar in the young and older men, whereas little or no increases in plasma epinephrine concentrations were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Interferons and central regulation of feeding
Authors: Plata-Salaman C. R.
Published: December 2017

Interferons (IFNs) are immunomodulators with neuromodulatory activities. To study the effects of IFNs on the central regulation of feeding, rats were subjected to various applications. The results show the following. 1) Intracerebroventricular microinfusion of rat IFN (15-225 IU/rat) decreased short-term (2-h) food intake in rats. Computerized analysis of behavioral patterns demonstrated a reduction of meal size and meal duration, whereas meal frequency slightly increased. Nighttime and total daily food intakes were not significantly affected. 2) Short-term food intake suppression by intracerebroventricular rat IFN was accompanied by a small increase in cerebrospinal fluid and rectal temperatures. 3) Intracerebroventricular microinfusion of heat-treated rat IFN or of recombinant human interferon-alpha (rhIFN-alpha) did not affect food intake. Only one dose of rhIFN-gamma (400 ng/rat) decreased 2-h food intake. These results are consistent with the species specificity to the effects of IFNs. 4) Peripheral administration of rat IFN in doses equivalent to those administered centrally had no effect on food intake. The results suggest that IFN acts directly in the central nervous system to decrease short-term feeding.
Modulation of sleep by cortisone in normal and bacterially infected rabbits
Authors: Toth L. A. , Gardiner T. W. , Krueger J. M.
Published: December 2017

Infectious disease is known to alter both sleep patterns and hydrocortisone (cortisol) concentrations in rabbits. Moreover, the sleep-altering effects of microbial infections are likely to be mediated via endogenous immune modulators whose actions are attenuated by glucocorticoids. To evaluate the relationships between sleep and glucocorticoids during infectious disease, the effects of cortisone administration (20 mg/kg, im) on sleep were examined before and after inoculation of rabbits with Staphylococcus aureus or Escherichia coli. When administered alone, cortisone did not alter the amount of time spent in slow-wave sleep (SWS) but did reduce electroencephalographic (EEG) slow-wave amplitudes during SWS, the number of bouts of SWS and the amount of time spent in rapid-eye-movement sleep. The duration of individual bouts of SWS was increased after cortisone treatment. Bacterially infected rabbits developed biphasic changes in sleep patterns that were characterized by an initial increase and a subsequent decrease both in SWS time and in EEG slow-wave amplitudes during sleep. Cortisone treatment attenuated these effects in S. aureus-inoculated rabbits. In contrast, cortisone treatment did not alter the initial phase of enhanced sleep in E. coli-inoculated rabbits but did attenuate the subsequent sleep suppression. These data indicate that glucocorticoid administration is associated with an attenuated sleep response in bacterially inoculated rabbits.
BAT thermogenic activity and capacity are reduced during lactation in ground squirrels
Authors: Nizielski S. E. , Billington C. J. , Levine A. S.
Published: December 2017

The effect of lactation on brown adipose tissue (BAT) thermogenic activity and capacity as well as on uncoupling protein (UCP) gene expression has been studied in the 13-lined ground squirrel. Lactating animals were studied after approximately 21 days of lactation. Parameters of thermogenesis were also studied in a group of postpregnant animals from which litters had been removed at 1-2 days postpartum. A group of animals that did not bear litters served as nonpregnant controls. BAT pad weights, protein concentration, and mitochondrial mass were all significantly decreased relative to nonpregnant controls and postpregnant animals. Specific binding of GDP and total GDP bound were significantly decreased in lactating animals relative to both nonpregnant and postpregnant animals. Scatchard analysis of GDP binding indicated that binding affinity (Kd) was unaffected by treatment. UCP concentrations were reduced by 26% during lactation, whereas total UCP content was reduced by 70%. A 3-wk period after pup removal was sufficient for UCP concentrations to return to nonpregnant levels, although total UCP content remained reduced. The changes in UCP concentrations were accompanied by parallel alterations of gene expression. UCP mRNA-to-beta-actin mRNA ratios during lactation were 30% of the levels found in nonpregnant controls and postpregnant animals. The results presented here clearly indicate that BAT activity and capacity are suppressed during lactation in the 13-lined ground squirrel.
Circadian properties of anticipatory activity to restricted water access in suprachiasmatic-ablated hamsters
Authors: Mistlberger R. E.
Published: December 2017

This study provides evidence that anticipation of daily water access in hamsters is regulated by nonphotically entrainable circadian oscillators located outside of the suprachiasmatic nuclei (SCN). Intact and SCN-ablated hamsters receiving 2 h/day water access ate large meals (representing 17-55% of daily food intake) during the 2-h access time. Two of nine SCN-intact hamsters, five of five hamsters with partial SCN ablations, and seven of nine hamsters with total SCN ablations showed anticipatory wheel-running rhythms synchronized to water access time. These anticipation rhythms usually disappeared during subsequent ad libitum water access but reappeared when the hamsters were water deprived for 2 days. When the water restriction schedule was shortened to an 18-h interval in six SCN-ablated hamsters, an 18-h activity rhythm emerged that usually did not persist during water deprivation. When the schedule was lengthened to 30-h intervals, several hamsters showed 27- to 29-h rhythms that did not stably synchronize to water access time. These results indicate that hamsters, like rats, possess a non-SCN-based water- and/or food-entrainable, self-sustaining oscillator with circadian limits to entrainment.