bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of volume expansion on renal sympathetic nerve activity and cardiovascular and renal function in lambs
Authors: Smith F. G. , Klinkefus J. M. , Robillard J. E.
Published: December 2017

To assess the cardiopulmonary baroreflex in the immature animal, effects of volume expansion on changes in right atrial pressure, renal sympathetic nerve activity, and renal function were measured in chronically instrumented newborn (4-8 days; n = 13) and older lambs (4-5 wk; n = 14). Studies were carried out for 30 min before and 2 h after volume expansion with 6% Dextran 70 (25 ml/kg). Right atrial pressure increased by 4.0 +/- 0.5 mmHg in newborns and by 8.8 +/- 0.6 mmHg in older lambs within 15 min of volume expansion (P less than 0.001). After volume expansion, heart rate decreased in newborns from 237 +/- 6 beats/min to a nadir of 211 +/- 7 beats/min 2 h later (P less than 0.001) but remained constant at control levels of 148 +/- 9 beats/min in older lambs. Maximal inhibition of renal sympathetic nerve activity was achieved at 15 min in older lambs (-50.1 +/- 7.5%) and at 60 min (-58.3 +/- 10.9%) in newborns in which there was a prolonged sympathoinhibition (P less than 0.001). There was also a significant diuretic response in both groups but a limited natriuretic response to volume expansion in newborns (P greater than 0.05) compared with older lambs (P less than 0.001). These data demonstrate the presence of the cardiopulmonary baroreflex in the first week of life in lambs. The sustained sympathoinhibition and bradycardia seen in response to volume expansion in newborns but not in older lambs support the hypothesis that the reflexes controlling arterial pressure and blood volume change with postnatal maturation.
Stretch-mediated visceral smooth muscle growth in vitro
Authors: Karim O. M. , Pienta K. , Seki N. , Mostwin J. L.
Published: December 2017

An in vitro model of smooth muscle stretch was developed to study mechanical stimulus as a possible mediator of visceral smooth muscle growth and differences in the growth response of smooth muscle from young and old animals. De novo DNA synthesis as measured by the aphidicolin-sensitive specific activity of DNA was used as an index of cell growth. Compared with old tissue, the rate of aphidicolin-sensitive DNA synthesis in smooth muscle from young animals was 3-5 and 1.5-2 times greater in bladder and taenia coli, respectively. Stretch of bladder muscle and taenia coli strips from young animals for 6 h increased the aphidicolin-sensitive specific activity of DNA 3-fold (P less than 0.01) and 1.5-fold (P less than 0.01), respectively. Tissue from old animals, however, under the same conditions increased the rate of aphidicolin-resistant DNA synthesis, possibly implying DNA repair. Autoradiography showed only labeled myocyte nuclei. These results indicate that homeostatic mechanisms modulating myocyte growth in visceral smooth muscle can respond to mechanical stimulus in the absence of other trophic factors.
Reduction of glutamine synthetase mRNA in hypertrophied skeletal muscle
Authors: Falduto M. T. , Young A. P. , Smyrniotis G. , Hickson R. C.
Published: December 2017

Skeletal muscle glutamine synthetase (GS) expression is reduced by endurance exercise and is increased when normal innervation is interrupted. This investigation was undertaken to determine whether GS expression is downregulated by the increased contractile activity associated with functional overload. Plantaris muscles overloaded for 30 days by synergist ablation were 70% heavier than those in sham-operated and unoperated control muscles. GS mRNA levels from hypertrophied muscles, measured by Northern and dot-blot hybridization, were reduced to 30% of controls. Changes in total RNA concentration and the proportion of poly(A)+ RNA in the total RNA pool did not account for the decline in GS mRNA. Despite reduced levels of GS mRNA, GS enzyme activity (nmol.h-1.mg protein-1) was unchanged in the hypertrophied muscles (overload, 79 +/- 5; control, 82 +/- 4). To further examine the lack of relationship between GS mRNA and enzyme activity, the concentration of glutamine, a known posttranslational modifier of GS activity, was measured. Consistent with the observed enzyme activities, muscle glutamine was unchanged in hypertrophied muscle (overload, 6.2 +/- 0.3; control, 5.8 +/- 0.4 mumol/g tissue). These results suggest that translational or posttranslational regulation, other than through alterations in glutamine concentration. may play a role in maintaining GS enzyme levels in hypertrophied muscle. Moreover, the regulation of GS activity in muscle hypertrophy may differ from the regulation with endurance training, in which changes in enzyme activity parallel changes in mRNA.
Temperature dependence of electrophysiological properties of guinea pig and ground squirrel myocytes
Authors: Herve J. C. , Yamaoka K. , Twist V. W. , Powell T. , Ellory J. C. , Wang L. C.
Published: December 2017

