bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Carotid Baroreceptor Stimulation and Renal Denervation on the Medullary Concentration Gradient in Rat Kidneys
Authors: Keeler R.
Published: April 2011

Unilateral stimulation of carotid baroreceptors in unanesthetized rats treated with desoxycorticosterone acetate caused highly significant decreases in solute content and osmolar concentration in the inner renal medulla. There was also a corresponding decrease in urine osmolality and a large increase in the excretion of sodium. In rats subjected to water diuresis, the changes in medullary tissue composition were similar but sodium excretion was very low, indicating that the natriuretic response was not a result of medullary 'washout' per se.Renal denervation had no significant effect on medullary tissue composition and did not prevent the dissipation of the cortico–medullary concentration gradient following carotid baroreceptor stimulation.It is concluded that the changes in inner medullary composition are mediated by a humoral agent.
The Effects of Acute Carbon Monoxide Intoxication on the Cerebral Energy Metabolism of the Rat
Authors: MacMillan V.
Published: April 2011

The cerebral metabolic effects of 30 min exposure to 0.5, 1.0, 1.5, and 2.0% carbon monoxide (CO) and 60 min exposure to 1.0% CO were studied in lightly anesthetized rats by measurement of brain tissue contents of glycolytic and citric acid cycle intermediates, as well as tissue energy phosphates. The results indicate that cerebral energy homeostasis is maintained until advanced levels of CO intoxication (2.0%) are reached. Animals exposed to 2.0% CO developed significant decreases in systemic blood pressure, with attendent decreases in cerebral ATP, increases in ADP and AMP, plus early depletions of tissue citrate and α-oxyglutarate. The similarity of this pattern to that previously documented for various cerebral oligemic states suggests a possible modifying role for altered cerebral perfusion in its production. A correlation between conscious behavior and cerebral energy state was suggested by the observation that unanesthetized animals exposed to 1.0% CO for 30 and 60 min retained consciousness, whereas animals exposed to 2.0% CO for 30 min became unresponsive late on in the exposure. A comparison of CO induced changes in intermediary metabolites, energy phosphates, intracellular pH, and cytoplasmic redox state with those seen in hypoxemia indicate no basic qualitative or quantitative differences in the metabolic response of brain tissue to the two conditions.
Biochemical Criteria for the Evaluation of Drug Efficiency on Adjuvant Arthritis and Nephrotoxic Serum Nephritis in the Rat: Studies with Phenylbutazone, L-Asparaginase, Colchicine, Lysine Acetylsalicylate, and Pyridinol Carbamate
Authors: Sternberg Michel , Peyroux Jacques , Grochulski Andrzej , Engler Robert , Feret Jacques , Moisy Monique , Lagrue Gilbert , Jayle Max-Fernand
Published: April 2011

The levels of serum orosomucoid, haptoglobin, and seromucoid were evaluated as possible quantitative criteria for the estimation of drug efficiency in adjuvant arthritis and nephrotoxic serum nephritis. In adjuvant arthritis, haptoglobin, seromucoid, and chiefly orosomucoid serum levels were generally very sensitive to anti-inflammatory agents such as phenylbutazone and pyridinol carbamate, and to immunosuppressive agents such as L-asparaginase. There was a significant correlation between the serum levels of these glycoproteins and the arthritis scores. In nephrotoxic serum nephritis, seromucoid levels were correlated with the proteinuria of the autologous phase and were found to be a good complementary criterion for the analysis of the efficiency of pyridinol carbamate, colchicine, lysine acetylsalicylate, and L-asparaginase.
A Somatomedin Assay using Normal Rabbit Cartilage in Clinical Studies
Authors: Bala R. Marvin , Hankins Catherine , Smith Glen R.
Published: April 2011

Somatomedin (SM) is a growth hormone (GH) dependent biological growth factor in serum. A SM assay, using mechanically sliced discs from young normal rabbit costal cartilage was developed and evaluated. This assay is as sensitive and precise, while much less laborious and costly, than the hypophysectomized rat cartilage SM assay. The elevated serum SM levels in patients with acromegaly returned to normal in two patients who were cured, and remained elevated in four incompletely treated patients. The low serum SM levels in five GH deficient patients were increased to normal after treatment with human GH. SM levels were normal in 10 patients with normal GH levels and short stature due to various causes. SM levels in serum were very low in patients with chronic renal insufficiency; the mean SM level increased significantly after renal transplantation, however, it increased only minimally after hemodialysis. SM levels were subnormal in 14 patients with severe chronic liver disease. One patient with severe acute liver disease had low serum SM levels which increased after clinical recovery. These results further suggest that the liver produces SM, while the relationship of the kidney and SM is not clear.
Effect of Pyrazole on Ethanol Metabolism in Ethanol-Tolerant Rats
Authors: Kalant H. , Khanna J. M. , Endrenyi L.
Published: April 2011

