bluuebunny/crossref_metadata_2025 huggingface dataset:
Micturition reflexes in the in vitro neonatal rat brain stem-spinal cord-bladder preparation
Authors: Sugaya K. , De Groat W. C.
Published: December 2017

An in vitro neonatal (1-7 day) rat brain stem-spinal cord-bladder (BSB) preparation was used to examine the central control of micturition. Isovolumetric bladder contractions occurred spontaneously or were induced by electrical stimulation of the ventrolateral brain stem, spinal cord, bladder wall (ES-BW), or by perineal tactile stimulation (PS). Transection of the spinal cord at the L1 segment increased the amplitude of ES-BW- and PS-evoked contractions, and subsequent removal of the spinal cord further increased spontaneous and ES-BW-evoked contractions but abolished PS-evoked contractions. Hexamethonium (1 mM), a ganglionic blocking agent, mimicked the effect of cord extirpation. Tetrodotoxin (1 microM) blocked ES-BW- and PS-evoked contractions but enhanced spontaneous contractions. Bicuculline methiodide (10-50 microM), a gamma-aminobutyric acid A receptor antagonist, increased the amplitude of spontaneous, ES-BW- and PS-evoked contractions. These results indicate that PS-evoked contractions are mediated by spinal reflex pathways, whereas spontaneous and ES-BW-evoked contractions that are elicited by peripheral mechanisms are subject to a tonic inhibition dependent on an efferent outflow from the spinal cord. PS-evoked micturition is also subject to inhibitory modulation arising from sites rostral to the lumbosacral spinal cord. Although electrical stimulation of bulbospinal excitatory pathways can initiate bladder contractions in the neonatal rat, these pathways do not appear to have an important role in controlling micturition during the first postnatal week.
Muscarinic receptor characterization in differentiating avian exocrine cells
Authors: Hildebrandt J. P. , Shuttleworth T. J.
Published: December 2017

The type of muscarinic acetylcholine receptor in exocrine cells of the avian nasal gland in the undifferentiated quiescent (naive) stage and in the partly differentiated salt-secreting (stressed) stage was characterized by ligand binding experiments and by probing receptor messenger RNA with oligonucleotide probes specific for the mammalian receptor subtypes. Competition-binding studies using l-quinuclidinyl [phenyl-4-3H]benzilate and a series of other ligands indicated the presence of only one type of receptor in both cell types. Pharmacological characterization of its ligand-binding properties revealed similarities with the mammalian M3 type. However, 4-[[[(3-chlorophenyl)amino]carbonyl]oxy]-N,N,N-trimethyl-2-butyn-1 - aminium chloride, generally a partial agonist in cells expressing mammalian M1 receptors, released calcium from intracellular stores in naive and stressed cells. To resolve this, we attempted to characterize the salt gland receptor by molecular means. Northern analysis of salt gland mRNA revealed weak signals only with oligonucleotide probes corresponding to the mammalian m1 receptor type. However, at higher stringencies these signals faded, indicating that the salt gland receptor may resemble the mammalian m1 subtype but has probably a considerable degree of sequence divergence. Such divergence may also explain the observed differences in pharmacological behavior between the avian and the mammalian glandular receptors.
Altered pressure natriuresis in chronic angiotensin II hypertension in rats
Authors: van der Mark J. , Kline R. L.
Published: December 2017

Angiotensin II (ANG II; 10 or 30 ng/min iv) was infused for 7-10 days in unilaterally adrenalectomized and nephrectomized Sprague-Dawley rats drinking 1% NaCl. The acute pressure-natriuresis relationship was studied under Inactin anesthesia in volume-expanded rats with fixed neurohumoral influences on the remaining kidney. Renal interstitial hydrostatic pressure (RIHP) was measured using a catheter implanted into the renal cortex. Arterial blood pressure before laparotomy was 149 +/- 3 (SE) mmHg (n = 6) and 152 +/- 6 mmHg (n = 16) for ANG II-infused rats (10 and 30 ng/min, respectively) and 123 +/- 5 mmHg (n = 6) and 123 +/- 7 mmHg (n = 16) for the respective control rats. Compared with values in control rats, ANG II-infused rats had significantly (P < 0.05) lower urine flow and absolute and fractional sodium excretion at renal artery pressures of 115-150 mmHg. There were no significant differences between RIHP measured in control and ANG II-hypertensive rats. The shift in the pressure-diuresis, pressure-natriuresis, and pressure-fractional sodium excretion relationships was similar with both doses of ANG II and was reversed by the acute administration of losartan (10 mg/kg iv). In all groups of rats, renal blood flow was autoregulated, whereas glomerular filtration rate was not autoregulated in ANG II-infused rats and was significantly lower than that in control rats at the lower level of renal artery pressure. The data indicate that rats with ANG II-induced hypertension have a rightward shift of the pressure-natriuresis curve caused primarily by a decrease in fractional excretion of sodium. The lack of effect of chronic ANG II infusion on filtration fraction and RIHP suggests that the increased tubular reabsorption was due to a direct action of ANG II on renal tubules. The reversal of these effects by losartan suggests that the shift in the pressure-natriuresis curve in ANG II-induced hypertension is mediated by the AT1-receptor subtype.
Pregnancy alters cerebrovascular adaptation to high-altitude hypoxia
Authors: Hull A. D. , Longo L. D. , Long D. M. , Pearce W. J.
Published: December 2017

