bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood-brain barrier permeability of 11C-labeled alcohols and 15O-labeled water
Authors: Raichle ME , Eichling JO , Straatmann MG , Welch MJ , Larson KB , Ter-Pogossian MM
Published: December 2017

The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.
Interaction of gastrin I, secretin, and cholecystokinin on gallbladder smooth muscle
Authors: Ryan J , Cohen S
Published: December 2017

The effect of cholecystokinin (CCK), the octapeptide of cholecystokinin (CCK-OP), gastrin I, and secretin was studied on guinea pig gallbladder smooth muscle in vitro. Both CCK and CCK-OP stimulated gallbladder contraction, with CCK-OP being more potent. Gastrin I, over a wide dose range, had no effect on gallbladder contractility. Secretin alone also showed no effect on gallbladder smooth muscle but in combination with CCK-OP it produced a noncompetitive type of inhibition. Michaelis-Menten kinetics showed the calculated maximum response of the secretin plus CCK-OP interaction to be less than with CCK-OP alone. There was no change in the dose required to achieve half-maximal response, D50. These studies indicate that: a) CCK-OP has a greater effect on gallbladder contractility than CCK, b) gastrin I has no effect on gallbladder muscle tone, and c) secretin acts as a noncompetitive antagonist of CCK-OP. These findings suggest that gallbladder motor function may be determined in part by the interaction of secretin and CCK rather than solely in response to CCK.
Placental amino acid uptake. III. Transport systems for neutral amino acids
Authors: Enders RH , Judd RM , Donohue TM , Smith CH
Published: December 2017

The human placenta is known to concentrate nearly all amino acids intracellularly for transfer to the fetus. To clarify the mechanism and regulation of this process we have determined the specificity of the principal placental transport systems for neutral amino acids. With the use of competitive inhibition techniques, three transport systems of overlapping specificity have been elucidated. These correspond approximately to the "A", "L", and "ASC" systems of Christensen and associates. In the placenta the specificity of these systems is as follows: A system - alpha aminoisobutyric acid (AIB), glycine, proline, N-methylalanine, alanine, serine, threonine, and glutamine; L system - isoleucine, valine, phenylalanine, BCH, alanine, serine, threonine, and glutamine; and ASC system - alanine, serine, threonine, and glutamine. Placental AIB uptake previously has been shown to increase with preincubation of tissue in vitro. This increase has now been found to be limited to the A system. Activity of the other two systems is essentially unaffected, demonstrating that the transport pathways are separately regulated.
Mechanism of action of aspirin on canine gastric mucosa
Authors: Kuo YJ , Shanbour LL
Published: December 2017

Using an in vivo chambered canine stomach preparation, exposure of the gastric mucosa to 5, 10, and 20 mM aspirin(pH 3.0) resulted in a decrease in electrical potential difference (PD) and in an increase in resistance (R) within 30 min. In vitro, exposure of the mucosal side of the isolated canine gastric mucosa to 5, 10, and 20 mM aspirin (pH 3.0) for 1 h or of 1 mM aspirin (pH 3.0) for longer than 1 h resulted in marked permeability changes, i.e., increases in the undirectional fluxes of Na+ and Cl-, as well as inhibition of net ion fluxes. These concentrations of nonionized aspirin (pH 3.0) also reduced the R and PD. However, 1 mM aspirin (pH 3.0) or 20 mM ionized aspirin (pH 7.4) depresses the active transport of ion, increases R, but does not increase the ionic permeability. Mucosal adenosine triphosphate (ATP) content is reduced by mucosal instillation of aspirin (pH 3.0). These results demonstrate that the initial action of aspirin is inhibition of ion transport which is followed by an increase in permeability.
Effect of a fixed pyloric opening on gastric emptying in the cat and dog
Authors: Stemper TJ , Cooke AR
Published: December 2017

The effect of preventing pyloric closure on the rate of gastric emptying without alteration of the gastroduodenal junction was studied in six dogs and four cats with gastric fistulas. Each had a Teflon cannula with an internal diameter of 1.0 or 1.25 cm (dog) and 0.6 cm (cat) sewn into the pyloric channel. At the completion of the initial series of tests, the cannulas were removed and the studies repeated. Test meals were 240 and 480 ml of water, acid (120 mM HC1), and hyperosmotic glucose (555 mM) in the dogs and 50 ml of water, acid (100 mM HC1) and fat (20 mM Na oleate) in the cats. Phenol red was used as a nonabsorbable marker. The residual volumes were collected at 15-40 min in the dogs and 15-20 min in the cats. In both species, the rate of emptying of all the meals was unaffected by the pyloric cannula. In the dog, added secretions were greater with the pyloric cannula in place, suggesting reflux of duodenal contents. This study indicates that while the pylorus is unimportant in the gastric emptying of liquids in the dog and cat, it may have a role in prevention of duodenal reflux.
Blood flow and relative tissue PO2 of brain and muscle: effect of various gas mixtures
Authors: Weiss HR , Cohen JA , McPherson LA
Published: December 2017

