bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric emptying changes are neither necessary nor sufficient for CCK-induced satiety
Authors: Conover K. L. , Collins S. M. , Weingarten H. P.
Published: December 2017

If gastric emptying plays a significant role in the satiety produced by exogenous cholecystokinin octapeptide (CCK-8) then 1) the effects on emptying and feeding should share similar kinetics and 2) peptides that inhibit emptying should also inhibit feeding. In the first experiment, CCK-8 (5.6 micrograms/kg) injected immediately before the introduction of an intragastric load (10 ml saline) or presentation of a test meal (15% sucrose) produced a rapid inhibition of both emptying and feeding. In contrast, the same dose administered 15 min before testing caused no inhibition of emptying, even though it retained the ability to reduce meal size. In experiment 2, the abilities of the peptides pentagastrin (100 micrograms/kg), bombesin (8 and 16 micrograms/kg), and secretin (2.86, 14.3, and 28.6 micrograms/kg) to reduce food intake and inhibit emptying were tested. Pentagastrin influenced neither food intake nor gastric emptying. Bombesin caused a small transient delay in emptying but a large and sustained eating suppression. However, a high dose of secretin caused no significant reduction of food intake, in spite of the fact that it inhibited emptying to the same degree as 1.4 micrograms/kg CCK-8, which does reduce intake. These results suggest that the inhibition of emptying by CCK is not sufficient to explain the satiety effect of CCK-8.
Processing of pulmonary afferent input patterns by respiratory I-beta neurons
Authors: Bajic J. , Zuperku E. J. , Hopp F. A.
Published: December 2017

To characterize the dynamics of the control of respiratory I-beta neurons by slowly adapting pulmonary stretch receptors, the neuronal discharge responses to lung inflation and electrically induced vagal input patterns were analyzed. Unitary recordings from single medullary I-beta neurons and whole phrenic nerve activity were recorded in chloralose-urethan-anesthetized paralyzed cats. Neuronal discharge patterns were quantified in terms of cycle-triggered histograms. The net response to a test afferent input pattern generated during neural inspiration was expressed as the difference between the central component of I-beta activity and the total response. The central component was obtained during control respiratory cycles in which lung inflation occurred during neural expiration and no vagal feedback occurred during neural inspiration. For a set of test inflations with different ramp rates, the net responses, measured at fixed times with respect to the onset of neural inspiration, were linearly related to transpulmonary pressure. However, the slopes of these relationships increased as a function of time during neural inspiration. Neuronal responses to electrically induced ramp vagal input patterns were similar to those produced by ramp inflation. The net response due to electrically induced ipsilateral step patterns consisted of a rapid excitatory and a slow inhibitory component, whereas only the slow inhibitory component was observed for contralateral patterns. The implications of these findings with respect to the modes of neural processing and effects on phrenic output patterns are discussed.
Blood-brain barrier disruption using mannitol: time course and electron microscopy studies
Authors: Cosolo W. C. , Martinello P. , Louis W. J. , Christophidis N.
Published: December 2017

Blood-brain barrier disruption with a hyperosmolar agent, mannitol, has previously been demonstrated to increase intracerebral methotrexate levels in rats. To determine the optimum conditions for blood-brain barrier disruption without producing neurological sequelae, adult Sprague-Dawley rats were infused with mannitol via the internal carotid artery at rates varying from 0.25 to 0.5 ml.s-1.kg-1. Methotrexate and Evans blue were used as markers of blood-brain barrier disruption. The optimum rate of mannitol that produced blood-brain barrier disruption without neurological sequelae was 0.25 ml.s-1.kg-1 for 20 s. The duration of blood-brain barrier opening was maximal for approximately 5 min and then rapidly reversed. Methotrexate levels on the mannitol-infused side were four to five times that of the noninfused hemisphere. Light microscopy and electron microscopy did not demonstrate any consistent changes that could be attributed to blood-brain barrier disruption nor did it elucidate the mechanism. This model should prove useful in the investigation of the treatment of intracerebral tumors with blood-brain barrier disruption. This study shows that maximal intracerebral methotrexate levels were obtained when methotrexate was infused before or within 5 min of the mannitol infusion.
Chronic CEI alters effect of low Na+ diet in normal and coarcted pups. I. BP, renin, and GFR
Authors: Bagby S. P. , Fuchs E.
Published: December 2017

To assess the renin-angiotensin (RA) dependence of evolving neonatally induced coarctation hypertension (NICH) in inbred pups, we randomized sex-matched littermates to a high dose of converting-enzyme inhibitor (CEI:MK-421) or placebo from the time of neonatal aortic banding (coarcted) vs. no banding (control). In phase 1 studies, pups were examined serially on normal diet (Bagby and Fuchs, Hypertension In press.): chronic CEI lowered systolic blood pressure (BP) equally in coarcted and controls and failed to prevent systolic BP excess in coarcted dogs. In phase 2 studies, the same pups were exposed to a low sodium (LS) diet at 4 mo of age, a time when the untreated NICH model exhibits increased forelimb systolic BP. Measurements of systolic BP, RA components, renal function, and extracellular volume (ECV) were made before and serially during 12 days on the LS diet. Responses of coarcted and control pups to the LS diet were similar, with or without CEI, providing no evidence for exaggerated angiotensin II (ANG II) dependence in evolving NICH. Independently of coarctation status, chronic CEI significantly modified RA and renal functional responses to the LS diet: a greater renin rise but abnormal renin substrate fall, thus no rise in ANG I or ANG I generation rate; a greater rise in creatinine and a trend toward a greater fall in glomerular filtration rate (GFR). Despite these findings compatible with sustained ANG II deficit, chronic CEI unexpectedly failed to impair maintenance of systolic BP during a superimposed LS diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Validation of single-sample doubly labeled water method
Authors: Webster M. D. , Weathers W. W.
Published: December 2017

