bluuebunny/crossref_metadata_2025 huggingface dataset:
Loose-coupled mitochondria in chronic glucagon-treated hyperthermic ducklings
Authors: Barre H. , Berne G. , Brebion P. , Cohen-Adad F. , Rouanet J. L.
Published: December 2017

In chronic glucagon-treated ducklings (GT) showing thermogenic and hyperthermic responses without shivering to glucagon test injection and in control ducklings (TN; both aged 44 +/- 1 days and reared at thermoneutrality), subsarcolemmal (S) and intermyofibrillar (I) mitochondria from gastrocnemius muscle and mitochondria from liver were isolated. Respiration and cytochrome oxidase activity were determined in these isolated mitochondria by polarography and creatine kinase activity by spectrophotometry, both at 25 degrees C. In GT ducklings, the powerful thermogenesis observed in vivo after a glucagon test injection may be due to the uncoupling effect of released free fatty acids (FFA) in loose-coupled mitochondria because their respiration increased as a function of FFA concentration, and the loose coupling of these mitochondria was reversed by addition of albumin. In all types of mitochondria from GT ducklings, the increase in respiration because of FFA was about double that in mitochondria from controls. There was no change in creatine kinase activity from liver and I mitochondria, but a 16% decrease in this enzyme activity (expressed per mg mitochondrial protein) from S mitochondria was shown despite a strong increase in cytochrome oxidase activity from liver mitochondria (+114% if expressed per g tissue) and from muscle mitochondria (I, +53 or +48%; S, +41 or +97% if expressed per mg mitochondrial protein or per g tissue, respectively). These results support a coupling defect in liver and skeletal muscle mitochondria from the GT hyperthermic ducklings and an uncoupling reinforcement by FFA.
Dietary obesity and weight cycling: effects on blood pressure and heart rate in rats
Authors: Contreras R. J. , Williams V. L.
Published: December 2017

The overconsumption of rich and palatable foods and "yo-yo" dieting are feeding patterns involved in obesity and possibly hypertension in humans. We therefore examined the effects of diet-induced obesity and weight cycling on the blood pressure and heart rate levels of 60-day-old male normotensive Sprague-Dawley (S-D) and spontaneously hypertensive (SHR) rats. Six months on a high-fat and high-sucrose diet (HF/M) produced a greater obesity in S-D rats than in SHR rats. The caloric intakes of S-D rats fed the HF/M diet were greater than the caloric intakes of pellet-fed controls, whereas those of SHR rats were similar. The obesity of both strains was associated with hyperinsulinemia, heavier white (retroperitoneal) and brown (interscapular) fat pads, heavier heart weights, and tachycardia. Despite these changes, diet-induced obesity failed to increase systolic blood pressure obtained under light ether anesthesia or mean arterial pressure in the conscious state. Paradoxically, the blood pressures of SHR rats fed HF/M diet were reduced perhaps as a result of the high polyunsaturated fat component of the diet. A second S-D dietary obese group was alternated between 2-wk periods of unrestricted HF/M diet and 50% restricted pellet chow. Although their body weights were similar to pellet-fed controls, three cycles of weight loss and weight regain resulted in the consumption of increased dietary fat, increased food efficiency, heavier fat pads, and hyperinsulinemia. Heart rate and to some extent blood pressure fluctuated with diet, being elevated during HF/M feeding and reduced during restricted pellet feeding. Although weight cycling intensified the physiological responses to food ingestion, we found that weight cycling in dietary obese S-D rats did not elevate blood pressure levels.
Renal responses to exercise-induced lactic acidosis
Authors: McKelvie R. S. , Lindinger M. I. , Heigenhauser G. J. , Sutton J. R. , Jones N. L.
Published: December 2017

Five healthy males performed four 30-s bouts of maximal exercise, separated by 4 min of rest, on an isokinetic cycle ergometer. Arterial blood and urine samples were taken from indwelling catheters at rest, immediately postexercise, and for 90 min of recovery. Inulin was continuously infused to measure glomerular filtration rate (GFR). Arterial plasma [Na+], [K+], and [Cl-] increased (P less than 0.05) with exercise; plasma lactate concentration ([Lac-]) increased from 1.3 +/- 0.2 to 21.0 +/- 1.0 (SE) meq/l (P less than 0.05). A significant decrease in the GFR occurred after exercise and during recovery associated with reductions in renal Na+ and K+ excretion (P less than 0.05). Renal excretion of Lac- reached a maximum of 293 +/- 79.4 mu eq.kg-1.h-1 (P less than 0.05), with Cl- excretion reaching a minimum of 4.8 +/- 0.95 mu eq.kg-1.h-1 (P less than 0.05). Urine [Lac-] was 189 +/- 25.6 meq/l, and urine [Cl-] was 6 +/- 1.7 meq/l at 30 min of recovery. There was a curvilinear relationship between urine [Cl-] and [Lac-] (r = -0.86; P less than 0.0001). Net Lac- production was estimated from arterial [Lac-] and after assuming a distribution volume. Less than 2% (13.1 meq) of the total estimated Lac- produced (678 meq) was excreted in the urine. Decreases in urine [Cl-] act to limit the fall in urine pH that accompanies increases in urine [Lac-].
Human selenite metabolism: a kinetic model
Authors: Patterson B. H. , Levander O. A. , Helzlsouer K. , McAdam P. A. , Lewis S. A. , Taylor P. R. , Veillon C. , Zech L. A.
Published: December 2017

