bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of endothelin-1 and homologous trout endothelin on cardiovascular function in rainbow trout
Authors: Hoagland Todd M. , Weaver Leroy , Conlon J. Michael , Wang Yugi , Olson Kenneth R.
Published: December 2017

The cardiovascular effects of endothelin (ET)-1 and the recently sequenced homologous trout ET were examined in unanesthetized trout, and vascular capacitance curves were constructed to evaluate the responsiveness of the venous system to ET-1. A bolus dose of 667 pmol/kg ET-1 doubled ventral aortic pressure; produced a triphasic pressor-depressor-pressor response in dorsal aortic pressure (PDA); increased central venous pressure, gill resistance, and systemic resistance; and decreased cardiac output, heart rate, and stroke volume. These responses were dose dependent. Bolus injection of trout ET (333 or 1,000 pmol/kg) produced essentially identical, dose-dependent cardiovascular responses as ET-1. Dorsal aortic infusion of 1 and 3 pmol ⋅ kg−1⋅ min−1ET-1 and central venous infusion into the ductus Cuvier of 0.3 and 1 pmol ⋅ kg−1⋅ min−1produced similar dose-dependent cardiovascular responses, although the increase in PDAbecame monophasic. The heightened sensitivity to central venous infusion was presumably due to the more immediate exposure of the branchial vasculature to the peptide. Infusion of 1 pmol ⋅ kg−1⋅ min−1ET-1 decreased vascular compliance but had no effect on unstressed blood volume. These results show that ETs affect a variety of cardiovascular functions in trout and that branchial vascular resistance and venous compliance are especially sensitive. The multiplicity of effectors stimulated by ET suggests that this peptide was extensively integrated into cardiovascular function early on in vertebrate phylogeny.
Effect of NPY in the hypothalamic paraventricular nucleus on uncoupling proteins 1, 2, and 3 in the rat
Authors: Kotz C. M. , Wang C. F. , Briggs J. E. , Levine A. S. , Billington C. J.
Published: December 2017

Neuropeptide Y (NPY) injected into the hypothalamic paraventricular nucleus (PVN) stimulates feeding and decreases uncoupling protein (UCP)-1 mRNA in brown adipose tissue (BAT). The present studies were undertaken to determine whether UCP-2 in white adipose tissue (WAT) and UCP-3 in muscle are regulated by NPY in the PVN. PVN-cannulated male Sprague-Dawley rats were injected with either saline or NPY (PVN, 117 pmol, 0.5 μl) every 6 h for 24 h. NPY in the PVN stimulated feeding and decreased UCP-1 mRNA in BAT independent of NPY-induced feeding. UCP-2 mRNA in WAT was unchanged by NPY. In acromiotrapezius muscle, NPY decreased UCP-3 mRNA, but this was reversed by restricting food intake to control levels. In biceps femoris muscle, NPY alone had no effect on UCP-3 mRNA, but UCP-3 mRNA was significantly increased in the NPY-treated rats that were restricted to control levels of intake. These results suggest that UCP-2 in WAT and UCP-3 in muscle are not subject to specific regulation by NPY in the PVN.
Interstitial pH, K+, lactate, and phosphate determined with MSNA during exercise in humans
Authors: MacLean David A. , Imadojemu Virginia A. , Sinoway Lawrence I.
Published: December 2017

The purpose of the present study was to use the microdialysis technique to simultaneously measure the interstitial concentrations of several putative stimulators of the exercise pressor reflex during 5 min of intermittent static quadriceps exercise in humans ( n = 7). Exercise resulted in approximately a threefold ( P < 0.05) increase in muscle sympathetic nerve activity (MSNA) and 13 ± 3 beats/min ( P < 0.05) and 20 ± 2 mmHg ( P < 0.05) increases in heart rate and blood pressure, respectively. During recovery, all reflex responses quickly returned to baseline. Interstitial lactate levels were increased ( P < 0.05) from rest (1.1 ± 0.1 mM) to exercise (1.6 ± 0.2 mM) and were further increased ( P < 0.05) during recovery (2.0 ± 0.2 mM). Dialysate phosphate concentrations were 0.55 ± 0.04, 0.71 ± 0.05, and 0.48 ± 0.03 mM during rest, exercise, and recovery, respectively, and were significantly elevated during exercise. At the onset of exercise, dialysate K+ levels rose rapidly above resting values (4.2 ± 0.1 meq/l) and continued to increase during the exercise bout. After 5 min of contractions, dialysate K+ levels had peaked with an increase ( P < 0.05) of 0.6 ± 0.1 meq/l and subsequently decreased during recovery, not being different from rest after 3 min. In contrast, H+ concentrations rapidly decreased ( P < 0.05) from resting levels (69.4 ± 3.7 nM) during quadriceps exercise and continued to decrease with a mean decline ( P < 0.05) of 16.7 ± 3.8 nM being achieved after 5 min. During recovery, H+ concentrations rapidly increased and were not significantly different from baseline after 1 min. This study represents the first time that skeletal muscle interstitial pH, K+, lactate, and phosphate have been measured in conjunction with MSNA, heart rate, and blood pressure during intermittent static quadriceps exercise in humans. These data suggest that interstitial K+ and phosphate, but not lactate and H+, may contribute to the stimulation of the exercise pressor reflex.
Myocardial renin is neither necessary nor sufficient to initiate or maintain ventricular hypertrophy
Authors: Katz Stephen A. , Opsahl John A. , Wernsing Shane E. , Forbis Lynn M. , Smith Juline , Heller Lois J.
Published: December 2017