We have experimentally validated a single-sample variant of the doubly labeled water method for measuring metabolic rate and water turnover in a very small passerine bird, the verdin (Auriparus flaviceps). We measured CO2 production using the Haldane gravimetric technique and compared these values with estimates derived from isotopic data. Doubly labeled water results based on the one-sample calculations differed from Haldane values by less than 0.5% on average (range -8.3 to 11.2%, n = 9). Water flux computed by the single-sample method differed by -1.5% on average from results for the same birds based on the standard, two-sample technique (range -13.7 to 2.0%, n = 9).
Neuronal histamine modulates feeding behavior through H1-receptor in rat hypothalamus
Authors: Fukagawa K. , Sakata T. , Shiraishi T. , Yoshimatsu H. , Fujimoto K. , Ookuma K. , Wada H.
Published: December 2017

To clarify the physiological role of hypothalamic neuronal histamine in control of food intake, ingestive behavior and neuronal activity were investigated under blockade or diurnal fluctuation of hypothalamic neuronal histamine. Histamine H1- but not H2-receptor antagonist potently induced feeding in a dose-related manner after infusion into rat third cerebroventricle at 1100 h. Elicitation was attenuated after infusion at 1940 h when histamine content in the hypothalamus was low and was abolished after intraperitoneal pretreatment with 0.11 mmol alpha-fluoromethylhistidine (alpha-FMH), a specific suicide inhibitor of histidine decarboxylase. Electrophoretic application of a histamine H1-receptor antagonist to ventromedial hypothalamic neurons specifically suppressed activities of glucose-responding neurons that are related to food intake. The suppressive effect was also attenuated by intraperitoneal pretreatment with alpha-FMH. These results suggest that feeding induced by histamine H1-receptor antagonists is due to blockade of neuronal histamine at the site of histamine H1-receptors, at least in part, in the ventromedial hypothalamus and that diurnal fluctuation of feeding behavior may reflect circadian variation of neuronal histamine level.
Effects of althesin and urethan-chloralose on neurohumoral cardiovascular regulation
Authors: Faber J. E.
Published: December 2017

The cardiovascular effects of althesin (ALT) and urethan-chloralose (UC) anesthesia were compared in conscious, chronically instrumented rats. Althesin had no effect on arterial pressure or base-line resistance in the renal, superior mesenteric, and hindquarters vasculatures but increased heart rate. In contrast, UC decreased arterial pressure, heart rate, and mesenteric resistance. Although UC attenuated depressor responses to nitroglycerin, neither anesthetic significantly altered regional vascular reactivity to intravenous phenylephrine and nitroglycerin. The cardiac chronotropic baroreflex was examined by comparing the slope of the curves relating maximal changes (delta) in heart rate (pulse interval) that occurred at the point coinciding in time with the maximal changes in mean arterial pressure produced by phenylephrine and nitroglycerin. Neither anesthetic significantly altered the baroreflex slope (delta pulse interval/delta mean arterial pressure) for pressor and depressor stimuli. Both anesthetics attenuated the sympathoexcitatory response to cerebroventricular angiotensin II, although ALT had less of a depressive effect (pressor response during ALT and UC = 65 and 30%, respectively, of conscious). Plasma renin activity (PRA) and the hemodynamic response to peripheral angiotensin-receptor antagonism were significantly increased (PRA by almost 6-fold) during UC, whereas ALT was without effect. Similarly, UC but not ALT induced vasopressin-dependent vascular tone. Ganglionic blockade indicated that peripheral neurogenic tone was not altered by ALT anesthesia. These data suggest that althesin produces fewer hemodynamic disturbances than urethan-chloralose and largely maintains cardiovascular regulation intact.
Molecular mechanisms of osmosis
Authors: Kiil F.
Published: December 2017

Osmosis across a semipermeable membrane is usually treated in terms of thermodynamics, but the equations for osmosis can also be derived from kinetic considerations. Since fewer solvent molecules bombard the semipermeable membrane from the solution side, a kinetic pressure difference (osmotic potential) is generated into pore openings. Intermolecular forces cancel each other and do not affect the osmotic potential. On the other hand, osmotic flow is dependent on intermolecular cohesive forces permitting the generation of large negative pressures in the membrane pores. Osmosis is therefore a unique property of liquids, whereas intermolecular cohesive forces do not affect diffusion. Osmotic pressure up to 180 atm can be correctly determined from the reduction in saturated vapor pressure above the solution because osmotic pressure and reduction in vapor pressure to some extent are analogous phenomena. Osmotic pressures up to 180 atm may also be correctly determined from kinetic considerations by accounting for binding between solvent and solute molecules (4-5 water molecules per solute molecule for sucrose solutions).
Rumen volume, saliva flow rate, and systemic fluid homeostasis in dehydrated cattle
Authors: Silanikove N. , Tadmor A.
Published: December 2017