Adult male rats were pair-fed liquid diets, providing 37% of calories as ethanol or sucrose, for 1 month. Alcohol dehydrogenase (ADH) activity in the cytosol fractions of liver homogenates from the two groups did not differ with respect to total activity per 100 g body weight, Km for ethanol, or Ki for pyrazole. Other rats, fed in the same way, were fasted for 18–24 h, then given an intraperitoneal injection of pyrazole followed 1 h later by an injection of ethanol, 3 g/kg. Blood alcohol curves showed an unexplained slower rise to maximum level in the chronic alcohol group. Both groups showed a period of several hours in which the blood alcohol stayed at the respective maximum concentrations, which were higher in the control group. After 7–8 h the alcohol concentration began to fall in both groups, significantly more rapidly in the chronic alcohol-fed animals. A kinetic analysis shows that the results are adequately explained by the known effects of pyrazole on the ADH–mitochondrial system. The results are interpreted as evidence against the function of any microsomal ethanol oxidizing system in vivo.
Studies on Z-Fraction. I. Isolation and Partial Characterization of Low Molecular Weight Ligand-Binding Protein from Rat Hepatic Cytosol
Authors: Warner Margaret , Neims Allen H.
Published: April 2011

The Z-fraction has been defined operationally as a ligand-binding (bilirubin sulfobromophthalein) portion of rat hepatic cytosol that elutes in the molecular weight region of 104 daltons after gel filtration. Polyacrylamide gel electrophoreses under different conditions, as well as binding stoichiometry, confirm the anticipated heterogeneity of the Z-fraction. Three factors have contributed to the subsequent resolution of the Z-fraction and partial characterization of that protein within the fraction with ligand-binding properties (Z-protein): (1) the use of hexachlorophene as ligand; (2) the inclusion of glycerol, 20%, during isolation to prevent aggregation and loss of binding-activity; and (3) the development of a charcoal binding assay. Upon ion exchange chromatography, the Z-fraction resolves into a group of distinct protein components and an unidentified material with a high 260/280 nm absorbancy ratio. The one protein component with binding capacity exhibits homogeneity on polyacrylamide gel electrophoresis (11% gel, Ann. N.Y. Acad. Sci. 121, 404–427, 1964; and 15% gel with SDS). With use of the charcoal method, apparent dissociation constants for the interaction between Z-protein and hexachlorophene, bilirubin and L-thyroxine, were found to be 20, 50, and 350 μM, respectively. The Scatchard plot generated upon extrapolation an n value of 1.0 with assumption of a molecular weight for Z-protein of 104 daltons.
Utilization of Calcium Pools During Pharmaco or Electromechanical Coupling in Smooth Muscle
Authors: Bose D. , Innes I. R.
Published: April 2011

Isometric contraction of cat spleen capsule due to noradrenaline had a fast and a slow phase. These phases were due to a tightly and a loosely bound (or extracellular) pool of calcium, respectively. Depolarization due to high potassium caused mainly a reduction of the slow phase. In sodium-loaded spleen strips recovering from potassium deprivation, the sodium pump is electrogenic and the muscle cells are probably hyperpolarized. In this situation also the slow phase of noradrenaline response is reduced. It is concluded that both depolarization and hyper-polarization affect the utilization of loosely bound calcium and that tightly bound calcium may be released during 'pharmacomechanical coupling' in splenic smooth muscle.
Adrenocorticotropin Secretion Rates Following Histamine Injection in Adult and Newborn Dogs
Authors: Cowan John S.
Published: April 2011

The metabolic clearance rate (MCR) for ACTH in adult dogs was previously shown not to vary significantly with varying plasma ACTH concentrations or among dogs. This is confirmed here for pups aged 1–7 days. Hence, ACTH secretion rates can be continuously calculated from a continuous function of plasma ACTH vs. time. Each of seven adult dogs under Nembutal anesthesia received two or three intravenous (i.v.) injections of histamine with increasing doses. The first injections in each dog ranged from 7 to 50 μg/kg, while the last dose was 62–108 μg/kg. A total of 16 injections were given. Twelve pups (two litters of six) aged 1–7 days each received one injection of histamine of 76–116 μg/kg (i.v.). ACTH concentrations in plasma were determined by an adrenal cell suspension bioassay before, and 6 times after each injection. Nine pups also underwent determinations of their MCR for ACTH, with plateau concentrations determined at three times during an ACTH infusion. Continuous curves of ACTH secretion rates were calculated for all 28 histamine injections, showing that all except the 1-day-old pups secrete considerable ACTH when stressed. Compared to adult dogs, the pups show lower secretion rate peaks and shorter periods of rapid secretion. Changes in plasma glucocorticoids also suggest that the adrenal cortex of newborn dogs can respond to ACTH by increased glucocorticoid secretion.
Stress Response Patterns of Plasma Corticosterone, Prolactin, and Growth Hormone in the Rat, Following Handling or Exposure to Novel Environment
Authors: Seggie Jo A. , Brown Gregory M.
Published: April 2011

Corticosterone, prolactin, and growth hormone responses to 5 s of handling or 3 min of novel environment were compared in rats at crest and trough of the diurnal adrenal rhythm 0,5, 15, 30, and 60 min after stimulation. All hormones responded to stimulation, corticosterone and prolactin with a dramatic rise, and growth hormone with a precipitous fall. Resting corticosterone levels evidenced the expected diurnal variation, and prolactin but not growth hormone also showed a baseline diurnal variation of small magnitude at the times studied. Growth hormone response characteristics were unaffected by time of day or type of stimulation. Both corticosterone and prolactin response profiles differed at both times of day and following both types of stimulation. Corticosterone and prolactin levels were highly correlated and each was negatively correlated with growth hormone levels. This study confirms that hormone responses to stress are complex and depend not only on the stimulus but the context of stimulation.
In Vitro Production of Prostaglandins by Isolated Aorta Strips of Normotensive and Hypertensive Rats
Authors: Rioux F. , Regoli D.
Published: April 2011