We tested the hypothesis that the myocardial renin-angiotensin system (RAS) is both necessary and sufficient to initiate and maintain all classes of ventricular hypertrophy. Myocardial and plasma renin and angiotensinogen were measured in rats during initiation and maintenance of ventricular hypertrophy associated with DOCA implants and 1% NaCl drinking water, with and without the AT1 ANG II receptor blocker losartan. Additional groups of rats were given a low-sodium diet (0.04%) for 3 wk. Ventricular hypertrophy was initiated within 7 days and maintained for 35 days in DOCA-treated rats despite significantly low myocardial and plasma renin, normal or low myocardial and plasma angiotensinogen, or the presence of losartan. Furthermore, there was no ventricular hypertrophy in low-salt diet-fed animals despite increased myocardial and plasma renin levels and normal angiotensinogen levels. Therefore, the myocardial RAS is not necessary to initiate or maintain cardiac hypertrophy in DOCA-treated rats and is not sufficient to initiate cardiac hypertrophy in low-salt diet-fed rats. Additionally, myocardial renin and angiotensinogen were significantly correlated with corresponding plasma levels.
Phosphorylating pathways and fatigue development in contractingXenopussingle skeletal muscle fibers
Authors: Stary Creed M. , Hogan Michael C.
Published: December 2017

To investigate the differential contribution of oxidative and substrate-level phosphorylation to force production during repetitive, maximal tetanic contractions, single skeletal muscle fiber performance was examined under conditions of high-oxygen availability and anoxia. Tetanic force development (P) was measured in isolated, single type-1 muscle fibers (fast twitch; n = 6) dissected from Xenopus lumbrical muscle while being stimulated at increasing frequencies (0.25, 0.33, and 0.5 Hz), with each frequency lasting 2 min. Two separate work bouts were conducted, with the perfusate [Formula: see text]being either 0 or 159 mmHg. No significant ( P < 0.05) difference was found in the initial peak tensions (P0) between the high (334 ± 57 kPa) and the low (325 ± 41 kPa) [Formula: see text]treatment. No significant difference in P was observed between the treatments during the first 50 s. However, a significant difference in force production was observed between the high (P/P0= 0.96 ± 0.02) and the low [Formula: see text] condition (P/P0= 0.92 ± 0.02) by 60 s of work. After 60 s, steady-state force production was maintained during the high compared with the low [Formula: see text] condition until stimulation frequency was increased, at which point developed tension during the high [Formula: see text] condition began to decline. Time to fatigue (P/P0= 0.3) was reached significantly sooner during the low (250 ± 16 s) than the high[Formula: see text] condition (367 ± 28 s). These results demonstrate that during the first 50 s of 0.25-Hz contractions, substrate-level phosphorylation has the capacity to maintain force and ATP hydrolysis when oxidative phosphorylation is absent. This period was followed by an oxygen-dependent phase in which force generation was maintained during the high [Formula: see text]condition (but not during the low [Formula: see text]condition) until the onset of a final fatiguing phase, at which a calculated maximal rate of oxidative phosphorylation was reached.
Insulin-like growth factor I mediates high-fat diet-induced adipogenesis in Osborne-Mendel rats
Authors: Marques Brenda G. , Hausman Dorothy B. , Latimer Amanda M. , Kras Krystyna M. , Grossman Barbara Mullen , Martin Roy J.
Published: December 2017

To determine if high-fat (HF) diet-induced changes in adipose tissue cellularity are associated with the presence of paracrine growth factor(s) that alter preadipocyte proliferation, Osborne-Mendel rats were fed either a HF (76% energy) or a low-fat (LF, 12% energy) diet for 85 days. HF-fed rats had greater ( P < 0.05) fat pad size, total fat cell number, number of small (30–70 μm) and large (80–140 μm) adipocytes, and percentage of 100- to 140-μm adipocytes compared with LF-fed rats. Preadipocytes in primary cell culture treated with inguinal adipose tissue conditioned medium (ATCM) prepared from HF-fed rats had greater ( P < 0.05) proliferation compared with cultures treated with ATCM from LF-fed rats. Proliferative capacity of ATCM prepared from HF-fed rats was attenuated after the stripping of the medium of insulin-like growth factor I using an immunomagnetic bead separation system. These data are consistent with the concept that insulin-like growth factor I is involved in the paracrine regulation of adipogenesis.
Pressor effects of orexins injected intracisternally and to rostral ventrolateral medulla of anesthetized rats
Authors: Chen Chiung-Tong , Hwang Ling-Ling , Chang Jaw-Kang , Dun Nae J.
Published: December 2017

Orexin A and B, two recently isolated hypothalamic peptides, have been reported to increase food consumption upon intracerebroventricular injections in rats. In addition to the hypothalamus, orexin A-immunoreactive fibers have been observed in several areas of the medulla that are associated with cardiovascular functions. The present study was undertaken to evaluate the hypothesis that orexins may influence cardiovascular response by interacting with neurons in the medulla. Intracisternal injections of orexins A (0.0056–7.0 nmol) or B (0.028–0.28 nmol) dose dependently increased mean arterial pressure (MAP) by 4–27 mmHg and heart rate (HR) by 26–80 beats/min in urethan-anesthetized rats, with orexin A being more effective in this regard. MAP and HR were not changed by intravenous injection of orexins at higher concentrations. Microinjection of orexin A (14 pmol/50.6 nl) to the rostral ventrolateral medulla, which was confirmed by histological examination, increased MAP and HR. Our results indicate that, in addition to a role in positive feeding behavior, orexins may enhance cardiovascular response via an action on medullary neurons.
Skeletal and cardiac muscle protein turnover during cold acclimation in young rats
Authors: McAllister T. A. , Thompson J. R. , Samuels S. E.
Published: December 2017