This work was carried out to test the hypothesis that the high level of salivary secretion containing much Na+ and the volume of fluid sequestered in the foregut of ruminants play an important part in water and Na+ homeostasis. Saliva flow and composition and water and Na+ balance in the rumen have been measured in hydrated and dehydrated cows with esophageal fistulas. Reduction of voluntary feed intake in beef cattle during water deprivation was related to the stage of dehydration. Salivary secretion rate was linearly related to voluntary feed intake (r = 0.96) and inversely and linearly related to plasma osmolality (r = 0.88). The reduction in the volume of water stored in the rumen contributed to the major portion (55%) of the total water loss. Utilization of gut water attenuated the rise in blood plasma osmolality, and this may be connected with an animal's ability to continue eating despite dehydration.
Effects of sustained lymph drainage on cardiovascular function and thoracic duct lymph in sheep
Authors: Valenzuela G. J. , Hewitt C. W. , Kramer G. C. , Do Y. , Hseuh W. A.
Published: December 2017

We studied the effect of lowering the plasma protein concentration on the cardiovascular function and thoracic duct lymph in awake adult sheep. Hypoproteinemia was induced in seven nonpregnant, splenectomized sheep by drainage of the thoracic duct lymph over a 5-day period. The plasma protein went from a mean of 6.4 +/- 0.2 (SE) to 4.9 +/- 0.2 g/dl on day 5, and the lymph-to-plasma protein concentration ratio decreased from 0.74 +/- 0.01 on day 1 to 0.48 +/- 0.04 on day 5. The percentage composition of the protein fractions in plasma and lymph remained unchanged. Lymph flow was 1.79 +/- 0.37 and 1.28 +/- 0.10 ml/min for days 1 and 5, respectively. Renin concentration in plasma increased 50-fold by day 5. Arterial pressure fell from 102.9 +/- 5.4 to 72.7 +/- 4.4 mmHg by day 5. Mean hematocrit was 28.9 +/- 1.7 at day 1, which was not significantly different than 24.6 +/- 2.9 at day 5 and indicated that the plasma volume did not decrease. Body weight also did not change significantly. There was a decrease in the transcapillary protein escape rate, determined as the thoracic lymph flow rate multiplied the lymph protein concentration, that suggests adaptations in the microcirculation to decrease vascular-to-interstitial protein transfer during hypoproteinemia. Hypoproteinemic animals also demonstrated greater vascular retention of a fluid volume challenge. In conclusion, the sheep adaptations to sustained hypoproteinemia produced by lymph drainage were a significant decrease in arterial pressure, large increases in vascular compliance and renin concentration, and reduced transcapillary escape rate of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Osmotic thresholds for AVP release with the use of plasma and urine AVP and free water clearance
Authors: Moses A. M.
Published: December 2017

Eleven hydrated normal subjects were infused with hypertonic saline so that plasma osmolalities (POsmol) ranged from 280 to 306 mosmol/kg. Linear relationships were calculated between POsmol and plasma and urine arginine vasopressin (AVP) in the 11 individual subjects. There was an excellent linear correlation between POsmol and plasma and urine AVP, with the latter as concentration or rate of excretion. The highest correlation coefficient occurred when urine AVP was expressed as microunits of AVP per 100 milliliters of glomerular filtrate. The smallest coefficient of variation of the slopes occurred when urine AVP was expressed as microunits of AVP per minute. The osmotic thresholds obtained by abscissal intercepts from relating POsmol to urine AVP per minute or per 100 milliliters of glomerular filtrate were 285.9 and 285.5 mosmol/kg, respectively. These values did not differ from the mean osmotic threshold obtained by traditional free water clearance changes (285.8 mosmol/kg). Analysis of the relationship between plasma osmolality and plasma AVP resulted in the greatest variation in slope and osmotic threshold, with the latter being significantly lower than that obtained by free water clearance changes. The data also demonstrated a much more rapid rise of urine than of plasma AVP under the stated conditions of osmotic stimulation.
Gluconeogenesis in perfused livers from dexamethasone-treated chickens
Authors: Kobayashi T. , Iwai H. , Uchimoto R. , Ohta M. , Shiota M. , Sugano T.
Published: December 2017

Gluconeogenesis was studied in hemoglobin-free perfused livers from chickens that had received daily injections of dexamethasone sulfate for 5 days. Dexamethasone increased to approximately 160% the level of plasma glucose and doubled the content of hepatic glycogen in fed chickens. In the isolated perfused livers from chickens starved for 48 h after the last dexamethasone injection, the rates of production of glucose from lactate decreased by approximately 30% and biphasic changes in glucose production from fructose proceeded in parallel with biphasic changes in the production of lactate and pyruvate. Quinolinate had no effect on gluconeogenesis in both groups. NH4Cl markedly inhibited the production of glucose from pyruvate-lactate mixtures in dexamethasone-treated chickens but stimulated in controls. Aminooxyacetate reversed the effects of NH4Cl in dexamethasone-treated chickens. The data presented provide evidence indicating that the reaction of mitochondrial alanine aminotransferase plays an important role in the regulation of the hepatic gluconeogenesis in dexamethasone-treated chickens.
Capillary and mitochondrial unit in muscles of a large lizard
Authors: Conley K. E. , Christian K. A. , Hoppeler H. , Weibel E. R.
Published: December 2017

