bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth
Authors: Istfan N. W. , Ling P. R. , Blackburn G. L. , Bistrian B. R.
Published: December 2017

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of “whole body” protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.
Reduced osmotic thirst in healthy elderly men
Authors: Phillips P. A. , Bretherton M. , Johnston C. I. , Gray L.
Published: December 2017

In response to water deprivation or heat stress, healthy elderly men experience reduced thirst compared with a young control group. Because water deprivation and heat stress produce hypertonicity as well as reduced extracellular fluid volume, the aim of this study was to determine whether the elderly also experience reduced thirst in response to hypertonicity without extracellular fluid volume depletion. To achieve this, after an overnight fast, healthy community-dwelling nonsmoking old (65-78 yr, n = 7) and young (20-32 yr, n = 7) men received 120-min hypertonic (0.855 M) and isotonic (0.154 M) saline infusions (0.06 ml.min-1.kg-1) in double-blind randomized order at least 2 wk apart. Both groups had increased thirst (P less than 0.001) and water intake (P less than 0.05) after the hypertonic saline infusion compared with the isotonic saline infusion. However, despite similar plasma sodium increases and less plasma volume expansion during the hypertonic saline infusion compared with the young group, the old group was less thirsty (P less than 0.01) and drank less room-temperature tap water (young 11.1 +/- 1.2 ml/kg, old 3.9 +/- 0.6 ml/kg, P less than 0.001). This reduced thirst in the old group seemed to be mainly due to a lower thirst sensitivity (P less than 0.05) to hypertonicity, although there was also a tendency toward an increased thirst threshold. Plasma arginine vasopressin increases were similar for the old and young groups with hypertonic saline, without significant changes during the isotonic saline infusion in either group.
Renal denervation does not prevent hypertension in Lyon hypertensive rats
Authors: Boussairi E. H. , Julien C. , Ducher M. , Barres C. , Vincent M. , Sassard J.
Published: December 2017

The effects on blood pressure (BP) of a single and repeated renal denervations (RD) were compared in genetically hypertensive (LH) and normotensive (LN) rats of the Lyon strain. Indirect BP was measured by the tail-cuff method, and direct BP was measured through an aortic catheter in conscious quiet rats receiving a normal-sodium diet. Single RD (10 wk of age) did not reduce BP in both LN and LH rats. Repeated RD (4, 7, and 10 wk of age) partly prevented the age-related increase in tail-cuff BP but did not affect the directly recorded BP in 11-wk-old LH rats. Single and repeated RD reduced the renal norepinephrine content by greater than 90%. Both procedures did not alter the BP lowering effects of angiotensin-converting enzyme inhibition and of ganglionic blockade. It is concluded that renal nerves are not necessary for the development and the maintenance of hypertension in LH rats.
mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides
Authors: Gunion M. W. , Rosenthal M. J. , Morley J. E. , Miller S. , Zib B. , Butler B. , Moore R. D.
Published: December 2017

Four experiments were done to determine which receptor type(s) mediates the effects of third ventricular microinjections of four opioid peptide agonists on blood levels of glucose, free fatty acids, and corticosterone. Tests were performed in unanesthetized adult male albino rats having chronic intraventricular cannulas; blood samples were taken from the tail tip at 0, 15, 30, 60, 90, and 120 min postmicroinjection. In experiment 1, the agonists DAGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), beta-endorphin, DSLET (d-Ser2-Leu-enkephalin-Thr), and dynorphin A-(1-17) (0, 0.3, 1, 3, and 10 nmol/rat) produced three distinct patterns of changes in serum glucose, free fatty acid, and corticosterone values. Experiment 2 showed that the effects of DAGO and beta-endorphin were inhibited by prior injection with the opiate-receptor blocker naloxone (1 mg/kg sc) and that the effects of dynorphin were not diminished. Experiment 3 determined that dynorphin effects were also not diminished by naloxone given intraventricularly. Experiment 4 found that blockade of the mu-receptor by intraventricular pretreatment with the specific antagonist beta-funaltrexamine (20 micrograms/rat, 24 h before) completely abolished the effects of DAGO and beta-endorphin on glucose and corticosterone. The mu-receptor is critical to the mediation of the hyperglycemia and hypercorticosteronemia induced by the central administration of opiate agonists. These results imply that mu-opioid binding sites previously identified in central autonomic regions may be involved in the regulation of circulating glucose and corticosterone.
Drinking after osmotic challenge depends on circadian phase in rats with free-running rhythms
Authors: Johnson R. F. , Johnson A. K.
Published: December 2017

Rhythmic phase-dependent modulation of the amount of water intake of rats occurs after several types of dipsogenic treatments. Previous studies conducted on rats in light-dark cycles confound direct effects of the light-dark cycle with the effects of circadian rhythmicity entrained to the light-dark cycle. The present study isolates the effect of circadian phase on the amount of drinking induced by injection of hypertonic saline. Free-running rhythms were induced in rats, and then water intake was measured after injections of both hypertonic and isotonic saline at different phases of the rats' circadian cycle. After injections of hypertonic saline, rats drank more water in their active phase than in their inactive phase. No difference in the amount of intake was found in rats that received isotonic saline at different phases of their circadian rhythms. The results indicate a circadian modulation of the drinking induced by cellular dehydration.
Developmental changes in adenylyl cyclase and GTP binding proteins in brown fat
Authors: Chaudhry A. , Granneman J. G.
Published: December 2017