The effect of long-term cold exposure on skeletal and cardiac muscle protein turnover was investigated in young growing animals. Two groups of 36 male 28-day-old rats were maintained at either 5°C (cold) or 25°C (control). Rates of protein synthesis and degradation were measured in vivo on days 5, 10, 15, and 20. Protein mass by day 20 was ∼28% lower in skeletal muscle (gastrocnemius and soleus) and ∼24% higher in heart in cold compared with control rats ( P < 0.05). In skeletal muscle, the fractional rates of protein synthesis ( ksyn) and degradation ( kdeg) were not significantly different between cold and control rats, although ksynwas lower (approximately −26%) in cold rats on day 5; consequent to the lower protein mass, the absolute rates of protein synthesis (approximately −21%; P < 0.05) and degradation (approximately −13%; P < 0.1) were lower in cold compared with control rats. In heart, overall, ksyn(approximately +12%; P < 0.1) and kdeg(approximately +22%; P < 0.05) were higher in cold compared with control rats; consequently, the absolute rates of synthesis (approximately +44%) and degradation (approximately +54%) were higher in cold compared with control rats ( P < 0.05). Plasma triiodothyronine concentration was higher ( P < 0.05) in cold compared with control rats. These data indicate that long-term cold acclimation in skeletal muscle is associated with the establishment of a new homeostasis in protein turnover with decreased protein mass and normal fractional rates of protein turnover. In heart, unlike skeletal muscle, rates of protein turnover did not appear to immediately return to normal as increased rates of protein turnover were observed beyond day 5. These data also indicate that increased rates of protein turnover in skeletal muscle are unlikely to contribute to increased metabolic heat production during cold acclimation.
Hyperthermia stimulates energy-proteasome-dependent protein degradation in cultured myotubes
Authors: Luo Guang-Ju , Sun Xiaoyan , Hasselgren Per-Olof
Published: December 2017

Previous studies suggest that elevated temperature stimulates protein degradation in skeletal muscle, but the intracellular mechanisms are not fully understood. We tested the role of different proteolytic pathways in temperature-dependent degradation of long- and short-lived proteins in cultured L6 myotubes. When cells were cultured at different temperatures from 37 to 43°C, the degradation of both classes of proteins increased, with a maximal effect noted at 41°C. The effect of high temperature was more pronounced on long-lived than on short-lived protein degradation. By using blockers of individual proteolytic pathways, we found evidence that the increased degradation of both long-lived and short-lived proteins at high temperature was independent of lysosomal and calcium-mediated mechanisms but reflected energy-proteasome-dependent degradation. mRNA levels for enzymes and other components of different proteolytic pathways were not influenced by high temperature. The results suggest that hyperthermia stimulates the degradation of muscle proteins and that this effect of temperature is regulated by similar mechanisms for short- and long-lived proteins. Elevated temperature may contribute to the catabolic response in skeletal muscle typically seen in sepsis and severe infection.
Regulation of NHE3 activity by G protein subunits in renal brush-border membranes
Authors: Albrecht Frederick E. , Xu Jing , Moe Orson W. , Hopfer Ulrich , Simonds William F. , Orlowski John , Jose Pedro A.
Published: December 2017

NHE3 activity is regulated by phosphorylation/dephosphorylation processes and membrane recycling in intact cells. However, the Na+/H+exchanger (NHE) can also be regulated by G proteins independent of cytoplasmic second messengers, but the G protein subunits involved in this regulation are not known. Therefore, we studied G protein subunit regulation of NHE3 activity in renal brush-border membrane vesicles (BBMV) in a system devoid of cytoplasmic components and second messengers. Basal NHE3 activity was not regulated by Gsα or Giα, because antibodies to these G proteins by themselves were without effect. The inhibitory effect of D1-like agonists on NHE3 activity was mediated, in part, by Gsα, because it was partially reversed by anti-Gsα antibodies. Moreover, the amount of Gsα that coimmunoprecipitated with NHE3 was increased by fenoldopam in both brush-border membranes and renal proximal tubule cells. Furthermore, guanosine 5′- O-(3-thiotriphosphate) but not guanosine 5′- O-(2-thiodiphosphate), the inactive analog of GDP, increased the amount of Gsα that coimmunoprecipitated with NHE3. The α2-adrenergic agonist, UK-14304 or pertussis toxin (PTX) alone had no effect on NHE3 activity, but UK-14304 and PTX treatment attenuated the D1-like receptor-mediated NHE3 inhibition. The ability of UK-14304 to attenuate the D1-like agonist effect was not due to Giα, because the attenuation was not blocked by anti-Giα antibodies or by PTX. Anti-Gβcommonantibodies, by themselves, slightly inhibited NHE3 activity but had little effect on D1-like receptor-mediated NHE3 inhibition. However, anti-Gβcommonantibodies reversed the effects of UK-14304 and PTX on D1-like agonist-mediated NHE3 inhibition. These studies provide concrete evidence of a direct regulatory role for Gsα, independent of second messengers, in the D1-like-mediated inhibition of NHE3 activity in rat renal BBMV. In addition, β/γ dimers of heterotrimeric G proteins appear to have a stimulatory effect on NHE3 activity in BBMV.
Role of intrarenal α2-adrenoceptors in the renal responses to xylazine in rats
Authors: Menegaz Rubia G. , Kapusta Daniel R. , Cabral Antonio M.
Published: December 2017