We asked whether capillaries and mitochondria form a structural and functional unit in the musculature of the Cuban iguana (Cyclura nubila) similar to that found in mammals. We found a significant correlation between capillary length density [Jv(c, f)] and mitochondrial volume density [Vv(mt, f)] of the musculature with a slope that revealed that on average 3.5 km of capillaries were associated with each milliliter of mitochondria (vs. approximately 11 km/ml in mammals). These capillaries had a diameter of 9 microns (vs. 4.5 microns in mammals), and the mitochondria had a surface density of the inner membranes of 25 m2/ml (vs. 30-45 m2/ml in mammals). These dimensions resulted in ratios of capillary to mitochondrial volume (0.22 ml/ml) and capillary wall to mitochondrial membrane surface area (39 cm2/m2) that were similar in Cyclura to those found in mammals (approximately 0.18 ml/ml and 35-52 cm2/m2, respectively). Also in agreement with mammalian values were the average oxidative capacity of the mitochondria derived from maximum rate of O2 consumption (VO2max) during exercise at 37 degrees C and the inner mitochondrial membrane surface area [S(im)] of the musculature [VO2max/S(im) = 0.04 vs. 0.06-0.15 ml O2.m-2.min-1 in mammals]. These common structural and functional relationships support the notion that capillaries and mitochondria represent a similar fundamental unit in muscles of both Cyclura and mammals.
SCN lesions abolish ultradian and circadian components of activity rhythms in LEW/Ztm rats
Authors: Wollnik F. , Turek F. W.
Published: December 2017

A trimodal locomotor activity pattern has been observed in LEW/Ztm rats. Complete and partial lesions of the suprachiasmatic nucleus (SCN) were used to determine whether the same neural substrate may underlie the circadian rhythms and the ultradian modulation of wheel-running activity in these rats. Whereas sham lesions had little or no effect on the wheel-running activity pattern, complete SCN lesions resulted in a complete loss of circadian and ultradian activity components under free-running or 12:12 h light-dark cycle (12:12 LD) conditions. Ultradian and circadian activity components were still present after partial SCN lesions. Periodogram analysis for any given animal revealed that the ultradian periods were always submultiples of the entrained or free-running circadian period. Furthermore there was a high correlation between the amplitudes of circadian and ultradian spectral estimates, but with a different slope in males and females. These results indicate that in LEW/Ztm rats the SCN contributes to the control of both the circadian wheel-running rhythm and the trimodal ultradian modulation of that behavior.
Regional blood flow of exercise-trained younger and older cold-exposed rats
Authors: McDonald R. B. , Hamilton J. S. , Stern J. S. , Horwitz B. A.
Published: December 2017

O2 consumption (thermogenesis) and regional blood flows (measured using radioactively labeled microspheres) were evaluated in younger (12 mo) and older (24 mo) sedentary and exercised male Fischer 344 (F-344) rats. These variables were measured at rest and during exposure to 6 degrees C. Exercise-trained rats were run on a motor-driven treadmill 5 days/wk, 1 h/day, at 20 m/min for 6 mo. Resting rates of O2 consumption did not differ with age or exercise training. However, thermogenesis during cold exposure was significantly greater in the older exercised rats than in the other three groups. This difference did not reflect a greater contribution from brown fat as indicated by the fact that total blood flow to the brown fat depots during cold exposure was not greater in the older exercised vs. the other rat groups. Neither exercise training nor age had a significant effect on specific resting blood flow (expressed as ml.min-1.g tissue mass-1) to most of the organs measured, including heart, kidney, brown fat, white fat, and skeletal muscle. The notable exception to this was in the spleen of the older sedentary animals where flow was diminished compared with that in the older exercised animals. We conclude that aging, between 12 and 24 mo of age, and/or exercise training have only a minor effect on regional blood flow of F-344 rats during rest or cold exposure and that the enhanced thermogenesis seen in cold-exposed older exercised vs. sedentary F-344 rats cannot be explained by a greater contribution from brown fat.
Central vasopressin V1-receptors mediate indomethacin-induced antipyresis in rats
Authors: Wilkinson M. F. , Kasting N. W.
Published: December 2017

Central microinjection or infusion of an arginine vasopressin (AVP) V1-receptor antagonist within the brain of the conscious, unrestrained, and febrile rat inhibited or abolished the antipyretic effects of peripherally administered indomethacin (Indo). The degree of Indo-induced antipyresis was determined by 2-h thermal indexes (degree C.h) calculated from the time of Indo injection. Microinjection of saline or V1-receptor antagonist within the ventral septal area (VSA) of the rat brain immediately followed by intraperitoneal Indo evoked antipyretic responses of -1.63 +/- 0.17 and -0.24 +/- 0.09 degrees C.h, respectively (P less than 0.01). Infusion of the VSA with saline or V1-receptor antagonist before and after Indo resulted in thermal indexes of -1.35 +/- 0.16 and 0.13 +/- 0.30 degree C.h, respectively (P less than 0.01). Central microinjection of a V2-receptor antagonist did not significantly effect Indo-induced antipyresis compared with paired saline controls. Neither saline nor the V1-receptor antagonist affected nonfebrile body temperature when microinjected into the VSA. These data indicate the importance of AVP V1-receptors within the VSA in mediating the potent fever-reducing properties of the antipyretic drug Indo. Furthermore, these data call into question whether prostaglandin synthesis inhibition is a sufficient explanation of drug-induced antipyresis.
Increased GABA shunt activity in VMN of three hyperphagic rat models
Authors: Beverly J. L. , Martin R. J.
Published: December 2017