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.
Circadian rhythms and patterns of performance before and after simulated jet lag
Authors: Tapp W. N. , Natelson B. H.
Published: December 2017

We have developed a rhesus monkey model that enables us to investigate physiological rhythms and circadian effects on performance in an integrated framework. Monkeys worked for 8 h/day on a two-component task (a vigilance trial followed by a discrimination trial) for their daily food aliquot. Concurrently, we recorded activity and temperature rhythms around the clock. To test the model, we studied rhythms and performance during entrainment to a 24-h light cycle and after a 6-h phase advance. Results from this animal model displayed many of the essential characteristics seen in similar human experiments. During stable entrainment, temperature rhythms reached their maximum amplitude in late afternoon, with activity rhythms reaching their maximum amplitude several hours earlier. Performance exhibited consistent task-dependent variations over the course of daily sessions. Speed of discrimination performance was fastest at the beginning of the session, and speed of vigilance performance was fastest several hours later. After a 6-h phase advance, monkeys exhibited transient internal desynchrony with activity resynchronizing faster than temperature. Both vigilance and discrimination were impaired after the phase shift, with vigilance exhibiting larger-magnitude and longer-lasting impairments than discrimination. A second drop in performance was seen 10-14 days after the phase shift. These data replicate and extend earlier work in humans and show that this model can be used in the study of chronobiological questions that would be too expensive or too impractical to do with humans.
Somatosensory inhibition of vagal baroreflex bradycardia: afferent nervous mechanisms
Authors: Nosaka S. , Murata K.
Published: December 2017

Sensory receptors, afferent fibers, and spinal ascending pathways involved in somatosensory inhibition of baroreflex vagal bradycardia (BVB) were studied in chloralose-urethan-anesthetized rats. BVB was induced by electrical stimulation of the aortic depressor nerve (ADN). Among mechanical and thermal stimuli applied on a hindlimb, hot water (55 degrees C) immersion was most effective to inhibit BVB. Static hindlimb muscle contraction by ventral root stimulation also produced BVB inhibition that was abolished by muscle relaxation. These findings suggest that thermal nociceptors and muscle receptors, probably chemoreceptors, trigger BVB inhibition when activated. Furthermore, afferent fiber groups responsible for BVB inhibition due to sciatic nerve (ScN) or sural nerve (SU) stimulation were determined. BVB was largely inhibited by activation of A delta-fibers of the ScN or SU, but C-fiber contribution to BVB inhibition was also ascertained by means of selective C-fiber activation. Finally, courses of spinal pathways mediating ScN inhibition of BVB were localized as follows. First, ADN-vagal baroreflex arc of one side was interrupted by unilateral vagotomy. Then ScN inhibition of BVB provoked by the remaining reflex arc was analyzed after spinal cord hemisection at C1 and subsequent lesioning of the cord on the nonsectioned side. Regardless of whether the spinal cord was hemisectioned on any side with respect to the target reflex arc, stimulation of the ScN of either side still inhibited BVB, unless the lateral funiculus of nonsectioned side was extensively lesioned. In conclusion, the spinal BVB-inhibitory pathways are multifold, projecting to bilateral baroreflex vagal centers by crossing the midline at spinal or/and medullary levels.
In vivo control of phosphofructokinase: system models suggest new experimental protocols
Authors: Connett R. J.
Published: December 2017

There is still uncertainty as to how much control of in vivo rates of glycolysis by phosphofructokinase (PFK) depends on cytosolic phosphate energy state. Three models of PFK kinetics incorporating sensitivity to pH, adenine nucleotides, and inorganic phosphate (Pi) were embedded in the physiological "phosphate energy system" of creatine-containing tissues [Connett, R.J. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949-R959, 1988]. Effects of changes in phosphate energy state and total adenine nucleotide and phosphate pools on steady-state kinetics were examined. Analyses mimicking in vitro experiments indicated no activity at the pH and [ATP] of working muscles. When tested using the coordinated changes in Pi and adenine nucleotides expected in vivo, all models showed reasonable activity. Control was dominated by [Pi] in the normal physiological range of energy states. The almost linear response to phosphate energy state, measured by creatine charge (phosphocreatine/total creatine), is insensitive to the absolute size of the adenine nucleotide pool. A step to almost full activation occurred when phosphocreatine buffering of [ATP] was exceeded. Several experimental studies are suggested.
Cardiac and abdominal vagal afferent inhibition of primate T9-S1 spinothalamic cells
Authors: Hobbs S. F. , Oh U. T. , Chandler M. J. , Foreman R. D.
Published: December 2017

Effects of electrically stimulating vagal afferents were determined on lumbosacral spinothalamic tract (STT) neurons in the T9-S1 segments. Stimulating left or right vagal afferents inhibited 20 (50%) and excited 4 (10%) of 40 STT neurons. Vagal stimulation reduced activity of the 20 inhibited cells by 71 +/- 6% and reduced the average activity of all 40 STT neurons by 28% from 11.5 +/- 1.3 to 8.3 +/- 1.4 impulses/s (P less than 0.01). Effects of activating thoracic and abdominal or just abdominal vagal afferents were also determined. Stimulating right abdominal vagal afferents inhibited 4 (11%), excited 1 (3%), and did not affect 30 (86%) of the STT neurons and overall did not significantly affect STT cell activity. In contrast, in 33 of these cells stimulation of afferents in the right cervical vagus inhibited 16 (48%), excited 2 (6%), and did not affect 15 (45%) neurons and overall significantly reduced cell activity by 29% (P less than 0.01). These data and those of Ammons et al. (J. Neurophysiol. 50: 926-940, 1983; Circ Res. 53: 603-612, 1983; J. Neurophysiol. 54: 73-89, 1985) suggest that cardiopulmonary but not abdominal vagal afferent input reduces STT cell activity in many spinal segments. This inhibitory vagal reflex may play a role in protecting the heart.
mu-Opioid peptide modulation of cardiovascular and sympathoadrenal responses to stress
Authors: Marson L. , Kiritsy-Roy J. A. , Van Loon G. R.
Published: December 2017