We have previously shown alterations in cerebrovascular composition, contractility, and endothelial function in normoxic pregnant (P) and chronically hypoxic nonpregnant (HNP) adult sheep compared with nonpregnant normoxic controls (NP). This study focuses on a fourth group, pregnant sheep exposed to chronic high-altitude hypoxia (HP) (110 days at 3,820 m). The combined challenges of pregnancy and high-altitude hypoxia resulted in significant alterations in cerebrovascular function that were not simply the summation of the responses seen in the P and HNP animals. Compared with NP, HP arteries had increased protein content and increased intracranial arterial wall thickness. Both P and HP arteries showed increased contractility, while HNP artery maximum tensions were depressed. Endothelial function was depressed in the P common carotid and was enhanced in all HNP arteries. In contrast, an increased endothelial response was shown only in the HP common carotid. Thus, for contractility, the effects of pregnancy predominated in the HP arteries. For endothelial function, hypoxia effects were dominant in the common carotid but not in the intracranial arteries. Clearly, cerebrovascular characteristics are dynamic in nature, with artery-specific responses to both pregnancy and hypoxia.
Angiotensin II-mediated pressor effect of rat joining peptide
Authors: Yoshida M. , Hamakubo T. , Inagami T.
Published: December 2017

In an attempt to determine the mechanism of pressor action of centrally administered rat joining peptide (rJP), a pro-opiomelanocortin (POMC)-derived peptide, we investigated its action on the angiotensin and adrenergic system in the brain stem. In conscious spontaneously hypertensive rats with chronic cannulas in the cisterna magna and abdominal aorta, the pressor effect of synthetic rJP in the cisterna magna was markedly inhibited by pretreatment with losartan, an antagonist of angiotensin (ANG) II receptor specific for its AT1 subtype, and also by the nonspecific antagonist [Sar1,Ile8]ANG II but not by AT2-specific PD-123319. Pretreatment with captopril did not alter the pressor response. Adrenergic receptor antagonists, yohimbine and propranolol, did not change the pressor response. The intracisternal joining peptide administration (10 and 30 nmol) increased the concentration of immunoreactive ANG II in cerebrospinal fluid 2.4- and 5.7-fold, respectively. These results indicate that the pressor response to rJP is mediated by the release of central ANG II and AT1 receptor. This study details a biological response to rJP, the only POMC-derived peptide whose action has not been identified previously.
Left heart and arterial baroreceptors interact in control of plasma vasopressin, renin, and cortisol in awake dogs
Authors: Andersen J. L. , Andersen L. J. , Thrasher T. N. , Keil L. C. , Ramsay D. J.
Published: December 2017

Arterial hypotension induced by constriction of the ascending aorta (AA) causes increases in left atrial pressure (LAP) and plasma atrial natriuretic peptide (ANP), but no change in plasma arginine vasopressin (AVP), plasma renin activity (PRA), or cortisol. In the present study, we tested the hypothesis that the rise in left heart pressure during constriction of the AA suppressed the stimulation of AVP, renin, and cortisol secretion in response to arterial hypotension. Dogs were prepared with inflatable cuffs around the AA, the pulmonary artery (PA), and the thoracic inferior vena cava (IVC) and with catheters in the left and right atria and abdominal aorta. In one series of experiments, the AA was constricted to lower mean arterial pressure (MAP) 10 or 20% below control for 15 min. Then, either the PA or the IVC was constricted to bring LAP back to control levels but without altering the degree of arterial hypotension. Constriction of the AA alone led to significant increases in LAP and plasma ANP but no change in plasma AVP, cortisol, or PRA. Reducing LAP to control levels by constriction of either the PA or IVC led to significant and similar increases in plasma AVP, cortisol, and PRA. Plasma ANP fell significantly 10 min after LAP was normalized by constriction of the IVC but not when LAP was normalized by constriction of the PA, because PA constriction caused a significant rise in right atrial pressure that stimulated ANP secretion. The increases in plasma AVP and PRA after normalizing LAP by constriction of the PA were compared with the increases obtained during identical falls in MAP induced by constriction of the IVC alone, a maneuver that lowers LAP below control. The increases in plasma AVP in the two conditions were identical, indicating that the stimulation of left heart baroreceptors alone can account for the suppression of AVP secretion in response to unloading arterial baroreceptors. In contrast, there was a greater rise in PRA during hypotension caused by constriction of the IVC alone compared with the condition in which LAP was normalized but plasma ANP remained elevated. This suggests that increased left heart pressure inhibits renin secretion in response to arterial hypotension by reflex mechanisms and by increased plasma ANP concentration.
Interleukin-1 alpha in human sweat is functionally active and derived from the eccrine sweat gland
Authors: Sato K. , Sato F.
Published: December 2017