When suspended in oxygenated Krebs solution at 37 °C, strips derived from thoracic aortae of spontaneously hypertensive rats maintain their initial intrinsic tone and release prostaglandin-like material in the suspending medium, while similar preparations from normal Wistar rats relax progressively and produce significantly smaller amounts of prostaglandins.Indomethacin, a potent antagonist of prostaglandin synthesis, has two major effects: it favors the relaxation of both strips of hypertensive rats and of normal rats; and it inhibits the accumulation of prostaglandin-like material in the suspending medium, as evaluated with a specific and sensitive biological assay (rat stomach strip or chick rectum).Carotid and femoral arteries taken from the same animals show similar differences as the aorta strips, with regard to the production of prostaglandin-like material. The generation of prostaglandin is markedly decreased by the absence of O2, while it is unaffected by the absence of the extracellular Ca2+. It is proposed that the absence of relaxation of aorta strips taken from hypertensive, compared to normal rats, is due to increased intramural synthesis and release of prostaglandins.
Polypeptide Hormone Receptors: Characteristics and Applications
Authors: Posner Barry I.
Published: April 2011

Major developments in the area of polypeptide hormone receptors have been reviewed. Receptors are high affinity, high specificity binding sites which appear to be located largely. Plot entirely, on the plasma membrane of cells. Receptors are proteins intimately associated with and influenced by lipids. Receptor sites and degrading sites appear to be readily distinguishable entities. The binding of hormone to receptor is distinct and has been dissociated from subsequent steps leading to hormonal response. There is no direct relationship between receptor occupancy and the magnitude of target tissue response to hormone. So called 'spare' receptors can be viewed thermodynamically as enhancing target tissue sensitivity to hormone. The binding of hormone to receptor appears to be a point at which regulation of tissue sensitivity can be influenced either through altering the affinity for hormone or the number of receptors. One factor apparently involved in the regulation of receptor levels is the hormone itself. Receptors have been used to develop assay procedures which have significantly complemented the bioassay and radioimmunoassay. Finally, the measurement of receptor levels in disease has provided new insights into pathophysiology.
Time Course of Onset and Decay of Humoral Natriuretic Activity in the Rat
Authors: Pearce James W. , Veress Anthony T. , Sonnenberg Harald
Published: April 2011

The natriuretic activity shown in earlier cross-circulation experiments to develop in the blood of rats undergoing sustained vascular expansion has been further characterized. Following whole blood infusion and urine reinfusion of the donor rat, a cross-circulated isovolaemic partner exhibits a natriuresis of gradual onset, requiring 60–80 min to reach a peak (0.04–3.24 μequiv./min per gram kidney weight). The gradual feature of recipient natriuresis was unchanged by infusing the donor rat 1 h prior to cross-circulation. Once developed, the recipient natriuresis was sustained when fluid depletion by the renal response was prevented, but was reversible with a half-life of about 30 min on interruption of the cross-circulation; reconnection of cross-circulation promptly restored recipient natriuresis. No significant natriuresis (0.04–0.16 μequiv./min per gram kidney weight) occurred in the recipients if the donors in comparable cross-circulations were not infused. These findings confirm that a natriuretic activity develops in the blood as a consequence of vascular expansion, and reveal that the activity has a slowly developing and reversible action on the renal natriuretic mechanism.
The Effect of Synthetic TRH on Transmembrane Potential and Membrane Resistance of Adenohypophysial Cells
Authors: York D. H. , Baker F. L. , Kraicer J.
Published: April 2011

An evaluation of the stimulus–secretion coupling hypothesis was undertaken by the intracarotid administration of synthetic thyroid releasing hormone (TRH) while recording the transmembrane potential (Vm) and membrane resistance (Rm) of cells in the adenohypophysis of propylthiouracil pretreated male rats. Of those 75 cells which responded to TRH administration with a change in membrane parameters, the most predominant effect was a depolarization with a decrease in Rm observed in 21 cells, or no change in Vm but an increase in Rm observed in 23 cells. These results are discussed in terms of the thyrotrophs and other cells comprising the adenohypophysis.
Effect of Drugs on Effective Vascular Compliance in Acute Heart Failure
Authors: Larochelle Pierre , Ogilvie Richard I.
Published: April 2011

Effective vascular compliance determined by the ΔV/ΔP relationship was measured repeatedly in anesthetized open-chest dogs without circulatory arrest utilizing a closed circuit venous bypass system with a constant cardiac output. Production of acute heart failure by gradual aortic constriction was associated with a significant decrease in total effective vascular compliance. The effect of loading and 20-min maintenance doses of different drugs on vascular compliance of animals in acute heart failure was studied. Phenoxybenzamine (total dose 2 mg/kg) produced a rapid and sustained increase in effective vascular compliance and theophylline (12 mg/kg) produced an increase which was more gradual in development than with phenoxybenzamine. Morphine (1 mg/kg) produced a rapid but transient increase in compliance. In contrast, ethacrynic acid (100 mg) or nitroglycerin (0.6 or 1.2 mg) did not alter vascular compliance significantly. These agents differ markedly in the magnitude and time-course of effect on effective vascular compliance.
Alterations of Hepatic Microsomal Drug Metabolism by Glucagon
Authors: Aranda Jacob V. , Renton Kenneth W.
Published: April 2011

