bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of orchiectomy and testosterone replacement to explore meal number-to-meal size relationship in male rats
Authors: Chai Jia-Ke , Blaha Vladimir , Meguid Michael M. , Laviano Alessandro , Yang Zhong-Jin , Varma Madhu
Published: December 2017

Because food intake is a function of meal number and meal size and because gender-related hormones are involved in feeding regulation, we explored effects of orchiectomy and testosterone replacement on the relationship between meal number and size and changes in resulting feeding patterns in adult male rats, randomized into orchiectomy and sham-operation groups. A rat eater meter measured feeding indexes for 1 wk before and 2 wk after castration and during 8 days of testosterone replacement. Orchiectomy leads to an immediate change in the meal number-to-size relationship, resulting in 1) change in pattern of feeding; 2) a significant decrease in dark-phase meal number; 3) a significant increase in dark-phase meal size, but insufficient to offset decrease in meal number, so total food intake significantly decreased during dark phase; 4) no significant change in light-phase meal number; and 5) an increase in meal size leading to an increased food intake during light phase, which offset decreased food intake in dark cycle and resulted in no net significant change in food intake after orchiectomy. Testosterone replacement acutely reversed effects of orchiectomy on meal number-to-meal size relationship, restoring feeding pattern. Data suggest that androgens immediately influence the meal number-to-meal size relationship. The speed of onset seen after orchiectomy suggests that the influence of testosterone on food intake may also occur partially via a nongenomic effect.
Regulation of brain renin-angiotensin system by benzamil-blockable sodium channels
Authors: Nishimura Masato , Ohtsuka Ken , Iwai Naoharu , Takahashi Hakuo , Yoshimura Manabu
Published: December 2017

Changes in the renin-angiotensin system (RAS) mRNAs in the brain and the kidney of rats after administration of DOCA and/or sodium chloride were assessed by use of a competitive PCR method. Benzamil, a blocker of amiloride-sensitive sodium channels, was infused intracerebroventricularly or intravenously for 7 days in DOCA-salt or renal hypertensive rats, and the effects of benzamil on the brain RAS mRNAs were determined. Renin and ANG I-converting enzyme (ACE) mRNAs were not downregulated in the brain of rats administered DOCA and/or salt; however, these mRNAs were decreased in the kidney. Intracerebroventricular infusion of benzamil decreased renin, ACE, and ANG II type 1 receptor mRNAs in the brain of DOCA-salt hypertensive rats but not in the brain of renal hypertensive rats. The gene expression of the brain RAS, particularly renin and ACE, is regulated differently between the brain and the kidney in DOCA-salt hypertensive rats, and benzamil-blockable brain sodium channels may participate in the regulation of the brain RAS mRNAs.
Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat
Authors: van Dijk Gertjan , Seeley Randy J. , Thiele Todd E. , Friedman Mark I. , Ji Hong , Wilkinson Charles W. , Burn Paul , Campfield L. Arthur , Tenenbaum Renata , Baskin Denis G. , Woods Stephen C. , Schwartz Michael W.
Published: December 2017

To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 μg) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to leptin-induced anorexia, we studied vehicle-infused rats with food available ad libitum and those that were pair-fed to leptin-treated animals. Although body weight was comparably reduced (−8%) and plasma glycerol was comparably increased (142 and 17%, respectively) in leptin-treated and pair-fed animals relative to controls, increases in plasma fatty acids and ketones were only detected (132 and 234%, respectively) in pair-fed rats. Resting energy expenditure (−15%) and gastrointestinal fill (−50%) were reduced by pair-feeding relative to the ad libitum group, but they were not reduced by leptin treatment. Relative to controls, leptin increased hypothalamic mRNA for corticotropin-releasing hormone (CRH; 61%) and for proopiomelanocortin (POMC; 31%) but did not reduce mRNA for neuropeptide Y. These results suggest that CNS leptin prevents metabolic/gastrointestinal responses to caloric restriction by activating hypothalamic CRH- and POMC-containing pathways and raise the possibility that these peripheral responses to CNS leptin administration contribute to leptin’s anorexigenic action.
Intermittent stimulation enhances function of conditioned muscle
Authors: Duan Changping , Trumble Dennis R. , Scalise Deborah , Magovern James A.
Published: December 2017

Skeletal muscle is highly adaptable in that its metabolic and contractile characteristics are largely regulated by its pattern of use. It is known that muscle phenotype can be manipulated via chronic electrical stimulation to enhance fatigue resistance at the expense of contractile power. Type 2A fibers are fatigue resistant, powerful, and considered most desirable for cardiac assist purposes. We have found that 12-wk of intermittent-burst stimulation produces a high percentage of 2A fibers and increases fatigue resistance and power in rabbit latissimus dorsi muscle. Fixed-load endurance tests were used to quantify fatigue resistance among normal and trained muscle groups. Control muscles were found to fatigue completely within 10–20 min. Muscles stimulated continuously for 6 wk retained 35% (71.5 ± 19.5 g ⋅ cm) of their initial stroke work at 40 min. Muscles stimulated 12 h/day for 12 wk had the highest initial stroke work (449.7 ± 92.4 g ⋅ cm) and the highest remaining stroke work (234.7 ± 50.1 g ⋅ cm) at 40 min. Results suggest that employing regular resting periods during conditioning preserves strength in fatigue-resistant muscle.
Effect of nitric oxide synthase inhibitors on short-term appetite and food intake in humans
Authors: Vozzo Rosalie , Wittert Gary A. , Horowitz Michael , Morley John E. , Chapman Ian M.
Published: December 2017