We wished to establish the presence of interleukin-1 (IL-1) in human sweat (5) and clarify its origin and mechanism of secretion. IL-1 alpha concentration ([IL-1 alpha]) in clean sweat from the back increased with the sweat rate, plateauing at the maximal sweat rate ([IL-1 alpha]max). The mean [IL-1 alpha]max was 545 pg/ml (n = 17) for men and 1,324 pg/ml for women in back sweat. The mean [IL-1 alpha]max for axillary sweat in men was 1,568 (n = 6). Palmar sweat was 9.2 ng/ml (n = 5) for IL-1 alpha and 7.9 ng/ml for IL-1 beta. [IL-1 alpha]max decreased to one-third that of the first sweat test, when second sauna sweat tests were conducted after 2 h of continuous sweating on the same day. Western blot analysis of the purified sweat IL-1 alpha fraction revealed bands at 17, 29, and 33 kDa. Immunoreactive IL-1 alpha was localized mainly in the secretory coil lumen, intercellular canaliculi, cytoplasm, mitochondria, and near plasma membranes. Polymerase chain reaction revealed the presence of IL-1 alpha mRNA in the sweat gland and in cultured human eccrine secretory coil cells. Both sweat IL-1 alpha and human recombinant IL-1 alpha at 500 pg/ml strongly stimulated interleukin-6 and interleukin-8 production in cultured fibroblasts. We conclude that the IL-1 alpha-like immunoreactive substance in sweat is IL-1 alpha itself, is derived from the sweat gland, and is biologically active at concentrations normally present in fresh sweat.
Functional capacity of nicotine-sensitive canine intrinsic cardiac neurons to modify the heart
Authors: Murphy D. A. , O'Blenes S. , Hanna B. D. , Armour J. A.
Published: December 2017

The capacity of intrinsic cardiac efferent parasympathetic and sympathetic neurons to modify the heart was investigated in nine anesthetized open-chest dogs with adrenal glands removed from the circulation. The effects elicited by intravenously administered isoproterenol, tyramine, and nicotine on cardiac variables were examined before and after acute decentralization of the heart. Major vessels, as well as other tissues at the base of the heart, were denuded by means of an ultrasonic aspirator that removed neural elements without damaging muscles or blood vessels. The efficacy of the acute decentralization was assured by testing cardiac responses elicited by right and left stellate ganglia and cervical vagosympathetic complex stimulations after surgery. Heart rate, atrial force, and both right and left ventricular intramyocardial systolic pressures were augmented similarly by isoproterenol and tyramine before and after acute decentralization, indicating that the surgery necessary to decentralize the heart did not obtund cardiac myocyte function. Power spectral analysis of heart rate and left ventricular chamber pressure rate of change indicated an almost complete lack of variability of these indexes after, but not before, acute decentralization. Despite these changes, similar cardiac augmentation was elicited by nicotine before and after acute decentralization. Cardiac augmentation was elicited by nicotine in acutely decentralized preparations after atropine administration but not after beta-adrenergic blockade. These data indicate that the canine intrinsic cardiac nervous system contains a significant population of nicotine-sensitive adrenergic neurons that modulate the heart. Furthermore, the intrinsic cardiac nervous system does not appear to be primarily responsible for the heart rate and ventricular pressure variability found in intact hearts.
Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO synthase in rat vascular smooth muscle cells
Authors: Beasley D. , Eldridge M.
Published: December 2017

Cytokine-inducible nitric oxide (NO) production has been implicated in the pathogenesis of septic shock. The present study was designed to determine which cytokines induce expression of the NO synthase gene in rat aortic vascular smooth muscle cells (VSMC) in vitro and whether NO synthase gene expression is inducible in vivo. NO synthase mRNA appeared after 4-h exposure to interleukin-1 beta (IL-1 beta), and levels continued to increase up to 24 h. Levels of NO synthase transcripts were greatest in VSMC treated with IL-1 beta (1 nM), lower in VSMC treated with Escherichia coli lipopolysaccharide (LPS; 100 micrograms/ml), and just detectable in VSMC treated with tumor necrosis factor-alpha (TNF-alpha; 1 nM). IL-1 beta, TNF-alpha, and LPS each induced NO synthase activity, assessed by release of nitrite, conversion of L-arginine to L-citrulline, and increased levels of guanosine 3',5'-cyclic monophosphate, whereas IL-2, IL-6, and interferon-gamma were ineffective. IL-1 beta was more potent and effective than TNF-alpha; however, submaximal concentrations of TNF-alpha acted synergistically with IL-1 beta to induce NO synthase gene expression and activity. Inducible NO synthase mRNA was present in aorta from rats 6 h after treatment with LPS (5 mg/kg), but not at 24 h. Synergistic activation of NO synthase gene expression in VSMC by IL-1 beta and TNF-alpha may contribute to hypotension in sepsis.
Role of endothelium-derived relaxing factor in hindlimb reactive and active hyperemia in conscious dogs
Authors: O'Leary D. S. , Dunlap R. C. , Glover K. W.
Published: December 2017

We tested in conscious dogs whether endothelium-derived relaxing factor (EDRF) mediates hindlimb reactive and active hyperemia. Hindlimb reactive hyperemia was observed in response to release of a 1-min occlusion of the terminal aorta, and in separate studies, hindlimb active hyperemic responses to graded dynamic (treadmill) exercise were observed before and after inhibition of EDRF production [NG-nitro-L-arginine methyl ester (L-NAME); 5 mg/kg iv)]. At rest, L-NAME significantly increased mean arterial pressure (MAP) from control levels (100.6 +/- 6.2 vs. 125.0 +/- 7.3 mmHg) and significantly decreased heart rate (HR) (94.1 +/- 4.6 vs. 65.7 +/- 3.8 beats/min), terminal aortic blood flow (TAQ) (0.51 +/- 0.01 vs. 0.33 +/- 0.03 l/min), and terminal aortic vascular conductance (TAC) (5.2 +/- 0.4 vs. 2.7 +/- 0.1 ml.min-1.mmHg-1). L-NAME also significantly reduced the hindlimb hyperemia induced by intra-arterial acetylcholine (5 micrograms/kg). During reactive hyperemia L-NAME significantly reduced both the duration and maximal increase in TAC (16.2 +/- 1.6 vs. 10.4 +/- 0.8 s and 24.5 +/- 3.3 vs. 21.0 +/- 3.1 ml.min-1.mmHg-1, respectively). During graded exercise, MAP was significantly higher and HR significantly lower at each work load after L-NAME. During mild exercise, TAQ was significantly lower after L-NAME, whereas at higher work loads, L-NAME had no significant effect on TAQ. TAC was significantly reduced at each work load after L-NAME, but the difference from control remained constant with increasing work load; L-NAME caused a constant offset in TAC during graded exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of gluconeogenesis by insulin and glucagon in the neonatal bovine
Authors: Donkin S. S. , Armentano L. E.
Published: December 2017