The effect of glucagon on the components of the hepatic microsomal electron transport chain (NADPH oxidase, NADPH cytochrome c reductase (EC 1.6.2.4), cytochrome P-450, and NADPH cytochrome P-450 reductase), and on two representative oxidative pathways (aminopyrine N-demethylation, a type I substrate oxidation; and aniline p-hydroxylation, a type II substrate oxidation) was determined. Microsomes from rats pretreated with glucagon (300 μg/kg per day for 3 days) showed a significant decrease in NADPH oxidation and in aminopyrine N-demethylation with a prolonged hexobarbital sleeping time, and a significant increase in aniline p-hydroxylation. Microsomes from rats pretreated with a lower dose of glucagon (30 μg/kg per day for 3 days) showed a significant decrease in the microsomal N-demethylation of aminopyrine. Glucagon had no effect when added in vitro to microsomes, suggesting that the in vivo effects of glucagon are mediated indirectly in the intact animal.
Effect of Dietary Dieldrin on the Liver and Drug Metabolism in the Female Swiss-Vancouver Mouse
Authors: Virgo Bruce B. , Bellward Gail D.
Published: April 2011

Female Swiss-Vancouver (SWV) mice, 13 weeks old, were exposed to dietary dieldrin for up to 10 weeks. Liver mass, hepatic microsomal protein and cytochrome P-450, and the in vitro metabolism of imipramine were determined at intervals. Dieldrin (5, 10, 15, and 20 ppm) caused hepatomegaly and increases in P-450; both effects were dose-related. All doses increased microsomal protein by about 30% (control value was 15.3 mg of protein per gram of liver). Maximal responses were attained by 2 weeks of exposure and maintained thereafter. Plateau liver masses at these respective doses were 111, 119, 133, and 162% of the control value (57.9 mg of liver per gram of body weight). Cytochrome P-450 was, respectively, 124, 142, 185, and 173% of the control value (0.93 nmol per milligram of microsomal protein). These changes decreased pentobarbital sleeping times by an average of 540% in animals fed 5, 15, or 25 ppm for 4 weeks. Similarly, the latency to the onset of anesthesia was increased by 26% at all doses. The N-oxidation and aryl-hydroxylation of imipramine increased with age, while demethylation decreased. The hydroxylation and demethylation of imipramine was increased after 2 and 4 weeks, respectively, of exposure to 20 ppm; N-oxidation was decreased. Longer exposure to lower doses caused similar changes. The changes in liver parameters and imipramine metabolism induced by 4 weeks exposure to 20 ppm were absent 6 weeks after exposure ceased.
The Effect of Lobar Obstruction on Regional Perfusion in the Intact Dog
Authors: Zidulka A. , Desmeules M. , Harvey J. , Anthonisen N. R.
Published: April 2011

The effect of acute obstruction of the right lower lobes (RLL) on the relative perfusion of different lung regions was studied using Xenon-133 in anesthetized artificially ventilated supine dogs. When the RLL were obstructed at functional residual capacity (FRC) and the rest of the lung was inflated to a transpulmonary pressure of 10 or 20 cm H2O (1 cm H2O = 94.1 N/m2), relative perfusion increased within 10 s to the obstructed lobes by 59 and 92%, respectively. The increase was less marked but still present (17 and 42%, respectively) when obstruction was maintained for 15 min, at a time when arterial hypoxemia had occurred. Hence, there was increased perfusion to an obstructed hypoxic region. The perfusion distribution correlated with the difference in alveolar pressure between the obstructed lobes and the unobstructed lobes such that relative perfusion was always increased to the low alveolar pressure region.
Experimental Cystinuria: the Cycloleucine Model. I. Amino Acid Interactions in Renal and Intestinal Epithelia
Authors: Craan André G. , Bergeron Michel
Published: April 2011

The injection of cycloleucine (1-aminocyclopentanecarboxylic acid (ACPC)) into rats produces a hyperexcretion of dibasic amino acids and cystine, an aberration resembling cystinuria. This may constitute a model of experimental cystinuria, and the transport of amino acids involved in this disease was studied with the techniques of everted intestinal sacs (in vitro) and microinjections into renal tubules (in vivo). In everted sacs from normal rats, there was a decrease in transfer and in accumulation of L-cystine (0.03 mM), L-lysine (0.065 mM) and L-valine (0.065 mM) when ACPC was on the mucosal (luminal) side. Dibasic amino acids such as L-ariginine and L-lysine caused a similar inhibition of the transport of L-cystine. However, when ACPC was on the serosal (antiluminal) side, a lesser effect was noted while arginine and lysine had no effect. Intestinal sacs from treated rats (ACPC, 300 mg/kg × 3 days) transferred and accumulated as much L-cystine as those from control rats. The interaction between cycloleucine and L-cystine was competitive at the luminal and non-competitive at the antiluminal side of the intestine. Cycloleucine inhibited L-lysine transport in a non-competitive fashion at either side of the intestine. L-Lysine also interacted in a non-competitive fashion with L-cystine transport at the luminal membrane. In proximal convoluted tubules, the presence of L-arginine or ACPC caused a decrease in the transport of L-cystine and L-lysine. L-Valine exerted no effect. Furthermore, L-lysine and ACPC did not impair the reabsorption of L-valine significantly.These results suggest a functional heterogeneity between luminal and antiluminal membranes of renal and intestinal epithelia and the existence, at both membranes, of different transport sites for cystine and dibasic amino acids.
Dopamine β-Hydroxylase in Rat Serum and Lymph: Changes with Age and Effect of Cold Exposure
Authors: Behrens W. A. , Depocas Florent
Published: April 2011