The effects of changing temperature on the electrophysiology of isolated cardiac myocytes of the guinea pig and Richardson's ground squirrel were studied by patch-clamp techniques. In cells from both species, the resting membrane potential declined on cooling from 36 to 12 degrees C by approximately 6 mV. The duration of the plateau of the action potential in guinea pig cells increased monotonically on cooling. In contrast, the action potential of ground squirrel cells showed a biphasic response, increasing in duration from 36 to 24 degrees C and then decreasing on cooling from 24 to 12 degrees C. From voltage-clamp studies, the properties of L-type calcium currents (ICa) on cooling were compared in the two species and were found to be similar: In both cases, ICa decreased in amplitude from approximately 2 nA peak current at 36 degrees C to less than 400 pA at 12 degrees C. The Q10 of both the maximum amplitude and time to peak for ICa in both species was approximately 1.8. The time for half inactivation had a greater Q10 of 2.5-3. It is concluded that, surprisingly, factors affecting the resting membrane potential and properties of L-type calcium channels are not major contributors to cardiac dysfunction on cooling. Rather, it is sarcoplasmic reticulum calcium release and reuptake that are likely to be the most important cold-sensitive processes.
Gastric motility and food intake in rats after lesions of hypothalamic paraventricular nucleus
Authors: Flanagan L. M. , Dohanics J. , Verbalis J. G. , Stricker E. M.
Published: December 2017

Systemic administration of cholecystokinin (CCK) or LiCl inhibits gastric motility and food intake in rats. Brain stem-projecting oxytocin (OT) neurons in the hypothalamic paraventricular nucleus (PVN) have been proposed to mediate the inhibitory effects of CCK and LiCl on gastric motility and food intake. In the present studies, we found that basal gastric motility was elevated in rats 12-20 h after knife-cut lesions of the PVN; however, this effect disappeared 3 days later. Furthermore, CCK and LiCl inhibited gastric motility at 12-20 h, 3 days, and 3 wk after PVN lesions, although their effects were blunted. Injection of the local anesthetic lidocaine into the PVN had effects similar to acute PVN lesions. In rats with PVN lesions, the inhibitory effects of CCK and LiCl on food intake were indistinguishable from those in sham-lesioned rats. We conclude that the PVN tonically inhibits gastric motility and that it participates in, but is not essential for, the inhibitory effects of CCK and LiCl on gastric motility and food intake in rats.
Differences in brown adipose tissue thermogenic responses between Long-Evans and Sprague-Dawley rats
Authors: Thornhill J. , Halvorson I.
Published: December 2017

Temperature experiments of 4- and 21 degrees C-acclimated conscious and anesthetized Sprague-Dawley (SD) and Long-Evans (LE) rats revealed that the LE groups or SD rats acclimated to 4 degrees C had significant increases in intracapsular brown adipose tissue (IBAT) temperature above core after ventromedial hypothalamic nucleus (VMH) electrical stimulation or after norepinephrine (NE) infusion (50 micrograms/kg total dose), whereas IBAT temperatures of SD rats (acclimated to 21 degrees C) rose only after intravenous NE. Another study of 21- or 4 degrees C-acclimated SD rats revealed that only the 4 degrees C-acclimated group showed graded increases in IBAT temperature after VMH electrical stimulation as current amplitude or total current duration (not pulse frequency) of the electrical stimulus was increased. In vitro analysis of isolated IBAT tissues of age-matched anesthetized LE or SD rats acclimated to 21 degrees C showed that many indicators of thermogenic capacity including mitochondrial uncoupling protein were significantly lower in the SD group. The results demonstrate that lean male SD rats acclimated to 21 degrees C have suppressed IBAT temperature responses to VMH electrical stimulation compared with lean LE rats due to a reduced thermogenic capacity of that tissue.
Differential baroreceptor reflex modulation by centrally infused angiotensin peptides
Authors: Campagnole-Santos M. J. , Heringer S. B. , Batista E. N. , Khosla M. C. , Santos R. A.
Published: December 2017

The present study was designed to investigate the effect of intracerebroventricular (icv) and intravenous (iv) infusion of angiotensin (ANG)-(1-7), ANG III, and ANG II on the baroreceptor control of heart rate (BHR) in conscious rats. Reflex changes in HR were elicited by bolus iv injection of either phenylephrine or sodium nitroprusside before and within 1 and 3 h of icv infusion of ANG II (n = 10), ANG III (n = 9), ANG-(1-7) (n = 9), or saline (n = 9) at a rate of 3 nmol.7.5 microliter-1.h-1. In another group of animals (n = 23), iv infusion of the same amount of ANG peptides was carried out at a rate of 0.7 ml/h. The average ratio of changes in HR in beats per minute and changes in mean arterial pressure (MAP, mmHg) was used as an index of BHR sensitivity. ANG II and ANG III produced a significant increase in the basal levels of MAP, but only during the first hour of infusion (iv or icv). No significant changes in baseline HR were observed. ANG-(1-7) and saline infusion did not change basal levels of HR or MAP (iv or icv). ANG II (iv and icv) and ANG III (icv) caused a significant decrease in the BHR sensitivity for reflex bradycardia. In contrast, icv infusion of ANG-(1-7) induced a significant increase in BHR sensitivity for reflex bradycardia (-3.0 +/- 0.3, 1 h, and -2.8 +/- 0.1 beats.min-1.mmHg-1, 3 h vs. -2.1 +/- 0.2 beats.min-1.mmHg-1, before infusion).(ABSTRACT TRUNCATED AT 250 WORDS)
Betaine transport in the gill of a marine mussel, Mytilus californianus
Authors: Wright S. H. , Wunz T. M. , Silva A. L.
Published: December 2017