Animal studies suggest that nitric oxide (NO) may be a physiological regulator of appetite; NO synthase (NOS) inhibition suppresses food intake in rats, mice, and chickens. It is not known whether NO has any effect on appetite in humans. We have used NG-monomethyl-l-arginine (l-NMMA) and NG-nitro-l-arginine methyl ester (l-NAME), both competitive, nonselective inhibitors of NOS, in two separate studies to evaluate the role of NO in the short-term regulation of appetite in humans. In study I, 13 men (18–25 yr) underwent paired studies, in randomized, double-blind fashion, after an overnight fast. l-NMMA (4 mg ⋅ kg−1⋅ h−1) or saline (0.9%) was infused intravenously at a rate of 40 ml/h for 1.5 h. In study II, eight men (18–26 yr) underwent three randomized, double-blind studies after an overnight fast. l-NAME (75 or 180 μg ⋅ kg−1⋅ h−1) or saline (0.9%) was infused intravenously at a rate of 20 ml/h for 120 min. Hunger and fullness were measured using visual analog scales; blood pressure and heart rate were monitored, and 30 min before the end of the infusion, subjects were offered a cold buffet meal. Total caloric intake and the macronutrient composition of the meal were determined. Both l-NMMA ( P = 0.052) andl-NAME ( P < 0.05; both doses) decreased heart rate, l-NMMA increased diastolic blood pressure ( P < 0.01), and l-NAME increased systolic blood pressure ( P = 0.052). Neither drug had any effect on caloric intake or sensations of hunger or fullness. Despite having significant effects on cardiovascular function in the doses used, neitherl-NMMA norl-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans.
Capsaicin-sensitive fibers are required for the anorexic action of systemic but not central bombesin
Authors: Michaud David , Anisman Hymie , Merali Zul
Published: December 2017

Bombesin (BN) suppresses food intake in rats whether given centrally or systemically. Although the brain BN-sensitive receptors are known to be essential for the anorexic effect of systemic BN, the mode of communication between the gut and the brain remains unclear. This study assessed whether the anorexic effect of systemic BN is mediated humorally or via neural circuits. Afferent neurons were lesioned using capsaicin (50 mg/kg sc) on postnatal day 2, and responses to BN were assessed during adulthood. Capsaicin treatment decreased body weight gain significantly from postnatal age 4–7 wk. Peripheral BN (4–16 μg/kg ip) dose dependently suppressed food intake in control animals. However, this effect was completely blocked in capsaicin-treated rats. In contrast to systemic effects, feeding-suppressant effects of centrally administered BN (0.01–0.5 μg icv) were not affected by capsaicin treatment. This research suggests that peripheral BN communicates with the brain via a neuronal system(s) whose afferent arm is constituted of capsaicin-sensitive C and/or Aδ-fibers, whereas the efferent arm of this satiety- and/or anorexia-mediating circuitry is capsaicin resistant.
Effects of slow and rapid cooling on catecholamine concentration in arterial plasma and the skin
Authors: Kozyreva T. V. , Tkachenko E. Y. , Kozaruk V. P. , Latysheva T. V. , Gilinsky M. A.
Published: December 2017

Norepinephrine (NE) and epinephrine (Epi) concentrations in arterial plasma and in skin tissue were measured chromatographically before and after external cooling. Urethan-anesthetized rats were cooled either slowly (0.004–0.006°C/s) or rapidly (0.03– 0.05°C/s). Blood samples were drawn three times from each animal: 1) before cooling and at a rectal temperature decreased 2) by 0.5°C and 3) by 3–4°C. Skin samples were taken from controls and from rapidly or slowly cooled rats at a rectal temperature lowered by 0.5°C. The resting mean values were 36.7 ± 0.3°C for rectal temperature, 0.62 ± 0.079 and 1.09 ± 0.203 ng/ml for plasma NE and Epi, and 85.6 ± 4.1 and 137.6 ± 34.3 ng/g for skin NE and Epi. A decrease in rectal temperature by 0.5°C at rapid cooling produced a 2.6-fold increase of NE and a 2.8-fold increase of Epi in plasma. Concomitantly, there was a significant decrease in skin NE concentration by 28% and Epi by 86%. At a rectal temperature decreased by 0.5°C after slow cooling, plasma catecholamines did not change; at unaltered skin NE concentration, there was a reduction in skin Epi concentration (60%). When rectal temperature was lowered by 3–4°C, the increase in plasma NE was virtually the same at both cooling rates and only plasma Epi increased more after deep rapid cooling than slow cooling. Thus the sympathoadrenal system may be differently activated depending on cooling rate. Rapid cooling, when the dynamic activity of the skin cold receptors is involved in the cold response, may provide conditions for an earlier activation of the sympathoadrenal system. This may evidence the functional significance of the dynamic activity of the skin cold receptors in the formation of the cold defense responses.
Role of nitric oxide in the early renal hemodynamic response after unilateral nephrectomy
Authors: Valdivielso José M. , Pérez-Barriocanal Fernando , García-Estañ Joaquin , López-Novoa José M.
Published: December 2017