Hepatocyte monolayers from neonatal calves were used to determine the effects of glucagon and insulin on incorporation of carbon from [2-14C]propionate, [1-14C]lactate, [U-14C]lactate, and [1,3-14C]glycerol into glucose and glycogen. Glucagon increased gluconeogenesis (nmol substrate incorporated into glucose or glycogen.micrograms DNA-1.h-1) from propionate and lactate but not from glycerol. Insulin decreased gluconeogenesis from [2-14C]propionate but was without effect on gluconeogenesis from [U-14C]lactate or [1,3-14C]glycerol. Net de novo glycogenesis (nmol substrate retained in cell glycogen.micrograms DNA-1.h-1) from propionate, lactate, and glycerol was decreased by glucagon and increased by insulin. Glucagon effects on gluconeogenesis, but not glycogenesis, were mimicked by dibutyryl adenosine 3',5'-cyclic monophosphate. Lactate flux through pyruvate carboxylase accounts for > or = 91% of lactate carbon flux to glucose, and this proportion was unchanged by glucagon or insulin. Gluconeogenesis from propionate and lactate is regulated by substrate concentration and glucagon in bovine hepatocyte monolayers. The data indicate that, in neonatal bovine liver, glucagon acts on a process common to lactate and propionate to increase gluconeogenesis, and insulin opposes these effects on gluconeogenesis from propionate but not lactate.
Persistence of circadian rhythmicity in hibernating ground squirrels
Authors: Grahn D. A. , Miller J. D. , Houng V. S. , Heller H. C.
Published: December 2017

The body temperatures (Tb) of golden-mantled ground squirrels maintained under constant dim light (< 20 1x red light) at an ambient temperature of 10 degrees C were monitored via telemetry throughout the hibernation season. During euthermia, when Tb ranged from 34 to 39 degrees C, these animals exhibited robust circadian Tb rhythms. During bouts of hibernation, when Tb rhythms persisted, although the amplitudes of the rhythms were considerably dampened compared with euthermia. The periods of the intrabout Tb rhythms were within the ranges observed during euthermia and were stable within an individual bout but varied between hibernation bouts. Arousals from hibernation occurred at a fixed phase angle of the Tb cycle. Once the period of an intrabout Tb rhythm was determined, it was possible to predict the timing of arousal from the hibernation bout to within 1 h of any 24-h period. This study confirms previous speculation about the persistence of circadian rhythms in golden-mantled ground squirrels during deep hibernation and demonstrates that the circadian system is involved in the timing of periodic arousals from hibernation.
Effects of 17 beta-estradiol and progesterone on pressor responses in conscious ovariectomized rats
Authors: Conrad K. P. , Mosher M. D. , Brinck-Johnsen T. , Colpoys M. C.
Published: December 2017

Attenuation of pressor responsiveness to several administered vasoconstrictors is a constant feature of normal gestation in humans and other species, such as the rat. However, the mechanism of this physiological adaptation remains uncertain. Because plasma levels of 17 beta-estradiol (E2) and progesterone (P) increase markedly during pregnancy, we tested the hypothesis that these hormones may mediate the reduced pressor responses. Seven days after bilateral ovariectomy and chronic instrumentation of rats, the pressor responses of arginine vasopressin, angiotensin II, and norepinephrine were tested on two occasions > or = 48 h apart. Then E2, P, or a combination of E2 and P was administered by subcutaneous implantation of 21-day-release steroid pellets. Pressor responses were again tested at various times throughout the period of steroid treatment. The plasma concentrations of the steroids were assessed by radio-immunoassay, and doses of the hormones were given that both approximated and exceeded circulating levels found in our laboratory for gravid rats. Despite chronic elevation of plasma E2 and/or P, we did not observe consistent attenuation of pressor responsiveness in any of the steroid-treatment regimens, nor was a decline in mean arterial pressure observed, which is typically found in rats during late gestation. In conclusion, we are unable to support the hypothesis that E2 and/or P contributes to the diminished pressor responsiveness of rat pregnancy.
Dual core and shell temperature regulation during sea acclimatization in Gentoo penguins (Pygoscelis papua)
Authors: Dumonteil E. , Barre H. , Rouanet J. L. , Diarra M. , Bouvier J.
Published: December 2017