The integumental epithelium of Mytilus californianus gill accumulates amino acids directly from seawater against chemical gradients exceeding 10(7) to 1. In the present report, we confirm the presence of betaine in Mytilus tissue and identify a transport process in the gill for this organic osmolyte. Betaine content of gill tissue from animals acclimated to 100% seawater (980 mosM) was 45 mmol/kg wet wt, similar to that of taurine (53 mmol/kg). The kinetics of betaine uptake were adequately described by the Michaelis-Menten equation, with a Kt of 6 microM and Jmax of 7 mumol.g-1.h-1. Betaine transport was inhibited by L-proline and related structural analogues, and by alanine. L-Proline transport, which involves both high- and low-affinity pathways, was partially inhibited by betaine. The low-affinity proline pathway transports lysine. Betaine and L-lysine showed no reciprocal inhibitory interactions. This pattern of structural specificity suggested that betaine transport in the gill is confined to the alanine-proline pathway. Uptake of 0.5 microM betaine into gills was inhibited by 97% when Na+ in seawater was replaced with Li+. Activation of betaine transport in the gill was a near-linear function of the external Na+ concentration up through 100% artificial seawater (ASW, 425 mM Na+). Acute exposure of the gill to 60% ASW inhibited betaine uptake by 83%. Maintenance of normal osmotic concentration (980 mosM, by addition of mannitol to 60% ASW) reduced inhibition to 31%, similar to the level predicted from the availability of Na+.(ABSTRACT TRUNCATED AT 250 WORDS)
Splanchnic nerve response to A5 area stimulation in rats
Authors: Huangfu D. , Hwang L. J. , Riley T. A. , Guyenet P. G.
Published: December 2017

Microinjection of the excitatory amino acid N-methyl-D-aspartate (NMDA, 0.5 nmol) into ventrolateral pons (the A5 area) of halothane-anesthetized, paralyzed rats increased splanchnic (sSND) and renal sympathetic nerve discharges (approximately 45%) and usually decreased lumbar SND. These effects were accompanied by 1) regionally specific changes in vascular resistances, 2) an increase in the gain of the sympathetic baroreflex, and 3) modest reductions in blood pressure and heart rate. sSND activation was greatest when NMDA injections were made in the vicinity of A5 noradrenergic (NE) cells. Injection of 6-hydroxydopamine (6-OH-DA) into A5 area (after 15 days) destroyed 83% of NE neurons and reduced NMDA activation of sSND by 76%. Stimulation of sSND by NMDA in A5 area was reduced 1) 1-2 h after bilateral intraspinal injection of 6-OHDA, but not vehicle or 5,7-dihydroxytryptamine, and 2) by administration of prazosin [alpha 1-NE receptor antagonist, 1 mg/kg iv or 10-20 micrograms intrathecal (it)], but not by idazoxan (alpha 2-NE receptor antagonist, 10-20 micrograms it) or propranolol (0.2 mg/kg iv). We conclude that A5 NE cells have a visceral vasomotor sympathoexcitatory function mediated in large part by their spinal projection.
Molecular biology approaches to comparative study of Na(+)-glucose cotransport
Authors: Pajor A. M. , Hirayama B. A. , Wright E. M.
Published: December 2017

The rabbit intestinal Na(+)-glucose cotransporter has been cloned and sequenced. The cDNA encoding the cotransporter has been used in two general lines of research related to comparative aspects of Na(+)-glucose cotransport that are reviewed here. First, defined regions of the predicted amino acid sequence were used to raise antibodies, and the species distribution of epitopes recognized by those antibodies was investigated. Intestinal brush-border membranes from mammals, birds, an amphibian, and a reptile were all found to contain protein that were recognized by the antibodies in Western analysis. The cDNA encoding the rabbit intestinal Na(+)-glucose cotransporter was also used directly to examine the species distribution of related mRNA in Northern studies and to isolate new cDNAs encoding other Na(+)-glucose cotransporters. Northern blots revealed the presence of related mRNAs in intestines of mammals and a fish, as well as rabbit kidney and gills of marine mussels. The cDNAs encoding mammalian Na(+)-glucose cotransporters and bacterial Na(+)-dependent cotransporters for proline and pantothenate share sequence homology. There has been evolutionary conservation of the structure and function of the Na(+)-glucose cotransporter, and there appears to be a gene family that codes for the Na(+)-coupled cotransporters.
Hypothalamic and cortical sympathetic responses relay in the medulla of the rat
Authors: Cechetto D. F. , Chen S. J.
Published: December 2017