The pH optimum for rat serum dopamine β-hydroxylase (DBH) (3,4-dihydroxyphenylethyl-amine, ascorbate:oxygen oxidoreductase (β-hydroxylating)(EC 1.14.17.1) was 4.0 in acetate buffer; other requirements were as reported by others. DBH activity in serum of 20-day-old fetuses is slightly higher than in that of their mothers. Levels of the enzyme in blood a few hours after birth are almost five times greater than in the adult, remain high during the suckling period, then drop rapidly during the 4th week after birth to about three times the adult level, which is then slowly reached over the next few weeks. These fluctuations in serum DBH activity coincide with the period of intense development and maturation of the sympathetic nervous system.There was no significant effect of cold exposure on blood DBH activity when newborn, suckling, weanling or adult warm- and cold-acclimated rats were exposed to cold. Similarly, exposure to cold that elicited two- to threefold increases in O2 consumption failed to increase DBH activity in thoracic duct lymph. Therefore serum and lymph DBH activities are not sensitive indices of sympathetic secretory activity in the intact rat.
Effect of Metiamide on Acid Secretion from Isolated Kitten Fundic Mucosa
Authors: Tepperman B. L. , Schofield B. , Tepperman F. S.
Published: April 2011

Isolated kitten fundic mucosa demonstrates low rates of spontaneous acid secretion in vitro when bathed in Krebs–Henseleit solution, and responds consistently to histamine, pentagastrin, and acetylcholine placed in the bath. High rates of spontaneous secretion or secretion in response to histamine and pentagastrin were significantly inhibited by addition of metiamide (5 × 10−3 M); but mucosa stimulated by constant addition of acetylcholine chloride (10−4 M) was not inhibited by metiamide at the same concentration.
Failure of Vasopressin to Prevent the Natriuretic and Diuretic Response to Unilateral Stimulation of Carotid Baroreceptors
Authors: Keeler R.
Published: April 2011

Unanesthetized rats treated with deoxycorticosterone acetate were continuously infused with a maximally effective dose of vasopressin (50 μU/min per 100 g). After a control period of 2 h the animals were subjected to a 2 h period of unilateral stimulation of the carotid baroreceptors. There was a large natriuretic response accompanied by diuresis and a fall in urine osmolality. It was concluded that neither the natriuretic nor the diuretic response could be explained by inhibition of vasopressin secretion. Analysis of kidney tissue indicated that the diuresis was associated with partial dissipation of the inner medullary concentration gradient.
Evidence for Ca2+-activated K+ Conductance in Cat Spinal Motoneurons from Intracellular EGTA Injections
Authors: Krnjević K. , Puil E. , Werman R.
Published: April 2011

Ethylene glycol bis-(β-aminoelhyl ether)-N,N′-tetraacetic acid, injected by iontophoresis from triple-barrelled intracellular micropipettes, consistently raised the membrane resistance and depressed the post-spike after hyperpolarization (AHP), but did not slow the falling phase of the action potential. [Ca2+]i-activated K+ channels appear to play a significant role in the genesis of the AHP and in the control of the resting potential, but not in the repolarization phase of the action potential.
Sensitization of effector responses by modification of agonist disposition mechanisms
Authors: Kalsner Stanley
Published: April 2011

Much confusion arises in the field of agonist–effector supersensitivity phenomena due to the often encountered lack of discrimination between agonist disposition mechanisms functioning, in the system under study, as access barriers and as terminating mechanisms. Access barriers limit agonist approach to the receptor region and terminating mechanisms serve to remove agonist from the site of action. The assumption of a quantitative identity in these two functions is not often warranted and the effects inhibition of these processes have on the magnitude of effector responses and on their duration can differ strikingly, both qualitatively and quantitatively.
Effects of α-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs
Authors: Chou Shyan-Yih , Liebman Paul H. , Ferder Leon F. , Levin Daniel L. , Cacciaguida Roy J. , Porush Jerome G.
Published: April 2011

The α-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 μg kg−1 min−1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic thoracic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265 ± 56 (SEM) to 370 ± 65 μequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distal sodium load did not change significantly. In normal dogs, distal tubular sodium reabsorption decreased significantly from 73.4 ± 2.8% to 63.1 ± 4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of α-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased α-adrenergic activity does not play a significant role in the sodium retention of these animals.
Effects of catecholamines injected into the septal area of the rat brain on natriuresis, kaliuresis and diuresis
Authors: Camargo Luis A. Arruda , Saad Wilson A. , Netto Cincinato R. Silva , Gentil Cleber G. , Antunes-Rodrigues José , Covian Miguel R.
Published: April 2011