Penguins are able to maintain a high and constant body temperature despite a thermally constraining environment. Evidence for progressive adaptation to cold and marine life was sought by comparing body and peripheral skin temperatures, metabolic rate, and thermal insulation in juvenile and adult Gentoo penguins exposed to various ambient temperatures in air (from -30 to +30 degrees C) and water (3-35 degrees C). Juvenile penguins in air showed metabolic and insulative capacities comparable with those displayed by adults. Both had a lower critical temperature (LCT) close to 0 degree C. In both adults and juveniles, the intercept of the metabolic curve with the abscissa at zero metabolic rate was far below body temperature. This was accompanied by a decrease in thermal insulation below LCT, allowing the preservation of a threshold temperature in the shell. However, this shell temperature maintenance was progressively abandoned in immersed penguins as adaptation to marine life developed, probably because of its prohibitive energy cost in water. Thus adaptation to cold air and to cold water does not rely on the same kind of reactions. Both of these strategies fail to follow the classical sequence linking metabolic and insulative reactions in the cold.
Inhibitory effect of neuropeptide Y on adrenergic and cholinergic transmission in rat urinary bladder and urethra
Authors: Tran L. V. , Somogyi G. T. , De Groat W. C.
Published: December 2017

The effects of porcine neuropeptide Y (NPY) on electrically evoked release of [3H]norepinephrine ([3H]NE) and [3H]acetylcholine ([3H]ACh) were investigated in isolated preparations of the rat lower urinary tract. In the urethra, NPY (0.02-0.5 microM) decreased the release of [3H]NE in a dose-dependent manner (10-53%). In the bladder base the inhibitory effect of NPY on [3H]NE release was not dose dependent. A low concentration (0.1 microM) decreased the release (38%), whereas a high concentration (0.5 microM) had no effect. However, in atropine-treated preparations, 0.5 microM NPY elicited a significant inhibition (43%). These observations suggest that 0.5 microM NPY elicits two opposing actions: a direct inhibitory action on adrenergic terminals and an indirect disinhibitory action to eliminate heterosynaptic cholinergic inhibition of [3H]NE release. In both tissues the action of NPY on [3H]NE release was not significantly modified by the alpha-adrenergic blocking agent yohimbine (1 microM). [3H]ACh release in the bladder body was not altered by 0.1 microM NPY but was suppressed (39%) by 1 microM NPY. The effect of NPY (1 microM) on [3H]ACh release was dependent on the frequency of stimulation. NPY suppressed the release at 2-Hz stimulation but had no significant effect at 20 Hz. These results suggest that NPY may have an important role in the neural regulation of the lower urinary tract by exerting differential effects on the release of cholinergic and adrenergic transmitters via autoinhibition and heterosynaptic interactions.
Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity
Authors: Eberhart G. P. , West D. B. , Boozer C. N. , Atkinson R. L.
Published: December 2017

We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.
Effect of intrahypothalamic insulin on sympathetic nervous function in rats drinking a high-sucrose solution
Authors: Porter J. P.
Published: December 2017

Hyperinsulinemia has been associated with increased sympathetic nervous activity. However, direct injection of insulin into the hypothalamus of anesthetized rats produces sympatho-inhibition. This discrepancy could be due to confounding effects of anesthesia or insulin resistance on central neural function. The effect of injecting saline or insulin (3.0 or 30 mU) into the ventromedial hypothalamus on mean arterial pressure, heart rate, and renal nerve activity (RNA) was investigated in conscious rats and in rats anesthetized with urethan or pentobarbital. Insulin decreased RNA in conscious rats but had no effect in pentobarbital-anesthetized rats. In urethan-anesthetized rats with hyperglycemia, the insulin increased RNA. Drinking a 10% sucrose solution enhanced the sympathoexcitatory effect of insulin in the urethan-anesthetized rats but had no effect in the other two groups. The sucrose solution did not affect insulin sensitivity in any group; however, urethan anesthesia did produce insulin resistance. These data show that central effects of insulin are sensitive to anesthesia and do not support a sympathoexcitatory role for insulin in the ventromedial hypothalamus of conscious rats, at least in relation to the renal sympathetic nerves.
Type II corticosteroid receptor stimulation increases NPY gene expression in basomedial hypothalamus of rats
Authors: White B. D. , Dean R. G. , Edwards G. L. , Martin R. J.
Published: December 2017

Evidence has suggested that glucocorticoids may increase neuropeptide Y (NPY) activity and gene expression. In the present study, we sought to determine the corticosteroid receptor subtype through which glucocorticoids increase NPY gene expression in the basomedial hypothalamus. This was accomplished by continuous administration of selective type I and II corticosteroid agonists in adrenalectomized Sprague-Dawley rats. Dot-blot analysis was performed, and the amount of NPY mRNA was determined. Additionally, serum insulin and glucose concentrations were determined. Type II receptor stimulation increased NPY mRNA levels in the basomedial hypothalamus above that of sham animals. This implies that type II receptor stimulation by high physiological concentrations of serum corticosterone may also increase NPY gene expression in the basomedial hypothalamus. The type II receptor agonist-induced increase in NPY gene expression did not appear to be mediated by a decrease in serum insulin concentrations. The present results may have relevance to the increased gene expression of NPY observed in the basomedial hypothalamus of obese Zucker rats and in food-deprived animals.
Rat hypothalamic NPY mRNA and brown fat uncoupling protein mRNA after high-carbohydrate or high-fat diets
Authors: Giraudo S. Q. , Kotz C. M. , Grace M. K. , Levine A. S. , Billington C. J.
Published: December 2017