Previously, investigations have indicated that the efferent pathway for sympathetic responses originating in the insular cortex (IC) must initially synapse in the lateral hypothalamic area (LHA). The LHA projects to both the ventrolateral medulla (VLM) and directly to the thoracic spinal cord. To determine the role of the VLM in mediating sympathetic responses from the IC and the LHA, in alpha-chloralose-anesthetized rats, renal nerve responses were recorded following electrical stimulation of these two forebrain sites before and after bilateral injection (300 nl) of cobalt (a synaptic blocking agent) into the VLM. The results demonstrated that a complete block of the increase in sympathetic nerve activity following stimulation of the IC or the LHA could be obtained with cobalt injections into the VLM. The most effective injection sites were located in the rostral ventrolateral medulla at the rostrocaudal middle and posterior regions of the C1 group of neurons. Chemical stimulation with DL-homocysteic acid, in the LHA, to activate cell bodies only evoked a decrease in arterial blood pressure and sympathetic nerve activity. These responses were also blocked by cobalt injection into the VLM. Injections of cobalt into the nucleus of the solitary tract did not block sympathetic responses elicited from the LHA. These results indicate that the efferent pathway for sympathetic responses from the IC through the LHA goes to the preganglionic region of the spinal cord via a mandatory synapse in the VLM.
Both CCK-A and CCK-B/gastrin receptors are present on rabbit vagus nerve
Authors: Lin C. W. , Miller T. R.
Published: December 2017

Cholecystokinin (CCK) receptors on vagal afferents have been implicated in many of the actions of the brain-gut peptide CCK, including satiety. Autoradiographic studies in rats have demonstrated the presence of CCK-A-type receptors on vagus nerves. However, direct and detailed characterization of this important CCK receptor site has never been reported with membrane-binding techniques. Using 125I-Bolt-on-Hunter-CCK octapeptide (125I-BH-CCK-8) and the recently discovered selective agonists and antagonists of CCK receptors, we have delineated the properties of CCK receptors on rabbit vagus nerve. 125I-BH-CCK-8 binding sites appeared to be homogeneous by the Scatchard analysis, with a dissociation constant of 0.14 nM and a maximum binding of 72 fmol/mg protein. However, competition studies using selective CCK ligands showed that the vagal CCK receptors are heterogeneous. A71378, a selective CCK-A agonist, showed biphasic displacement curves, with the high-affinity portion (less than 10 nM) accounting for approximately 60% and the low-affinity portion for approximately 40%. Competitive binding studies using A63387, a selective CCK-B/gastrin receptor agonist, also showed biphasic displacement curves, with the high-affinity portion (less than 30 nM) at approximately 40% and the low-affinity portion at approximately 60%. Under conditions which selectively examined vagal CCK-A or CCK-B/gastrin receptors, we demonstrated that a number of CCK subtype selective agonists and antagonists possessed similar affinities for the vagal CCK-A and -B/gastrin receptors as those found on the guinea pig pancreas (CCK-A) and cerebral cortex (CCK-B), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Alterations in oxytocin prohormone processing during early development in the fetal sheep
Authors: Morris M. , Castro M. , Rose J. C.
Published: December 2017

Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma.
Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation
Authors: Brooks V. L. , Keil L. C.
Published: December 2017

Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Injection of cobalt protoporphyrin into the medial nuclei of the hypothalamus elicits weight loss
Authors: Galbraith R. A. , Kow L. M. , Pfaff D. , Kappas A.
Published: December 2017

Intracerebroventricular administration of small amounts (0.1 mumol/kg body wt) of cobalt protoporphyrin (CoPP), a synthetic analogue of heme, results in transient hypophagia and prolonged reduction in body weight of rats. Statistically significant hypophagia is detectable within 3 h of CoPP infusion. These changes are accompanied by prompt and sustained reductions in running wheel revolutions, a measure of spontaneous locomotor activity. Bilateral intrahypothalamic injections of CoPP at far lower doses (4 nmol/rat) resulted in similar findings following infusion into the paraventricular, dorsomedial, and ventromedial nuclei, but the compound had no such effect when injected into the thalamus or the lateral hypothalamic area. These effects were also observed following microinjection of the natural metalloporphyrin, heme, into the medial hypothalamic nuclei. Inorganic cobalt, iron, protoporphyrin, and magnesium protoporphyrin injected similarly were without such effect. These findings provide further evidence that the site of the previously described actions of CoPP in reducing food intake and body weight in rats resides, at least in part, in the medial hypothalamus. Furthermore, this study expands the spectrum of metalloporphyrins that act in the central nervous system to elicit these changes from synthetic compounds such as CoPP to heme, the natural, physiological metalloporphyrin.
A network model of respiratory rhythmogenesis
Authors: Ogilvie M. D. , Gottschalk A. , Anders K. , Richter D. W. , Pack A. I.
Published: December 2017

A mathematical model of the three-phase respiratory network proposed by Richter et al. (News Physiol. Sci. 1: 109-112, 1986) is developed and its properties are examined. The model reproduces the experimentally determined trajectories of membrane potential for the five physiologically distinct types of neurons included. Stepwise parameter changes can produce a respiratory rhythm with only two separate electrophysiological phases, result in apnea, or produce more complex patterns of firing. The phase-resetting behavior of the model was obtained with perturbing stimuli and is comparable to experimentally determined phase-resetting data. There is reasonable agreement between model predictions and experimental results. In the model, the properties of the phase singularity make termination of the respiratory rhythm by an appropriately timed perturbation virtually impossible, which is in agreement with experimental observations. The rhythm can be stopped by alterations that simulate the effect of input from the superior laryngeal nerve; the rhythm is locked in the postinspiratory phase. We conclude that our results are consistent with the concept of a network oscillator as the source of the respiratory rhythm.
Sex differences in central cholinergic and angiotensinergic control of vasopressin release
Authors: Stone J. D. , Crofton J. T. , Share L.
Published: December 2017