This study examined the contribution of intrarenal α2-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (UNaV) responses in ketamine-xylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the α2-adrenoceptor antagonist yohimbine (5 μg) significantly decreased V from 58 ± 8 to 35 ± 7 μl ⋅ min−1⋅ g kidney wt−1and UNaV from 2.8 ± 0.4 to 2.1 ± 0.4 μeq ⋅ min−1⋅ g kidney wt−1without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bilaterally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yohimbine (15 μg) significantly reduced left and right kidney V, with no effects on UNaV. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg), 20 min after intravenous injection, significantly decreased V from 63 ± 9 to 13 ± 2 μl ⋅ min−1⋅ g kidney wt−1and UNaV from 4.5 ± 0.5 to 1.1 ± 0.1 μeq ⋅ min−1⋅ g kidney wt−1. In RDNX rats, this dose of yohimbine reduced V and UNaV, but the magnitude was blunted compared with intact rats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and UNaV to similar magnitudes in intact and RDNX groups. Together, these findings indicate that intravenous xylazine acts by renal nerve-dependent and -independent mechanisms to enhance renal excretory function in ketamine-anesthetized rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal action to augment the renal excretion of water and sodium via a presynaptic α2-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.
Regulation of myofibrillar protein turnover during maturation in normal and undernourished rat pups
Authors: Fiorotto Marta L. , Davis Teresa A. , Reeds Peter J.
Published: December 2017

The study tested the hypothesis that a higher rate of myofibrillar than sarcoplasmic protein synthesis is responsible for the rapid postdifferentiation accumulation of myofibrils and that an inadequate nutrient intake will compromise primarily myofibrillar protein synthesis. Myofibrillar (total and individual) and sarcoplasmic protein synthesis, accretion, and degradation rates were measured in vivo in well-nourished (C) rat pups at 6, 15, and 28 days of age and compared at 6 and 15 days of age with pups undernourished (UN) from birth. In 6-day-old C pups, a higher myofibrillar than sarcoplasmic protein synthesis rate accounted for the greater deposition of myofibrillar than sarcoplasmic proteins. The fractional synthesis rates of both protein compartments decreased with age, but to a greater degree for myofibrillar proteins (−54 vs. −42%). These decreases in synthesis rates were partially offset by reductions in degradation rates, and from 15 days, myofibrillar and sarcoplasmic proteins were deposited in constant proportion to one another. Undernutrition reduced both myofibrillar and sarcoplasmic protein synthesis rates, and the effect was greater at 6 (−25%) than 15 days (−15%). Decreases in their respective degradation rates minimized the effect of undernutrition on sarcoplasmic protein accretion from 4 to 8 days and on myofibrillar proteins from 13 to 17 days. Although these adaptations in protein turnover reduced overall growth of muscle mass, they mitigated the effects of undernutrition on the normal maturational changes in myofibrillar protein concentration.
Relationship of atypical melatonin rhythm with two circadian clock outputs in B6D2F1 mice
Authors: Li Xiao-Mei , Liu Xu-Hui , Filipski Elisabeth , Metzger Gérard , Delagrange Philippe , Jeanniot Jean-Philippe , Lévi Francis
Published: December 2017

Circadian rhythms in body temperature, locomotor activity, and the circadian changes of plasma and pineal melatonin content were investigated in B6D2F1mice synchronized by 12 h of light and 12 h of darkness. During 8 wk continuous recording, activity and temperature displayed a marked stable and reproducible circadian rhythm, with both peaks occurring near the middle of darkness. Both 24- and 12-h rhythmic components were also significantly detected. Mean plasma melatonin concentration rose steadily during the light span and reached a maximum (30.6 ± 10.0 pg/ml) at 11 h after light onset (HALO), then gradually decreased after the onset of darkness to a nadir (4.7 ± 0.4 pg/ml) at 20 HALO. Mean pineal content followed a pattern parallel to that of plasma concentration (peak at 11 HALO: 17.7 ± 1.0 pg/gland; trough at 17 HALO: 4.7 ± 1.0 pg/gland). In addition, a second sharp peak was observed at 21 HALO (20.2 ± 3.5 pg/gland). Plasma and pineal contents displayed large and statistically significant circadian changes, with a composite rhythm of period (24 + 12 h). This mouse model has predominant production and secretion of melatonin during the day. This possibly contributes to a similar coupling between chronopharmacology mechanisms and the rest-activity cycle in these mice and in human subjects.
Hepatoportal bumetanide-sensitive K+-sensor mechanism controls urinary K+ excretion
Authors: Morita Hironobu , Fujiki Nobuhiro , Miyahara Taro , Lee Ken , Tanaka Kunihiko
Published: December 2017