We measured the influence of diet composition on hypothalamic neuropeptide Y (NPY) message and brown fat uncoupling protein (UCP) mRNA using different diets. Sprague-Dawley rats ate ad libitum either chow, a high-carbohydrate (HC), an intermediate-carbohydrate (IHC), a high-fat (HF), or an intermediate-fat (IHF) diet, all with equal protein content (g/kcal). The HF and IHF groups ate less food mass and, except for HC, all groups consumed similar kilocalories during the study. After 1 wk, we killed the animals and extracted total RNA from arcuate nucleus, cortex, and brown adipose tissue (BAT). Arcuate NPY mRNA in the HF group was significantly (P < 0.001) lower than in the HC and chow group. There were no differences between groups in NPY message in cortex or NPY protein in the paraventricular nucleus. BAT UCP message levels were significantly higher (P = 0.001) in the HF group. Thus HF compared with HC and chow diet reduces expression of NPY mRNA in hypothalamic nuclei and increases expression of BAT UCP message.
Ventilatory and metabolic effects of repeated hypoxia in conscious newborn rabbits
Authors: Trippenbach T.
Published: December 2017

To estimate posthypoxia depressing effects on newborns, ventilatory and metabolic effects of repeated hypoxia were studied in 1- to 3-day-old (group 1) and 2-wk-old (group 2) conscious rabbits. In group 1 (n = 18), ventilation was measured by means of a flow plethysmograph. The barometric method was used in group 2 (n = 21). In an additional 19 pups of group 1 and 17 rabbits of group 2, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured with an open-flow method. In control animals minute ventilation (VE), respiratory rate, tidal volume, VO2, and VCO2 were recorded at 10-min intervals for approximately 100 min in room air. All variables did not change with time. Separate sets of newborns were exposed five times for 10 min to 10% O2 in N2. Each exposure was followed by 10 min of recovery in room air. VE measured during recoveries after hypoxia always returned to normal in group 1. In group 2, the normoxic VE during the last recovery was greater than the first value in hypoxia-treated rabbits (P < 0.05) and greater than the last value in control rabbits (P < 0.02). Although the VE response to hypoxia was not affected by repetitive exposures in group 2, at minute 5 of the fifth exposure the VE response was greater than that during the first trial in group 1 (P < 0.02). Repetitive exposures had no effects on metabolic response to hypoxia in all pups. Results of this study indicate that hypoxia-related central inhibition, if developed during the exposures, is reversed by 10 min of breathing room air in newborns.(ABSTRACT TRUNCATED AT 250 WORDS)
Relative contribution of type I and II corticosterone receptors in VMH lesion-induced obesity and hyperinsulinemia
Authors: Thomas T. L. , Devenport L. D. , Stith R. D.
Published: December 2017

Ventromedial hypothalamic (VMH) lesion-induced obesity is accompanied by hyperinsulinemia and hyperphagia, which are dependent upon corticosterone (Cort) for their expression. Whether Cort exerts these actions through its stimulation of type I or II Cort receptor populations is unknown. Therefore, food intake and weight gain were measured in obese adrenalectomized VMH-lesioned rats given continuous infusion of various doses of either a type I-receptor agonist (aldosterone), a type II-receptor agonist (RU-28362), or several combination doses. Similarly, the receptor population responsible for lesion-induced hyperinsulinemia was identified. Type II receptor stimulation restored the hyperphagia, weight gain, and hyperinsulinemia of adrenalectomized VMH-lesioned animals, while type I receptor stimulation blocked their weight loss.
Role of hypothalamic neuropeptide Y gene expression in body weight regulation
Authors: Davies L. , Marks J. L.
Published: December 2017

Hypothalamic neuropeptide Y (NPY) may be involved in the hyperphagia that follows food deprivation associated with significant weight loss. However, it is unclear whether NPY is involved in body weight regulation under more physiological circumstances. Consequently, we measured body weight, food intake, arcuate nucleus (ARC) NPY mRNA, serum glucose, and insulin in male Wistar rats after 48 h of food deprivation and various refeeding protocols. Food deprivation produced a twofold increase in NPY mRNA, whereas 3 days of ad libitum refeeding returned body weight and NPY mRNA to control. If hyperphagia was prevented for 5 days during refeeding, then neither body weight nor NPY mRNA normalized. There were strong negative correlations between ARC NPY mRNA and both loss of body weight and serum insulin levels. These data suggest that hypothalamic NPY gene expression plays a role in control of body weight under physiological conditions. The data further suggest that NPY mRNA may be decreased by peripheral insulin levels.
L-arginine improves transmission of perfusion pressure to the renal interstitium in Dahl salt-sensitive rats
Authors: Patel A. R. , Granger J. P. , Kirchner K. A.
Published: December 2017

L-Arginine normalizes pressure natriuresis in Dahl salt-sensitive (DS) rats. To determine the role of renal interstitial hydrostatic pressure (RIHP) in this phenomenon, we measured RIHP determined by servo-null during acute changes in renal perfusion pressure in anesthetized DS rats receiving L-arginine (300 mg.kg-1.day-1 ip) or vehicle for 3 wk. Dahl salt-resistant (DR) rats were controls. As observed previously, the slope of the pressure-natriuresis relationship was greater (P < 0.05) in L-arginine-treated DS rats than vehicle DS rats and not different from DR rats. The slope of the relationship between renal perfusion pressure and RIHP was greater (P < 0.05) in DR rats than vehicle DS rats. In L-arginine-treated DS rats the slope of this relationship was greater (P < 0.05) than that in vehicle DS rats and not different from DR rats. Removal of the renal capsule blunted the pressure-natriuresis relationship in L-arginine-treated DS rats but had no effect in vehicle DS rats. Thus L-arginine improves transmission of perfusion pressure into the renal interstitium in DS rats and may contribute to the improved pressure-natriuresis response.
Circadian and ultradian rhythms of plasma thyroid hormone concentrations in lactating dairy cows
Authors: Bitman J. , Kahl S. , Wood D. L. , Lefcourt A. M.
Published: December 2017