During the perinatal period, norepinephrine (NE)-stimulated adenylyl cyclase activity increased in interscapular brown adipose tissue (IBAT) membranes and then declined to adult levels by 23 days postpartum. The developmental patterns of NE- and NaF-stimulated activities were identical, indicating that the developmental increase in transmitter-stimulated activity resulted from the increased interaction of alpha-subunit of guanine nucleotide-binding stimulatory protein of adenylyl cyclase (Gs alpha) with the catalytic subunit (C). This increased Gs alpha-C interaction was the result of an increase in Gs alpha specific activity, as assessed in cyc- reconstitution assays, as well as an increased C activity, as assessed by forskolin-Mn(2+)-stimulated adenylyl cyclase activity. Although adenylyl cyclase activity increased during the perinatal period, total Gs alpha levels significantly declined because of the loss of the small-molecular-mass form of Gs alpha. Thus the ratio of large to small form of Gs alpha increased threefold and might have contributed to the perinatal increase in activity. Gi alpha-like proteins, as assessed by pertussis toxin-catalyzed [32P]ADP ribosylation, declined dramatically after birth. However, this loss of Gi alpha did not contribute to developmental changes in adenylyl cyclase activity because pertussis toxin treatment failed to alter NE-stimulated activity. In contrast to G alpha subunits, there were no changes in membrane levels of G beta subunits.
Angiotensin II does not contribute to rapid reflex control of arterial pressure
Authors: Brown D. R. , Yingling J. D. , Randall D. C. , Aral H. M. , Evans J. M. , Charles J. B. , Knapp C. F. , Raisch R. , Ott C. E.
Published: December 2017

Pharmacological blockade of the renin-angiotensin converting enzyme reportedly alters the heart rate (HR) power spectrum in conscious dogs, suggesting that these hormones contribute to the short-term regulation of arterial blood pressure. We tested this possibility using four independent procedures. First, HR power spectrum was determined in seven awake dogs before and after administration of enalaprilat (300 ng/kg), a converting-enzyme inhibitor. There were no significant changes in the average amplitude for the spectral peak between 0.003 and 0.1 Hz (i.e., the "low-frequency peak"). Second, the HR power spectrum was measured in 11 awake rabbits before and after treatment with deoxycorticosterone acetate (1 mg.kg-1.day-1) and salt (0.9% saline ad libitum) for 7 days to depress plasma renin levels. There were no significant changes in the amplitude of the HR power spectrum, although mean HR decreased from 206 +/- 3 to 184 +/- 4 beats/min after treatment. In the third experiment, another group of rabbits (n = 8) was tested after 2 wk on a low-salt diet to elevate plasma angiotensin levels and then after 2 wk on a normal salt diet. Once again there were no significant effects on the HR power spectrum. Finally, tranquilized dogs (n = 9) were subjected to sinusoidally varying lower body negative pressure at selected frequencies of 0.008-0.12 Hz. Tests were conducted in the control state and after administration of an angiotensin receptor antagonist (saralasin, 1 microgram.kg-1.min-1). Lower body negative pressure-induced fluctuations in arterial blood pressure were similar in both states. We find no evidence for the role of the renin-angiotensin system in the moment-to-moment regulation of arterial pressure and HR.
Endothelin action on cerebral circulation in unanesthetized goats
Authors: Garcia J. L. , Gomez B. , Monge L. , Garcia-Villalon A. L. , Dieguez G.
Published: December 2017

The effects of endothelin 1 on the internal maxillary artery blood flow, measured as an index of cerebral blood flow, were examined in six unanesthetized goats under control conditions, hypercapnia induced by inhalation of 10% CO2 in air, hypertension by intravenous infusion of norepinephrine, and hypotension by intravenous injection of diazoxide. Under control, administration of endothelin (0.01-0.3 nmol) into the internal maxillary artery produced dose-dependent sustained decreases in cerebral blood flow and increases in cerebrovascular resistance; higher doses (0.1 and 0.3 nmol) also caused hypertension and bradycardia. During hypercapnia or hypertension, endothelin did not significantly affect cerebral blood flow, and only higher doses (0.1 and/or 0.3 nmol) increased cerebrovascular resistance, but this was lower than under control. However, under hypotension endothelin evoked a higher reduction in cerebral blood flow and increment in cerebrovascular resistance, and systemic effects were also more marked than under control. Therefore endothelin is a potent cerebral vasoconstrictor, and this effect is very attenuated during hypercapnia and hypertension but is increased under hypotension.
Pressure natriuresis and cortical and papillary blood flow in inbred Dahl rats
Authors: Roman R. J. , Kaldunski M.
Published: December 2017

