bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of the sympathetic innervation of rat interscapular brown adipose tissue via intercostal nerves
Authors: Foster David O. , Depocas Florent , Zuker Michael
Published: April 2011

The interscapular brown adipose tissue (IBAT) of cold-acclimated white rats was partially denervated by cutting in most cases four of the five intercostal nerves going to one of its two bilaterally located, lobular pads. After 24 h the functional ability and the degree of residual sympathetic innervation of the pads and of their lobes were assessed (in separate groups of rats): the former by measuring tissue blood flow as an index of sympathetically mediated calorigenesis during exposure of the animals to −6 °C, the latter by measuring the residual noradrenaline (NA) content of the tissue. Only the four anterior intercostal nerves contributed significantly to the sympathetic innervation of IBAT pads. On average their contributions were unequal, but there was considerable variation between rats in the relative contribution of each nerve. The measurements on lobes of the pads indicated that the sympathetic fibers supplied by a given intercostal nerve were not distributed uniformly throughout the pad. For example, measurements of NA indicated that on average the fibers of the fourth nerve were four times as abundant in the lateral lobe as in the posterior lobe. But at this level of analysis also there was wide variation between rats. The variation in the participation of each intercostal nerve in the sympathetic innervation of rat IBAT and in the distribution of each nerve's fibers to different parts of the IBAT pad could be of genetic origin or it could reflect a considerable degree of flexibility during development of the innervation of IBAT. Because of the observed variation, it is suggested that if functional responses of IBAT evoked by electrical stimulation of intercostal nerves are to be recorded from a highly localized area of the tissue, stimulation of all the nerves probably would be required to obtain responses that are consistent between animals.
Absence of blocking effects on cardiac slow calcium channels by the intracellular calcium antagonist 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene
Authors: Lynch Joseph J. , Rahwan Ralf G.
Published: April 2011

Extensive pharmacological evidence supports the contention that 2-n-propyl-3-dimcthylamino-5,6-methylenedioxyindene hydrochloride (pr-MDI) is a calcium antagonist with a predominantly intracellular site of action. On the other hand, electrophysiological evidence points to a possible membrane slow inward calcium channel blocking property of this agent. To gain further insight as to the site of action of pr-MDI, the interactions between the negative inotropic action of this agent and the positive inotropic actions of excess extracellular calcium (which directly penetrates the myocardial cells through the slow calcium channels), isoproterenol (which indirectly augments calcium influx through the slow calcium channels), and ouabain (which enhances calcium influx through membrane calcium entry routes distinct from the slow calcium channels) were investigated in the isolated, electrically driven guinea pig left atrium. Although excess extracellular calcium, isoproterenol, and ouabain reversed the negative inotropic effect of pr-MDI, an analysis of the concentration–response relationships to all three positive inotropic agents in the presence and the absence of pr-MDI demonstrated that this agent did not significantly inhibit the contractile effects of calcium, isoproterenol, or ouabain, at pr-MDI concentrations which exhibit intrinsic negative inotropic effects. It is concluded that pr-MDI does not block the membrane slow inward calcium channel nor other presumptive membrane routes of calcium entry into myocardial cells at concentrations of 10−4 M or less. At very high concentrations (T × 10−4 M) some inhibition of slow channel calcium influx may occur.
Contribution of renal sympathetic nerves to the urinary excretion of norepinephrine
Authors: Lappe Rodnhy W. , Henry David P. , Willis Lynn R.
Published: April 2011