In conscious, unrestrained rats, the intracerebroventricular injection of the cholinergic agonist, carbachol, or angiotensin II resulted in the transient stimulation of vasopressin secretion, elevation of mean arterial blood pressure, and reduction of heart rate. After the injection of carbachol (25 ng) into a lateral cerebral ventricle, the plasma vasopressin concentration in male rats was increased to twice that of female rats in each phase of the estrous cycle; mean arterial blood pressure was elevated more in males than females, whereas heart rate fell to the same extent in both sexes. In contrast, the increase in the plasma vasopressin concentration of males after the injection of angiotensin II (20 ng) was one-half that of females, and the hypertensive and bradycardic responses were similar in both sexes. Phase of the female estrous cycle had no effect on the responses to either agent. These findings indicate that central cholinergic and angiotensinergic mechanisms controlling vasopressin release are influenced differently by gender. The role of the gonadal steroid hormones in these mechanisms remains to be determined.
Effects of aging on entrainment and rate of resynchronization of circadian locomotor activity
Authors: Zee P. C. , Rosenberg R. S. , Turek F. W.
Published: December 2017

The phase angle of entrainment of the circadian rhythm of the locomotor activity rhythm to a light-dark (LD) cycle was examined in young (2-5 mo old) and middle-aged (13-16 mo old) hamsters. An age-related phase advance in the onset of locomotor activity relative to lights off was seen during stable entrainment to a 14:10-h LD cycle. In addition, the effects of age on the rate of reentrainment of the circadian rhythm of locomotor activity were examined by subjecting young and middle-aged hamsters to either an 8-h advance or delay shift of the LD cycle. Middle-aged hamsters resynchronized more rapidly after a phase advance of the LD cycle than did young hamsters, whereas young hamsters were able to phase delay more rapidly than middle-aged hamsters. The age-related phase advance of activity onset under entrained conditions, and the alteration of responses in middle-aged hamsters reentraining to a phase-shifted LD cycle, may be due to the shortening of the free-running period of the circadian rhythm of locomotor activity with advancing age that has previously been observed in this species.
Reflex cardiovascular response to exercise is modulated by circulating vasopressin
Authors: Stebbins C. L.
Published: December 2017

Peripheral vasopressin (AVP) can act centrally to sensitize the arterial baroreflex and/or peripherally to attenuate regional blood flow by a direct vascular effect. Because plasma concentrations of AVP increase during exercise, this study examined the possibility that AVP is capable of modulating the reflex cardiovascular response to static muscle contraction. Thus, in anesthetized cats, the pressor [mean arterial pressure (MAP)], myocardial contractile (dP/dt), and heart rate responses to 30-45 s of electrically induced static contraction of the hindlimb muscles were compared before and after intravenous injection of the V1 receptor antagonist d[CH2)5Tyr(Me)]-AVP (V1-x, n = 7), V1-x plus the V2 receptor antagonist [d(CH2)5,D-Phe2,Ile4,Arg8,Ala9]vasopressin (V2-x, n = 5), or the ganglionic blocker hexamethonium chloride (n = 5). In three additional cats, the contraction-induced cardiovascular response was monitored before and after injection of V1-x + V2-x and after hexamethonium. Subsequent to treatment with V1-x, the MAP and dP/dt responses to contraction were augmented by 18 +/- 5 and 22 +/- 10%, respectively (P < 0.05). After injection of V1-x + V2-x, the MAP and dP/dt responses were augmented to a similar extent (32 +/- 6 and 40 +/- 17%, respectively; P < 0.05). However, there was no difference in the magnitude of augmentation of these responses between the two conditions. The heart rate response was not altered by either treatment. Ganglionic blockade eliminated the cardiovascular responses to contraction. Last, when the pressor and contractile responses to contraction were initially augmented by administration of V1-x + V2-x, subsequent ganglionic blockade abolished the entire cardiovascular response.(ABSTRACT TRUNCATED AT 250 WORDS)
Advance shift of feeding circadian rhythm induced by obesity progression in Zucker rats
Authors: Fukagawa K. , Sakata T. , Yoshimatsu H. , Fujimoto K. , Uchimura K. , Asano C.
Published: December 2017

To determine the relation between the circadian rhythm of ingestive behavior and the progression of obesity in Zucker rats, ingestion and ambulation were analyzed at four different developmental stages. The obese rats were disrupted gradually in nocturnal patterns of feeding, drinking, and ambulation with the progression of obesity, although the lean littermates maintained the patterns during whole test periods. Analysis of autocorrelogram revealed that circadian rhythms of those behaviors remained throughout the whole test periods. Least-squares spectrum ascertained the following. 1) The obese made advance shift of acrophases in feeding and drinking circadian cycles, but not in ambulation. 2) Amplitudes in those behavioral measures decreased with the progression of obesity. 3) Mesor in the obese feeding was not affected, although that in the lean feeding decreased. The findings indicate that disruption of the light-dark cycle in ingestion of the obese was not due to disappearance of circadian rhythm but to transformation by both decreased amplitude and advance shift of the circadian cycle.
Metabolic responses to forced dives in Pekin duck measured by indirect calorimetry and 31P-MRS
Authors: Stephenson R. , Jones D. R.
Published: December 2017