The present study examined whether alterations in papillary blood flow, renal interstitial pressure (RIHP), and the pressure-natriuretic (PN) response are associated with the development of hypertension in inbred Dahl salt-sensitive (Dahl-S) rats. The PN responses were compared in 18- to 20-wk-old, Inactin-anesthetized, inbred Dahl salt-sensitive (S/Jr) and salt-resistant (R/Jr) rats fed a low-(0.3%) and a high- (8.0%) sodium chloride diet. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Neural and hormonal influences on the kidney were controlled by renal denervation and by fixing plasma norepinephrine, vasopressin, corticosterone, and aldosterone levels by intravenous infusion. The slope of the PN relationship in S/Jr rats maintained on a low-salt diet was 62% lower than that observed in R/Jr rats; however, whole kidney, cortical, and papillary blood flows and RIHP were not significantly different at any perfusion pressure studied. Glomerular filtration rate (GFR) was 25% lower in S/Jr rats than in R/Jr animals maintained on a low-salt diet. The slopes of the PN responses were similar in S/Jr and R/Jr rats exposed to a high-salt diet, but the entire relationship was shifted toward higher pressures by 20 mmHg in the S/Jr rats. Control cortical and papillary blood flows measured at control mean arterial pressures of 126 +/- 3 and 167 +/- 5 mmHg in R/Jr and S/Jr rats, respectively, were not significantly different. However, cortical and papillary blood flows were 25% lower in the S/Jr than in the R/Jr rats exposed to a high-salt diet when compared at equivalent renal perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Satiating effect of bombesin is mediated by receptors perfused by celiac artery
Authors: Kirkham T. C. , Gibbs J. , Smith G. P.
Published: December 2017

The abdominal site or sites for the satiety action of exogenous, peripherally administered bombesin (BN) were investigated. By use of a chronic arterial catheterization technique, the effects of 1, 2, and 4 micrograms/kg BN on liquid food intake of nondeprived male rats were assessed. Comparisons were made between the effects of these doses infused into the celiac or superior mesenteric arteries or injected intraperitoneally. The satiating potency of exogenous BN was significantly enhanced by direct administration into the celiac artery, which directly perfuses the stomach, pancreas, liver, spleen, and proximal duodenum. By this route, 4 micrograms/kg BN produced greater than 60% suppression of 15-min food intake. By contrast, BN infused into the superior mesenteric artery was no more effective than intraperitoneal injection. Celiac infusion of 1 micrograms/kg BN produced a suppression (30%) of intake that was equivalent to, or exceeded, that obtained after intraperitoneal injection or superior mesenteric infusion of 4 micrograms/kg. These results strongly support an upper abdominal, and possibly gastric, site for the satiety action of peripherally administered BN.
Allometry of cooling, supercooling, and freezing in the freeze-tolerant turtle Chrysemys picta
Authors: Claussen D. L. , Zani P. A.
Published: December 2017

Although several vertebrates are freeze tolerant, little is known of the relationship between body size and the kinetics of cooling and freezing. We compared these responses for six hatchling and eight adult Chrysemys picta from an Ohio population. All turtles initially recovered from freezing, and all adults, but only two hatchlings (which experienced ice contents of approximately 35%), exhibited long-term survival. Rapid thawing may have compromised hatchling survival. Turtle water content was inversely related to body mass, but we found no significant correlation between the extent of supercooling and body size. Prefreezing and postfreezing cooling rates scaled with body mass to the -0.55 and -0.40 power, respectively, but the latter rate was more than two orders of magnitude slower. Theoretical (assuming 20% bound water) and calorimetric estimates of body ice agreed reasonably well. Ice contents were both body mass and time dependent. The absolute rate of ice formation scaled with body mass to the 0.4 power. Body size strongly influences the freezing response of ectotherms and deserves more attention.
Heterogeneous binding sites for alpha-atrial natriuretic peptide in human umbilical cord and placenta
Authors: Salas S. P. , Power R. F. , Singleton A. , Wharton J. , Polak J. M. , Brown J.
Published: December 2017

The distributions of atrial natriuretic peptide (ANP) clearance receptors in human umbilical cord and placenta were investigated by using des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-2 3) (C-ANP) as a specific ligand of this receptor to displace bound alpha-125I-labeled ANP. alpha-125I-ANP bound reversibly to umbilical venous and arterial intima and to fetal placental and maternal decidual tissues, with dissociation constants of 1.24 +/- 0.51, 0.58 +/- 0.19, 1.86 +/- 0.51, and 1.07 +/- 0.25 mM, respectively. Binding was reversed by 1 microM unlabeled alpha-ANP but not by unrelated peptides such as gastrin. The 1 microM C-ANP displaced bound alpha-125I-ANP from the intima of umbilical artery but not that of the vein. The specific reversible binding of alpha-125I-ANP to placental decidua but not to fetal placenta was also displaced by 1 microM C-ANP. Therefore high-affinity binding sites for alpha-ANP on the intima of the umbilical artery and on placental decidua differ from those on the umbilical vein and on fetal placental tissue; the binding sites of the intima of the umbilical artery and of the decidua in humans are consistent with clearance receptors for alpha-ANP.
Beta-adrenergic blockade and lipoprotein lipase activity in rat tissues after acute exercise
Authors: Paulin A. , Lalonde J. , Deshaies Y.
Published: December 2017