Increased activity of the renal sympathetic nerves may result in increased urinary excretion of norepinephrine (NE). In the present study, unilateral electrical stimulation of the renal nerves of the rabbit was employed to test this hypothesis. Stimulation of the renal nerves to one kidney at 2 Hz (group I) produced no significant alteration of plasma NE concentration, glomerular filtration rate (GFR), or NE excretion by either kidney. Stimulation at 4 Hz (group II) caused statistically significant reductions of GFR and urine flow in experimental kidneys, but the urinary excretion of NE, per millilitre GFR, and the CNE/GFR ratios were significantly greater than prestimulation values. In another group of animals (group III), an inhibitor of cation-specific tubular transport, cyanine 863 (6 mg/kg, i.v.), significantly reduced the prestimulation urinary excretion of NE by 60–70% when compared with that of groups I or II. Stimulation of the renal nerves (4 Hz) in the animals of group III caused a significant reduction in GFR in the experimental kidney but did not alter the urinary excretion of NE or the CNE/GFR ratios. The results of these studies indicate that an increase in renal nerve activity causes an increase in the urinary excretion of NE, and that tubular secretion is responsible for the excretion of the neuronally released catecholamine.
Functional localization of pulmonary stretch receptors in the tracheobronchial tree of the kitten
Authors: Marlot Daniel , Mortola Jacopo P. , Duron Bernard
Published: April 2011

Seven kittens age 5 to 8 days were anaesthetized with ketamine, tracheotomized, cannulated just below the larynx, paralyzed, and ventilated. The thorax was widely opened and an expiratory load equal to the transpuimonary pressure at functional residual capacity (PLFRC) added. Single vagal fibers were dissected from the peripheral cut end of the right vagus nerve. Thirty-eight receptor discharges modulated during the respiratory cycle (pulmonary stretch receptors, PSR) were studied; 4 (10.5%) were tonically active at PLFRC while the remaining 34 had a mean threshold at 3.2 cmH2O. All the receptors progressively increased their discharge frequency with higher pressures reaching a plateau between 8–10 cmH2O. By occluding the airways at different levels of the tracheobronchial tree 32 PSR were functionally localized: none were found in the extrathoracic trachea; 3 (9.5%) were located in the intrathoracic trachea, 12 (37.5%) at the carina, main bronchi, and lobar bronchi, and 17 (53%) inside the lobes. All three tracheal receptors were tonic PSR. Previously obtained data from adult mammals indicate that 27–60% of PSR are tonically active and most of these are located in the trachea. The low incidence of tonically active PSR in the kitten may suggest a delayed functional maturation of the tracheal receptors.
Chronic alcohol feeding and its withdrawal on the structure and function of the rat liver plasma membrane: a study with 125I-labelled glucagon binding as a metabolic probe
Authors: Lee Hung , Hosein E. A.
Published: April 2011

The effect of chronic alcohol administration on the structure and function of the rat liver plasma membranes has been investigated. Chronic alcohol administration did not affect the yield of these membranes using conventional isolation procedures. The extent of plasma membrane enrichment or contamination with other interior membranes was identical in the control and alcoholic preparations. The binding of 125I-labelled glucagon to these experimental liver plasma membranes was significantly decreased. Scatchard analysis of the high affinity sites showed a significant reduction [Formula: see text] in receptor number rather than binding affinity, which was not altered. This anomaly persisted through 72-h withdrawal of alcohol. These data suggest that very stable changes were induced in these liver plasma membranes after prolonged alcohol ingestion.
Time course of changes in plasma vasopressin during atrial distension
Authors: Ledsome J. R. , Wilson N. , Ngsee J.
Published: April 2011

Distension of the left atrium in chloralose anaesthetized dogs causes a diuresis and dilution of the urine. It has been reported previously that if distension of the atrium is maintained then urine flow reaches a peak after 50 min and then declines. A radioimmunoassay was used to measure plasma arginine vasopressin (AVP) at 10-min intervals before, during, and after atrial distension for 90 min. Plasma AVP decreased during atrial distension and did not increase until after the atrial distension was removed.Urine volume and free-water clearance increased and urine osmolality decreased, to reach maximum changes after 50 min. Although there was then a decline in some experiments, after reaching the peak changes, the mean values of the group did not show any statistically significant decline. Thus the urinary changes were also present for the 90 min of left atrial distension. The results are consistent with the hypothesis that the.diuretic response to left atrial distension is dependent upon decreased release of AVP from the neurohypophysis.
Aniline and hexobarbital hydroxylases from rat lung and kidney: neither sex dependent nor inducible with phenobarbital
Authors: Lister Janet L. , Virgo Bruce B.
Published: April 2011