The effects of mu- and delta-opioid receptor activation on sympathoadrenal and cardiovascular responses to stress were examined in conscious rats. The mu-selective agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) or the delta-selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) was injected into a lateral cerebral ventricle, then rats were stressed by restraint. Plasma catecholamines were measured, and arterial blood pressure and heart rate were recorded continuously. Restraint stress evoked increases in plasma catecholamines and heart rate in saline-pretreated rats. Both DAGO and DPDPE increased basal plasma levels of catecholamines and blood pressure, and DAGO, 5 nmol, produced bradycardia. DAGO, 5 nmol, but not DPDPE, potentiated the plasma catecholamine responses to restraint. However, the presence of DAGO or DPDPE during restraint resulted in decreases in heart rate and blood pressure. The effects of DAGO and DPDPE on plasma catecholamines, heart rate, and blood pressure were blocked by a mu-selective dose of naloxone but were not reversed by the delta-selective antagonist ICI 174864. These results indicate that mu-receptor stimulation during restraint stress facilitates sympathoadrenal and parasympathetic outflow and results in vasodilatation of some peripheral vascular beds.
Freezing-induced changes in the heart rate of wood frogs (Rana sylvatica)
Authors: Layne J. R. , Lee R. E. , Heil T. L.
Published: December 2017

During the first few hours of freezing the cardiovascular system must distribute cryoprotectant throughout the body of freeze-tolerant frogs. This study presents initial documentation of the changes in heart rate of wood frogs (Rana sylvatica) during nonlethal freezing. Heart rate was determined by measuring the electrocardiogram of frogs. Within 1 min of the onset of freezing the heart rate nearly doubled to approximately 8.0 beats/min. The heart rate began to slow after the first hour of the freeze, and the heart completely stopped beating near the completion of ice formation approximately 20 h later. Recordings from a single frog revealed that the heart beat resumes within 1 h after thawing and near-normal function is achieved after only a few hours. The release of the latent heat of fusion caused a rise in body temperature (1.7 degrees C) for a few hours and was closely correlated with an increase in the heart rate. However, other factors such as reduction in blood volume, increase in blood viscosity, and progressive hypoxia may prominently influence cardiac function indirectly. Regardless, the heart functions long enough to distribute glucose throughout the body during the first few hours of the freeze.
Fluid secretion and microvillar ultrastructure in mosquito malpighian tubules
Authors: Bradley T. J. , Snyder C.
Published: December 2017

The Malpighian tubules of fourth instar larvae, pupae, and female adults of the mosquito Aedes taeniorhynchus were examined with regard to in vitro fluid secretion rate and the ultrastructural features of the microvillar border of the primary cells. In vitro fluid secretion rates were determined after stimulation with 5-hydroxytryptamine. While larval tubules are capable of rapid fluid secretion, the tubules of pupae exhibit very low rates of secretion, indistinguishable from 0 nl/h. The capacity to secrete fluid returns after the pupal-adult molt and is further enhanced after blood feeding. Similar results were obtained in tubules stimulated in vitro with dibutyryl adenosine 3',5'-cyclic monophosphate. Ultrastructural examination of the microvillar border of the primary cells of the Malpighian tubules revealed that the period of reduced secretion capacity in the pupal tubules is correlated with a marked reduction in microvillar volume, microvillar surface area, and mitochondrial content in the microvillar border. The results suggest that microvilli of a certain size and containing extensions of mitochondria are required for rapid fluid transport. The absence of these conditions in pupal tubules cannot be overcome by in vitro stimulation with known secretagogues and therefore represents a physiological limit on transport performance in the pupal tubules of mosquitoes.
Myocardial function in sepsis and endotoxin shock
Authors: Abel F. L.
Published: December 2017

Myocardial function in sepsis and endotoxin shock is reviewed. Clinical, whole animal, and isolated tissue studies are compared to answer the question whether sepsis and/or endotoxin directly damage the myocardium. Myocardial performance is considered relative to control of preload, afterload, and heart rate. Despite the fact that these vary widely in different studies, there is overwhelming evidence that myocardial performance is depressed in both sepsis and endotoxin shock. The depression is dose related, occurs early after large doses of endotoxin but may follow a hyperdynamic phase in sepsis or after low doses of endotoxin. Endotoxin itself does not appear to be the depressant factor; the final depressant substance(s) is unknown. Calcium transport by the sarcoplasmic reticulum is depressed. This defect is more prominent in the endocardium than in the epicardium. Myocardial adenosinetriphosphatase (ATPase) and norepinephrine stores may be depleted. The septic myocardium has an increased dependence on sympathetic nerve stimulation. There is little evidence that the cause of the myocardial depression is an inadequate coronary blood flow.
Effect of vagotomy on brain and plasma atrial natriuretic peptide during hemorrhage
Authors: Phillips M. I. , Kimura B. , Wang H. , Hoffman W. E.
Published: December 2017