To determine whether a K+-sensor mechanism exists in the hepatoportal region, periarterial hepatic afferent nerve activity responses to intraportal injection of KCl were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to intraportal injection in a K+ concentration-dependent manner, and the increase was attenuated by inhibition of the Na+-K+-2Cl− cotransporter by bumetanide in a dose-dependent manner. These results suggest that a bumetanide-sensitive K+-sensor mechanism exists in the hepatoportal region. Stimulation of this mechanism by intraportal KCl infusion elicited an immediate and powerful kaliuresis with no significant change in the plasma K+ concentration; this was significantly greater than the kaliuresis induced by intravenous KCl infusion and was attenuated by severing the periarterial hepatic nervous plexus. These results indicate that a hepatoportal bumetanide-sensitive K+-sensor mechanism senses the portal venous K+ concentration and that stimulation of this sensor mechanism causes kaliuresis, which is mainly mediated by the periarterial hepatic nervous plexus.
LPS-induced liver injury ind-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor
Authors: Nowak Monika , Gaines Gregory C. , Rosenberg Jason , Minter Rebecca , Bahjat F. R. , Rectenwald John , MacKay Sally L. D. , Edwards Carl K. , Moldawer Lyle L.
Published: December 2017

Lipopolysaccharide andd-galactosamine induced lethality and apoptotic liver injury is dependent on endogenously produced tumor necrosis factor (TNF)-α. The present study was undertaken to determine whether membrane-associated or secreted TNF-α signaling through the p55 or p75 receptor was responsible for survival and hepatic injury after lipopolysaccharide administration ind-galactosamine-sensitized mice. Transgenic mice expressing null forms of TNF-α, the p55 and p75 receptor, and mice expressing only a cell-associated form of TNF-α were challenged with 8 mgd-galactosamine and 100 ng lipopolysaccharide. Mortality and apoptotic liver injury were only seen in wild-type and p75 knockout mice. p75 Knockout mice had significantly higher concentrations of plasma TNF-α than any other experimental group ( P ≤ 0.05) and tended to have the highest mortality and liver injury. In contrast, p55 and TNF-α knockout mice and animals expressing only a cell-associated form of TNF-α exhibited no mortality or liver injury. We conclude that survival and apoptotic liver injury in response to lipopolysaccharide and d-galactosamine are dependent exclusively on secreted TNF-α signaling through the p55 receptor.
Relationship between increasing duodenal lipid doses, gastric perception, and plasma hormone levels in humans
Authors: Feinle Christine , Grundy David , Otto Bärbel , Fried Michael
Published: December 2017

Duodenal lipid causes gastric relaxation, CCK secretion, and nausea. Vasopressin has been implicated in motion sickness-related nausea. We hypothesized that increasing doses of lipid enhance gastric relaxation and CCK-vasopressin secretion, resulting in a dose-related exacerbation of nausea. Nine healthy subjects received isotonic saline or lipid (1, 2, or 3 kcal/min, L1, L2, L3) duodenally. Changes in gastric volume, sensations, and plasma hormone levels were assessed during infusions and isobaric gastric distensions. Lipid infusions increased gastric volume, plasma CCK (but not vasopressin) levels, and gastric compliance during distensions, compared with saline. Plasma CCK levels were related to the dose of lipid administered [CCK levels at 30 min (pmol/l), saline: 1.1 ± 0.2, L1: 1.8 ± 0.2, L2: 3.0 ± 0.2, L3: 4.3 ± 0.6]. During distensions, nausea increased in intensity with increasing doses of lipid [score (where 0 is no sensation and 100 is strongest sensation), saline: 7 ± 4, L1: 19 ± 7, L2: 44 ± 7, L3: 66 ± 8]; however, no further rise in plasma CCK occurred. Because neither lipid nor distension alone induced significant nausea, we conclude that the interaction between these stimuli together with a modulation by CCK is responsible for the effects observed. Vasopressin is not involved in lipid- and distension-induced nausea.
Hyperthermia impairs liver mitochondrial function in vitro
Authors: Willis W. T. , Jackman M. R. , Bizeau M. E. , Pagliassotti M. J. , Hazel J. R.
Published: December 2017

The effects of temperature on the relationships among the rates of pyruvate carboxylation, O2uptake ( Jo), oxidative phosphorylation ( Jp), and the free energy of ATP hydrolysis ( Gp) were studied in liver mitochondria isolated from 250-g female rats. Pyruvate carboxylation was evaluated at 37, 40, and 43°C. In disrupted mitochondria, pyruvate carboxylase maximal reaction velocity increased from 37 to 43°C with an apparent Q10of 2.25. A reduction in ATP/ADP ratio decreased enzyme activity at all three temperatures. In contrast, in intact mitochondria, increasing temperature failed to increase pyruvate carboxylation (malate + citrate accumulation) but did result in increased Joand decreased extramitochondrial Gp. Jpwas studied in respiring mitochondria at 37 and 43°C at various fractions of state 3 respiration, elicited with a glucose + hexokinase ADP-regenerating system. The relationship between Joand Gpwas similar at both temperatures. However, hyperthermia (43°C) reduced the Jp/ Joratio, resulting in lower Gpfor a given Jp. Fluorescent measurements of membrane phospholipid polarization revealed a transition in membrane order between 40 and 43°C, a finding consistent with increased membrane proton conductance. It is concluded that hyperthermia augments nonspecific proton leaking across the inner mitochondrial membrane, and the resultant degraded energy state offsets temperature stimulation of pyruvate carboxylase. As a consequence, at high temperatures approaching 43°C, the pyruvate carboxylation rate of intact liver mitochondria may fail to exhibit a Q10effect.
Acute effects of light on body temperature and activity in Syrian hamsters: influence of circadian phase
Authors: Song Xiaowei , Rusak Benjamin
Published: December 2017