We evaluated the involvement of nitric oxide (NO) in the early hemodynamic response to uninephrectomy (UNX) in rats. Animals were uninephrectomized, and 48 h after removal of the kidney, the effect of infusing NG-nitro-l-arginine methyl ester (l-NAME) on renal function was studied. Glomeruli were isolated, and glomerular nitrite and cGMP productions were measured. In addition, endothelial constitutive NO synthase (NOS III) and inducible NO synthase (iNOS) were assessed by Western blot and by measuring the conversion of arginine to citrulline. UNX animals showed an increase in renal plasma flow that was inhibited by l-NAME in a higher proportion than in sham-operated (SO) animals. No differences were observed in systemic NO-dependent vascular tone, since mean arterial pressure showed similar increments in SO and UNX rats. Glomeruli from UNX animals showed an increase in glomerular nitrite production that was blunted byl-NAME addition. Also, cGMP levels were increased in glomeruli from UNX animals, and this increase was inhibited byl-NAME. Western blot analysis showed no differences in NOS III but a higher iNOS amount in glomeruli from UNX than in those from SO rats. No significant differences between UNX and SO rats were found in calcium-dependent NOS enzymatic activity in the renal cortex. However, calcium-independent enzymatic activity was markedly higher in the renal cortex of UNX than in those from SO animals. In conclusion, glomeruli from rats 48 h after UNX had a greater production of NO than those from SO animals. This increased glomerular NO production is based on an increase in the iNOS isoform. Increased glomerular NO synthesis seems to play a role in the decreased renal vascular resistance observed after unilateral nephrectomy in rats.
Regulation ofP-450 4A activity in the glomerulus of the rat
Authors: Ito Osamu , Roman Richard J.
Published: December 2017

We recently reported that an enzyme of the cytochrome P-450 4A family is expressed in the glomerulus, but there is no evidence that 20-hydroxyeicosatetraenoic acid (20-HETE) can be produced by this tissue. The purpose of present study was to determine whether glomeruli isolated from the kidney of rats can produce 20-HETE and whether the production of this metabolite is regulated by nitric oxide (NO) and dietary salt intake. Isolated glomeruli produced 20-HETE, dihydroxyeicosatrienoic acids, and 12-hydroxyeicosatetraenoic acid (4.13 ± 0.38, 4.20 ± 0.38, and 2.10 ± 0.20 pmol ⋅ min−1⋅ mg protein−1, respectively) when incubated with arachidonic acid (10 μM). The formation of 20-HETE was dependent on the availability of NADPH and the[Formula: see text] of the incubation medium. The formation of 20-HETE was inhibited by NO donors in a concentration-dependent manner. The production of 20-HETE was greater in glomeruli isolated from the kidneys of rats fed a low-salt diet than in kidneys of rats fed a high-salt diet (5.67 ± 0.32 vs. 2.83 ± 0.32 pmol ⋅ min−1⋅ mg protein−1). Immunoblot experiments indicated that the expression of P-450 4A protein in glomeruli from the kidneys of rats fed a low-salt diet was sixfold higher than in kidneys of rats fed a high-salt diet. These results indicate that arachidonic acid is primarily metabolized to 20-HETE and dihydroxyeicosatrienoic acids in glomeruli and that glomerular P-450 activity is modulated by NO and dietary salt intake.
Primary and adaptive changes of A-type K+ currents in sympathetic neurons from hypertensive rats
Authors: Robertson Walter P. , Schofield Geoffrey G.
Published: December 2017

The A-type K+ current ( I A) of superior cervical ganglion neurons acutely isolated from spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats was compared under whole cell voltage clamp. Activation parameters were similar in each strain. Steady-state inactivation was shifted approximately −6 mV in SHR, where one-half inactivation occurred at −81 mV vs. −75 mV in WKY rats. The shift was not present in prehypertensive SHR but remained in adult enalapril-treated SHR and, therefore, may represent a primary alteration of I A properties. I A amplitudes evoked from physiological potentials were similar, despite inactivation of a greater fraction of the current in the SHR. Comparing maximal I A densities revealed that current density is elevated in the SHR, which compensates for the inactivation shift. Current density decreased with age in WKY neurons but did not significantly decline in SHR neurons unless hypertension was prevented with enalapril. Thus adult SHR neurons may retain a high I Adensity as an adaptive response to offset potential hyperexcitability resulting from the hyperpolarized I A inactivation.
Can gender differences during exercise-heat stress be assessed by the physiological strain index?
Authors: Moran Daniel S. , Shapiro Yair , Laor Arie , Izraeli Sharona , Pandolf Kent B.
Published: December 2017