These experiments investigated the change in brain, atrial, and plasma concentrations of atrial natriuretic polypeptide (ANP) after a 33% hemorrhage and the role of vagal nerve input in these changes. In rats, hemorrhage decreased plasma ANP from 246 +/- 48 to 41 +/- 7 pg/ml, but in a hypothalamic tissue block ANP increased from 19.0 +/- 0.9 to 25.5 +/- 0.6 ng/g tissue (P less than 0.05). Bilateral vagotomy was followed by a very large increase in plasma ANP to 703 +/- 198 pg/ml. Atrial pressures, however, fell after vagotomy from 2 +/- 2 to 1 +/- 1 mmHg. Therefore, the effect was not due to increased atrial stretch. Right atrial ANP levels were also elevated by vagotomy, but left atrial ANP concentrations did not change with vagotomy or hemorrhage. After hemorrhage in vagotomized rats, plasma ANP decreased to 79 +/- 6 pg/ml. After vagotomy, the ANP concentration in the hypothalamic block did not rise in response to hemorrhage. The results indicate that the vagus nerves provide a tonic inhibition of ANP levels in atria and plasma. The results cannot be explained by atrial distension. The results show independence of brain and plasma ANP and uncover a tonic vagal inhibition of ANP release.
Activity of most rostral ventromedial medulla neurons reflect EEG/EMG pattern changes
Authors: Grahn D. A. , Heller H. C.
Published: December 2017

Studies in lightly anesthetized animals have demonstrated neurons in the rostral ventromedial medulla (RVM) that respond to specific modalities of peripheral stimulation. We initiated this study to investigate putative thermoafferent processing in such RVM neurons. Our results indicate that most RVM neuronal responses are not specific for the applied stimulus but reflect changes in cortical activation. Electroencephalogram/electromyogram (EEG/EMG) and RVM single unit activity was recorded in lightly urethan-anesthetized rats. Five distinct EEG/EMG patterns were observed. Their expression was a function of skin and core temperatures. Pinches and strong thermal manipulations caused a desynchronization of a synchronized EEG pattern and an increase in EMG activity. The activity of 38 of the 51 RVM neurons sampled correlated with changes in EEG/EMG activity. Thirteen neurons were not affected by changes in EEG/EMG activity. One unit responded to temperature manipulations within an EEG/EMG state, suggesting that a small portion of RVM neurons may transmit thermoafferent information.
Potent cholecystokinin antagonist L 364718 stimulates food intake in rats
Authors: Reidelberger R. D. , O'Rourke M. F.
Published: December 2017

The cholecystokinin (CCK) receptor antagonist L 364718 was used to examine the role of CCK in control of food intake. Effects of L 364718 (0.01-1 mg/kg ip) on the feeding response to a maximal inhibitory dose of cholecystokinin COOH-terminal octapeptide (CCK-8; 8 nmol/kg ip) and on food intake alone were determined in rats fed ad libitum during the dark cycle. CCK-8 suppressed feeding by 48%. L 364718 reversed this effect dose dependently; the minimal effective dose was 0.03 mg/kg, and complete reversal occurred at 0.1 and 0.3 mg/kg. L 364718 (0.03 mg/kg) caused a parallel, rightward shift in the dose-response curve to CCK-8 [1-128 nmol/kg, half-maximal effective dose (ED50) increased 16-fold] but did not alter the maximal response, consistent with competitive-like kinetics. L 364718 stimulated liquid and solid food intake dose-dependently by 11-35%. The minimal effective dose was 0.1 mg/kg; maximal stimulation occurred at 0.3 mg/kg. Duodenal infusion of bile-pancreatic juice did not alter the response. These results support an important role for CCK in control of food intake.
Role of renal nerves in response to volume expansion in conscious newborn lambs
Authors: Smith F. G. , Sato T. , McWeeny O. J. , Torres L. , Robillard J. E.
Published: December 2017

The present study was designed to determine the influence of renal nerves in mediating the renal response to volume expansion in conscious newborn lambs. Bilateral renal denervation (n = 9) or sham surgery (n = 14) was carried out in newborn lambs 3 to 4 days before performing experiments. Lambs were between 6 and 12 days of age when studied. Chronic denervation did not alter basal neonatal renal function nor renal hemodynamics. Volume expansion with isotonic saline equal to 5% of body weight was associated with a fall in hematocrit and an increase in mean arterial blood pressure, glomerular filtration rate, urine flow rate, and Na+ excretion in intact and denervated lambs. In intact lambs, atrial natriuretic factor increased from 98 +/- 28 to 176 +/- 48 ng/ml during volume expansion and remained elevated for 1 h after volume expansion. In addition, plasma renin activity fell from 21 +/- 5 to 8 +/- 1 ng.ml-1.h-1 and aldosterone levels fell from 160 +/- 24 to 59 +/- 7 pg/ml by 150 min after the start of volume expansion. Similar changes in atrial natriuretic factor, plasma renin activity, and aldosterone were observed in denervated lambs. However, the increase in glomerular filtration rate, Na+ excretion, and fractional excretion of Na+ after volume expansion were significantly less in denervated than in intact lambs. Thus, in the newborn, the renal nerves do not appear to play a role in influencing basal renal hemodynamics and renal function but, as in the adult, the renal sympathetic nervous system does play a role in regulating fluid and electrolyte excretion during hypervolemia.
Sepsis does not alter red blood cell glucose metabolism or Na+ concentration: a 2H-, 23Na-NMR study
Authors: Hotchkiss R. S. , Song S. K. , Ling C. S. , Ackerman J. J. , Karl I. E.
Published: December 2017