The present experiments were aimed at evaluating the acute effects of exercise on lipoprotein lipase (LPL) activity in untrained rats. The activity of LPL was measured in postheparin plasma (PHP) before and at various times after a 1-h run on a treadmill (22 m/min, O degrees grade). LPL in PHP was 50% below pre-exercise levels immediately and 3 h after the run but was increased 65% over resting levels 24 h postexercise. To further characterize the very early fall in LPL activity in response to exercise and to assess the possible involvement therein of the beta-adrenergic pathway, LPL in heart, vastus lateralis muscle (VLM), and white (WAT) and brown (BAT) adipose tissues was determined at rest and immediately after exercise in rats that were treated or not with nadolol (25 mg.kg-1.day-1 for 30 days). Immediately after 1 h of exercise, there was a reduction in total enzyme activity in WAT (40% below resting levels), BAT (-58%), VLM (-53%), and heart (-30%). Exercise reduced serum triacylglycerol levels (-64%) and doubled those of nonesterified fatty acids. beta-Adrenergic blockade did not affect any of these variables. Both exercise and nadolol lowered serum cholesterol levels by approximately 20%, but the effects were not additive. These results show that the global intravascular pool of LPL undergoes divergent, time-dependent alterations in response to a single bout of moderate exercise. The acute downregulation of postheparin plasma LPL immediately after exercise reflected a fall in the total enzyme pool of all tissues studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral vascular resistance and regional blood flows in hypertensive Dahl rats
Authors: Boegehold M. A. , Huffman L. J. , Hedge G. A.
Published: December 2017

The aim of this study was to determine whether different organs undergo similar increases in vascular resistance with hypertension in the Dahl salt-sensitive rat. Cardiac output and organ blood flows were measured with microspheres in anesthetized salt-sensitive and salt-resistant rats fed a high- (7%) or normal- (0.45%) salt diet for 4 wk. High salt intake produced hypertension only in salt-sensitive rats. Cardiac index for the hypertensive group was not different from that for any other group, whereas peripheral resistance index was elevated in proportion to arterial pressure. There were no differences among groups in the fraction of cardiac output supplying the myocardium, intestine, diaphragm, spinotrapezius muscle, or gracilis muscle. The fraction of cardiac output supplying the kidneys was lower in salt-sensitive rats (13%) than in salt-resistant rats (17%) and, among salt-sensitive rats, lowest in the high-salt group. Therefore all the organs studied contribute to increased total peripheral resistance in the hypertensive Dahl rat, with the renal vasculature undergoing the largest resistance increase. Different muscles undergo similar increases in vascular resistance, despite differences in the microvascular abnormalities accompanying salt-induced hypertension.
Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole
Authors: Hotchkiss R. S. , Rust R. S. , Dence C. S. , Wasserman T. H. , Song S. K. , Hwang D. R. , Karl I. E. , Welch M. J.
Published: December 2017

Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis. We employed the novel hypoxic marker [18F]fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat. A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion. No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats. Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs. 20% decrease, P less than 0.05) and an increased retention of [18F]fluoromisonidazole in skeletal muscle of the septic rats. We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis. The greater reduction in muscle blood flow and the increased retention of [18F]fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia.
Regression of high-affinity carrier-mediated intestinal transport of taurine in adult cats
Authors: Wolffram S. , Hagemann C. , Scharrer E.
Published: December 2017

The sulfur-containing beta-amino acid taurine is an essential nutrient for cats. Owing to some metabolic peculiarities, cats are more dependent on dietary sources of taurine than other mammals. We therefore studied taurine uptake by intestinal brush-border membrane vesicles (BBMV) isolated from cat small intestine. Taurine uptake by feline BBMV was not influenced by a transmembrane Na+ gradient compared with Na(+)-free conditions. Kinetic analysis of initial taurine uptake yielded no evidence for a carrier-mediated transport process. These findings cannot be attributed to an overall inability of cumulative substrate uptake in our vesicle preparations because D-glucose uptake was strongly Na+ dependent, showing the overshoot phenomenon typically associated with active transport in vesicle experiments. Furthermore, L-leucine transport was mediated by a single Na(+)-dependent carrier mechanism (maximal transport velocity 1.2 nmol.mg protein-1.s-1, Km = 2.1 mM). In contrast to taurine uptake by feline BBMV, transport of taurine by pig intestinal BBMV was markedly enhanced by an inwardly directed Na+ gradient. Thus, differing from other mammalian species, taurine uptake across the intestinal brush-border membrane of the adult cat seems not to be mediated by a specific transport mechanism. Therefore taurine absorption from the gastrointestinal tract will possibly become a limiting factor for maintenance of taurine homeostasis in the cat under conditions of decreased dietary taurine intake.
Plasma profiles of IL-6-like and TNF-like activities in brain-dead dogs
Authors: Huber T. S. , Kluger M. J. , Harris S. P. , D'Alecy L. G.
Published: December 2017

The progression to somatic death after brain death is poorly understood. The role of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in this progression is unknown. TNF-like and IL-6-like plasma activities were assayed in a canine model of brain death in the presence and absence of a lipopolysaccharide (LPS) challenge (0.22 micrograms/kg). Bioassays for TNF-like and IL-6-like activities used WEHI and B9 cell lines, respectively. Brain death was induced by elevating and maintaining intracranial pressure above systolic arterial pressure. Anesthesia and the operative procedure did not cause a significant increase of either cytokine. Brain death (n = 8) itself did not cause a significant elevation of either cytokine compared with the sham brain-death control (n = 6) despite a significant decrease in mean arterial pressure (35 +/- 3 vs. 115 +/- 5 mmHg at 5 h). The brain-dead group treated with LPS (n = 6) responded with a significant elevation in IL-6-like and TNF-like activities compared with the vehicle-treated group. The rise of IL-6-like activity in response to LPS was greater in the brain-dead group than in the sham brain-dead group (n = 3); no significant difference was noted for the TNF-like response. We conclude that the progression to somatic death after brain death cannot be explained by increases in circulating TNF-like or IL-6-like activities.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory modulation of sympathetic activity in neonatal swine
Authors: Gootman P. M. , Gandhi M. R. , Steele A. M. , Hundley B. W. , Cohen H. L. , Eberle L. P. , Sica A. L.
Published: December 2017