The effects of inspiring low O2 or high CO2, or low-O2-high-CO2 gas mixtures on tissue perfusion and tissue Po2 of brain and muscle were studied in 76 anesthetized rats. Under control conditions, relative tissue Po2 of cerebral white matter measured polarographically averaged 16.4 mmHg and 18.7 mmHg in the biceps brachii. With low-O2 gas mixtures, tissue Po2 declined in both brain and muscle, but more in muscle. Tissue Po2 increased under high-CO2 conditions, with the brain increasing to a greater extent. Control cerebral cortex tissue perfusion averaged 23.5 ml/min per 100 g and muscle was 18.3 ml/min per 100 g measured by H2 clearance. Brain perfusion increased under all experimental conditions. Muscle perfusion did not change with low O2 alone, but increased with low-O2-high-CO2 or high-CO2 gas mixtures. Brain perfusion increased under all conditions significantly more than muscle. The brain appeared better protected compared to skeletal muscle in terms of tissue Po2 and perfusion under the stress of hypoxia and hypoxic-hypercapnia. The effects of hypercapnia are also greater on the brain.
Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions
Authors: Strome DR , Clancy RL , Gonzalez NC
Published: December 2017

Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.
Cardiovascular and electrophysiological responses to sympathetic pathway stimulation
Authors: Barman SM , McCaffrey TV , Wurster RD
Published: December 2017

Anesthetized, vagotomized, and paralyzed cats were used to study the relationship between changes in blood pressure and T2 preganglionic nerve activity elicited by stimulation of descending spinal sympathoexcitatory pathways. While low-frequency stimulation (1-10 Hz) resulted in a depressor response, an attenuation of sympathetic nerve evoked discharges was noted after the second pulse of twin-pulse stimulations with 1,000- to 100-ms intervals between stimuli (corresponding to 1-10 Hz). High-frequency stimulation (greater than 10 Hz) resulted in a pressor response, while preganglionic nerve-evoked discharges were enhanced during twin-pulse stimulations with intervals between stimuli less than 50 ms (corresponding to greater than 20 Hz). These data suggest that the depressor response during low-frequency stimulation may be explained by impulses occurring during the silent period of the previous response. During this time the preganglionic neuron is inexcitable and spontaneous activity is abolished; therefore, the blood pressure falls. High-frequency stimulation may result in a pressor response by increasing the number of preganglionic neurons that are activated. This may be due to a process of temporal summation, with initial stimuli bringing cells closer to their threshold for firing and additional stimuli close in time causing these neurons to discharge.
Thiamine transport in the central nervous system
Authors: Spector R
Published: December 2017

Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.
Effect of lithium of responsiveness of rat uterine smooth muscle to angiotensin
Authors: Freer RJ , Smith AB
Published: December 2017

Studies were carried out to investigate the effect of Na+ deprivation on the response of rat uterine smooth muscle to angiotensin II (AII). Replacement of Na+ with Li+ in a low-Ca2+-, Mg2+-free solution resulted in a concentration-dependent inhibition of both AII and acetylcholine (ACh)-induced contractions. Inhibition was noted at 10% Li+ substitution and was usually complete when 50% of the Na+ was replaced by Li+. The inhibition was not observed when an equivalent amount of tris(hyroxymethyl)aminomethand (Tris+) or sucrose was used to replace Na+. However, elevation of Ca2+ concentration from 0.2 to 0.5 mM did prevent full expression of the Li+ inhibition of AII. The Li+ effect was rapid in onset (60% inhibition after 5 min preincubation) and readily reversible following removal of the Li+. If, however, the tissue was placed in a depolarizing solution (151 mM KCL), Li+ inhibition of AII WAS NO LONGER OBSERVED. These results are interpreted to mean that Li+ interferes with an essential Ca2+-dependent step involved in membrane excitation following agonist-receptor interaction. The results are discussed in relation to a previously suggested model for AII-induced contractions in this tissue.
Cardiovascular effects of cerebroventricular ouabain perfusion in the adult dog
Authors: Holloway LS  , Bradley IB , Janssen H , O'Brien LJ
Published: December 2017

Cerebroventricular perfusion with artificial cerebrospinal fluid containing 10(-5) M ouabain was performed in adult dogs in order to describe the time course of the cardiovascular effect of intraventricular ouabain and to evaluate treatments to eliminate the cardiovascular effect. The central effect of ouabain caused a 56% increase in blood pressure above control values and a 35% increase in heart rate with various cardiac arrhythmias. Both alpha- and beta-adrenergic blocking drugs given intravenously.altered the pressure and rate effects ou ouabain, whereas vagotomy attenuated the effect.
Effect of carotid sinus nerve stimulation pattern on cardiorespiratory responses
Authors: Levy MN , Zieske H
Published: December 2017