A physiological strain index (PSI) based on rectal temperature (Tre) and heart rate (HR) was recently suggested to evaluate exercise-heat stress. The purpose of this study was to evaluate PSI for gender differences under various combinations of exercise intensity and climate. Two groups of eight men each were formed according to maximal rate of O2 consumption (V˙o 2 max). The first group of men (M) was matched to a group of nine women (W) with similar ( P > 0.001)V˙o 2 max (46.1 ± 2.0 and 43.6 ± 2.9 ml ⋅ kg−1 ⋅ min−1, respectively). The second group of men (MF) was significantly ( P < 0.001) more fit than M or W with V˙o 2 max of 59.1 ± 1.8 ml ⋅ kg−1 ⋅ min−1. Subjects completed a matrix of nine experimental combinations consisting of three different exercise intensities for 60 min [low, moderate, and high (300, 500, and 650 W, respectively)] each at three climates {comfortable, hot wet, and hot dry [20°C 50% relative humidity (RH), 35°C 70% RH, and 40°C 35% RH, respectively]}. No significant differences ( P > 0.05) were found between matched genders (M and W) at the same exposure for sweat rate, relativeV˙o 2 max(%V˙o 2 max), and PSI. However, MF had significantly ( P < 0.05) lower strain than M and W as reflected by %V˙o 2 max and PSI. In summary, PSI applicability was extended for exercise-heat stress and gender. This index continues to show potential for wide acceptance and application.
Blood-borne, albumin-bound prostaglandin E2may be involved in fever
Authors: Romanovsky Andrej A. , Ivanov Andrei I. , Karman Elena K.
Published: December 2017

Although the involvement of blood-borne PGE2in fever has been hypothesized by several authors and has substantial experimental support, the current literature often rejects this hypothesis because several attempts to induce fever by a peripheral PGE2failed. However, it is usually ignored that the amphipathic molecules of PGE2are readily self-associating and that such an aggregation could have prevented the peripherally administered PGE2(free form) from expressing its pyrogenic activity, thus leading to false negative results. To ensure disaggregation of PGE2, we prepared its complex within a carrier protein, human serum albumin (HSA). HSA was purified with activated charcoal and polymixin B-polyacrylamide gel and incubated with PGE2for 1 h at 37°C. Adult Chinchilla rabbits were injected intravenously with PGE2-HSA complex in either the higher (75 μg/kg PGE2:30 mg/kg HSA) or the lower (15 μg/kg:6 mg/kg) dose, and the rectal temperature (Tr) was measured. In the controls, either the ligand alone or the carrier alone was administered. At the higher dose, neither free PGE2nor albumin alone was pyrogenic, whereas the PGE2-HSA complex produced a fever characterized by a short latency (<10 min) and a maximal Trrise of 0.7 ± 0.2°C. At the lower dose, none of the substances affected the Tr. This study demonstrates a marked pyrogenic activity of the intravenous PGE2-HSA, but not of the free PGE2. Administration of a preformed complex may be more physiologically relevant than administration of the free ligand because of the ligand’s disaggregation, protection from enzymatic degradation, and facilitated delivery to targets. Our study supports the hypothesis that peripheral PGE2is involved in fever genesis.
Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes
Authors: Smith Scott M. , Wastney Meryl E. , Morukov Boris V. , Larina Irina M. , Nyquist Laurence E. , Abrams Steven A. , Taran Elena N. , Shih Chih-Yu , Nillen Jeannie L. , Davis-Street Janis E. , Rice Barbara L. , Lane Helen W.
Published: December 2017

The loss of bone during spaceflight is considered a physiological obstacle for the exploration of other planets. This report of calcium metabolism before, during, and after long-duration spaceflight extends results from Skylab missions in the 1970s. Biochemical and endocrine indexes of calcium and bone metabolism were measured together with calcium absorption, excretion, and bone turnover using stable isotopes. Studies were conducted before, during, and after flight in three male subjects. Subjects varied in physical activity, yet all lost weight during flight. During flight, calcium intake and absorption decreased up to 50%, urinary calcium excretion increased up to 50%, and bone resorption (determined by kinetics or bone markers) increased by over 50%. Osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, increased after flight. Subjects lost ∼250 mg bone calcium per day during flight and regained bone calcium at a slower rate of ∼100 mg/day for up to 3 mo after landing. Further studies are required to determine the time course of changes in calcium homeostasis during flight to develop and assess countermeasures against flight-induced bone loss.
Renal medullary interstitial infusion of norepinephrine in anesthetized rabbits: methodological considerations
Authors: Correia Anabela G. , Bergström Göran , Lawrence Andrew J. , Evans Roger G.
Published: December 2017

We tested methods for delivery of drugs to the renal medulla of anesthetized rabbits. Outer medullary infusion (OMI) of norepinephrine (300 ng ⋅ kg−1 ⋅ min−1), using acutely or chronically positioned catheters, reduced both cortical (CBF; 15%) and medullary perfusion (MBF; 23–31%). Inner medullary infusion (IMI) did not affect renal hemodynamics, whereas intravenous infusion reduced CBF (15%) without changes in MBF. During OMI of [3H]norepinephrine, much of the radiolabel (∼40% with chronically positioned catheters) spilled over systemically. Nevertheless, autoradiographic analysis showed the concentration of radiolabel was about fourfold greater in the infused medulla than the cortex. In contrast, during IMI, only ∼5% of the infused radiolabel spilled over into the systemic circulation and ∼64% was excreted by the infused kidney. The resultant intrarenal levels of radiolabel were considerably less with IMI compared with OMI. In rabbits, OMI therefore provides a useful method for targeting agents to the renal medulla, but given the considerable systemic spillover with OMI, its utility is probably limited to substances that are rapidly degraded in vivo.
Hypoxic hypometabolism in the anesthetized turtle,Trachemys scripta
Authors: Hicks James W. , Wang Tobias
Published: December 2017