Spontaneous efferent sympathetic activity (cervical sympathetic and splanchnic nerves) was recorded simultaneously with efferent phrenic discharge, with aortic pressure, and with the electrocardiogram in less than 1- to 51-day-old neonatal swine anesthetized with Saffan (alfaxalone). Power spectral analyses of sympathetic discharge revealed a frequency range of 4-36 Hz, with peaks distributed in four regions of the spectrum (4-6 Hz, 8-15 Hz, 16-22 Hz, and 28-36 Hz). Inspiratory modulation was readily apparent since sympathetic power spectral energy was greatest during the time of phrenic activity. Alterations in pulmonary afferent inputs (e.g., lung inflation tests and/or vagotomy) altered both phrenic and sympathetic activity. Use of the respiratory-cardiac modulation ratio indicated that respiratory modulation of sympathetic activity was greater than cardiac modulation. Complex afferent inputs, i.e., fictive Valsalva maneuver, indicated an immaturity of integration within the cardiovascular regulatory system. The adult patterns of blood pressure changes and heart rate responses were delayed until approximately 1 mo of age. Calculations of Valsalva ratios (ratio of maximal R-R interval to minimal R-R interval) indicated delayed onset of heart rate responses, reflecting the maturation of cardiovascular reflexes during the neonatal period.
Thermal dehydration-induced thirst in rats: role of angiotensin II
Authors: Barney C. C. , Williams J. S. , Kuiper D. H.
Published: December 2017

Dehydration can be brought about by either water deprivation or by heat exposure (thermal dehydration). Angiotensin II has been shown to have a role in water deprivation-induced thirst. The current study was designed to determine whether angiotensin II is involved in thirst caused by thermal dehydration. Male Sprague-Dawley strain rats were dehydrated by exposure to a 40 degree C environment for 2-4 h or by water deprivation for 44 h. Water deprivation but not heat exposure significantly increased plasma renin activity. Neither ureteric ligation nor nephrectomy significantly altered water intake after thermal dehydration. Captopril, an inhibitor of angiotensin converting enzyme, given at a dose of 100 mg/kg ip, significantly decreased water intake in water-deprived rats but not in thermally dehydrated rats. Angiotensin II therefore does not appear to play a role in the control of water intake of thermally dehydrated rats. The physiological responses to dehydration in rats are dependent on the way in which the dehydration is brought about.
Hormonal and circulatory responses to chronically controlled increments in right atrial pressure
Authors: Shin Y. , Lohmeier T. E. , Hester R. L. , Kivlighn S. D. , Smith M. J.
Published: December 2017

To study the time-dependent changes in the secretion of atrial natriuretic peptide (ANP) in response to chronic stimulation by controlled increments in atrial pressure, we developed methodology for precise control of right atrial pressure (RAP) in dogs by employing an externally adjustable occluder around the pulmonary artery and a servo-control system. During 7 days of servo-control of RAP at 6.3 +/- 0.1 mmHg above control levels (1.3 +/- 0.1 mmHg), the 24-h coefficient of variation in RAP was 1/45 the variation that occurred under control conditions. After 30 min of increased RAP, mean arterial pressure (MAP) was reduced from 101 +/- 4 to 84 +/- 3 mmHg in association with increments in plasma renin activity (PRA) from 0.6 +/- 0.1 to 2.5 +/- 0.9 ng angiotensin I (ANG I).ml-1.h-1 and in the plasma concentrations of ANP, arginine vasopressin (AVP), and epinephrine from 93 +/- 18 to 484 +/- 61 pg/ml, from 0.5 +/- 0.1 to 9.2 +/- 2.4 pg/ml, and from 82 +/- 27 to 585 +/- 133 pg/ml, respectively. In comparison, on day 7 of servo-control of RAP, sodium balance was achieved and MAP remained depressed (82 +/- 4 mmHg) along with sustained increments in both plasma ANP concentration (482 +/- 67 pg/ml) and PRA (1.7 +/- 0.6 ng ANG I.ml-1.h-1); on the other hand, the plasma concentrations of AVP and epinephrine returned to control levels. This quantitative study indicates that ANP secretion does not chronically adapt to stimulation by increased atrial pressure and suggests that the plasma levels of ANP achieved in heart failure markedly increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in renal perfusion pressure.
Synchronous ultradian rhythms in adrenocortical secretion detected by microdialysis in awake rats
Authors: Jasper M. S. , Engeland W. C.
Published: December 2017