The effects of sepsis on intracellular Na+ concentration ([Na+]i) and glucose metabolism were examined in rat red blood cells (RBCs) by using 23Na- and 2H-nuclear magnetic resonance (NMR) spectroscopy. Sepsis was induced in 15 halothane-anesthetized female Sprague-Dawley rats by using the cecal ligation and perforation technique; 14 control rats underwent cecal manipulation without ligation. The animals were fasted for 36 h, but allowed free access to water. At 36 h postsurgery, RBCs were examined by 23Na-NMR by using dysprosium tripolyphosphate as a chemical shift reagent. Human RBCs from 17 critically ill nonseptic patients and from 7 patients who were diagnosed as septic were also examined for [Na+]i. Five rat RBC specimens had [Na+]i determined by both 23Na-NMR and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). For glucose metabolism studies, RBCs from septic and control rats were suspended in modified Krebs-Henseleit buffer containing [6,6-2H2]glucose and examined by 2H-NMR. No significant differences in [Na+]i or glucose utilization were found in RBCs from control or septic rats. There were no differences in [Na+]i in the two groups of patients. The [Na+]i determined by NMR spectroscopy agreed closely with measurements using ICP-AES and establish that 100% of the [Na+]i of the RBC is visible by NMR. Glucose measurements determined by 2H-NMR correlated closely (correlation coefficient = 0.93) with enzymatic analysis. These studies showed no evidence that sepsis disturbed RBC membrane function or metabolism.
Hemodynamic effects of calcitonin gene-related peptide in spontaneously hypertensive rats
Authors: Ando K. , Pegram B. L. , Frohlich E. D.
Published: December 2017

Systemic and regional hemodynamic effects of intravenously injected calcitonin gene-related peptide (CGRP), 220 and 650 pmol, were compared in nine Wistar-Kyoto (WKY) and nine spontaneously hypertensive rats (SHR). CGRP (higher dose) reduced mean arterial pressure (from 135 +/- 2 to 83 +/- 2 and from 179 +/- 4 to 116 +/- 3 mmHg; P less than 0.01, each, in WKY and SHR, respectively) through a fall (-38 +/- 4 and -40 +/- 3%; P less than 0.01) in total peripheral resistance associated with an unchanged cardiac output and an increased heart rate. The decreases in arterial pressure and total peripheral resistance were not different between these two strains. Of particular significance were the highly selective reductions in organ vascular resistances, being greatest in the cutaneous (-78 +/- 3 and -67 +/- 4%) and gastric (-80 +/- 3 and -84 +/- 2%) circulations in WKY and SHR, respectively (P less than 0.01). Reduction in coronary, cerebral, and hepatic vascular resistances, although significant (P less than 0.05, at least), were only moderately reduced compared with the two former circulations. These effects were similar in WKY and SHR and demonstrate that CGRP is a highly selective and potent natural vasodilating peptide that has the most striking effects in skin and stomach, suggesting possible modulator functions in regulating certain regional hemodynamics.
Effect of gastrointestinal flora on body temperature of rats and mice
Authors: Kluger M. J. , Conn C. A. , Franklin B. , Freter R. , Abrams G. D.
Published: December 2017

The purpose of these experiments was to test the hypothesis that gut flora influences the body temperature of rodents. Rats and mice were implanted with biotelemetry transmitters that enabled us to record both abdominal temperature and activity for long periods of time. Rats given nonabsorbable antibiotics in their drinking water, which reduced their gut flora, had a marked decrease in both their daytime and nighttime temperatures. Similar results were found with germfree mice. The circadian rhythms in body temperature of germfree and conventionalized mice were not different. However, the body temperatures of the germfree mice were lower than those of the conventionalized mice during both the daytime and nighttime. The decrease in body temperature in the germfree mice was not related to changes in activity. These results support the hypothesis that gut flora has a tonic stimulatory effect on both the daytime and nighttime body temperature of rodents.
Model of placental glucose consumption and glucose transfer
Authors: Hay W. W. , Molina R. A. , DiGiacomo J. E. , Meschia G.
Published: December 2017

Net ovine uteroplacental glucose consumption (Ro,up) and transfer rates to the fetus (Rf,up) were measured at different concentrations of maternal (GA) and fetal (Ga) arterial plasma glucose that were set and maintained independently by a glucose clamp procedure. Five GA/Ga combinations were studied: 70/15, 70/20, 70/30, 50/14, and 50/24 mg/dl. Rf,up was inversely related to Ga both at GA = 70 and GA = 50. Linear regression analysis of Rf,up vs. Ga for the GA = 70 and GA = 50 groups of observations revealed similar slopes (-0.286 +/- 0.012 vs. -0.217 +/- 0.028 dl.min-1.kg fetus-1) but a significantly higher intercept for the GA = 70 group (10.3 +/- 0.12 vs. 5.5 +/- 0.47 mg.min-1.kg fetus-1). In contrast, Ro,up increased significantly in response to an increase of Ga and had no significant dependence on GA. These results indicate that uteroplacental glucose metabolism occurs primarily in tissues that have direct access to glucose molecules carried by the umbilical circulation and that the glucose transport capacity of the placental barrier is greater on its fetal than its maternal surface. Uteroplacental glucose metabolic rate and its dependence on fetal glucose concentration are major factors that determine the magnitude and variability of the glucose concentration gradient (and thus the rate of net glucose transfer) between maternal and fetal plasma.
Propranolol inhibits O2-sensitive chemoreceptor activity in trout gills
Authors: Burleson M. L. , Milsom W. K.
Published: December 2017