A hypometabolic response during acute exposure to hypoxia has been measured in both endothermic and ectothermic vertebrates. In the turtle, we determined the metabolic response to normocapnic hypoxia and hypercapnic hypoxia. In addition, we tested the hypothesis that hypoxic hypometabolism was a regulated response that did not depend on O2availability. Metabolic, cardiovascular, and blood gas measurements were collected in anesthetized turtles under two conditions: during normocapnic hypoxia [fractional inspired O2[Formula: see text] = 0.1 and 0.05] and during hypercapnic hypoxia [[Formula: see text] = 0.1 and 0.05 plus fractional inspired CO2([Formula: see text]) = 0.05]. During normoxia, rate of O2consumption (V˙o2) was 0.82 ml ⋅ min−1⋅ kg−1and was reduced by nearly 30% at the lowest[Formula: see text]. Normocapnic hypoxia of[Formula: see text] = 0.1 had no significant effect on V˙o2. The addition of 5% CO2to the inspired air did not enhance the effects of hypoxia. Injections of 2,4-dinitrophenol increasedV˙o2during hypercapnic hypoxia in some animals to levels greater than those measured during normoxia. We conclude that hypoxia produces a hypometabolic state in anesthetized turtles, and the pharmacological stimulation ofV˙o2counteracts the effects of hypoxia on metabolism. The hypoxic hypometabolism in turtles most likely represents a regulated response and does not reflect limited O2availability at the cellular level. Finally, we hypothesize that hypoxemia induced by the right-to-left cardiac shunt often associated with diving may trigger the development of a hypometabolic state and therefore contribute to the prolongation of aerobic dive times.
Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus
Authors: Johanson C. E. , Szmydynger-Chodobska J. , Chodobski A. , Baird A. , McMillan P. , Stopa E. G.
Published: December 2017

Upregulation of certain growth factors in the central nervous system can alter brain fluid dynamics. Hydrocephalus was produced in adult Sprague-Dawley rats by infusing recombinant basic fibroblast growth factor (FGF-2) at 1 μg/day into a lateral ventricle for 2, 3, 5, or 10–12 days. Lateral and third ventricular enlargement progressively increased from 2 to 10 days. Ventriculomegaly was also induced by a 75% reduced dose of FGF-2. At 10–12 days, there was a 29% attenuation in cerebrospinal fluid (CSF) formation rate, from 2.5 to 1.8 μl/min ( P < 0.01). Choroid plexus, the main site of CSF secretion, had an augmented number of dark epithelial cells, which have previously been associated with decreased choroidal fluid formation. The twofold elevated resistance to CSF absorption, i.e., 0.8 to 1.7 mmHg ⋅ min−1 ⋅ μl−1, was attributable, at least in part, to enhanced fibrosis and collagen deposits in the arachnoid villi, a major site for CSF absorption. Normal CSF pressure (2–3 mmHg) was consistent with a patent cerebral aqueduct and reduced CSF formation rate. The FGF-2-induced ventriculomegaly is interpreted as an ex vacuuo hydrocephalus brought about by an altered neuropil and interstitium of the brain.
Effects of subfornical organ lesions on acutely induced thirst and salt appetite
Authors: Thunhorst Robert L. , Beltz Terry G. , Johnson Alan Kim
Published: December 2017

We examined the role of the subfornical organ (SFO) in stimulating thirst and salt appetite using two procedures that initiate water and sodium ingestion within 1–2 h of extracellular fluid depletion. The first procedure used injections of a diuretic (furosemide, 10 mg/kg sc) and a vasodilator (minoxidil, 1–3 mg/kg ia) to produce hypotension concurrently with hypovolemia. The resulting water and sodium intakes were inhibited by intravenous administration of ANG II receptor antagonist (sarthran, 8 μg ⋅ kg−1 ⋅ min−1) or angiotensin-converting enzyme inhibitor (captopril, 2.5 mg/h). The second procedure used injections of furosemide (10 mg/kg sc) and a low dose of captopril (5 mg/kg sc) to initiate water and sodium ingestion upon formation of ANG II in the brain. Electrolytic lesions of the SFO greatly reduced the water intakes, and nearly abolished the sodium intakes, produced by these relatively acute treatments. These results contrast with earlier findings showing little effect of SFO lesions on sodium ingestion after longer-term extracellular fluid depletion.
Blood glucose patterns and appetite in time-blinded humans: carbohydrate versus fat
Authors: Melanson Kathleen J. , Westerterp-Plantenga Margriet S. , Saris Wim H. M. , Smith Françoise J. , Campfield L. Arthur
Published: December 2017