Metabolic signals have been proposed as controls of energy balance. Glucose utilization for gamma-aminobutyric acid (GABA) synthesis was evaluated in diet-restricted and streptozotocin-diabetic rats. Rates for glucose flux through the GABA shunt and glutamate decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis, were measured in ventro-medial nucleus (VMN) and lateral hypothalamic (LHA) homogenates. Rates of GAD activity were elevated in the VMN of both restricted and diabetic rats but did not change in the LHA of either model. The rate of glucose flux through the GABA shunt in the VMN was increased in restricted rats but were decreased in the VMN of diabetic rats. Restricted rats allowed to feed ad libitum initially ate 160% of the amount the control rats ate. GAD activity rates in the VMN returned to near control levels after 2 days of refeeding. Obese Zucker rats (fa/fa) also had higher rates of GAD activity and glucose flux through the GABA shunt in the VMN but not in the LHA. The increased rate of GABA synthesis may represent increased GABAergic activity in the VMN and may possibly be involved in feeding behavior and energy balance.
Capsaicin abolishes lipoprivic but not glucoprivic feeding in rats
Authors: Ritter S. , Taylor J. S.
Published: December 2017

To assess the contribution of visceral sensory neurons to feeding induced by blockade of glucose and fatty acid metabolism, adult rats were anesthetized and treated systemically with capsaicin, a toxin that destroys fine-diameter unmyelinated primary sensory neurons, including many visceral sensory neurons. Rats were maintained on a fat-supplemented diet throughout experimentation. For feeding tests, intake of this diet was measured hourly for 6 h after systemic blockade of fatty acid or glucose utilization with mercaptoacetate (MA) or 2-deoxy-D-glucose (2-DG), respectively, after simultaneous administration of MA and 2-DG and after saline injection. 2-DG stimulated a dose-related feeding response that was similar in magnitude in both capsaicin and vehicle-treated rats. MA also stimulated a dose-related feeding response in vehicle-treated rats. However, capsaicin-treated rats did not eat in response to MA. In addition, 2-DG and MA were additive in their stimulation of feeding in vehicle-treated controls, but capsaicin-treated rats ate the same amount after 2-DG plus MA as they did in response to 2-DG alone. Thus glucoprivation and lipoprivation activate anatomically and chemically distinct receptors for the metabolic control of feeding.
Effect of nicardipine and atriopeptin on transcapillary shift of fluid and proteins
Authors: Valentin J. P. , Ribstein J. , Mimran A.
Published: December 2017

The possibility that calcium antagonists may alter extracellular fluid partition, as already suggested for atrial natriuretic peptide (ANP), was explored in anephric anesthetized rats by measuring changes in hematocrit and plasma proteins during infusion of synthetic ANP-(103-126) and the dihydropyridine derivative nicardipine. In response to ANP (1 micrograms.kg-1.min-1) or nicardipine (0.1 microgram.kg-1.min-1), which had a similar effect on arterial pressure, hematocrit increased by 9 +/- 0.1 and 5.4 +/- 0.3%, respectively, whereas plasma protein concentration increased to a lesser extent (3.9 +/- 0.3 and 3.7 +/- 0.2%, respectively). The simultaneous infusion of ANP and nicardipine had no additive effect on hematocrit, whereas the effect on arterial pressure was markedly enhanced. In additional experiments, an attempt was made to estimate the vascular leak of albumin in various tissues, using a quantitative Evans blue technique. Both ANP and nicardipine increased dye extravasation in skeletal and cardiac muscle, whereas ANP but not nicardipine increased extravasation in intestine. No significant change was observed in brain, liver, and lungs. These results suggest that nicardipine and ANP reduce plasma volume by an extrarenal mechanism. This fluid shift, possibly resulting from hemodynamic changes at the capillary level, is associated with a marked transfer of plasma albumin out of the vascular compartment.
Na-dependent L-glutamate transport by eel intestinal BBMV: role of K+ and Cl-
Authors: Romano P. M. , Ahearn G. A. , Storelli C.
Published: December 2017

L-[3H]glutamate uptake into eel (Anguilla anguilla) intestinal brush-border membrane vesicles (BBMV) was a sigmoidal function of extravesicular Na, suggesting that two or more cations accompanied the amino acid during transport. L-[3H]glutamate influx illustrated the following kinetic constants: apparent membrane binding affinity (Kapp) = 0.80 +/- 0.12 mM; influx velocity (Jmax) = 2.61 +/- 0.31 nmol.mg protein-1.min-1; and permeability coefficient (P) = 0.65 +/- 0.10 microliters.mg protein-1. min-1. Results from the imposition of diffusion potentials across vesicle membranes using K-valinomycin or H-carbonyl-cyanide p-chloromethoxyphenylhydrazone suggested that Na-dependent L-glutamate transport was sensitive to transmembrane electrical potential difference. Extravesicular aspartate was a competitive inhibitor of L-[3H]glutamate influx [inhibitory constant (Ki) = 0.28 +/- 0.04 mM]. Intravesicular K and extravesicular Cl ions enhanced maximal amino acid influx and transient L-glutamate accumulation against a concentration gradient (overshoot). Intravesicular K reduced the Kapp of the membrane to L-glutamate, whereas extravesicular Cl increased L-glutamate Jmax. A model for L-[3H]glutamate transport is suggested involving the cotransport of at least two Na and one L-glutamate that is activated by one intravesicular K ion and at least two extravesicular Cl ions.
Effects of ouabain on neuronal thermosensitivity in hypothalamic tissue slices
Authors: Curras M. C. , Boulant J. A.
Published: December 2017