To establish whether adrenal corticosterone secretion is episodic and whether episodes are random or periodic events, adrenal extracellular fluid was sampled in awake rats by intra-adrenal microdialysis. Experiments conducted 1 or 2 days postsurgery between 1000 and 1830 h consisted of continuous collection of dialysate at intervals of 10 min. Pulses detected by PC-Pulsar had an interpulse interval of 54.1 +/- 4.5 and 51.3 +/- 5.0 min on days 1 and 2, respectively. Fourier analysis was used to determine whether significant periodicity was present. Six of seven of the day 1 animals had significant secretory rhythmicity, with a predominant periodicity at 60-80 min. In day 2 animals, in addition to a period near 50-80 min, a lower-frequency rhythm with a period near 213 min was identified. Autocorrelation analysis produced results qualitatively similar to Fourier analysis. Secretion rates were normalized based on maximal adrenal responses to adrenocorticotropic hormone and averaged at each time point. When the composite series was subjected to Fourier analysis, a significant rhythmicity (period 58 min) was still detectable in the day 1 animals. When composite data for the day 2 animals were analyzed, in addition to a component near 60-80 min, a lower frequency component near 320 min was present. The persistence of periodicity after time averaging suggests that corticosterone pulses are synchronized between animals. Cross-correlation analysis of individual pairs of data series supported synchronization in many cases. These results suggest that pulsatile secretion of corticosterone in rats has a primary periodicity near 60 min and is synchronized across animals. The mechanism responsible for this synchronization is unknown.
Intracerebroventricular administration of cobalt protoporphyrin elicits prolonged weight reduction in rats
Authors: Galbraith R. A. , Kappas A.
Published: December 2017

Intracerebroventricular administration of the synthetic heme analogue cobalt protoporphyrin (CoPP) results in a dose-dependent decrease in body weight in rats. Among several other metalloporphyrins tested, this effect was found to be specific to cobalt chelated in native or minimally modified protoporphyrin rings. Metabolic balance studies showed that the initial effect of intracerebroventricular treatment with CoPP (0.4 mumol/kg body wt) was a transient reduction in food intake. However, following resumption of normal food intake and growth rate, absolute body weights remained reduced for prolonged periods of time (200-300 days) in both male and female rats. Heme oxygenase activity was induced and cytochrome P-450 activities were reduced in both brain and hypothalamus following intracerebroventricular administration of CoPP. The proximate mechanism of action of this synthetic heme analogue is not known at present, but it appears to act in the central nervous system, probably in the vicinity of the hypothalamus, to reduce the body weight set point of treated animals.
Elevations of plasma glucose do not support taste-to-postingestive consequence learning
Authors: Gowans S. E. , Weingarten H. P.
Published: December 2017

We examined whether elevations in plasma glucose are a sufficient postingestive consequence to support taste-to-postingestive consequence learning. Because real, but not sham, feeding supports taste-to-postingestive consequence learning, we recorded changes in plasma glucose during sham and real feeding. For the 1st 15 min of the meal, both sham and real feeding produced similar elevations in plasma glucose. Thereafter, real feeding produced sustained elevations in plasma glucose, whereas sham feeding did not. However, mimicking the plasma glucose profile of real feeding in the sham feeding rat by infusing glucose intravenously did not produce taste-to-postingestive consequence learning. Using radiolabeled sucrose, we determined that the rise in plasma glucose during sham feeding results from absorption of nutrient. We conclude that elevations in plasma glucose in isolation are not a sufficient consequence to support taste-to-postingestive consequence learning.
Development of passive permeability characteristics of rat placenta during the last third of gestation
Authors: Atkinson D. E. , Robinson N. R. , Sibley C. P.
Published: December 2017

To investigate how the passive permeability of the rat placenta changes during the last third of gestation we measured the unidirectional maternofetal clearance (Kmf) of three polar nonelectrolytes. We found that Kmf (microliters.min-1.g placenta-1) for all three tracers increased between days 15 and 22 (term is 23 days). The increase was less for the largest tracer, [14C]inulin (3.5-fold increase from 0.5 +/- 0.1 to 1.6 +/- 0.1 microliters.min-1.g placenta-1), than for the smaller tracers, [14C]mannitol (7-fold increase from 1.6 +/- 0.1 to 10.9 +/- 0.4 microliters.min-1.g placenta-1) and 51Cr-labeled EDTA (9.5-fold increase from 0.8 +/- 0.04 to 7.6 +/- 0.7 microliters.min-1.g placenta-1). These data suggest that whilst the overall permeability of the rat placenta increases during this period of pregnancy, restriction to the diffusion of large (greater than or equal to 1.5 nm molecular radius) polar nonelectrolytes also increases.
Dietary lipids modify receptor- and non-receptor-dependent components of alpha 1-adrenoceptor-mediated contraction
Authors: Hodgkin D. D. , Boucek R. J. , Purdy R. E. , Pearce W. J. , Fraser I. M. , Gilbert R. D.
Published: December 2017