The effects of propranolol on the activity of O2-sensitive chemoreceptors innervated by cranial nerve IX were studied using an isolated, perfused first gill arch preparation from rainbow trout (Onchyrhyncos mykiss). Perfusing the gill with hypoxic perfusate resulted in an increase in chemoreceptor activity. Propranolol (100-200 nmol) added to the perfusate inhibited O2-receptor discharge during both normoxia and hypoxia and attenuated the response to bolus injections of NaCN (25 micrograms). These results suggest that a beta-adrenergic mechanism is involved in O2 chemoreception. They further suggest that the inhibitory effects of propranolol on branchial, O2-sensitive chemoreceptors may contribute to the attenuated hypoxic ventilatory reflex observed in intact fish after propranolol injections.
Urea transport across urinary bladder and salt acclimation in toad (Bufo viridis)
Authors: Shpun S. , Katz U.
Published: December 2017

The fluxes of urea across the urinary bladder of the toad Bufo viridis have been studied under conditions of acclimation to tap water or 500 mosM NaCl solution. The [14C]urea fluxes were measured simultaneously with [3H]inulin to test for nonspecific leakage. The fluxes are quite high (Ktrans = 75 x 10(-7) cm/s at 5 mmol/l urea) and are similar in either the mucosal-to-serosal or the opposite direction. “Summer” rates were five to six times higher than the “winter” rates. Antidiuretic hormone (ADH), theophylline, and forskolin increased the fluxes to variable degrees (two to five times), similar in the two acclimation conditions. Phloretin inhibited the urea fluxes by nearly 50%. 1,3-Dimethylurea and thiourea, but not acetamide, competed with the urea fluxes effectively. The fluxes of urea were not affected by the osmotic water flow, although both responded to ADH. It is concluded that urea transport across the urinary bladder of B. viridis is by facilitated diffusion through a specific pathway independent of water flux. The inhibitory effect of the structural analogues on the urea flux was affected by salt acclimation, whereas most other characteristics did not differ significantly at 5 mmol/l external urea under the two conditions of acclimation.
Cardiovascular, renal, and endocrine responses in male quadriplegics during head-out water immersion
Authors: Tajima F. , Sagawa S. , Iwamoto J. , Miki K. , Freund B. J. , Claybaugh J. R. , Shiraki K.
Published: December 2017

The present study was undertaken to determine the relative influence of the action of the central nervous system on the mechanism of water-immersion-induced diuresis by comparing physiological responses of quadriplegic (QP) and normal subjects. After overnight fasting seven male QP subjects with complete cervical cord transections (C5-C8) and six normal men were tested before, during, and after 3 h of head-out immersion (HOI) in thermoneutral water (34.5-35.0 degrees C). The reversible increase in urine flow and the total urine volume (309 +/- 53 ml in 3 h) in QP subjects were comparable with that of the normal subjects (318 +/- 96 ml in 3 h). While osmolal excretion was increased in QP subjects, its magnitude was less when compared with that of normal subjects. Instead, the increased urine flow in QP subjects was characterized by increased glomerular filtration rate (GFR) and free water clearance, in contrast to a predominantly osmotic diuresis with no changes in GFR in the normal subjects. The HOI elevated (P less than 0.05) systolic pressure only in QP subjects, whereas the increase in cardiac output was the same in both groups. While plasma renin activity and aldosterone responses to HOI in QP subjects were comparable with those of normal individuals, plasma atrial natriuretic factor (ANF) in QP subjects was twofold higher (P less than 0.05) during HOI, and the approximately threefold increase in ANF (P less than 0.05) in QP subjects due to HOI was the same as that of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Facilitated transport of L-phenylalanine across blood-nerve barrier of rat peripheral nerve
Authors: Wadhwani K. C. , Smith Q. R. , Rapoport S. I.
Published: December 2017

L-Phenylalanine transport across the blood-nerve barrier was studied by perfusing Ringer solution containing trace amounts of L-[14C]phenylalanine and [3H]dextran (a vascular marker) through the hindlimb of an anesthetized rat. At the end of perfusion, a segment of sciatic nerve was removed, frozen, desheathed, and processed for radioactivity counting. The permeability-surface area product of the blood-nerve barrier (PABNB) to L-[14C]phenylalanine decreased from 58 +/- 9 X 10(-5) to 1.7 +/- 0.3 X 10(-5) (SE) ml.s-1.g wet wt-1, as the perfusate concentration of unlabeled L-phenylalanine was increased to 10 mM. D-Phenylalanine had less of an inhibitory effect on L-[14C]phenylalanine uptake than did L-phenylalanine. PABNB did not change in the presence of 50 mM alpha-(methylamino)isobutyric acid (MeAIB) in the perfusion medium, nor by replacing NaCl by Tris.HCl. However, addition of 50 mM 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH) reduced PABNB to 2.1 +/- 0.3 X 10(-5) ml.s-1.g wet wt-1 (n = 4). PA at epiperineurial barrier (PAper) of L-[14C]phenylalanine at the epiperineurial barrier, determined from in situ incubation, was 1.4 +/- 0.2 X 10(-5) ml.s-1.g wet wt-1 (n = 6) and was unaffected by 10 mM L-phenylalanine concentration in the incubation medium. The results demonstrate for the first time carrier-mediated transport system for L-phenylalanine at the blood-nerve barrier of the rat peripheral nerve.
Pressor and sympathetic responses to dorsal raphe nucleus infusions of TRH in rats
Authors: Mattila J. , Bunag R. D.
Published: December 2017