To determine the role of the electrogenic Na+-K+ pump in neuronal thermosensitivity, single-unit activity was recorded in rat hypothalamic tissue slices before, during, and after perfusions containing 10(-5) or 10(-6) M ouabain, a specific pump inhibitor. Most neurons were recorded in the preoptic-anterior hypothalamus. Some neurons were also tested with high magnesium-low calcium perfusions to determine ouabain's effects on neuronal activity during synaptic blockade. When the neurons were characterized according to thermosensitivity, 24% were warm sensitive, 8% were cold sensitive, and 68% were temperature insensitive. Ouabain increased the firing rate of 60% of all neurons. Ouabain did not reduce the thermosensitivity of cold-sensitive and warm-sensitive neurons; however, temperature-insensitive neurons became more warm sensitive during ouabain perfusion. This increase in warm sensitivity did not occur with ouabain plus high Mg2+-low Ca2+ perfusion, suggesting that Ca2+ is important in this response. These results indicate that the Na-K pump is not responsible for the thermosensitivity of hypothalamic cold-sensitive or warm-sensitive neurons; however, this pump may be actively employed by many neurons that remain insensitive to temperature changes.
Acute-phase behavior of factor VIII procoagulant and other acute-phase reactants in rabbits
Authors: Noe D. A. , Murphy P. A. , Bell W. R. , Siegel J. N.
Published: December 2017

We measured the plasma concentrations of factor VIII procoagulant (FVIII:C) in rabbits in two laboratory models of inflammation and after injections of purified homologous interleukin 1 (IL-1). The mean FVIII:C activities 2-4 days following the intramuscular injection of turpentine were significantly elevated, as were the concentrations of fibrinogen and C-reactive protein (CRP). By contrast, rabbits given 50 ng of bacterial lipopolysaccharide intravenously developed increased levels of FVIII:C but not of fibrinogen or CRP. We then studied plasma levels of FVIII:C, fibrinogen, and CRP after injections of either form of purified rabbit IL-1. If the rabbits' temperatures were monitored, FVIII:C levels increased in a log dose-related manner. This effect was not seen unless the rabbits were restrained and was seen in restrained rabbits even if the temperatures were not monitored. Fibrinogen and CRP levels did not change after IL-1 injections. These findings demonstrate that FVIII:C is an acute-phase reactant as judged by its response to turpentine inflammation or endotoxin injections, and to injections of IL-1 in restrained rabbits. FVIII:C appears to be a more sensitive acute-phase reactant than either fibrinogen or CRP. Neither of the latter proteins responded to low-dose endotoxin injections nor to either form of purified homologous IL-1. The doses of IL-1 given did cause fever, neutrophil leukocytosis, and hypoferremia.
Phase resetting of respiratory rhythm: effect of changing respiratory "drive"
Authors: Eldridge F. L. , Paydarfar D. , Wagner P. G. , Dowell R. T.
Published: December 2017

We studied the effect of changing drive on resetting of respiratory rhythm in anesthetized cats and in a model (Van der Pol) of a limit-cycle oscillator. In cats, rhythm was perturbed by brief mesencephalic stimuli. Stimulus time in the cycle (old phases) and times of onset of rescheduled breaths (cophases) were measured. Previous study [Paydarfar and Eldridge, Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R55-R62, 1987] showed distinct types of phase resetting that depended on strength of stimuli. In this study, stimulus strength was kept constant, but respiratory drive was changed by increasing PCO2, by stimulating carotid sinus nerve, or by cooling intermediate areas of ventral medulla. Type 0 (strong) resetting occurred when respiratory drive was low, type 1 (weak) resetting when drive was high, and a phase singularity when drive was intermediate. Phase-resetting patterns generated by the model showed the same behavior when a drive parameter was changed. The findings support the idea that continuous limit-cycle dynamics underlie generation of respiratory rhythm. Increased respiratory drive, by increasing size of the limit cycle, reduces functional effectiveness of the same perturbing stimulus in causing phase resetting.
Plasma catecholamine and glucose concentrations during hemorrhagic hypotension in anesthetized dogs
Authors: Briand R. , Yamaguchi N. , Gagne J.
Published: December 2017