Urinary output of Na+ and K+, and volume of urine have been studied in conscious, unrestrained, water-loaded male rats following the intraseptal injection of catecholamines. Natriuresis and kaliuresis increased after injecting noradrenaline (NA), the intensity being dose related. The dose–response curve suggests that a monomolecular interaction takes place between NA and pharmacological receptors present in the septal area. No change was observed in diuresis. Systematic mapping of the septal area yielded about the same results for all sites except a zone located in the lateral nucleus that was more sensitive. An alpha blocker (dibenamine), injected intraseptally before NA, showed an inhibitory effect while a beta blocker (propranolol) yielded a potentiation effect. These same effects of the blocking agents were observed when adrenaline was used instead of NA. Lidocaine, which inhibits the re-uptake of NA, showed an enhancement of the natriuretic and kaliuretic effect of NA, and the same effect was observed when the enzymatic destruction of NA was prevented by nialamide, an inhibitor of monoaminoxidase. Dopamine showed a natriuretic effect, but no effect was observed on K+ and urine output. Serotonin had no action on natriuresis, kaliuresis and diuresis.
Application of a multiwire proportional chamber to the detection of axoplasmic transport
Authors: Snyder R. E. , Reynolds R. A. , Smith R. S. , Kendal W. S.
Published: April 2011

A new technique for the detection of the axoplasmic transport of β-radioactively labelled materials is described wherein a multiwire proportional chamber is used to measure the distribution of activity along peripheral nerve fibers which are maintained in vitro. The operating principles of the chamber are described and basic construction parameters given. Potential radiolabels are discussed.Two types of studies were performed at room temperature in vitro using sciatic nerves of the amphibian Xenopus laevis: static and dynamic. In the static study the nerve ganglion was incubated for a suitable period of time in either L-[U-14C]leucine or L-[35S]methionine after which the ganglion was removed and the activity in the remaining nerve assayed with the chamber. In the dynamic study the nerve activity was assayed by the chamber while incubation proceeded so that a dynamic picture of transport could be observed. Using the second approach, transport rates were observed which are in agreement with others which have been reported in the literature.Some advantages and limitations of the technique are discussed.
A compartmental model for bilirubin kinetics in isolated perfused rat liver
Authors: Anwer M. Sawkat , Gronwall Ronald
Published: April 2011

Bilirubin kinetics were studied in an isolated, perfused rat liver system using unconjugated [14C]bilirubin (UC[14C]B) and Δ-amino[4-14C]levulinic acid (A[14C]LA) to derive a suitable compartmental model. Plasma disappearance of UC[14C]B, plasma appearance of conjugated [14C]bilirubin (C[14C]B) and biliary excretion of C[14C]B were followed for 90–120 min following injection of UC[14C]B. Hepatic content of labeled bilirubin 12 min after the injection of UC[14C]B was determined directly in five separate perfusion experiments. UCB was found to reflux back to plasma from liver in two experiments using A[14C]LA. Bilirubin binding to red blood cells (6–8% of the perfusate level) and the components of the perfusion apparatus (4–6% of perfusate level) was estimated by performing a control experiment without the liver. A six compartment model was necessary and adequate to explain the experimental data and current knowledge of bilirubin metabolism: (1) UCB bound to red blood cells and the perfusion apparatus, (2) plasma UCB, (3) liver UCB, (4) liver CB, (5) plasma CB, and (6) bile CB. The proposed model could serve as a reference point for studies of bilirubin kinetics in whole animals for normal and abnormal states.
The effects of selenium on the metabolism of methionine in sheep
Authors: Hidiroglou M. , Zarkadas C. G.
Published: April 2011

Two groups of sheep fed a diet of hay known to produce nutritional muscular dystrophy, one group of which received selenium supplementation, were used to study the effects of selenium on the metabolism of administered L-[35S](methionine by rumen microflora. Rumen bacterial proteins of the Se supplemented sheep contained significantly higher levels of radiosulfur than the bacterial protein of the non-supplemented sheep. Of the L-[35S]methionine present in the rumen liquor samples from Se-supplemented sheep 2 h after administration, 13.3% of the amino acid, which was measured as methionine sulfone, was found in the microbial proteins. A large proportion of the administered labeled methionine was resynthesized as cyst(e)ine which may account in part for that determined as cysteic acid in rumen bacterial and plasma proteins. The observed low levels of radiosulfur found in rumen microflora from selenium deficient wethers, indicates that the presence of selenium profoundly affects the rate of methionine metabolism and the distribution of methionine in rumen bacterial and protozoal proteins.In another experiment, the effect of selenium on the metabolism of L-[Me-3H]methionine was studied. The selenium status of the sheep had no significant effect (P > 0.05) on the distribution of 35S radioactivity in the blood plasma and tissues.
Epinephrine-induced hepatic potassium movements before and after adrenergic blockade
Authors: Guthrie Stephen D. , Murphy Quillian R.
Published: April 2011

The epinephrine-induced loss and subsequent uptake of K+ by the liver was studied by measuring hepatic arterio–venous K+ differences and splanchnic blood flows in anesthetized dogs with chronically implanted portal vein catheters and celiac and superior mesenteric artery flow probes. When epinephrine was administered intraportally, neither α- nor β-adrenergic blockade, singly or in combination, had significant effects upon the hyper-kalemic or the hypokalemic phases in either hepatic venous or systemic arterial blood. It was concluded that the movements of K+ into and out of the liver caused by epinephrine are not mediated by the classical adrenergic receptors as defined by inhibition by specific blocking agents.
Blockade of histamine-induced contractions of guinea pig ileum by β-haloalkylamines
Authors: Kenakin T. P. , Cook D. A.
Published: April 2011