Light exposure at night causes an acute increase in human body temperature, which normally falls during the night. This change is largely attributable to the suppression by light of the nocturnal rise in melatonin levels. Little is known, however, about the effects of light on body temperature in nocturnally active mammals in which the nightly peak in melatonin secretion coincides with the circadian phase of elevated, rather than decreased, body temperature. We investigated the effects of a 1-h exposure to light on body temperature and activity of Syrian hamsters, Mesocricetus auratus, at two phases during the night and at two phases during the projected day. Brain or abdominal temperature was recorded continuously using implanted radio transmitters while locomotor activity was monitored simultaneously using a passive infrared movement detector. Responses to light exposure were strongly circadian phase dependent; light during the night caused elevations in both brain and core body temperature, whereas light during the projected day did not. Temperature increases at night could not be attributed solely to activity increases at the onset of light pulses, indicating a contribution from nonbehavioral mechanisms of thermogenesis. These results provide the first evidence for circadian modulation of acute temperature responses to light in a nocturnal mammal.
Photic phase response curve in Octodon degus: assessment as a function of activity phase preference
Authors: Kas Martien J. H. , Edgar Dale M.
Published: December 2017

Light exposure during the early and late subjective night generally phase delays and advances circadian rhythms, respectively. However, this generality was recently questioned in a photic entrainment study in Octodon degus. Because degus can invert their activity phase preference from diurnal to nocturnal as a function of activity level, assessment of phase preference is critical for computations of phase reference [circadian time (CT) 0] toward the development of a photic phase response curve. After determining activity phase preference in a 24-h light-dark cycle (LD 12:12), degus were released in constant darkness. In this study, diurnal ( n = 5) and nocturnal ( n = 7) degus were randomly subjected to 1-h light pulses (30–35 lx) at many circadian phases (CT 1–6: n= 7; CT 7–12: n = 8; CT 13–18: n = 8; and CT 19–24: n = 7). The circadian phase of body temperature (Tb) onset was defined as CT 12 in nocturnal animals. In diurnal animals, CT 0 was determined as Tb onset + 1 h. Light phase delayed and advanced circadian rhythms when delivered during the early (CT 13–16) and late (CT 20–23) subjective night, respectively. No significant phase shifts were observed during the middle of the subjective day (CT 3–10). Thus, regardless of activity phase preference, photic entrainment of the circadian pacemaker in Octodon degus is similar to most other diurnal and nocturnal species, suggesting that entrainment mechanisms do not determine overt diurnal and nocturnal behavior.
Energy intake-independent modulation of triglyceride metabolism by glucocorticoids in the rat
Authors: Mantha Line , Deshaies Yves
Published: December 2017

This study aimed to dissociate the peripheral effects of adrenalectomy (ADX) on triglyceride (TG) metabolism from those it exerts centrally on energy intake and to determine the impact of diet composition therein. Rats were fed either rodent chow or a diet high in sucrose and fat (HSF) and were adrenalectomized or left intact and pair fed to the ADX animals. Liver TG content, an index of hepatic TG production, was not affected by ADX, but was increased twofold by the HSF diet. ADX decreased the rate of hepatic TG secretion by 41% in chow-fed but not in HSF-fed animals. Triglyceridemia and postheparin plasma lipase activities remained largely unchanged by treatments. ADX decreased insulinemia fivefold in chow-fed rats, but less so in HSF-fed animals. Likewise, subcutaneous and visceral adipose depots were 40–60% smaller in ADX than in intact pair-fed rats given chow, but the effect of ADX was dampened by consumption of the HSF diet. Although smaller, adipose tissues of ADX rats maintained a higher activity of lipoprotein lipase (LPL) than those of intact pair-fed rats, whereas muscle LPL was decreased. The study confirms that in the presence of reduced energy intake, corticosterone contributes to the maintenance of adipose stores and that the consequences of its absence tend to be attenuated when a high-energy diet is fed. The study further shows that, contrary to ad libitum feeding conditions, most determinants of TG metabolism, such as hepatic TG stores, triglyceridemia, postheparin plasma LPL, and adipose tissue LPL, are minimally affected by glucocorticoids when consumption of a high-energy diet is restricted, suggesting that glucocorticoids affect TG metabolism mostly indirectly through their central action on ingestive behavior.
Correlation structure of end-expiratory lung volume in anesthetized rats with intact upper airway
Authors: Zhang Xiaobin , Bruce Eugene N.
Published: December 2017

The correlation structure of breath-to-breath fluctuations of end-expiratory lung volume (EEV) was studied in anesthetized rats with intact airways subjected to positive and negative transrespiratory pressure (i.e., PTRP and NTRP, correspondingly). The Hurst exponent, H, was estimated from EEV fluctuations using modified dispersional analysis. We found that H for EEV was 0.5362 ± 0.0763 and 0.6403 ± 0.0561 with PTRP and NTRP, respectively (mean ± SD). Both H were significantly different from those obtained after random shuffling of the original time series. Also, H with NTRP was significantly greater than that with PTRP ( P = 0.029). We conclude that in rats breathing through the upper airway, a positive long-term correlation is present in EEV that is different between PTRP and NTRP.
Ontogeny of neuronal nitric oxide synthase, NOS I, in the developing porcine kidney
Authors: Solhaug Michael J. , Dong Xui Q. , Adelman Raymond D. , Dong Ke-Wen
Published: December 2017