We assessed the extent to which a possible synchronization between transient blood glucose declines and spontaneous meal initiation would lend support to the interpretation of a preload study with isoenergetic (1 MJ) isovolumetric high-fat or simple carbohydrate (CHO) preload drinks. Ten men (18–30 yr) fasted overnight and then were time blinded and made aware that they could request meals anytime. At first meal requests, volunteers consumed a preload; ad libitum meals were offered at subsequent requests. Postabsorptively, transient declines in blood glucose were associated with meal requests (χ2 = 8.29). Subsequent meal requests occurred during “dynamic declines” in blood glucose after the peak induced by drink consumption (100%). These meal requests took twice as long to occur after high-fat than after CHO preloads (fat = 126 ± 21, CHO = 65 ± 15 min), consistent with differences in interpolated 65-min satiety scores (fat = 38 ± 8.2, CHO = 16 ± 4). Postprandially, transient blood glucose declines were associated with meal requests (χ2 = 4.30). Spontaneous meal initiations were synchronized with transient and dynamic blood glucose declines. Synchronization of intermeal interval and dynamic declines related to higher satiating efficiency from high-fat preloads than from simple CHO preloads.
Functional significance of the pattern of renal sympathetic nerve activation
Authors: Dibona Gerald F. , Sawin Linda L.
Published: December 2017

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 ± 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.
Low environmental temperature modulates gustatory nerve activity and behavioral responses to NaCl in rats
Authors: Shimizu Yasutake , Tonosaki Keiichi
Published: December 2017

We studied the effects of cold ambient temperature on chorda tympani nerve responses to taste stimuli such as sucrose, NaCl, quinine HCl (QHCl), and HCl in rats. The electrophysiological recordings of the whole chorda tympani nerves from control (22°C) and cold-exposed (4°C) rats revealed that the responses to sucrose, HCl, and QHCl were unaffected by cold exposure. In contrast, the nerve responses to NaCl were enhanced time dependently, reaching a maximum 7–14 days after cold exposure. Responses to sodium acetate were likewise elevated as they were to NaCl, whereas those to KCl were unchanged after cold exposure. In addition, the residual NaCl responses after lingual application of the sodium-channel blocker amiloride in cold-exposed rats were similar to those in control animals. It is thus most likely that cold exposure potentiates the chorda tympani nerve responses to Na+, but not to Cl−. Behavioral studies with the two-bottle preference test showed that the cold-exposed rats refused to drink NaCl solutions at 0.05 and 0.1 M, the concentrations being preferred by control animals. These results suggest that the ambient temperature influences taste cell function, and that the enhanced NaCl response of the chorda tympani nerve is related to the avoidance of NaCl intake under cold environment.
Ionic mechanisms underlying spontaneous muscle contractions in the liver fluke,Fasciola hepatica
Authors: Graham M. K. , McGeown J. G. , Fairweather I.
Published: December 2017

Spontaneous contractions of liver fluke muscle were abolished in Ca2+-free saline and by 100 μM nifedipine and reduced by 5 mM cadmium chloride, suggesting that they are dependent on extracellular Ca2+. Caffeine (5 mM) significantly increased contraction amplitude and frequency. Ryanodine (100 μM) failed to block the caffeine response but significantly reduced spontaneous contraction frequency, suggesting that intracellular stores have a functional role. Cyclopiazonic acid (5 μM) had no effect on the caffeine response or spontaneous activity. 3-Isobutyl-1-methylxanthine (IBMX), forskolin, and 8-bromoadenosine 3′,5′-cyclic monophosphate significantly increased spontaneous contractions, which implies that cAMP has a regulatory function in motility. Caffeine, however, produced no measurable increase in cAMP. The caffeine effect was inhibited by cadmium chloride and nifedipine, whereas IBMX-induced increases in amplitude were reduced by cadmium chloride. Thus caffeine and cAMP appear capable of opening plasma membrane Ca2+channels, but the involvement of cAMP in caffeine responses has not been proved.
Effects of acute anoxia on heart function in crucian carp: importance of cholinergic and purinergic control
Authors: Vornanen Matti , Tuomennoro Jarkko
Published: December 2017

The objective of this study was to characterize the effects of acute anoxia on contractile and electrical activity in the heart of an anoxia-tolerant fish species, the crucian carp ( Carassius carassius L.). Responses of atrial and ventricular tissue or isolated cells to NaCN, adenosine, and carbachol were determined to examine the effects of anoxia on cardiac performance and to clarify the possible role of local purinergic modulation and parasympathetic nervous control in the function of the anoxic fish heart. The contractility of the crucian carp heart is strongly decreased by acute anoxia. A rapid reduction in cardiac contractility is attained by reflex bradycardia and suppression of atrial contractility. These responses are mediated by muscarinic cholinergic receptors through the opening of inwardly rectifying potassium channels and are likely to protect the cardiac muscle from hypoxic/anoxic damage. The depletion of tissue oxygen content also directly depresses heart rate and cardiac force. Ultimately, an increase in cytosolic Ca2+concentration occurs that activates sarcolemmal Ca2+extrusion through the Na+-Ca2+-exchange and generates an inward exchange current with consequent depolarization of the resting membrane potential and possible cell death. At physiological concentration, the effects of adenosine on contractile and electrical activity were relatively weak, suggesting that the purinergic system is not involved in the acute anoxia response of the crucian carp heart.
Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension
Authors: Curtis Kathleen S. , Cunningham J. Thomas , Heesch Cheryl M.
Published: December 2017

Fos and dopamine β-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 ± 2.5 mmHg) than in virgin female rats (121 ± 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.
Evaluating physiological strain during cold exposure using a new cold strain index
Authors: Moran Daniel S. , Castellani John W. , O’Brien Catherine , Young Andrew J. , Pandolf Kent B.
Published: December 2017