The reflex responses to steady and intermittent stimulation of the carotid sinus nerve (CSN) were compared in anesthetized dogs. Intermittent stimulation was less effective than steady stimulation in reducing the arterial blood pressure, and the disparity was exaggerated after acute sinoaortic denervation. With the sinoaortic nerves intact, at low mean stimulation frequencies the heart rate responses were greater during intermittent than during steady CSN stimulation. At higher mean stimulation frequencies, however, steady CSN stimuli were more effective than were the intermittent type. After sinoaortic denervation, steady stimuli evoked greater heart rate responses than did intermittent stimuli over the entire mean frequency range studied. Reflex changes in respiratory depth and frequency were also greater during steady than during intermittent CSN stimulation. The greater efficacy of steady than of intermittent stimulation in evoking.the observed reflex cardiovascular and respiratory changes is probably ascribable to the pronounced frequency limitation at the first synapse of the baroreceptor reflex in the brain.
Effect of beta-adrenoreceptor blockade on rat cardiac and skeletal muscle pH
Authors: Clancy RL , Gonzalez NC , Fenton RA
Published: December 2017

The effect of catecholamines on the intracellular pH of rat cardiac and skeletal muscle during varying extracellular acid-base states was determined. Intracellualr pH (pHi) was calculated from the distribution of [14C]DMO. Acid-base disturbances were produced by placing the animals in an environmental chamber containing 10 or 20% CO2 or by administering HCL or NaHCO3. Two hours later the animals were anesthetized with sodium pentobarbital and blood and tissue samples obtained. In one series of animals, the effects of catecholamines were attenuated by administering the beta-adrenoreceptor antagonist MJ 1999 (Sotalol). In animals breathing 20% CO2, cardiac muscle pH was lower in beta-blocked than unblocked animals (6.69 vs. 6.78). During metabolic acidosis, cardiac muscle pH of beta-blocked animals was lower than that of unblocked animals (6.75 vs. 6.84). The same relationship was observed for skeletal muscle during metabolic acidosis-beta blockade pHi, 6.66; unblocked pHi, 6.77. The pHi of beta-blocked versus unblocked animals was not significantly different under normal acid-base conditions or metabolic alkalosis for cardiac or skeletal muscle. The effective buffer value of both tissue over the normal acidotic range was decreased by the beta-blocking agent. These results indicate that catecholamine release accompanying acidosis attenuates the change in pHI and increases the effective buffer value of cardiac and skeletal muscle.
Angiotensin II binding to renal glomeruli from sodium-loaded and sodium-depleted rats
Authors: Beaufils M , Sraer J , Lepreux C , Ardaillou R
Published: December 2017

125I-labeled angiotensin II (125I-labeled AII) and [3H]angiotensin II ([3H]AII) bind specifically to isolated rat glomeruli. Three groups of receptor sites could be defined by the KD value (7.1 +/- 0.3 X 10(-11, 3.4 +/- 0.2 X 10(-10), and 1.6 X 10(-9) M, respectively) and the number of receptor sites (11.6 +/- 1.2, 29.4 +/- 3.9, and 113.8 +/- 3.8 fmol/mg glomerular protein, respectively). Both association and dissociation constants for 125I-labeled AII were greater than those for [3H]AII, but their ratio (KD) remained unchanged. Specificity of binding to these three groups of receptor sites was demonstrated by the following: 1) inhibition of binding of labeled AII by unlabeled hormone or by antagonists; and 2) reversibility of binding, independent of either hormone or receptor degradation. Binding was increased in glomerular preparations from acutely and chronically sodium-loaded rats, compared with glomerular preparations from acutely and chronically sodium-depleted rats. This change in binding resulted from both a change in the number of receptor sites and modification of the affinity of AII for its receptors. KD was higher in preparations from sodium-depleted rats (12.9 +/- 3.3 and 14.6 +/- 3.9 X 10(-11) M in chronically and acutely depleted rats, respectively) than in those from sodium-loaded rats (2.7 +/- 0.2 and 3.9 +/- 1 X 10(-11) M in chronically and acutely sodium-loaded rats, respectively). Changes in the binding of AII to its glomerular receptors could play a role in the adaptation of glomerular filtration rate to the sodium balance.
Adenosine relaxation of isolated vascular smooth muscle
Authors: Herlihy JT , Bockman EL , Berne RM , Rubio R
Published: December 2017

Adenosine relaxed hog carotid media strips contracted with norepinephrine (NE) and potassium (K+). Adenosine (3 X 10(-6)M) was more effective in relaxing the NE contractures than those produced by K+. In both cases, adenosine's efficacy decreased with increasing concentrations of the stimulating agent. A high adenosine concentration (1 X 10(-3)M) was necessary to elicit relaxation of completely depolarized (124 mM K+) media strips and equimolar concentrations of aminophylline caused greater relaxation than did adenosine. Adenosine inhibited the Ca2+ dose-response curves of strips stimulated with 20 mM and 30 mM K+ and its effect was dependent on the Ca2+ concentration. Neither 1 X 10(-6)M nor 1 X 10(-4)M adenosine produced any change in the cAMP content of vascular strips. Only at high concentrations did adenosine increase the cAMP content of vascular strips, but the increase was signficantly more than that observed with the same dose of aminophylline. The present results are consistent with the possibility that adenosine relaxes vascular smooth muscle by directly altering Ca2+ permeability and/or membrane potential; they do not support a role for cAMP in the adenosine-induced relaxation of vascular smooth muscle.
Effects of anoxia and glucose depletion on isolated veins of the dog
Authors: Vanhoutte PM
Published: December 2017