Hemorrhage-induced hepatic glycogenolytic responses were compared in pentobarbital-anesthetized dogs with a temporary functional adrenalectomy (ADRX) and in dogs with an acute hepatic denervation (HNX). Plasma concentrations of catecholamines [CAs; epinephrine (E), norepinephrine (NE), and dopamine (DA)] were determined in aortic (AO), hepatic venous (HV), portal venous (PV), and adrenal venous (ADV) blood collected simultaneously before, during, and after hemorrhage (H). Plasma glucose (GL) concentrations were measured in AO and HV blood. AO blood was bled (5.3 +/- 0.5 ml.kg-1.min-1, n = 42) until AO systolic pressure dropped to half (72.9 +/- 4.7 mmHg) of its control value (148.0 +/- 4.4 mmHg), and the hypotension was maintained for 5 min. In control dogs (CTL; n = 12), H markedly increased ADV CAs with a predominant increase in E over NE and DA. AO CAs increased similarly. By contrast, however, changes in HV CAs were characterized by a significant increase in NE that was more pronounced than the increases in E and DA. The increases in NE were associated with significant increases in both HV GL and AO GL. In dogs with ADRX (n = 10), AO CAs remained unchanged during H, but both HV NE and HV GL rose concomitantly to an extent similar to that observed in CTL dogs. In dogs with HNX (n = 10), HV NE remained unchanged during H, but HV GL increased to an extent similar to that observed in dogs with ADRX, along with significant increases in AO CAs. In dogs with HNX combined with ADRX (n = 10), HV NE and AO CAs did not change at all during H, resulting in a marked attenuation (50%, P less than 0.05) of the increasing response of HV GL.(ABSTRACT TRUNCATED AT 250 WORDS)
Alternative mechanism for attenuated pressor responses in AV3V-lesioned dogs
Authors: Tramposch A. F. , Lopes O. U. , Chernicky C. L. , Ferrario C. M.
Published: December 2017

We lesioned the periventricular tissue of the anteroventral portion of the third cerebral ventricle (AV3V) of dogs to evaluate the mechanism that accounts for blunting of the pressor activity of angiotensin II (ANG II). AV3V lesions were done with a microknife using a transbuccal approach; the procedure denervated the organum vasculosum of the laminae terminalis, the nucleus medianus, and the medial preoptic nucleus. Two to four days after surgery, the conscious AV3V-lesioned dogs showed adipsia and their blood contained increased quantities of Na+ (175 +/- 2 meq/l) and an elevated osmolality (352 +/- 5 mosmol/kg). Cardiac rate was faster (131 +/- 8 beats/min) in AV3V-lesioned dogs, but their mean arterial pressure (MAP) was within normal values (99 +/- 4 mmHg). These changes were accompanied by an almost 18-fold increase in the plasma levels of immunoreactive ANG II (irANG II). In contrast, plasma vasopressin (AVP) levels fell to nondetectable values. Pressor responses produced by intravenous infusions of ANG II or injections of norepinephrine (NE) were significantly blunted 3 days after AV3V ablation. Short-term treatment of eight AV3V-lesioned dogs with the synthetic AVP analogue, 1-desamino-8-D-arginine vasopressin, reduced plasma Na+ and irANG II levels. The pressor activity of peripheral infusions of ANG II was restored to prelesion values, whereas pressor responsiveness to NE remained depressed. These data suggest that the blunting of the pressor action of ANG II in AV3V-lesioned dogs is an expression of a disorder in the regulation of renal and behavioral mechanisms maintaining fluid balance and AVP secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Normal atrial natriuretic peptide release after acute and chronic stimuli in hypophysectomized rats
Authors: Hoffman A. , Keiser H. R.
Published: December 2017

To test the hypothesis that the pituitary gland has a role in modulating the release of atrial natriuretic peptide (ANP) from atrial myocytes, we applied different stimuli of both acute and chronic nature to rats 8-10 days after hypophysectomy (Hypx). Acute rapid cardiac pacing at a rate of 500 beats/min in anesthetized rats caused a marked increase in plasma levels of ANP (from 76 +/- 7 to 237 +/- 60 pg/ml, P less than 0.05) despite a marked decrease of blood pressure. This response was similar to that of paced control rats, but because the basal levels were lower in Hypx rats, the relative increase in ANP was larger in the experimental group. Studies were also done in a chronic model of high-output congestive heart failure produced by an aortocaval fistula in hydrocortisone-supplemented rats. Although these rats had low blood pressure 2-3 days after surgery, there were marked increases in right atrial pressures associated with high plasma levels of ANP (194 +/- 24 pg/ml) that were not significantly different from controls (221 +/- 26 pg/ml, P greater than 0.05). These results indicate that the role of the pituitary in ANP release is indirect, and no specific hypophyseal factor is required for this response. Hemodynamic parameters are the important determinants of ANP secretion, even in hypophysectomized rats.
Decreasing pH of rat embryos and fluids estimated by transplacental distribution of DMO
Authors: Collins M. D. , Duggan C. A. , Schreiner C. M. , Scott W. J.
Published: December 2017

Utilizing the transplacental distribution of a weak acid, 5,5-dimethyloxazolidine-2,4-dione (DMO), we have measured the pH of cells within the rat embryo in vivo on days 11.5-14 of gestation. This is a period of rapid organogenesis in this species when the cells of many organ systems begin to change from a proliferative mode into a differentiated state. We found that intracellular pH of the day 11.5 rat embryo is 7.47 +/- 0.03 and decreases steadily to day 14 at which time it reaches 7.11 +/- 0.03. Because there is a concomitant fall in proliferative rate over this span of development, we suggest this correlation to be additional evidence of an association between proliferation and alkalinization of the cell interior. A number of other compartments including embryo plasma, amniotic fluid, exocoelomic fluid, and yolk sac have a decreasing concentration of DMO as development advances, indicative of a steadily declining pH. These changes could have developmental and pharmacokinetic implications.
Modulation of fetal cardiovascular responsiveness to norepinephrine by autonomic nervous system
Authors: Brace R. A. , Cheung C. Y.
Published: December 2017