Dietary lipid modulation of alpha-adrenoceptor (adrenergic receptor)- and non-adrenoceptor-mediated contractile properties of isolated rat abdominal aortic segments were assessed during the early developmental period. Rats were raised from conception to 90 days of age on semisynthetic diets containing various types and amounts of lipids. Aortic segments from three groups of rats fed high-fat diets (15% wt/wt) consisting of olive oil, corn oil, or lard as the sole lipid sources were compared with those from rats fed a low-fat control diet containing corn oil (5% wt/wt). alpha-Adrenoceptor activities were assessed by measuring the norepinephrine dose response of the tissue rings with and without partial inactivation of alpha-receptors by benextramine. alpha-Adrenoceptor sensitivity to norepinephrine increased, whereas receptor affinity decreased significantly in rats raised on high-fat diets. Qualitative features of dietary lipids influenced non-adrenoceptor-dependent aspects of vascular contractility. Diets rich in polyunsaturated fatty acids (high- and low-fat corn oil) raised the maximum response to norepinephrine and the contractile response to 60 mM potassium compared with more-saturated diets (olive oil and lard). These results demonstrate an effect of chronic feeding of high dietary fat on alpha-adrenoceptor-mediated contractility of abdominal aortic rings from young Sprague-Dawley rats. Qualitative features of dietary lipids also appear to modify receptor-independent parameters of the contractile response of the arterial tissue rings in these animals.
Compartmental analysis and glomerular filtration in chick embryos
Authors: Murphy M. J. , Brown S. C. , Clark N. B. , Feng J. Q.
Published: December 2017

We have developed microtechniques that allow the determination of compartmental fluid distribution and glomerular filtration rate in chick embryos during three significant developmental periods: phase 1, the developmental period when the mesonephros alone is functioning; phase 2, periods of simultaneous meso/metanephric kidney function; and phase 3, the period during late development when the metanephros completely replaces the degenerated mesonephros. Water content of tissues is greater in younger embryos (89.4 +/- 0.2%, day 10) compared with older animals (78.3 +/- 0.5%, day 18). Although all major tissue components show an absolute increase in mass during this period, the embryo proper increases at five times the rate of the extraembryonic tissues. Glomerular filtration rate increases during development from 0.61 +/- 0.08 ml/h at day 10 to 2.31 +/- 0.11 ml/h at day 18. Glomerular filtration rate scales to body mass with an allometric exponent identical to adult birds only if total tissue mass (embryo + membranes) is considered. Our data suggest that significant errors in allometry will be encountered when scaling measurements are made on embryonic or fetal amniotes without taking into consideration the extraembryonic tissues.
Inhibitory renorenal reflexes: a role for renal prostaglandins in activation of renal sensory receptors
Authors: Kopp U. C. , Smith L. A.
Published: December 2017

In anesthetized rats, activation of renal sensory receptors with a mechanical stimulus (increased ureteral pressure) and a chemical stimulus (renal pelvic perfusion with 0.9 M NaCl) results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion, i.e., a contralateral inhibitory renorenal reflex. Because both interventions are known to increase renal prostaglandin (PG) synthesis, we examined whether renal PGs were involved in the renorenal reflex response to renal sensory receptor stimulation. In the first part, mechanical and chemical activation of renal sensory receptors was performed in the absence and presence of renal pelvic perfusion with indomethacin or meclofenamate (0.2 micrograms/min). Indomethacin inhibited the ipsilateral afferent renal nerve activity response to increased ureteral pressure (7 +/- 2 vs. 38 +/- 10%, P less than 0.01) and renal pelvic perfusion with 0.9 M NaCl (3 +/- 3 vs. 28 +/- 5%, P less than 0.01) and the contralateral diuretic and natriuretic responses in the absence of any renal hemodynamic changes. Similar effects were produced by meclofenamate. In the second part, mechanical and chemical activation of renal sensory receptors was performed in the presence of renal pelvic perfusion with vehicle, indomethacin, and indomethacin plus PGE2 (20 micrograms/min). Addition of PGE2 to the renal pelvic perfusate in indomethacin-treated kidneys restored the responses to mechanical and chemical activation of renal sensory receptors to levels not different from their pre-indomethacin control values. We conclude that PGs in the renal pelvic area are involved in inhibitory renorenal reflex responses to mechanical and chemical activation of renal sensory receptors.
Pregnancy-induced changes in ovine cerebral arteries
Authors: Hull A. D. , Long D. M. , Longo L. D. , Pearce W. J.
Published: December 2017

We examined the effects of pregnancy on the ovine cerebral vasculature by comparing several characteristics of isolated endothelium-intact segments of three intracranial arteries including the middle cerebral (MCA), posterior communicating (PC), and basilar (BAS) arteries taken from pregnant sheep (138-143 days gestation, term approximately 145 days) and nonpregnant controls. For comparison, segments of the extracranial common carotid (COM) artery were also studied. With pregnancy, vessel water content increased (5.4-5.8%) in all arteries except the PC. Additionally, cellular protein content increased in all arteries (4.4-50.0%). Arterial stiffness, as determined by passive stress-strain determinations, was significantly decreased during pregnancy in the MCA but not in the larger arteries. Maximum contractile responses, when normalized to vessel wall cross-sectional area, were consistently greater in arteries from pregnant than in those from nonpregnant animals (10.1-49.7%). Relaxation to the endothelium-independent guanylate cyclase stimulator S-nitroso-N-acetyl penicillamine (SNAP) increased with pregnancy only in the distal MCA (approximately 17%). Endothelium-dependent relaxation to the calcium ionophore A23187 decreased only in the larger and more proximal COM (-39%). Thus pregnancy was associated with an increase in production of contractile force, a decrease in peripheral vascular stiffness, a decrease in the relaxant response to A23187 in the COM, and an increase in the relaxant response to SNAP in the MCA. Together, these findings indicate that pregnancy has widespread and important vessel specific cerebrovascular consequences that affect not only arterial composition, but also contractility and endothelial reactivity.
Quantitative changes in long-chain fatty acids during fetal and early postnatal development in rats
Authors: Cunnane S. C. , Chen Z. Y.
Published: December 2017