The basal activities of aniline hydroxylase (AH), hexobarbital hydroxylase (HH), and ethylmorphine N-demethylase (ED) were measured in the 9000 × g supernatant of kidneys and lungs from male and female rats. No ED activity was detected in any tissue although all tissues N-demethylated three other substrates. The activities of AH and HH were not sex dependent in either kidney or lung. Similarly, pulmonary and renal microsomal protein concentrations were independent of sex. In addition, cytochrome P-450 levels in the kidney were the same in males and females (pulmonary P-450 was not measured). The pulmonary hydroxylases were more active than the renal enzymes in both sexes. In males, phenobarbital (ip, 50 rng∙kg−1∙day−1 for 3 days) failed to induce AH or HH in either kidney or lung; it did not increase the weight or microsomal protein levels of these organs and it also failed to increase renal P-450. Thus, the basal activities of AH and HH in lungs and kidneys are not different in male and female rats and are not increased by phenobarbital.
Pharmacology of acetaldehyde
Authors: Brien J. F. , Loomis C. W.
Published: April 2011

The pharmacological effects of acetaldehyde on the cardiovascular system, the liver, monoamine neurotransmitter metabolism, brain function and behaviour, and voluntary ethanol drinking are reviewed. The pharmacological effects of acetaldehyde, produced during the interaction of ethanol with the aldehyde dehydrogenase inhibitors disulfiram, calcium carbimide (calcium cyanamide), and 1-aminocyclopropanol (the pharmacologically active hydrolytic product of coprine) are discussed. The proposed involvement of acetaldehyde in the pharmacological effects of ethanol is critically assessed. The literature up to the end of 1981 has been reviewed.
The effects of the ionophore A-23187 on the rat vas deferens
Authors: Warenycia M. W. , Vohra M. M.
Published: April 2011

The calcium ionophore A-23187 induced spontaneous, rhythmic contractions in the rat isolated vas deferens in a concentration-dependent manner. Contractions were blocked by phentolamine and were abolished following pretreatment with reserpine. In tissues preloaded with [3H]noradrenaline, A-23187 (10 μM) caused a time-dependent increase in the release of tritium. The findings suggest that A-23187-induced contractions in the rat vas deferens are secondary to the release of endogenous noradrenaline from the adrenergic nerves, as are contractions induced in this preparation by X-537A (another calcium ionophore) described earlier by other investigators.
Regulation of cyclic GMP phosphodiesterase in the submandibular gland of adult rat
Authors: Yokoyama Noriko , Murota Yumiko , Negishi Tetsuo , Saito Masao , Furuyama Shunsuke
Published: April 2011

Cyclic GMP phosphodiesterase was investigated in the submandibular gland of the adult rat to elucidate the regulatory mechanisms of cGMP concentration in this gland. Ca2+ sensitivity was easily demonstrated as in other tissues using EGTA in the buffer for elution from DEAE-cellulose. The presence of inhibitor proteins for basal and calmodulin-activated portions of Ca2+-dependent phosphodiesterase was suggested. The inhibitor for the basal activity of Ca2+-dependent phosphodiesterase was deemed to be a heat-labile protein, which decreased Vmax, but had no effect on the Km value for cGMP. The presence of more than one kind of inhibitor for the calmodulin-activated portion of the Ca2+-dependent phosphodiesterase was also suggested. One of these, which was not absorbed on DEAE-cellulose, was a heat-labile protein which caused an increase of Km for cGMP, but no change of Vmax.
The changes in ventilation and heart rate at the start of treadmill exercise
Authors: Duffin James , Bechbache Rafik R.
Published: April 2011