To determine if the developing kidney differs from the adult in the expression of the neuronal nitric oxide synthase, NOS I, these experiments measured mRNA gene expression by RNase protection assay and protein content by Western blot of NOS I in piglets at ages newborn and 3, 7, 10, 14, and 21 days and adult pigs. Whole kidney NOS I mRNA was greatest at birth and decreased progressively during renal maturation to adult levels. NOS I protein content paralleled this developmental pattern. Cortical NOS I protein was equivalent in newborn and 14-day-old piglets and was greater at both ages than the adult. Medullary NOS I protein was relatively greater than cortical in both immature ages and decreased from a peak at birth to adult levels. We conclude the following. 1) During postnatal maturation, renal NOS I mRNA and protein content show a pattern that is developmentally regulated. 2) This developmental pattern of NOS I after birth may, in part, contribute to the enhanced functional role of NO during renal maturation.
Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo
Authors: Takahashi Yasushi , Roman Christine , Chemtob Sylvain , Tse Mary M. , Lin Emil , Heymann Michael A. , Clyman Ronald I.
Published: December 2017

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents; however, they also have adverse fetal effects such as constriction of the fetal ductus arteriosus. Recently, selective COX-2 inhibitors have been used in the management of preterm labor in the hope of avoiding fetal complications. However, both COX-1 and -2 are expressed by cells of the ductus arteriosus. We used fetal lambs (0.88 gestation) to assess the ability of selective COX-2 inhibitors celecoxib and NS398 to affect the ductus arteriosus. Both selective COX-2 inhibitors decreased PGE2and 6ketoPGF1αproduction in vitro; both inhibitors constricted the isolated ductus in vitro. The nonselective COX-1/COX-2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro. We used a prodrug of celecoxib to achieve 1.4 ± 0.6 μg/ml, mean ± standard deviation, of the active drug in vivo. This concentration of celecoxib produced both an increase in pressure gradient and resistance across the ductus; celecoxib also decreased fetal plasma concentrations of PGE2and 6ketoPGF1α. Indomethacin (0.7 ± 0.2 μg/ml) produced a significantly greater fall in ductus blood flow than celecoxib and tended to have a greater effect on ductus resistence in vivo. We conclude that caution should be used when recommending COX-2 inhibitors for use in pregnant women, because COX-2 appears to play a significant role in maintaining patency of the fetal ductus arteriosus.
Inhibitory effect of gurmarin on palatal taste responses to amino acids in the rat
Authors: Harada Shuitsu , Kasahara Yasuo
Published: December 2017

Gurmarin (10 μg/ml), a protein extracted from Gymnema sylvestre, depressed significantly (40–50%) the phasic taste responses to sugars (sucrose, fructose, lactose, and maltose) and saccharin sodium recorded from the greater superficial petrosal nerve (GSP) innervating palatal taste buds in the rat. However, no significant effect of gurmarin was observed for taste responses to NaCl, HCl, and quinine hydrochloride. Phasic responses tod-amino acids that taste sweet to humans (His, Asn, Phe, Gln) were also depressed, but gurmarin treatment was without significant effect on taste responses to d-Trp andd-Ala, six l-amino acids (His, Asn, Phe, Gln, Trp, and Ala), and two basic amino acid HCl salts (Arg and Lys). With the exception of d-Trp, these inhibitory effects of gurmarin on GSP taste responses were related to the rat's preference for these substances.
Effects of temperature and calcium availability on ventricular myocardium from rainbow trout
Authors: Coyne Mary D. , Kim Catherine S. , Cameron John S. , Gwathmey Judith K.
Published: December 2017

We studied the mechanical and electrophysiological properties of ventricular myocardium from rainbow trout ( Oncorhynchus mykiss) in vitro at 4, 10, and 18°C from fish acclimated at 10°C. Temperature alone did not significantly alter the contractile force of the myocardium, but the time to peak tension and time to 80% relaxation were prolonged at 4°C and shortened at 18°C. The duration of the action potential was also prolonged at 4°C and progressively shortened at higher temperatures. An alteration of the stimulation frequency did not affect contraction amplitude at any temperature. Calcium influx via L-type calcium channels was increased by raising extracellular calcium concentration ([Ca2+]o) or including Bay K 8644 (Bay K) and isoproterenol in the bathing medium. These treatments significantly enhanced the contractile force at all temperatures. Calcium channel blockers had a reverse-negative inotropic effect. Unexpectedly, the duration of the action potential at 10°C was shortened as [Ca2+]oincreased. However, Bay K prolonged the plateau phase at 4°C. Caffeine, which promotes the release of sarcoplasmic reticulum (SR) calcium, increased contractile force eightfold at all three temperatures, but the SR blocker ryanodine was only inhibitory at 4°C. Our results suggest that contractile force in ventricular myocardium from Oncorhynchus mykiss is primarily regulated by sarcolemmal calcium influx and that ventricular contractility is maintained during exposure to a wide range of temperatures.
Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles
Authors: Yu Fushun , Göthe Sten , Wikström Lilian , Forrest Douglas , Vennström Björn , Larsson Lars
Published: December 2017