Canine vein strips were mounted for isometric tension recording. Anoxia did not affect basal tension of saphenous and pulmonary strips mounted in standard Krebs-Ringer solution or after 30 min of incubation in glucose-free solution. Anoxia depressed the strength of spontaneous contractions of mesenteric veins; in glucose-free solution (30 min), anoxia relaxed the strips. Veins placed in glucose-free solution for more than 60 min contracted with anoxia; this contraction was not inhibited by iproveratril. When the vein strips were contracted by norepinephrine or KCl, anoxia depressed the contractions, most in mesenteric and least in saphenous preparations; this depression was greater in the absence of glucose. When oxygen was present, the absence of glucose had little effect on the response to vasoactive agents. Contractions with acetylcholine were depressed by anoxia in mesenteric and pulmonary strips but were augmented in saphenous veins; the latter potentiation was inhibited by iproveratril and by incubation in glucose-free solution. Thus, especially in the saphenous vein, anaerobic glycolysis can provide most of the energy requirements, and intracellular substrates are available for oxidative metabolism.
Carbohydrate metabolism in fetal and neonatal rat brain during anoxia and recovery
Authors: Vannucci RC , Duffy TE
Published: December 2017

Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose.
Use of pyrazinamide to assess renal uric acid transport in the rat: a micropuncture study
Authors: Abramson RG , Levitt MF
Published: December 2017

Free-flow micropuncture studies were performed to evaluate renal uric acid transport in control and pyrazinamide-treated rats. In all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. [2-14C]uric acid was determined after column chromatographic separation from its labeled oxidation product in tubular fluid, plasma, and urine. Tubular fluid collections were obtained from the early and late proximal tubule under hydropenic conditions and from the early proximal tubule during volume expansion induced with 0.9% sodium chloride. These studies indicate that pyrazinamide, in the dose employed, provokes a uniform reduction in fractional uric acid excretion but simultaneously inhibits both net uric acid reabsorption and secretion in the early and late proximal tubule, respectively. In addition, these experiments unmasked uric acid reabsorption within the late proximal tubule and bidirectional transport beyond this nephron site. These studies also suggest at least two mechanisms for uric acid reabsorption; one sodium dependent, the other independent of sodium and water transport.
Neurophysiological studies on central chemosensor in medullary ventrolateral areas
Authors: Pokorski M
Published: December 2017

Nonphasic unit potentials were recorded with glass microelectrodes from the ventrolateral medullary areas in spontaneously breathing cats. The firing rate changes were studied during metabolic acidosis and alkalosis induced by intravenous injections of 4 ml 0.1 N HCl and molar NaHCO3, respectively, and during CO2 rebreathing. Three groups of units were distinguished among 44 neurons: 1) 9 U were markedly sensitive to variations in acid-base parameters; each reacted in the opposite manner upon acidosis and alkalosis, and these reactions were reproducible. 2) Twelve units were responsive to touch of a contralateral limb with a prompt and massive rise in firing rate. 3) The remaining 23 U were classified as nonsensitive to any of the stimuli applied. All these 44 U were found to be intermingled. It is possible that the chemosensitive cells found may be part of the central chemosensor.
Effects of insulin on cardiac muscle contraction and responsiveness to norepinephrine
Authors: Lee JC , Downing SE
Published: December 2017

The effects of insulin (In) on contractile activity of isolated cardiac muscle were studied in right ventricular moderator band (MB) of piglets and papillary muscle (PM) of cats and kittens. The muscles were bathed in modified Krebs solution containing 5.6 mM glucose at 30 degrees C and gassed with 95% O2 and 5% CO2. They were paced at 24 contractions per minute isometrically at Lmax. Addition of In (1 U/ml) to the bath induced a biphasic inotropic response to piglet MB. The initial negative effect was due to the preservative (0.2% phenol) in the regular commercial In solution. Following the transitory depression, both active isometric tension (AT) and maximal rate of tension development increased to a maximum (about 120% of control) within 15 min and then declined slightly toward control. Similar positive responses were observed in both cat and kitten PM, but without the initial negative effect. Maximal responses were not diminished by the absence of glucose in the bath. Increases in AT and dT/dt of both MB and PM in response to NE were significantly attenuated in the presence of In compared with untreated muscle. These findings demonstrate that In elicits a positive inotropic effect on mammalian cardiac muscle and that it impairs the inotropic action of NE.
Influence of the oral cavity on insulin release in the rat
Authors: Steffens AB
Published: December 2017