In the longitudinal muscle strip of guinea pig ileum phenoxybenzamine (POB) produces a maximum parallel shift of 0.7 log units in the dose–response curve to histamine. In the presence of sodium thiosulfate in the wash fluid the parallel shift with retention of maximum response increases to about 2 log units, and a similar value is obtained for N-ethyl-N-(2-bromoethyl)-1′-naphthylamine. The agent N-ethyl-N-(2-chloroethyl)benzylamine produces a significantly smaller shift of dose–response curve of 1.53 log units before the maximum response becomes depressed. The receptor-specific depression of maximum response produced by higher doses of POB is reversed by sodium thiosulfate and by bovine serum albumin, while the parallel shift in dose–response curve is unaffected by both treatments. These findings may be explained by a hypothesis involving interaction of 2-haloalkylamines at two sites.
Blockade of LH–RH induced ovulation in immature rats by LH–RH antiserum
Authors: Hirsch M. A. , Givner M. L.
Published: April 2011

An in vivo method for the determination of biological potency of luteinizing hormone -releasing hormone (LH–RH) antiserum is described. The procedure involves antiserum blockade of LH–RH induced ovulation in immature rats primed with pregnant mare's serum. A modified method for the induction of LH–RH antibodies in rabbits is also detailed.
Cyclic nucleotides in spinal cells
Authors: Krnjevic K. , Meter W. G. Van
Published: April 2011

The most striking effects of intracellular injections of adenosine 3′5′-cyclic monophosphate (cAMP) into spinal mononeurons in cats are a speeding-up of the action potential, both its rising and falling phase, and a potentiation of the after-hyperpolarization; the latter probably indicates a marked enhancement of Ca2+ influx. In this respect, cAMP and guanosine 3′5′-cyclic monophosphate (cGMP) have similar actions, though cAMP appears to be more potent. It is suggested that through this mechanism, cyclic nucleotides may play an important role in synaptic facilitation. Changes in resting membrane potential and resistance are less conspicuous or predictable. By contrast, both agents, when injected into unresponsive cells, presumed to be neuroglia, regularly cause a drop in membrane resistance; this is associated with hyperpolarization and therefore likely to reflect an increase in membrane K+ conductance.
Lack of effect of alcohol on small intestinal binding of the vitamin B12 – intrinsic factor complex
Authors: Findlay J. , Sellers E. , Forstner G.
Published: April 2011

Absorption of 57Co-labelled vitamin B12 – intrinsic factor (IF) complex and its binding to mucosal precipitate and brush border fractions of rat small intestine was studied in rats pair-fed with a liquid diet containing ethanol 5 g/100 ml, 35% of calories, or isocalorically substituted sucrose. IF was obtained from rats fasted for 18 h, and for each experiment the amount of vitamin B12 added was the minimum required to achieve maximum binding to IF. Rats fed alcohol exhibited hepatic steatosis, proliferation of smooth endoplasmic reticulum, and disordered mitochondria after 6 weeks on the diet, and absorption of vitamin B12, fed with IF by stomach tube, was reduced significantly. In contrast, binding of 57Co-labelled vitamin B12 – IF complex to mucosal precipitate and brush border fractions was never less than that of fractions from control rats at 4, 8 and 12 weeks on the alcohol diet. Furthermore, binding to the brush border was significantly greater in alcohol-fed rats at 12 weeks whether expressed per unit of β-naphthylamidase (EC 3.4.1.1) activity or per milligram of protein. Total mucosal sucrase (EC 5.2.1.26) and β-naphthylamidase were unchanged or slightly increased (β-naphthylamidase at 12 weeks) on the alcohol-containing diet indicating that total brush border membrane was not reduced. Total brush border binding activity was the same in alcohol-fed and control rats at each time period. These results indicate that malabsorption of vitamin B12 in rats fed alcohol cannot be due to decreased binding of the vitamin B12 – IF complex by brush border membrane receptors, or secondary to a net decrease in membrane receptors.
Effects of reserpine on tissue calcium and contractility of rat and rabbit aorta
Authors: DeFelice A. , Joiner P.
Published: April 2011

Possible effects of reserpine on disposition and availability of tissue calcium stores for excitation–contraction coupling in isolated rat and rabbit aortae were examined. Control 40Ca uptake, 45Ca washout, and contraction in Ca2+-free medium (Ca2+-free PSS) indicate species differences in binding or disposition, apparent functional importance, and differential use of tissue calcium by adrenaline (Epi) and high K+ Rat aortae, normally refractory to Epi or high K+ after 7 min in Ca2+-free PSS, can gain labile calcium after brief exposure to Ca2+-rich PSS which supports short-lived responses to high K+ in Ca2+-free PSS. Rabbit aortae contain calcium stores which may sustain either Epi or high-K+ responses as well as more tightly held (or sequestered) stores released by Epi for contraction. After reserpine, decreased 45Ca uptake in a kinetically defined "fast" compartment likely to include membrane calcium could enhance availability of bound tissue as well as free Ca2+ in both species. Enhanced Epi response in Ca2+-free PSS is evidence of the former. Results suggest that increased availability of bound and possibly free calcium contribute to reserpine-induced supersensitivity, but supporting evidence will be required from tissue behavior after less rigorous treatment.
A dual mechanism for the anticonvulsant action of aminooxyacetic acid
Authors: Wood J. D. , Peesker S. J.
Published: April 2011