Pressor, tachycardic, and sympathoexcitatory responses to intracerebroventricularly (icv) infused thyrotropin-releasing hormone (TRH) were recorded in urethan-anesthetized rats to identify where centrally administered TRH acts in the brain. None of these responses was altered either by electrolytic lesions in the medial preoptic, posterior, or paraventricular hypothalamus or by chemical lesions produced by destroying catecholaminergic neurons with icv infused 6-hydroxydopamine. By contrast, when serotonergic neurons were similarly destroyed with 5,7-dihydroxytryptamine, TRH-induced tachycardia was inhibited. Attendant pressor responses were also inhibited by electrolytic lesions of the dorsal, but not of the median, raphe nucleus. Pressor and sympathoexcitatory responses elicited by infusing TRH directly into the dorsal raphe nucleus resembled those produced by icv infusion, and their magnitude diminished after pentolinium-induced ganglioplegia. These results are compatible with the interpretation that icv infused TRH may produce its cardiovascular and sympathetic effects by acting, at least in part, on serotonergic mechanisms located in the dorsal raphe nucleus.
Force and acid-base state of turtle cardiac tissue exposed to combined anoxia and acidosis
Authors: Wasser J. S. , Freund E. V. , Gonzalez L. A. , Jackson D. C.
Published: December 2017

We measured contractile force of ventricular strips form the turtle Chrysemys picta bellii exposed to 1 h of combined anoxia and acidosis (pH 7.0) at 20 degrees C. Strips either beat spontaneously (self-paced) or in response to electrical stimulation (paced at 12, 24, or 36 beats/min). Tissue [lactate] and intracellular pH (pHi) were measured in control strips and at the end of anoxia-acidosis. In self-paced strips, at normal extracellular Ca2+ concentration ([Ca2+]o) (1 mM), both rate and force fell significantly after 1 h of anoxia-acidosis to 54 and 17.1%, respectively, of control values. Increased [Ca2+]o to 10 mM at 30 min had a small but significant positive effect on both rate and force. Contractile force of paced strips also fell progressively during anoxia-acidosis, but the decrease varied directly with pacing frequency. Under all cases of anoxia-acidosis, pHi fell significantly from the control value of 7.53; in paced strips, acidosis was most severe at 36 beats/min (pHi 6.75), and in self-paced strips, pHi (approximately 6.85) was independent of [Ca2+]o. Based on this and previous work, we conclude that combined anoxia-acidosis, similar to that observed in vivo after prolonged anoxic submergence, profoundly depresses cardiac function. Both hypercalcemia and bradycardia improve performance in this extreme state, but these effects are not as great as when anoxia and acidosis occur alone.
Interleukin 1 and endotoxin activate soluble guanylate cyclase in vascular smooth muscle
Authors: Beasley D.
Published: December 2017

Our recent studies indicate that interleukin 1 (IL-1) and bacterial lipopolysaccharide inhibit agonist-induced contractions in rat aortic rings by an endothelium-independent mechanism. The present study investigated the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the vasodilatory action of IL-1 and endotoxin. Rat aortic rings were denuded of endothelium and incubated for 3 h in physiological salt solution containing no additions, IL-1 (20 ng/ml), or endotoxin (10 micrograms/ml). Contractions induced by phenylephrine (3 x 10(-7) M) were decreased by 40 and 85% in endotoxin- and IL-1-treated rings, respectively. IL-1 increased cGMP content 2.5-fold in the absence of and 5.5-fold in the presence of 3-isobutyl-1-methylxanthine (IBMX). Endotoxin also increased cGMP content in the absence and presence of IBMX (5.5- and 25-fold, respectively). Both IL-1- and endotoxin-induced increases in cGMP occurred 3-4 h after initial exposure. The guanylate cyclase inhibitors, LY 83583 and methylene blue, each abolished IL-1- and endotoxin-induced inhibition of contraction and IL-1-induced production of cGMP. Furthermore, hemoglobin, which binds nitric oxide, completely blocked IL-1-induced increases in cGMP. We conclude that IL-1 and endotoxin inhibit vascular contraction in vitro by increasing aortic cGMP content. Studies with inhibitors suggest IL-1 and endotoxin may induce endothelium-independent production of nitric oxide or another free radical that activates soluble guanylate cyclase.
Deactivation rate and shortening velocity as determinants of contractile frequency
Authors: Marsh R. L.
Published: December 2017

The kinetic properties of muscle that could influence locomotor frequency include rate of activation, rate of cross-bridge "attachment", intrinsic shortening velocity, and rate of deactivation. The latter two mechanisms are examined using examples from high-speed running in lizards and escape swimming in scallops. During running, inertial loading and elastic energy storage probably mitigate the effects of thermal alterations in intrinsic muscle shortening velocity. The result is a rather low thermal dependence of stride frequency over a 15-20 degree C temperature range. However, at lower temperatures, the longer times required for deactivation cause the thermal dependence of frequency to increase greatly. Scallops use a single muscle to swim by jet propulsion. In vivo shortening velocity in these animals also shows a low thermal dependence. As with high-speed running, the mechanics of jet propulsion may limit the effects of thermally induced changes in intrinsic shortening velocity. The largest thermal effect during swimming is on the initial phase of valve opening. The effects of temperature on the rate of deactivation of the adductor muscle could play an important role in limiting reextension of the muscle, which is dependent on elastic energy storage in the hinge ligament. These examples illustrate that the relative importance of various intrinsic contractile properties in controlling locomotor performance depends on the mechanics of the movements.
Daily injections of triazolam induce long-term changes in hamster circadian period
Authors: Van Reeth O. , Turek F. W.
Published: December 2017