Blood glucose and insulin levels were measured in undisturbed and free-moving rats. The insulin level rose in the 1st min after the start of food intake; the glucose level began to increase only in the 3rd min if a fluid carbohydrate-rich food was eaten. The insulin release followed a biphasic pattern. If the same quantity of food ingested orally was injected into the stomach in the same time as the animals needed to complete oral ingestion, delayed insulin release could be seen and the second phase of insulin release was exaggerated. The glucose level, which started to rise in the 3rd min, increased much more than during oral ingestion. With respect to insulin release the same phenomena could be observed if carbohydrate-free fluid food was used instead of carbohydrate-rich fluid food. It is argued that the oral cavity plays a major role in the first phase of insulin release, which in its turn seems to be important in the homeostasis of the blood glucose and insulin levels.
Oxygen toxicity: augmentation of antioxidant defense mechanisms in rat lung
Authors: Kimball RE , Reddy K , Peirce TH , Schwartz LW , Mustafa MG , Cross CE
Published: December 2017

In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung "antioxidant" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.
Participation of beta receptors in reflex vasodilatation in the dog
Authors: Rengo F , Trimarco B , Perez G , Chiariello M , de Caprio L , Sacca L , Condorelli M
Published: December 2017

The effects of propranolol, given by direct intraarterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid intravenous administration of norepinephrine, were studied in dogs. In these studies, both atropine and atropine plus propranolol did not significantly alter the maximum fall in vascular resistance in the perfused gracilis muscle following intravenous norepinephrine; however, if the reflex responses were evaluated as integrated areas of vasodilatation, atropine attenuated the vasodilatation and the administration of propranolol further attenuated the reflex. In fact, the value of the integrated areas of vasodilatation was 52.8 +/- 9 mmHg/min in the basal state, 39 +/- 6 mmHg/min after administration of atropine, and 24 +/- 7 mmHg/min after propranolol, whereas the integrated areas of the systemic hypertension did not show any modification. These results prompt us to conclude that the adrenergic beta receptors participate in the reflex vasodilatation, although the mechanism of their action needs further elucidation.
alpha- and beta-adrenergic receptors in regulation of ionic transport in frog cornea
Authors: Montoreano R , Candia OA , Cook P
Published: December 2017

The effect of catecholamines and adrenergic blocking agents on the transport of Cl- and Na+ of the isolated frog cornea was studied. Cl- transport was stimulated by the three catecholamines tested at 10(-6) to 10(-5) M concentration. The stimulation produced by 10(-6) M epinephrine was partially inhibited by both the alpha-blocker phentolamine and the beta blocker propranolol. The stimulation produced by 10(-6) M isoproterenol was not affected by 10(-5) M phentolamine but was completely prevented by 10(-5) M propranolol. The stimulation produced by 10(-5) M norepinephrine was completely blocked by the 10(-5) M propranolol and partially by 10(-5) M phentolamine. Catecholamines had no effect on the normally small Na+ transport. When the Na+ transport was previously increased by amphotericin B, epinephrine and isoproterenol produced a small and inconsistent stimulatory effect. Norepinephrine was without effect. It is concluded that both alpha- and beta-adrenergic receptors are present in the frog cornea and that the Cl- transport is increased by the stimulation of either receptor. The minimal effect on the Na+ transport further suggests the separation of pathways of the Cl- and Na+ transport in the frog cornea.
Adenosine and active hyperemia in dog skeletal muscle
Authors: Bockman EL , Berne RM , Rubio R
Published: December 2017

Adenosine as a possible mediator of active hyperemia in skeletal muscle was studied in hindlimbs of dogs. Sciatic nerve stimulation decreased vascular resistance to 55 +/- 5% (mean +/- SE) of the control value in hindlimbs perfused at a constant flow rate (61 +/- 6 ml/min). Venous plasma K+ concentrations were elevated after 2 min (from 4.0 +/- 0.2 to 4.8 +/- 0.2 meq/liter; P is less than 0.005) and 20 min (4.7 +/- 0.2 meq/liter; P is less than 0.001) of contraction, but the arteriovenous difference in plasma osmolality was changed only after 2 min of contraction (from -3.0 +/- 0.6 to -7.2 +/- 0.8 mosmol/kg H2O; P is less than 0.001). The muscle adenosine contents were not significantly elevated after 5 min of contraction, but were increased after 10 min (from 1.97 +/- 0.33 to 8.35 +/- 0.97 nmol/g; P is less than 0.05) and 25 min (from 1.64 +/- 0.22 to 7.57 +/- 2.20 nmol/g; P is less than 0.05) of contraction. Thirty minutes after contraction had ceased, the adenosine contents were significantly below control values (from 2.22 +/- 0.59 to 1.51 +/- 0.40 nmol/g; P is less than 0.005). Venous plasma adenosine concentrations did not increase during muscle contraction. No relationship was found between the increase in the plasma inorganic phosphate level and the activity of the muscles. These data indicate that the adenosine content of skeletal muscle is increased by contraction, and support the concept that adenosine may be a mediator of sustained active hyperemia.
Histidine decarboxylase activity in trauma-resistant rats
Authors: Reichard SM , Bunce R , Galvin MJ
Published: December 2017