A cold strain index (CSI) based on core (Tcore) and mean skin temperatures (T sk) and capable of indicating cold strain in real time and analyzing existing databases has been developed. This index rates cold strain on a universal scale of 0–10 and is as follows: CSI = 6.67(Tcore t − Tcore 0) ⋅ (35 − Tcore 0)−1 + 3.33(T sk t −T sk 0) ⋅ (20 −T sk 0)−1, where Tcore 0 andT sk 0are initial measurements and Tcore t andT sk t are simultaneous measurements taken at any time t; when Tcore t > Tcore 0, then Tcore t − Tcore 0 = 0. CSI was applied to three databases. The first database was obtained from nine men exposed to cold air (7°C, 40% relative humidity) for 120 min during euhydration and two hypohydration conditions achieved by exercise-heat stress-induced sweating or by ingestion of furosemide 12 h before cold exposure. The second database was from eight men exposed to cold air (10°C) immediately on completion of 61 days of strenuous outdoor military training, 48 h later, and after 109 days. The third database was from eight men repeatedly immersed in 20°C water three times in 1 day and during control immersions. CSI significantly differentiated ( P < 0.01) between the trials and individually categorized the strain of the subject for two of these three databases. This index has the potential to be widely accepted and used universally.
Frequency response characteristics of sympathetic transmission to skin vascular smooth muscles in rats
Authors: Stauss Harald M. , Stegmann Jens-Ulrich , Persson Pontus B. , Häbler Heinz-Joachim
Published: December 2017

Sympathetic modulation of cutaneous vasomotor waves in humans is most effective at frequencies up to 0.1 Hz. In contrast, sympathetic modulation of mesenteric vasomotor waves in rats is strongest in the frequency band between 0.2 and 0.75 Hz. Therefore, we addressed the question as to whether these different frequency response characteristics are due to species- or organ-specific disparities. Eleven Sprague-Dawley rats were instrumented with catheters in the carotid artery and in the jugular vein, together with electrodes on the centrally sectioned left lumbar sympathetic trunk (LST) and laser Doppler flow probes directed to the plantar surface of the skin of the left and right hind paws. In anesthetized rats, the LST was electrically stimulated at eight different stimulation frequencies, and the responses in laser Doppler blood flow were recorded in the skin of the ipsilateral and contralateral paw. At stimulation frequencies <0.2 Hz, LST stimulation induced corresponding oscillations in skin blood flow in the ipsilateral, but not in the contralateral, paw. These dynamic responses to LST stimulation in the ipsilateral paw were strongest at 0.05 and 0.075 Hz. At higher stimulation frequencies a tonic vasoconstriction was observed. It is concluded that organ-specific disparities exist in sympathetic transmission to vascular smooth muscles, whereas no species-specific differences are apparent in sympathetic transmission to cutaneous blood vessels of humans and rats.
20-HETE and the kidney: resolution of old problems and new beginnings
Authors: McGiff John C. , Quilley John
Published: December 2017

The protean properties of 20-hydroxyeicosatetraenoic acid (HETE), vasoactivity, mitogenicity, and modulation of transport in key nephron segments, serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 and mediator of selective renal effects of ANG II. Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular arterioles, responses that are maintained by 20-HETE inhibition of calcium-activated potassium channels. 20-HETE modulates ion transport in the proximal tubules and the thick ascending limb by affecting the activities of Na+-K+-ATPase and the Na+-K+-2Cl−cotransporter, respectively. The range and diversity of activity of 20-HETE derives in large measure from COX-dependent transformation of 20-HETE to products affecting vasomotion and salt and water excretion. Nitric oxide (NO) exerts a negative modulatory effect on 20-HETE formation; inhibition of NO synthesis produces marked perturbation of renal function resulting from increased 20-HETE production. 20-HETE is an essential component of interactions involving several hormonal systems that have central roles in blood pressure homeostasis, including angiotensins, endothelins, NO, and cytokines. 20-HETE is the preeminent renal eicosanoid, overshadowing PGE2and PGI2. This review is intended to provide evidence for the physiological roles for cytochrome P-450-derived eicosanoids, particularly 20-HETE, and seeks to extend this knowledge to a conceptual framework for overall cardiovascular function.
Energy cost of NaCl transport in isolated gills of cutthroat trout
Authors: Morgan John D. , Iwama George K.
Published: December 2017

Few studies have made direct estimates of the energy required for ion transport in gills of freshwater (FW) and seawater (SW) fish. Oxygen consumption was measured in excised gill tissue of FW-adapted cutthroat trout ( Oncorhynchus clarki clarki) to estimate the energy cost of NaCl transport in that osmoregulatory organ. Ouabain (0.5 mM) and bafilomycin A1(1 μM) were used to inhibit the Na+-K+and H+pumps, respectively. Both inhibitors significantly decreased gill tissue oxygen consumption, accounting for 37% of total tissue respiration. On a whole mass basis, the cost of NaCl uptake in the FW trout gill was estimated to be 1.8% of whole animal oxygen uptake. An isolated, saline-perfused gill arch preparation was also used to compare gill energetics in FW- and SW-adapted trout. The oxygen consumption of FW gills was significantly (33%) higher than SW gills. On a whole animal basis, total gill oxygen consumption in FW and SW trout accounted for 3.9 and 2.4% of resting metabolic rate, respectively. The results of both experiments suggest that the energy cost of NaCl transport in FW and SW trout gills represents a relatively small (<4%) portion of the animal’s total energy budget.
Functional roles played by the sympathetic supply to lip blood vessels in the cat
Authors: Izumi Hiroshi
Published: December 2017