Previous experiments in hamsters indicate that daily injections of the short-acting benzodiazepine, triazolam, can entrain the free-running circadian activity rhythm to the period of the injections and that, after discontinuation of triazolam injections, the period of the free-running activity rhythm remains close to that of the previous injection schedule for 20-50 cycles. In this paper, we extend these findings and demonstrate that 1) long-term treatment with triazolam can induce aftereffects on the period of the circadian clock underlying the activity rhythm that can last for up to 100 days, 2) triazolam-induced changes in period can lead to a loss of effect of daily injections of triazolam which can be restored if the time of injection is altered, and 3) chronic treatment with triazolam also alters the period of the circadian clock in animals entrained to a light-dark cycle, and such changes in period alter the phase relationship between the circadian clock and the entraining light-dark cycle.
Serotonin3 receptor antagonists block anorectic responses to amino acid imbalance
Authors: Hammer V. A. , Gietzen D. W. , Beverly J. L. , Rogers Q. R.
Published: December 2017

The role of serotonin3 (5-HT3) receptors in the initial food intake depression of rats ingesting amino acid imbalanced or high-protein diets was investigated. The 5-HT antagonists metergoline, pirenpirone, ICS 205-930, and MDL 72222, the dopamine antagonist pimozide, or the alpha-adrenergic antagonist phentolamine were injected 15-45 min before presentation of test diets. Food intake was measured at intervals for 3 days. The 5-HT3 antagonists, ICS 205-930 and MDL 72222, restored feeding of a mild isoleucine (Ile)-imbalanced diet to control levels, although MDL 72222 had a longer time course of action. ICS 205-930 also increased intake of a severe Ile-imbalanced diet and Thr-imbalanced diet but not a high-protein (44% casein) diet. Treatment with metergoline, which blocks 5-HT1, 5-HT2, and dopamine receptor sites but not 5-HT3 sites, increased intake of the basal diet at 3 and 6 h but did not significantly alter intake of the mild Ile-imbalanced diet. Although pimozide tended to increase intake of the mild imbalanced diet, neither dopamine nor alpha-adrenergic receptor antagonism significantly affected imbalanced diet intake. Thus 5-HT3 receptors may mediate the anorexigenic activity of 5-HT associated with feeding an amino acid-imbalanced diet.
Testosterone influences hibernation in golden-mantled ground squirrels
Authors: Lee T. M. , Pelz K. , Licht P. , Zucker I.
Published: December 2017

At different phases of the hibernation season, castrated male golden-mantled ground squirrels were implanted with capsules that either were filled with testosterone (T) or left empty (blank). Blank-treated animals hibernated normally when housed at 5 degrees C. Entry into hibernation was prevented in the majority of squirrels treated with T several days before the initial cold challenge. T concentrations that inhibited torpor (greater than 1.2 ng/ml) were comparable with those of intact males at the end of the hibernation season. In some squirrels, moderate T concentrations were compatible with hibernation, but torpor bout duration was shorter than normal. The inhibitory effect of T on hibernation did not appear to require aromatization of T to estradiol. We suggest that a steroid-independent mechanism triggers arousal from hibernation and that T-dependent processes determine whether hibernation is resumed at the end of an arousal period.
Baroreflex responses to acute changes in blood volume in humans
Authors: Thompson C. A. , Tatro D. L. , Ludwig D. A. , Convertino V. A.
Published: December 2017

To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low-pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baroreflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus-response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of forearm vascular resistance (FVR) and peripheral venous pressure (PVP) during low levels of lower body negative pressure (0 to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 +/- 1.73, -4.36 +/- 1.38, and -2.56 +/- 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post-flight impairment of the carotid-cardiac baroreflex.
Dissociative analysis of ventromedial hypothalamic obesity syndrome
Authors: Parkinson W. L. , Weingarten H. P.
Published: December 2017

Electrolytic lesions of the ventromedial hypothalamus (VMH) produce an obesity syndrome characterized by hyperphagia, adiposity, and heightened parasympathetic tone. Experiments were conducted to evaluate the possibility that these symptoms arise from damage to distinct and separated loci within the hypothalamus. Rats received either VMH lesions, perifornical hypothalamic (PFH) knife cuts, ventromedial hypothalamic nucleus (VMN) lesions, or sham surgery (Sham). When maintained ad libitum, VMH and PFH rats were hyperphagic, overweight, and became obese. VMN rats were not hyperphagic, nor did they gain excessive weight, but they did develop an obesity reflected as a significantly elevated level of carcass fat. Under restricted feeding conditions, both VMH and VMN rats became obese; PFH rats did not. Also, only VMH lesions and PFH knife cuts increased basal gastric acid secretion. These data demonstrate dissociations between hyperphagia and obesity, as well as between stomach secretion and obesity, in the VMH syndrome. The implications of these findings for a dissociative model of the VMH obesity syndrome are discussed.