Skeletal muscle is known to be a target for the active metabolite of thyroid hormone, i.e., 3,5,3′-triiodothyronine (T3). T3acts by repressing or activating genes coding for different myosin heavy chain (MHC) isoforms via T3receptors (TRs). The diverse function of T3is presumed to be mediated by TR-α1and TR-β, but the function of specific TRs in regulating MHC isoform expression has remained undefined. In this study, TR-deficient mice were used to expand our knowledge of the mechanisms by which T3regulates the expression of specific MHC isoforms via distinct TRs. In fast-twitch extensor digitorum longus (EDL) muscle, TR-α1-, TR-β-, or TR-α1β-deficient mice showed a small but statistically significant decrease ( P < 0.05) of type IIB MHC content and an increased number of type I fibers. In the slow-twitch soleus, the β/slow MHC (type I) isoform was significantly ( P < 0.001) upregulated in the TR-deficient mice, but this effect was highly dependent on the type of receptor deleted. The lack of TR-β had no significant effect on the expression of MHC isoforms. An increase ( P < 0.05) of type I MHC was observed in the TR-α1-deficient muscle. A dramatic overexpression ( P < 0.001) of the slow type I MHC and a corresponding downregulation of the fast type IIA MHC ( P < 0.001) was observed in TR-α1β-deficient mice. The muscle- and fiber-specific differences in MHC isoform expression in the TR-α1β-deficient mice resembled the MHC isoform transitions reported in hypothyroid animals, i.e., a mild MHC transition in the EDL, a dramatic but not complete upregulation of the β/slow MHC isoform in the soleus, and a variable response to TR deficiency in different soleus muscle fibers. Thus the consequences on muscle are similar in the absence of thyroid hormone or absence of thyroid hormone receptors, indicating that TR-α1and TR-β together mediate the known actions of T3. However, it remains unknown how thyroid hormone exerts muscle- and muscle fiber-specific effects in its action. Finally, although developmental MHC transitions were not studied specifically in this study, the absence of embryonic and fetal MHC isoforms in the TR-deficient mice indicates that ultimately the transition to the adult MHC isoforms is not solely mediated by TRs.
Effects of right atrial distension on the activity of magnocellular neurons in the supraoptic nucleus
Authors: Grindstaff Regina R. , Grindstaff Ryan J. , Cunningham J. Thomas
Published: December 2017

A small balloon placed at the junction of the superior vena cava and right atrium was used to stimulate cardiac volume receptors in pentobarbital sodium-anesthetized male rats. Extracellular recordings were obtained from antidromically identified vasopressinergic and oxytocinergic neurosecretory cells of the supraoptic nucleus. Cells were considered sensitive to the stimulus if balloon inflation resulted in a 30% change in firing frequency. Balloon inflation that did not stretch the caval-atrial junction had no significant effect on vasopressin neurons ( n = 51, P > 0.05). Stretch of the caval-atrial junction decreased the firing activity in 64 of 83 putative vasopressin neurons ( P < 0.01 compared with control). Stretch of the caval-atrial junction influenced the firing activity of only 3 of 26 antidromically activated oxytocinergic neurons, an effect not statistically different from control ( P> 0.05). When bilateral vagotomy was performed while recording from vasopressin neurons ( n = 5), sensitivity to stretch of the caval-atrial junction was eliminated. Cardiac receptors located at the junction of the superior vena cava and right atrium may be important in regulating the activity of vasopressinergic but not oxytocinergic neurons of the supraoptic nucleus.
NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior and sexual behavior
Authors: Ammar A. A. , Sederholm F. , Saito T. R. , Scheurink A. J. W. , Johnson A. E. , Södersten P.
Published: December 2017

Many studies have indicated that neuropeptide Y (NPY) stimulates and leptin inhibits food intake. In line with this, intracerebroventricular injection of NPY (10 μg) stimulated and leptin (10 μg) inhibited intake of a sucrose solution when female rats were required to obtain the solution from a bottle. However, NPY inhibited and leptin stimulated intake if the solution was infused intraorally. Thus NPY stimulates the responses used to obtain food but inhibits those used to consume food, and leptin has the opposite effects. To test the specificity of these responses the sexual behavior of male rats was examined. NPY-treated males showed minor deficits in sexual behavior but chose to ingest a sucrose solution rather than copulate with a female if offered the choice. By contrast, leptin-treated males ingested little sucrose and displayed an increase in ejaculatory frequency if given the same choice. It is suggested that NPY is not merely an orexigenic peptide, but one that directs attention toward food. Similarly, leptin may not be an anorexic peptide, but one that diverts attention away from food toward alternate stimuli.
Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds
Authors: Rayner Timothy E. , Cowin Allison J. , Robertson J. Gray , Cooter Rodney D. , Harries Richard C. , Regester Geoffrey O. , Smithers Geoffrey W. , Goddard Chris , Belford David A.
Published: December 2017

The ability of single growth factors to promote healing of normal and compromised wounds has been well described, but wound healing is a process requiring the coordinated action of multiple growth factors. Only the synergistic effect on wound healing of combinations containing at most two individual growth factors has been reported. We sought to assess the ability of a novel milk-derived growth factor-enriched preparation [mitogenic bovine whey extract (MBWE)], which contains six known growth factors, to promote repair processes in organotypic in vitro models and incisional wounds in vivo. MBWE stimulated the contraction of fibroblast-populated collagen lattices in a dose-dependent fashion and promoted the closure of excisional wounds in embryonic day 17 fetal rat skin. Application of MBWE increased incisional wound strength in normal animals on days 3, 5, 7, and 10 and reversed the decrease in wound strength observed following steroid treatment. Wound histology showed increased fibroblast numbers in wounds from normal and steroid-compromised animals. These data suggest the mixture of factors present in bovine milk exerts a direct action on the cells of cutaneous wound repair to enhance both normal and compromised healing.