Studies have been carried out to determine the possible role of nascent histamine in the development of traumatic shock. This was done by examining histidine decarboxylase (HD) activity of the lung, spleen, and plasma following exposure to trauma in normal and trauma-resistant rats. In normal rats, there was a significant increase in lung HD activity at 15 min and 4 h; and in the spleen the HD activity increased significantly at 4 h. In trauma-resistant rats exposed to trauma, there were no changes in enzyme activity in the lung and less pronounced changes in the spleen. The plasma HD activity remained stable in normal and resistant rats following episodes of trauma. Changes in total erythrocyte hemoglobin were observed in both normal and trauma-adapted rats following exposure to this stress, increasing significantly in normal rats, but decreasing in trauma-resistant rats. Blood volume decreased significantly at 4 h after trauma in normal animals; whereas only a slight decrease was noted in resistant animals. The data support the concept that newly formed histamine contributes to the pathogenesis of shock. It is also proposed that the increased resistance, characteristic of trauma-adapted rats, could be partly due to an inhibition of enzyme activation following trauma.
Heavy metal-induced alterations in ion transport by turtle urinary bladder
Authors: Schwartz JH , Flamenbaum W
Published: December 2017

Previous studies of heavy metal salt-induced acute renal failure demonstrated abnormalities of fluid and solute transport by nephron segments and alterations in glomerular filtration rate and renal hemodynamics. To determine the direct effects of uranyl nitrate (UN) or HgCl2 on ion transport, their effects were studied on the isolated urinary bladder of the turtle. Unidirectional 24Na+ and 36Cl- fluxes were measured across short-circuited bladders. The addition of 0.1 mM UN to the mucosal solution resulted in a 69.9 +/- 4% (SEM) decrease in short-circuit current (SCC) without change in transepithelial resistance. Net Na+ flux (7.95 +/- 0.81 mueq/h per 8 cm2) decreased by the same magnitude as the SCC, primarily due to a 5.75 +/- 0.76 mueq/h per 8 cm2 decrease in the mucosal- (M) to-serosal (S) Na+ flux. Net Cl- flux decreased also primarily due to a decrease in M-to-S Cl- flux. Addition of 0.4 mM UN to S did not measurably affect the SCC or ion fluxes. The addition of 10 muM HgCl2 in another group of bladders reduced SCC and M-to-S Na+ flux by 81 +/- 7% without change in Cl- fluxes or resistance. The removal of either UN or HgCl2 from M by washing did not reverse the decreased SCC, but after washing addition of either dithiothreitol, 2 mM, or amphotericin B, 20 mug/ml, to M completely reversed the effects of UN or HgCl2 on SCC. These studies suggest that heavy metal salts inhibit Na+ transport by the turtle bladder without altering passive ion fluxes.
Insulin kinetics after portal and peripheral injection of [125I] insulin. I. Data analysis and modeling
Authors: Pilo A , Navalesi R , Ferrannini E
Published: December 2017

The kinetics of insulin are commonly investigated by intravenous administration of labeled hormone, whereas native insulin is removed by the liver to some extent before mixing in the systemic circulation. A mathematical model has been developed which makes it possible to interpret the experimental data obtained by peripheral plasma sampling after portal and peripheral injection of the tracer. Equations are given that allow for the computation of metabolic clearance rate, initial distribution volume, production rate, and body mass of insulin. It is demonstrated that hepatic extraction can be calculated from the difference between the clearance rate values obtained after portal and peripheral injection of the tracer; an estimate of total hepatic catabolism is also derived. The assumptions and limitations underlying this mathematical analysis are discussed.
Pig reticulocytes: II. Characterization of density-fractionated maturing reticulocytes
Authors: Kim HD , Luthra MG , Hildenbrandt GR , Zeidler RB
Published: December 2017

A simple centrifugation technique initially developed for fractionation of human red cells in their own plasma has been found to be readily applicable to the separation of reticulocytes normally appearing in the pig soon after birth as well as to those induced in the adult pig by phenylhydrazine administration. The density of the naturally occurring reticulocytes, maximally amounting to 10-15% of total cells derived from a 7-day-old pig, varied from 1.073 to 1.101, in contrast to the mature cells, presumed to be the fetal cell type, whose density ranged in a narrower limit, from 1.101 to 1.106. In adult animals, the reticulocytosis amounting to more than 70% takes place in response to daily administration of phenylhydrazine for 7 days. The density of these reticulocytes varied widely from 1.068 to 1.094; in contrast, the density of the mature adult red cells ranged from 1.095 to 1.106. Among various physiological parameters examined, a marked decrease in cell size, cell water content, RNA, Na+ -K+ -ATPase, and Ca2+ -ATPase activities was observed in the course of reticulocyte maturation in vivo in the adult animal. All these physiological parameters were found to undergo a similar reduction from the top to the bottom fractions of the reticulocytes separated according to their density, suggesting that the separation technique employed here represents separation of reticulocytes according to their age.
Inhibition of H+ secretion in the frog gastric mucosa by ATP and related compounds
Authors: Sanders SS , Butler CF , O'Callaghan J , Rehm WS
Published: December 2017