We tested the hypothesis that forced-dived ducks experience a reduction in metabolic rate during prolonged submergence. Unidirectionally ventilated conscious ducks were subjected to forced dives by temporarily stopping the airflow in the ventilation system and simultaneously filling a face mask with cold water. A typical cardiovascular response to submergence was observed: bradycardia and maintained arterial blood pressure. Phosphorylated metabolite concentrations in the pectoral muscle were measured noninvasively by phosphorus magnetic resonance spectroscopy (31P-MRS). ATP content was constant, and phosphocreatine was depleted via the creatine kinase reaction at a rate similar to the resting rate of ATP turnover, which was estimated to be 0.9 mumol.min-1 x g-1 in resting perfused pectoral muscle of pentobarbital-anesthetized ducks. Oxygen from myoglobin supplied at most 12% of the ATP required by the resting muscle during dives. Whole animal postdive excess oxygen consumption and blood lactic acid accumulation suggested that the shortfall in aerobic metabolism during forced dives was compensated by an increase in anaerobic metabolism.
The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor
Authors: Smoller J. W. , Truett G. E. , Hirsch J. , Leibel R. L.
Published: December 2017

Corticotropin-releasing factor (CRF) appears to regulate several physiological systems that display prominent abnormalities in Zucker fatty (fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and feeding behavior. Moreover, central administration of CRF ameliorates the obese phenotype. In light of these observations, the gene for CRF is a plausible candidate for the defective gene in the Zucker fatty rat. We report here the use of molecular genetic linkage analysis to test the hypothesis that fa is a mutant allele of the CRF gene. A restriction fragment length polymorphism for CRF between Zucker (13M) and Brown Norway (BN) DNA allowed us to examine segregation of 13M and BN CRF alleles relative to fa in 58 obese (fa/fa) F2 progeny of a 13MBN fa/+F1 intercross. If fa = CRF, all animals homozygous for the fatty mutation should be homozygous for the 13M CRF allele. However, only 10/58 fa/fa animals were homozygous for the 13M CRF allele, indicating that fa and CRF are not allelic. Thus, although CRF may be important in the physiology of Zucker rat obesity, fa is not a CRF mutation. Using a mouse C57BL/6J Spretus F1 x C57BL DBA/2J F1 intercross, we were able to demonstrate that the mouse CRF gene is linked to the carbonic anhydrase II (Car-2) gene on mouse chromosome 3, in a region of synteny-homology with rat chromosome 2. Thus the rat CRF gene is probably located on chromosome 2.
Effects of intracranial self-stimulation on selected physiological variables in rats
Authors: Burgess M. L. , Davis J. M. , Wilson S. P. , Borg T. K. , Burgess W. A. , Buggy J.
Published: December 2017

The purpose of this investigation was to characterize selected metabolic, cardiovascular, and hormonal responses to reinforcing intracranial self-stimulation (ICSS) of the ventral tegmental area (VTA) in rats. Twenty male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the VTA of the brain. Rats were trained to lever-press for ICSS for 1 wk. While they adapted to the experimental environment by sitting in a metabolic operant chamber, they were connected to the electrode cable but did not lever-press. All animals were instrumented with arterial catheters. Rats receiving contingent stimulation (C-St; n = 10) performed 30 min of lever pressing in the metabolic operant chamber for reinforcing brain stimulation. Oxygen consumption (VO2), heart rate (HR), mean arterial pressure (MAP), and rectal temperature (Trec) increased with the onset and continuation of contingent brain stimulation over 30 min (P < 0.05). In addition, plasma norepinephrine (NE), epinephrine (Epi), and corticosterone increased significantly above resting values in C-St rats (P < 0.05). Five animals received investigator-delivered reinforcing brain stimulation (noncontingent stimulation; NC-St), with MAP, HR, VO2, NE, and Epi increasing significantly above resting values (P < 0.05). Trec and corticosterone were not responsive to noncontingent brain stimulation. With the exception of HR, nonstimulated controls (n = 5) did not experience increases above resting values in any of the variables measured. The responses suggest that contingent brain stimulation reward elicits heightened sympathetic arousal.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of baroreceptor reflex interneurons in the caudal ventrolateral medulla
Authors: Jeske I. , Morrison S. F. , Cravo S. L. , Reis D. J.
Published: December 2017