Circadian and ultradian rhythms of thyroxine and triiodothyronine were analyzed by radioimmunoassay on integrated 15-min blood samples collected for 48 h from six lactating dairy cows. Body temperatures were recorded every 1.4 min using radiotelemetry. The cows were housed in an environmental chamber at 19.0 +/- 0.5 degrees C (lights on between 0700 and 2300 h), fed daily at 0900 h, and milked at 0800 and 2000 h. Mean concentrations of plasma triiodothyronine and thyroxine exhibited similar circadian rhythms with minima (0500-1300 h) and maxima (1700-0200 h) separated by 12 h. Triiodothyronine peaked 2 h before thyroxine. The thyroxine circadian rhythm preceded a circadian body temperature rhythm by 2 h. Superimposed on the circadian rhythm was an ultradian rhythm with a 90-min period that was 15-20% of the mean thyroid hormone concentrations. Peak thyroxine and triiodothyronine concentrations were 50 +/- 2 and 1.58 +/- 0.17 ng/ml, and minimal concentrations were 42 +/- 2 and 0.94 +/- 0.17 ng/ml, respectively. Our data indicate that peripheral triiodothyronine is regulated independently of peripheral thyroxine concentration.
Plasma volume and ion regulation during exercise after low- and high-carbohydrate diets
Authors: Lindinger M. I. , Spriet L. L. , Hultman E. , Putman T. , McKelvie R. S. , Lands L. C. , Jones N. L. , Heigenhauser G. J.
Published: December 2017

This study compared plasma volume (PV) and ion regulation during prolonged exercise in control vs. glycogen-depleted (GD) conditions, with emphasis on the initial minutes of exercise. In two trials separated by 1-2 wk, four adult males cycled at 75% of peak oxygen consumption (VO2) until exhaustion (50 +/- 7 min for GD) or until the GD exhaustion time in the control trial. Blood was sampled from catheters placed in the brachial artery and retrograde in the femoral vein (fv). Arterial PV decreased rapidly and by 15 min PV was 83% (control) and 88% (GD) of initial. The decrease in PV was accompanied by a net osmotic flux of water from plasma and inactive tissues to contracting muscles. The significantly greater decrease in PV in control compared with GD was associated with a higher muscle lactate content (Lac-; 36 vs. 17 mumol/g dry wt, respectively). Increases in plasma [Cl-] and [Na+] were less than predicted from decreased PV, indicating net loss of these ions from the plasma compartment. Increases in arterial and fv [K+] were 50% greater than could be accounted for by decreased PV, corresponding with increased arterial and fv plasma K+ contents. The rapid net release of K+ and Lac- from contracting muscle during the first few minutes of exercise in both trials was abolished (control) or reversed (GD) within 15 min of beginning exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in brown adipose tissue composition during fasting and refeeding of diet-induced obese mice
Authors: Muralidhara D. V. , Desautels M.
Published: December 2017

The objective of this work was to evaluate how obesity would influence the changes in brown fat (BAT) thermogenic capacity during fasting-refeeding. Mice fed either chow or chow + high-fat supplement for 6 wk had body weights of 34 +/- 1 and 43 +/- 1 g, respectively. They were fasted for 48 h followed by ad libitum refeeding for up to 5 days. Loss of carcass fat was similar between food-deprived mice previously fed chow or chow + high-fat supplement. However, even after a 48-h fast, obese mice still had a carcass fat content much greater than that of chow-fed mice. Brown fat atrophy caused by food deprivation was characterized by reductions in tissue weight, fat, mitochondrial proteins and uncoupling protein (UCP), without change in tissue DNA. Obesity did not alter the rate or extent of brown fat atrophy. Upon refeeding 48-h-fasted lean and obese mice, there was recovery of BAT thermogenic capacity that was similar between the two groups. In chow-fed mice, an intact neural input was essential for recovery of BAT thermogenic capacity during refeeding. These results indicate that food deprivation triggers an immediate adaptive response in mice previously fed chow or chow + a high-fat supplement and that reduction in brown fat thermogenic capacity during fasting and its recovery during refeeding appear little affected by the size of the animal energy reserves.
Utilization of dipeptides by the caprine mammary gland for milk protein synthesis
Authors: Backwell F. R. , Bequette B. J. , Wilson D. , Calder A. G. , Metcalf J. A. , Wray-Cahen D. , MacRae J. C. , Beever D. E. , Lobley G. E.
Published: December 2017