The intramuscular injection of aminooxyacetic acid (AOAA) into mice elevated the concentration of γ-aminobutyric acid (GABA) in the brain, inhibited glutamic acid decarboxylase activity and delayed the onset of isonicotinic acid hydrazide induced seizures. Analyses of these results and of those obtained previously by the authors and other workers indicated that the anticonvulsant action of AOAA involved two mechanisms. One, involving GABA metabolism, was most effective 6 h after AOAA administration, and the other, not involving GABA, was maximally effective 1.5 h after AOAA injection and was completely absent after 6 h. Depending on the convulsant agent under study, the mechanism of the anticonvulsant action of AOAA was purely of the GABA type, purely of the non-GABA type or a combination of both types.
Characterization of natriuretic activity from posterior pituitary lobes
Authors: Quamme Gary A. , Hwang Peter , Friesen Henry G. , Dirks John H.
Published: April 2011

Previous studies have indicated the existence of natriuretic factors of hormonal nature with the posterior pituitary gland as a possible site of origin. It was in this light that a series of experiments was designed to examine the posterior pituitary for such factors. Acetic acid extracts of porcine and bovine posterior pituitary lobe tissue were subjected to gel filtration on Sephadex G-25. Several fractions in the molecular size range of 1000 were obtained which possessed potent natriuretic activity as assayed in rats. The activity of these fractions maximally increased sodium excretion to 6–8 μequiv./min, a 10- to 40-fold increase above control, when administered intraperitoneally to hydropenic, conscious rats. However, oxytocin and vasopressin, present in the posterior pituitary are natriuretic. These hormones were measured by radioimmunoassay, and invariably only those fractions which contained vasopressin and (or) oxytocin possessed natriuretic activity. Moreover, the extent of the natriuresis could be accounted for by the vasopressin and (or) oxytocin content of the test fractions. The natriuretic property of this material was abolished by treatment with thioglycollate. Further purification of natriuretic fractions by ion exchange resins, thin-layer chromatography and isoelectric focusing failed to resolve natriuretic activity from vasopressin and oxytocin. Similar results were observed following analysis of fractions isolated by gel filtration of acetic acid extracts of ventral hypothalamus tissue. The natriuretic fractions isolated from hypothalamic tissue were indistinguishable from oxytocin and vasopressin. These experiments suggest that the natriuretic activity in neurohypophyseal extracts can be attributed to oxytocin and vasopressin.
The thyroidal response to chronic goitrogenic stimulation and the persistence of effects of early goitrogenic stimulation
Authors: Leung Peter , March B. E.
Published: April 2011

The effects of overstimulation of the thyroid gland induced by the feeding of rapeseed meal or thiouracil during the growing period persisted for as long as 75 weeks after withdrawal of the source of goitrogen from the diet. Thyroid weight, thyroid iodine content and radioiodine uptake were all increased in birds which had received goitrogen during the growing period. Follicle diameter was greater and the height of epithelial cells was lower than in control birds. The thyroid changes in these birds were deduced to be compensatory because production characteristics were normal and distribution of a dose of radioiodine into thyronines (T3 + T4) was similar in the birds which had received goitrogen during the growing period and in the control birds. Birds which were being fed rapeseed meal at the time the thyroid glands were examined showed effects which varied in magnitude according to the length of time over which rapeseed meal had been fed. Thyroid weight, follicle diameter, amount of epithelial tissue present and the total amount of iodine in the thyroid glands increased, whereas coupling efficiency (radioiodine-labelled T3 + T4)/(monoiodotyrosine/diiodotyrosine) declined with time.
Effects of acidity, cations and alcoholic fractionation on absorption of heparin from gastrointestinal tract
Authors: Sue T. K. , Jaques L. B. , Yuen E.
Published: April 2011

Heparin was introduced into the stomach or duodenum of mice separately in doses of ca, 250 mg/kg. A slight anticoagulant effect in the systemic circulation was detected in whole blood clotting times and factor X inhibition. In contrast to most drugs, more heparin was absorbed from the stomach than from the intestine. Suppressing ionization of heparin by simultaneous administration of acid resulted in improved absorption of heparin from the small intestine. Heparin was separated with ethanol into five molecular weight fractions: I, 17 000; II, 13 200; III, 10 800, IV, 8 700; and V, 6 700. Each was introduced into the duodenum of mice with citric acid. The maximum hypocoagulability was produced with fraction IV. When administered in distilled water instead of in citric acid, this heparin fraction did not produce an anticoagulant effect. These studies demonstrated that improvement of heparin absorption from the gastrointestinal tract can be obtained by the combination of suppressing ionization and selecting molecular size.
The action of diazoxide analogs on aortic reactivity in normotensive and spontaneously hypertensive rats
Authors: Chona S. , Triggle D. J.
Published: April 2011

Diazoxide and four related 1,2,4-benzothiadiazines reduced the maximum responses to noradrenaline (NA) and KCl in aortic rings from normotensive and spontaneously hypertensive rats (SHR). These agents were more active against NA than against KCl responses, and more effective against either NA or KCl responses in aortae from hypertensive animals. Further studies with V (3-cyclopentenyl-6,7-dichloro-1,2,4-benzothiadiazine-1,1-dioxide), the most active member of the series, showed it to be significantly more effective against NA responses; when calcium was added to calcium-free solutions containing either NA or KCl, V was more effective in inhibiting either response in SHR aortae and was about 100 times more effective in inhibiting the calcium–NA responses. These data are consistent with previous findings that vascular smooth muscle from normotensive and SHR differs in sensitivity to diazoxide. However, the site(s) at which this difference is exhibited remains to be elucidated.