Addition of adenosine triphosphate (ATP) to the nutrient (submucosal-facing) solution of the histamine-stimulated in vitro frog (Rana pipiens) gastric mucosa produces a marked reduction in the H+ secretory rate and an increase in transmucosal potential difference (PD) and resistance in both Cl- and Cl-free media. The effects are reversible upon removal of ATP. The threshold concentration is between 1 and 2 mM, and 5 mM produce maximal inhibition. It is shown that the effects of ATP are not due to a change in pH or osmolarity of the nutrient fluid, or to a decrease in the Ca2+ and/or Mg2+ activities of the nutrient fluid. It is also shown that the inhibitory action of ATP is not dependent on a chelation complex between Ca2+ or Mg2+. Adenosine diphosphate also produces effects essentially the same as ATP whereas 5'-adenosine monophosphate and adenosine produce relatively little or no change.
Permeability of dog lung endothelium to sodium, diols, amides, and water
Authors: Perl W , Silverman F , Delea AC , Chinard FP
Published: December 2017

Bolus injection of T-1824-albumin, test indicator, and tritiated water into a jugular vein of the anesthetized dog and sequential sampling of blood from a carotid artery yielded multiple-indicator outflow patterns for the lung. Permeability-surface products of the test indicator for the lung endothelial barrier were obtained by comparison of test indicator with T-1824-albumin on the upslope of the test-indicator curve and correction for backdiffusion. The derived endothelial permeability coefficients, based on surface area/wet lung weight-500 cm2/g (mean +/- 2 SE, 10(-5) cm s(-1)), were: sodium ion, 2.9 +/- 0.8; ethylene glycol, 7.3 +/- 1.5; 1, 3-propranediol, 7.9 +/- 3.2; 1, 2-propanediol, 10 +/- 4; 1, 4-butanediol, 14 +/- 8; 1, 5-pentanediol, 21 +/- 6; 1, 6-hexanediol, 41 +/- 11; formamide, 16 +/- 9; acetamide, 13 +/- 4; propionamide, 31 +/- 12; butyramide, 42 +/- 24; valeramide, 79 +/- 12; tritiated water, 150 +/- 50. The backdiffusion correction varies from 8% for sodium to 75% for valeramide. A parallel-pathway model of blood-tissue passive exchange of small nonelectrolyte solutes is compatible with these results, with a lipid pathway through endothelial cells and an aqueous pathway possibly through interendothelial clefts.
Endogenous prostaglandins and mechanical tension in canine trachealis muscle
Authors: Yamaguchi T , Hitzig B , Coburn RF
Published: December 2017

Prostaglandin E (PGS) is synthesized and released in isolated canine trachealis muscle (CTM), and the PGE threshold concentration for an effect on isometric tension is very low, indicating this prostaglandin is a most likely candidate for an endogenous prostaglandin that modulates or regulates tension. Prostaglandin F (PGF) is also released, but the threshold concentration for a mechanical effect is probably too high for endogenous PGF to have a direct effect on tension in this muscle. Indomethacin and aspirin, at concentrations commonly used to inhibit prostaglandin synthetase, had effects on tension, membrane potential, and membrane resistance, but these effects were not appropriate if their only action was to inhibit PGE or PGF concentration in CTM. Release of PGE from CTM was increased fourfold by treatment with carbachol, but even under this condition, where presumably cell [PGE] was increased, electrophysiological studies failed to give convincing evidence that the actions of indomethacin on mechanical tension were related to inhibition of PGE or PGF synthesis.
PCO(2) and rate of formation of cerebrospinal fluid in the monkey
Authors: Martins AN , Doyle TF , Newby N
Published: December 2017

Changes in cerebrospinal fluid formation rate (VF) with hypocapnia were measured by the ventriculocisternal perfusion technique in 24 rhesus monkeys anesthetized with nitrous oxide. In addition cerebral blood flow (CBF) was measured by the hydrogen clearence methods, Vf in control animals declined at a mean rate of 2.3 mul/min each hour during the last 4.5 h of a 7-h perfusion although variables known to effect Vf remained stable. Three hours after perfusion began, Vf of normocapnic controls was 41.4 mul/min +/- 5.4; CBF, 59P ML/100 G PER MIN. When Pco(2) was reduced to half of control, Vf fell to 35.6 mul/min +/- 6.3 and CBF fell by 27%. When Pco(2) was doubled, Vf fell to 33.1 mul/min +/- 5.3 and CBF increased threefold. The difference in Vf id significant only for the hypercapnic group (p=0.01). When animals were used as their own controls, three were no significant differences in Vf with hypercapnia compared to normocapnia. These results indicated that in the monkey variations of Pco(2) within broad physiologic limits, which are sufficient to cause large changes in CBF, have little effect of Vf.
Acid-base changes in milk and blood of rats in acidosis and alkalosis
Authors: Yagil R , Lerner Z , Etzion Z , Berlyne GM
Published: December 2017