The quantitative importance of triacylglycerol as a source of total essential fatty acids during early postnatal development is reported in the accompanying article. Our objective here was to measure the quantitative changes in individual long-chain fatty acids in specific lipid classes of the carcass, liver, and brain of the developing rat mainly to describe the relative accumulation of long-chain vs. precursor fatty acids. Fatty acids in carcass phosphatidylcholine (micrograms/g) were lower at fetal days 18-21 than at either fetal day 15 or postnatal days +3 to +9. Individual long-chain fatty acids in liver phosphatidylcholine and phosphatidylethanolamine increased markedly by day +3 postnatally, whereas in brain phosphatidylethanolamine, the postnatal increase was delayed to between days +6 and +9. Fatty acids in carcass and liver triacylglycerols increased quantitatively by 10- to 300-fold from fetal day 21 to postnatal day +3 with amounts of both arachidonic and docosahexaenoic acid equaling linoleic acid. The ratios of linoleic and alpha-linolenic acids to respective long-chain products were significantly higher in triacylglycerols, whereas that of stearic to oleic acid was higher in phospholipids. We conclude that, during early postnatal life, oleic, linoleic, and alpha-linolenic acids are required in quantitatively greater amounts in triacylglycerols, whereas stearic acid and long-chain essential fatty acids are required in phospholipids.
Caudal brain stem systems mediate effects of bombesin-like peptides on intake in rats
Authors: Flynn F. W.
Published: December 2017

Intraoral intakes of sucrose (SI; 0.1 M) and distilled water (WI) were measured in tube-fed neurologically intact and tube-fed chronic supracollicular decerebrate (CD) rats after intraperitoneal injections of saline and bombesin (BN) and gastrin-releasing peptide (GRP) in concentrations of 1, 2.5, 5, and 10 micrograms/kg. Also, to determine whether BN and GRP administration interacted with taste processing, oral motor responses during the 1st min of the intraoral infusion were videotaped and subsequently analyzed to determine the number of ingestive and aversive taste reactivity (TR) responses. Injections of greater than or equal to 2.5 micrograms/kg BN reliably suppressed SI similarly in both control and CD rats. In response to GRP, the only group difference was that injections of 1 microgram/kg GRP reliably suppressed SI in control but not CD rats. Administration of greater than or equal to 2.5 micrograms/kg GRP suppressed SI similarly in both control and CD rats. Although SI was suppressed by peripheral administration of BN and GRP, these treatments had no effect on the TR responses elicited by sucrose in either group. To determine whether the effects of BN and GRP were selective for sweet nutritive stimuli, intraoral WI was also measured in control rats after the same treatments. Injections of 5 and 10 micrograms/kg BN and 10 micrograms/kg GRP reliably suppressed WI, but lower doses had no effect. BN and GRP had no reliable effect on the pattern of TR responses elicited by water. Intraoral WI by CD rats was minimal (less than 1 ml) after injections of saline, BN, and GRP, and hence peptide effects could not be reliably assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
Pressure natriuresis and angiotensin II in reduced kidney mass, salt-induced hypertension
Authors: Hall J. E. , Mizelle H. L. , Brands M. W. , Hildebrandt D. A.
Published: December 2017

In normal subjects, high sodium intake causes little change in mean arterial pressure (MAP). However, MAP is sodium sensitive after reduction of kidney mass. The present study examined the role of increased renal artery pressure and decreased angiotensin II (ANG II) formation in maintaining sodium balance during high sodium intake in dogs with reduced kidney mass. In seven dogs with pressure natriuresis intact, increasing sodium intake from 36 to 466 meq/day for 7 days raised MAP from 91 +/- 2 to 106 +/- 2 mmHg. Sodium excretion increased promptly and cumulative sodium balance increased by only 80 +/- 26 meq after 7 days of high sodium intake. When renal perfusion pressure was servo-controlled to prevent pressure natriuresis, comparable increases in sodium intake raised MAP from 88 +/- 2 to 128 +/- 4 mmHg after 7 days. Sodium excretion rose to match intake, but cumulative sodium balance increased by 226 +/- 34 meq after 7 days. In dogs in which ANG II levels were held constant by converting enzyme inhibition and constant ANG II infusion (2 ng.kg-1.min-1 iv), raising sodium intake for 7 days elevated MAP from 126 +/- 2 to 146 +/- 4 mmHg after 7 days while increasing cumulative sodium balance by 212 +/- 29 meq. When renal perfusion pressure was servo-controlled and ANG II levels held constant, raising sodium intake elevated MAP from 125 +/- 3 to 166 +/- 11 mmHg and increased cumulative sodium balance by 399 +/- 128 meq. These data indicate that pressure natriuresis and decreased ANG II formation are important in minimizing sodium retention and hypertension during high sodium intake. However, other mechanisms can increase sodium excretion independent of pressure natriuresis and suppression of ANG II during salt-induced hypertension.