Specific use by the mammary gland in vivo of amino acids (AA) of peptide origin has been demonstrated in lactating dairy goats using a dual-labeled tracer technique involving close-arterial (external pudic artery, EPA) infusion of 13C-labeled dipeptides. The extent of utilization does not appear to differ for glycyl-L-[1-13C]phenylalanine and glycyl-L-[1-13C]leucine, perhaps indicative of a common mechanism by which AA are incorporated from peptide into milk protein. [1-13C]phenyl-alanine of peptide origin appears to be concentrated within the red blood cell, suggesting a role for the erythrocyte in peptide metabolism in vivo. In conclusion, it appears that the lactating mammary gland of goats has the ability to utilize AA of peptide origin for milk protein synthesis, and while the mechanism by which [1-13C]AA are incorporated into milk protein is not clear, it may involve peptide hydrolysis by either mammary cell surface or red blood cell hydrolases followed by uptake of liberated AA by the mammary gland.
Na+ transport and pH in principal cells of frog skin: effect of antidiuretic hormone
Authors: Lyall V. , Belcher T. S. , Miller J. H. , Biber T. U.
Published: December 2017

Intracellular pH (pHi), apical membrane potential (Va), and fractional apical membrane resistance (FRa) were measured in principal cells of isolated frog skin (Rana pipiens) with double-barreled microelectrodes under short-circuit conditions. Basolateral exposure to 10 mU/ml arginine vasotocin (AVT) depolarized Va by 30 mV, decreased FRa by 33%, increased short-circuit current (Isc) by 17 microA, and increased pHi by 0.17 pH units. The response of Va, Isc, and pHi occurred concurrently. Forskolin, theophylline, and 8-(4-chlorophenyl-thio)-adenosine 3',5'-cyclic monophosphate caused similar changes in Va, Isc, and pHi. The enhanced response of Isc, Va, and FRa to short pulses of apical amiloride applied during AVT or cAMP exposure suggests an increase in apical Na+ conductance. The presence of cAMP agonists also enhanced the response of pHi to amiloride. We conclude that the AVT- and cAMP-induced increase in Na+ transport across the apical cell membrane is associated with a change in pHi. These data are consistent with the hypothesis that changes in pHi may play a role in the second messenger cascade initiated by the antidiuretic hormone.
Interactive effects of food deprivation and exercise on reproductive function in female hamsters
Authors: Powers J. B. , Jetton A. E. , Wade G. N.
Published: December 2017

Two experiments evaluated the combined effects of food deprivation and runningwheel access on estrous cycles and estrous behavior of female hamsters. In experiment 1, food deprivation on days 1 and 2 of the estrous cycle disrupted the next expected ovulation, and this effect was more, rather than less, robust in females allowed to exercise in running wheels while they were deprived. In experiment 2, a similar protocol was used except the females were ovariectomized and received sequential injections of estradiol benzoate (EB; 5 micrograms) and progesterone (P; 200 micrograms) separated by 48 h to induce lordosis, which was tested 4-5 after P. Food deprivation concomitant with hormonal treatment diminished lordosis durations, but this effect was significant only among the females that were permitted to run in activity wheels. Previous findings demonstrated that access to running wheels attenuated the inhibitory effects of short photoperiod exposure on hamster estrous cycles. In contrast, the present results indicate that this same manipulation exaggerates rather than diminishes the inhibitory effects of food deprivation on estrous cycles and hormone-induced behavioral estrus.
Regulation of the adrenomedullary catecholaminergic system after mild, acute stress
Authors: Betito K. , Mitchell J. B. , Bhatnagar S. , Boksa P. , Meaney M. J.
Published: December 2017

The time course of regulation of rat adrenomedullary phenylethanolamine N-methyltransferase (PNMT) and tyrosine hydroxylase (TH) activity was studied after a single episode of 20-min restraint stress. Significant increases in PNMT and TH activity were observed 18 h after the beginning of the stress. The time course of acute stress-induced regulation of PNMT and TH was examined for the influence of neural and hormonal input. Unilateral denervation was performed, and the animals were exposed to a single episode of restraint. PNMT activity increased similarly in both the innervated and denervated adrenals, with a significant increase observed at 36 h after the stress. TH activity was similar in both denervated and innervated adrenals, with a significant increase observed at 24 and 36 h after stress. Finally, suppression of endogenous corticosterone with dexamethasone delayed the stress-induced increase in activity of PNMT but not TH. The present study indicates that increases in catecholamine biosynthetic enzymes can be observed after a single episode of mild, acute stress. In addition, glucocorticoids appear to be important in the time course of the stress-induced increase in PNMT but not TH activity, whereas neural input does not seem to affect the time course of these increases.
Measurement of plasma protein synthesis rate in infant pig: an investigation of alternative tracer approaches
Authors: Jahoor F. , Burrin D. G. , Reeds P. J. , Frazer M.
Published: December 2017

To devise a new method to measure plasma protein synthesis, we tested the hypothesis that, when [U-13C]glucose is used to produce [U-13C]alanine, plasma pyruvate and alanine will be in isotopic equilibrium with the alanine used to synthesize plasma proteins. The incorporation of labeled leucine, lysine, and alanine into very-low-density lipoprotein (VLDL) apolipoprotein B (apoB)-100, albumin, and fibrinogen was measured in seven infant pigs by infusing [U-13C]glucose, [2H3]leucine, and [2H4]lysine. The plateau enrichments of plasma alanine (2.29 +/- 0.29), pyruvate (2.5 +/- 0.33), and apoB-alanine (2.33 +/- 0.25) were not different. The fractional synthesis rates of fibrinogen and albumin calculated using the isotopic enrichments of apoB-bound lysine, leucine, and alanine as the precursor were similar to those based on plasma alanine. These results suggest that the intrahepatic precursor alanine pool and plasma alanine were in isotopic equilibrium. Thus plasma protein synthesis can be measured by infusing [U-13C]glucose and using plasma alanine as precursor.