To determine the extent to which the autonomic nervous system modifies the fetal cardiovascular responses to exogenous norepinephrine (NE), NE was infused intravenously (0.39-39 micrograms/min) for 30 min into chronically catheterized sheep fetuses averaging 132 days gestation. The resulting changes in arterial pressure, venous pressure, heart rate, and blood volume were compared between fetuses with and without ganglionic blockade. Autonomic blockade did not alter the relationship between the rise in NE concentration and NE infusion rate. In fetuses with a blocked autonomic nervous system, the arterial pressure response to exogenous NE was shifted 0.8 log units to the left when compared with normal fetuses. The venous pressure response to NE infusion was not altered in the blocked fetuses when compared with normal fetuses. Heart rate in the autonomically blocked fetuses increased with plasma NE concentration, which was opposite to the initial suppression of heart rate during NE infusion in control fetuses. Fetal blood volume decreased progressively with increasing NE infusion rate in the blocked fetuses, which was similar in autonomically intact fetuses, except for an increase in blood volume at low NE infusion rates. Thus it appears that the autonomic nervous system modifies the fetal arterial pressure, heart rate, and blood volume responses to exogenous NE but not the response of venous pressure
Mechanisms of respiration-induced changes in vasomotor control exerted by rostral ventrolateral medulla
Authors: Cox B. F. , Brody M. J.
Published: December 2017

Efferent and afferent mechanisms involved in the differential depressor response to inactivating rostral ventrolateral medulla (RVLM) under conditions of normal (2.5 ml) and reduced (1.5 ml) tidal volume were examined in urethan-anesthetized rats. Under conditions of reduced tidal volume, bilateral microinjection of lidocaine (200 nl, 4%) into RVLM produced an attenuated fall in both mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) despite the fact that base-line levels of both are unchanged. The specificity of the differential response was tested by examination of regional hemodynamics. Microinjecting lidocaine into RVLM produced an attenuated fall in renal, mesenteric, and hindquarter vascular resistances in parallel with the attenuated fall in MAP produced by reducing tidal volume. Microelectrode stimulation of RVLM produced an increase in resistance in all three vascular beds. Of the neural sensory systems examined, both vagal and chest wall afferents appear to be involved in mediating the differential depressor response. These results demonstrate the importance of afferent sensory input to the medulla in determining sites of generation and maintenance of sympathetic vasomotor tone.
Breath-by-breath respiratory timing and volume control during periodic breathing
Authors: Carley D. W. , Maayan C. , Grimes J. , Shannon D. C.
Published: December 2017

We examined the control of respiratory pattern during non-rapid-eye-movement sleep-related periodic breathing (PB) in adults, with and without hypoxia. We analyzed 186 cycles of PB from 18 epochs occurring in eight subjects; the mean (+/- SD) cycle duration was 30.8 +/- 8.4 s. Significant oscillations occurred in inspired tidal volume (VT), inspiratory duration (TI), mean inspired flow, inspired minute ventilation, and expiratory duration (TE) (P less than 0.005). For each epoch of PB, moving cross-correlation (MCC) functions were employed to describe the time-dependent intervariable relationships between 1) TI vs. TE, 2) VT vs. TE, and 3) VT vs. breath duration (TT) as synchronization, a strong and consistent intervariable correlation; relative coordination (RC), a weaker interaction characterized by an unstable MCC function oscillating at a subharmonic of the PB frequency; or as independence, with no statistical evidence of interaction. Fourteen epochs showed RC between TI and TE, 11 and 12 of which also showed RC between VT and TE, and VT and TT, respectively. In 4 epochs negative synchronization was exhibited by all three variable pairs. In no case were the oscillations between any pair of variables independent. The modes of coupling between variables were not correlated to O2 saturation, end-tidal CO2 levels, or inspired O2 level. We conclude that during sleep-related PB a nonrandom but weak coupling usually exists between TI and TE, VT and TE, and VT and TT.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibitory modulation by cAMP of isoproterenol-induced prostacyclin synthesis in rabbit heart
Authors: Williams J. L. , Malik K. U.
Published: December 2017

beta-Adrenergic receptor activation in heart is associated with enhanced production of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins (PG). The purpose of the present study was to test the hypothesis that cAMP mediates or modulates PG synthesis elicited by activation of beta-adrenergic receptors in the isolated, perfused rabbit heart. Infusion of 8-(4-chlorophenylthio) (cpt)-cAMP (100 microM), an analogue of cAMP, or stimulation of endogenous cAMP generation with forskolin (2 microM) resulted in a reduction of perfusion pressure and an increase in heart rate and contractility but had no effect on 6-keto-PGF1 alpha output. 6-Keto-PGF1 alpha production elicited by a bolus injection of isoproterenol (Isop) (475 pmol), however, was reduced by greater than 50% in the presence of these agents, cpt-cAMP was also found to inhibit 6-keto-PGF1 alpha output elicited by the calcium ionophore A23187 but not that in response to exogenous arachidonic acid. Perfusion with the adenosine analogue adenylate cyclase inhibitor PIA (1 microM) enhanced by twofold Isop-stimulated output of 6-keto-PGF1 alpha, whereas cAMP accumulation was prevented. Isop-stimulated production of 6-keto-PGF1 alpha was inhibited by 50% in the presence of the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine (50 microM), Ro 20-1724 (300 microM), or cilostamide (5 microM), whereas both basal and Isop-stimulated cAMP accumulations were enhanced by these agents. These data suggest that cAMP acts as an inhibitory modulator of PG synthesis in response to beta-adrenergic receptor activation in rabbit heart.