Lactating white rats (Rattus norvegicus) were subjected to metabolic and respiratory acidosis and metabolic alkalosis. Before and during the various treatments, the acid-base status of heart blood and milk was determined. Acute metabolic acidosis lowered the pH of plasma and milk; Pco(2) and bicarbonate concentrations in plasma were lowered, and in milk Pco(2) was raised and the bicarbonate concentration remained unchanged. Respiratory acidosis and acetazolamide caused a drop in blood pH and in blood and milk bicarbonate concentrations; milk pH remained unchanged, but Pco(2) was raised in both plasma and milk. Acute metabolic alkalosis raised the blood pH and milk Pco(2); plasma Pco(2) and bicarbonate concentrations in blood and milk remained unchanged. The data show that greater changes occur in acid-base parameters of blood than milk when animals are exposed to acidifying and alkalinizing stimuli.
Effects of lactate and glutamine on palmitate metabolism in rat kindey cortex
Authors: Barac-Nieto M
Published: December 2017

Rat renal cortical slices were incubated with [1-(14)C]palmitate bound to 2.5% albumin. The following effects were found: a)1 mM palmitate utilization or oxidation to CO(2) varied according to the concentration of lactate in the media, it increased at 0.8 and 3.2 mM, was unchanged at 8 mM, and decreased at 16 mM. Esterification was stimulated at 3.2 mM lactate. b) Addition of glutamine (0.1 mM) instead of lactate stimulated incomplete and complete oxidation of palmitate (1 mM), whereas high medium glutamine (10 mM) inhibited palmitate (1 mM) utilization, esterification, and oxidation to CO(2) but increased its incomplete oxidation. The low rate of exogenous palmitate oxidation observed in this study and the finding that exogenous palmitate oxidation is only partially inhibited at very high concentrations of exogenous lactate or glutamine are consistent with the view that these exogenous substrates contribute little to the oxidative metabolism of rat renal cortex in vitro, which probably depends on the supply of substrates endogenous to the tissue.
Metabolic activity of brown adipose tissue in T3-treated hamsters
Authors: Rabi T , Cassuto Y
Published: December 2017

Triiodothyronine (T3) treatment induced marked hypertrophy of the brown adipose tissue (BAT), similar to that observed in cold-acclimated animals, although partly due to fat deposition. Similar to cold acclimation, T3 treatment also increased the oxidation of succinate by tissue slices without concomitant increase in isolated mitochondria. It is therefore suggested that thyroid hormones, like cold acclimation, effect conformational changes in the mitochondria, leading to greater expression of the succinic oxidase in the tissue. T3 treatment was not followed by any change in the respiratory activity of tissue slices in the presence of alpha-GP. Likewise, no change was found either in other oxidative activities tested in isolated mitochondria (e.g., NADH and cytochrome oxidases) or in the concentration of the components of the electron transport chain in the mitochondria.
Hormone-stimulated glycogenolysis in isolated goldfish hepatocytes
Authors: Birnbaum MJ , Schultz J , Fain JN
Published: December 2017

Hepatocytes isolated from the liver of the common goldfish Carassius auratus L. with crude bacterial collagenase maintained ATP levels for at least 2 h. Glycogenolysis was maximally activated by 1 X 10(-6) M epinephrine and 5.8 X 10(-9) M glucagon. In liver cells incubated in calcium-free buffer containing 1 mM ethylene glycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid, basal glycogenolysis was enhanced by the addition of 1-4 mM calcium but the elevation of cyclic AMP and glycogenolysis due to epinephrine was unaffected by calcium. The divalent cation ionophore A23187 did not alter basal or hormone-stimulated glycogenolysis. Isoproterenol was approximately as potent as epinephrine but phenylephrine was glycogenolytic only at very high concentrations. l-Propranolol competitively inhibited the increased glycogenolysis due to catecholamines but phentolamine was ineffective as a blocking agent. Isoproterenol and epinephrine stimulated glycogenolysis at lower concentrations than those required to elevate cyclic AMP accumulation. Phenylephrine was without effect on cyclic AMP. Propranolol competitively inhibited both epinephrine- and isoproterenol-stimulated cyclic AMP accumulation, but phentolamine did not block either response. Catecholamine-stimulated glycogenolysis in goldfish liver is apparently a beta-adrenergic effect. However, low concentrations of epinephrine enhance glycogenolysis without affecting total cyclic AMP.