In the anesthetized cat we used laser-Doppler flowmetry to investigate the part played by cervical superior sympathetic trunk (CST) fibers in the control of blood vessels in an orofacial area (the lower lip). The blood flow increase (antidromic vasodilatation) elicited by inferior alveolar nerve (IAN) stimulation was not affected by ongoing repetitive CST stimulation over the frequency range examined (0.2–10 Hz), although reflex parasympathetic vasodilatation was attenuated. The vasoconstrictor responses elicited by IAN stimulation in some preparations were reduced in a frequency-dependent manner (at 0.2–1 Hz) during ongoing CST stimulation (and replaced by vasodilator responses). The vasoconstrictor response evoked directly by brief CST stimulation was attenuated, but not transformed to a vasodilator response, by ongoing CST stimulation. Thus in the cat lower lip 1) sympathetic stimulation attenuated one type of vasodilator response (parasympathetic-mediated vasodilatation), but not another (antidromic vasodilatation), and 2) ongoing sympathetic (CST) stimulation at low frequencies (<1 Hz) prevented further sympathetic-mediated vasoconstriction.
Differential effects of lipopolysaccharide and cholecystokinin on sucrose intake and palatability
Authors: Cross-Mellor Shelley K. , Kent William D. T. , Ossenkopp Klaus-Peter , Kavaliers Martin
Published: December 2017

The differential effects of CCK and lipopolysaccharide (LPS) on sucrose intake and palatability were examined. Rats were injected with LPS (200 μg/kg ip) or NaCl (0.9%, vehicle) and 2 h later received a second injection of either CCK (8 μg/kg ip) or NaCl. In experiment 1, sucrose (0.3 M) intake was monitored for 1 h on three different test days 72 h apart, while in experiment 2, palatability was assessed by means of the taste reactivity test (TRT) on two separate days (72 h apart). In the TRT, orofacial and somatic responses to brief (30 s) intraoral infusions of sucrose were recorded and analyzed for response frequency. Singly, LPS and CCK reduced sucrose intake, with a more pronounced effect from combined LPS and CCK. LPS by itself did not alter sucrose palatability, as evidenced by continuous high levels of ingestive responding. In contrast, CCK-treated rats displayed a pattern of responding indicative of satiety, as did the combined LPS-CCK-treated rats. These results suggest that LPS does not induce hypophagia by altering palatability.
Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice
Authors: Mistry Anahita M. , Swick Andrew , Romsos Dale R.
Published: December 2017

Leptin inhibits food intake and increases metabolic rates in adult mice. Neonatal mice need to maximize food intake and also maintain high thermoregulatory metabolic rates to optimize survival, suggesting that leptin may function differentially in neonatal versus adult animals. The efficacy of exogenous leptin to alter these two physiological functions during development was thus examined in C57BL/6J lean (+/+ or ob/+) and ob/ ob(leptin-deficient) mice. Intraperitoneal leptin administration (1 mg/kg body wt) to lean and ob/ obpups from 7 to 10 days of age did not affect milk intake, oxygen consumption, body weight, or epididymal fat pad weights. Intracerebroventricular injection of 1 μg leptin to 9-day-old pups also failed to influence milk intake or oxygen consumption. Because neither lean nor ob/ obpups responded to exogenous leptin, high endogenous plasma leptin concentrations per se in these lean mice do not explain their resistance to leptin. Leptin administered intracerebroventricularly also failed to alter milk/food intakes of 17-day-old pups but markedly increased oxygen consumption of these older mice. By 28 days of age, intracerebroventricular leptin inhibited food intake. The well-defined actions of leptin to reduce food intake and enhance metabolic rates do not develop synchronously. The ability of leptin to accelerate metabolic rates is acquired early in life and independent of its anorectic action, which may promote survival of neonates.
Sustained effects of repeated restraint stress on muscle and adipocyte metabolism in high-fat-fed rats
Authors: Zhou Jun , Yan Xiaolang , Ryan Donna H. , Harris Ruth B. S.
Published: December 2017

Repeated restraint stress 3 h/day for 3 days in rats causes a temporary hypophagia but a sustained weight loss. We investigated whether poststress changes in peripheral tissue metabolism contributed to these responses. One day after the last restraint, insulin sensitivity, measured by oral glucose tolerance test, was improved in restrained rats. Restraint and pair-fed rats weighed less than controls, but body fat content was the same in all groups. Muscle glucose uptake, measured in vitro, was not changed by treatment, whereas in vitro adipocyte glucose uptake was substantially inhibited only in restrained rats. Adipocytes from restrained rats had elevated rates of fatty acid oxidation but not fatty acid esterification, indicating a shift in energy supply from glucose to fatty acids. Five days after the last restraint, the reduced weight of restrained and pair-fed rats resulted from loss of both lean and fat tissue. These results demonstrate that restraint caused sustained, tissue-specific changes in metabolism that may contribute to changes in body composition and body weight of the rats.