Interrupting neuronal activity in the caudal ventrolateral medulla (CVL) abolishes baroreceptor-mediated sympathoinhibition and vasodepressor responses. In the present study we identified CVL neurons that function as interneurons in the baroreceptor reflex arc. The mean antidromic onset latency of CVL neurons (5 ms) after stimulation in the rostral ventrolateral medulla (RVL) suggests that they transmit information to the RVL via unmyelinated axons. Stimulation of baroreceptor afferents in the aortic depressor nerve (ADN) excited CVL neurons projecting to the RVL with onset latencies between 15 and 45 ms. The short-latency ADN stimulus-evoked excitation of CVL barosensory interneurons preceded the onset of the ADN stimulus-evoked inhibition of RVL-spinal sympathoexcitatory neurons. Longer-latency ADN-evoked CVL neuronal responses may arise from activation of unmyelinated ADN afferents that can prolong the inhibition of RVL sympathoexcitatory neurons. The excitation of CVL barosensory interneurons resulting from the systolic pressure rise was followed by a period of decreased excitability of RVL sympatho-excitatory neurons, which was of comparable duration to the increase in the discharge probability of CVL neurons. Our characterization of baroreceptor reflex interneurons in the CVL suggests that transmission of baroreceptor information involves a complex activation of medullary interneurons responding selectively to different aspects of the arterial pressure stimulus.
Primary coronary vasodilation associated with pauses in heart rhythm during sleep
Authors: Dickerson L. W. , Huang A. H. , Nearing B. D. , Verrier R. L.
Published: December 2017

We observed 162 episodes of pause in heart rhythm in chronically instrumented dogs primarily during transitions from deep slow-wave sleep to other stages of sleep. These pauses lasted 1.1-8.0 s and were followed by increases in coronary blood flow (CBF) averaging 30% and ranging up to 84%. The postpause surges in CBF do not appear to be mediated by local metabolic factors because the flow surges occurred without significant changes in the heart rate x systolic blood pressure (HRxSBP) product, a standard index of cardiac metabolic activity. Enhanced vagal tone is suggested by the background of marked respiratory sinus arrhythmia, low average heart rates, and the hallmark event, the pause in heart rhythm. In a series of experiments in alpha-chloralose-anesthetized dogs, we demonstrated that direct vagus nerve stimulation can induce both the pause in heart rhythm and the postpause increase in CBF in a pattern similar to that observed during sleep. This response was markedly attenuated after pericoronary denervation. These observations provide suggestive evidence but not definitive proof that enhanced vagal activity may be involved in the increase in CBF after spontaneous pauses in heart rhythm during sleep.
Effects of weight cycling in rats allowed a choice of diet
Authors: Reed G. W. , Cox G. , Yakubu F. , Ding L. , Hill J. O.
Published: December 2017

We examined the effects of weight cycling, produced by bouts of weight loss and regain, on body weight, body composition, dietary fat intake, and energy efficiency. Three groups of adult female Wistar rats were followed for 116 days: control rats (n = 10) were allowed ad libitum access to three mixed diets with protein as a constant proportion of energy and fat provided at 10, 30, and 50% of energy; cycled rats (n = 10) had four bouts of food restriction (50% of baseline intake for 10 days) and refeeding (18-20 days of ad libitum access to the 3 mixed diets); maturity controls (n = 10) were treated identically to controls during the first two cycles and identical to cyclers during the final two weight cycles. At the end of the experiment, we could identify no negative effects of weight cycling on any of the measures taken, and in fact body weight and percentage body fat were lower in cyclers than controls. Dietary fat intake was not altered by weight cycling. In summary, weight cycling did not promote body weight or body fat gain.
Intravenous triglycerides fail to elicit satiety in sham-feeding rats
Authors: Greenberg D. , Smith G. P. , Gibbs J.
Published: December 2017

The satiating effect of intravenous fat infusions was investigated in sham-feeding rats. Intralipid infusions at loads of 2.5-10.0 kcal were administered into either the inferior vena cava or the hepatic-portal vein during sham feeding. Intravenous infusions of Intralipid by either route had no effect on sham feeding during 60-min tests. In earlier work we found that duodenal infusions of Intralipid rapidly inhibited sham feeding and elicited behaviours typical of satiety under test conditions identical to those of the present study. The lack of effect of intravenous infusions of Intralipid on sham feeding is further evidence for a preabsorptive site of action for the satiety effect of Intralipid.
Chronic angiotensin-converting-enzyme inhibition improves cardiac output and fluid balance during heart failure
Authors: Brands M. W. , Alonso-Galicia M. , Mizelle H. L. , Montani J. P. , Hildebrandt D. A. , Hall J. E.
Published: December 2017

The purpose of this study was to examine the sequential changes in renal and cardiovascular function produced by chronic Benazepril administration at different stages of heart failure in dogs. Heart failure was produced by rapid ventricular pacing in five dogs with a normally functioning renin-angiotensin system (angiotensin normal, AN) and six dogs chronically administered the angiotensin-converting-enzyme inhibitor (ACEI) Benazepril. After 7 days of pacing, cardiac output was significantly higher and total peripheral resistance (TPR) lower in the ACEI compared with the AN dogs. Cumulative sodium and water balance increased significantly in both groups, but after 7 days of pacing there were no significant differences between groups. However, the rate of increase in sodium and water balance was significantly less in the ACEI group. Effective renal plasma flow decreased in the AN and ACEI groups during pacing, but there were no between-group differences, and no significant changes in glomerular filtration rate (GFR) occurred in either group. In the AN dogs, pacing was continued for 7-21 days until the onset of decompensated heart failure. Urinary sodium excretion increased on the first day of ACEI infusion during this stage but returned to pre-ACEI levels during the next 2-3 days. No significant improvement in cardiac output was measured during ACEI in decompensated heart failure. These data suggest that chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less effective in later, decompensated stages.
Cortical spreading depression blocks prostaglandin E1 and endotoxin fever in rats
Authors: Monda M. , Pittman Q. J.
Published: December 2017

We have tested the hypothesis that the cortex may play a role in the development of fever. Male Sprague-Dawley rats equipped with AM transmitters for telemetric measurement of body temperature were given intracerebroventricular prostaglandin E1 (PGE1), corticotropin-releasing hormone (CRH), or intravenous E. coli endotoxin. Application of cotton pellets soaked with 3.3 M KCl to the frontal cortex (to induce spreading depression) significantly reduced fevers to PGE1 and endotoxin when compared with fever magnitude with 0.9% NaCl application to the cortex. Neither CRH-induced hyperthermia nor normal body temperatures were altered by the spreading depression. Our results reveal a novel action of spreading depression on thermoregulatory function and indicate cortical involvement in the development of fever.
Sodium appetite in response to sodium deficiency in baboons
Authors: Denton D. A. , Eichberg J. W. , Shade R. , Weisinger R. S.
Published: December 2017

Naive male baboons exhibit little hedonic intake of 300 mM NaCl but develop a robust Na appetite with Na deficiency. With the first episode of Na deficiency, increased drinking of saline solution occurs in the first 1-3 days, but correction of deficit is slow over 5-6 days. Na intake and repair of deficit become more rapid with experience. After three episodes of Na deficiency, the baboons immediately drink Na solution when given access and repair the deficit over 1-2 days. These experimental data showing an innate Na appetite in primates are important in relation to behavior of gorillas and chimpanzees in the wild and anthropological records of behavior toward salt sources. They open an avenue for physiological analysis of cerebral mechanisms subserving Na appetite in primates and humans.
The doubly labeled water method: errors due to deuterium exchange and sequestration in ruminants
Authors: Midwood A. J. , Haggarty P. , McGaw B. A.
Published: December 2017

The doubly labeled water (DLW) technique allows the CO2 production (rCO2) of free living animals to be estimated from the difference between the turnover of 2H2O and H218O in the body water. A fundamental assumption of this technique is that neither of the isotopes used are lost in products other than CO2 and H2O. We found, however, that 2H was lost in both exchangeable and nonexchangeable positions in the feces of sheep. Negligible amounts of 18O were lost in exchangeable positions. 2H losses led to a 0.75% (SE 0.06, n = 4) overestimation of the measured 2H2O flux, leading to an average error in rCO2 estimates of 20.3 l/day. For a typical rCO2 rate of 370 l/day, this would amount to an error of approximately 5% (range -7.0 to -4.3%, n = 4). Correction factors to account for this loss were presented. The error in rCO2 due to 2H sequestration into fat was calculated to be at most 2.1 l/day or about -0.66% in lambs with a rCO2 of 320 l/day. In a triply labeled water (TLW) study the maximum error in the estimation of fractionated evaporative water loss (X) would lead to a 0.81% underestimation of rCO2. We recommend that during a DLW study involving ruminant animals the correction factors presented here be used to compensate for 2H loss in feces. This may be particularly important where the diet has a high roughage content leading to a significant fecal dry matter production.
Effect of anoxia on excitatory amino acids in brain slices of rats and turtles: in vitro microdialysis
Authors: Young R. S. , During M. J. , Donnelly D. F. , Aquila W. J. , Perry V. L. , Haddad G. G.
Published: December 2017

Using in vitro microdialysis, we tested the hypothesis that anoxia-induced release of excitatory amino acids is greater in adult rat brain than in turtle brain. Ten minutes of anoxia produced significant elevation of glutamate (from 0.39 +/- 0.03 to 0.90 +/- 0.18 microM dialysate, means +/- SE, P < 0.05), aspartate (from 0.28 +/- 0.12 to 1.20 +/- 0.49 microM, P < 0.05), glycine, and alanine in the rat brain slice. During reoxygenation, alanine and glycine returned toward baseline values, whereas aspartate and glutamate remained elevated. In contrast, prolonged anoxia (60 min) in the turtle brain slice resulted in only minimal increase in aspartate (from 0.06 +/- 0.01 to 0.09 +/- 0.02 microM, P < 0.05) and, interestingly, a decrease in glutamate (from 0.50 +/- 0.11 to 0.33 +/- 0.09 microM, P < 0.05). Levels of glycine, alanine, and taurine were unchanged. We conclude that oxygen deprivation causes marked increase in excitatory amino acids in the anoxia-sensitive rat brain slice, while oxygen deprivation for an even longer period of time in the turtle brain slice produces substantially less change. We speculate that the difference in sensitivity to anoxia between rat and turtle is at least partly attributable to the major difference in interstitial levels of excitotoxic amino acids during oxygen deprivation.