The changes in ventilation and heart rate and end-expiratory volume which occur at the start of exercise from rest were measured in volunteers, at three treadmill grades (5, 10, 15%) each at three different speeds (2, 3, 4 miles per hour (mph); 3.2, 4.8, 6.4 km/h). A three by three factorial analysis of variance showed that the changes in ventilation and heart rate were a function of treadmill speed but not grade. The results of these experiments were interpreted as demonstrating that the speed of limb motion is a determinant of the changes in ventilation and heart rate at the start of treadmill exercise.
Stimulatory effect of thyrotrophin-releasing hormone (TRH) on the release of luteinizing hormone (LH) from rat anterior pituitary cells in vitro
Authors: Fujihara Noboru , Shiino Masataka
Published: April 2011

The effect of thyrotrophin-releasing hormone (TRH, 10−7 M) on luteinizing hormone (LH) release from rat anterior pituitary cells was examined using organ and primary cell culture. The addition of TRH to the culture medium resulted in a slightly enhanced release of LH from the cultured pituitary tissues. However, the amount of LH release stimulated by TRH was not greater than that produced by luteinizing hormone – releasing hormone (LH–RH, 10−7 M). Actinomycin D (2 × 10−5 M) and cycloheximide (10−4 M) had an inhibitory effect on the action of TRH on LH release. The inability of TRH to elicit gonadotrophin release from the anterior pituitary glands in vivo may partly be due to physiological inhibition of its action by other hypothalamic factor(s).
Rapid high-performance liquid chromatographic analysis of amiodarone and N-desethyl-amiodarone in serum
Authors: Brien J. F. , Jimmo S. , Armstrong P. W.
Published: April 2011

A rapid and reliable high-performance liquid chromatographic (HPLC) assay has been developed for the measurement of the antiarrhythmic drug, amiodarone (A), and its metabolite, N-desethyl-amiodarone (NDA), in serum. The procedure involves addition of absolute ethanol to serum, previously adjusted to pH 6, followed by centrifugation. The supernatant is analyzed by reverse-phase HPLC with ultraviolet–visible detection. There is no intereference from endogenous substances or other commonly used antiarrhythmic agents. The mean overall accuracy of the HPLC assay is 96.9 ± 9.1 (SD)% (n = 37) for A over the concentration range 0.10–10.00 μg/mL, and 99.8 ± 4.8 (SD)% (n = 32) for NDA over the concentration range 0.10–7.50 μg/mL. The within-day coefficient of variation is less than 7% for A and NDA. The lower limit of quantitative sensitivity is 0.10 μg/mL for A and NDA, and the lower limit of qualitative detection is 1.0 ng for both compounds.
Granulosa cell stimulation of thecal androgen synthesis
Authors: Lischinsky Adriana , Armstrong David T.
Published: April 2011

The role of granulosa cells on porcine follicular androgen synthesis was studied. Granulosa cells were cultured for 24 h either in Eagle's minimum essential medium (MEM) or in MEM plus follicle-stimulating hormone (FSH; 1 μg/mL). Thecal preparations were cultured with or without luteinizing hormone (LH), either in MEM, 50% "spent media" from granulosa cells control (MA) or 50% "spent media" from granulosa cells incubated with FSH (MB). In the absence of LH, MB stimulated accumulation of both Δ4-androstenedione (twofold) and testosterone (threefold). MB was found to contain high levels of C21-steroids, including progesterone and material which behaves chromatographically and immunologically like pregnenolone. These amounts of C21-steroids were able to stimulate thecal androgen production. The results suggest that granulosa cells contribute to thecal androgen production by providing steroid substrate. This would provide a means for granulosa cells to control the availability of aromatizable androgens.
Perifused adenohypophyseal cells: release of ACTH and kinetics of the response to secretagogues
Authors: Randle John , Jutisz Marian
Published: April 2011

The release of ACTH-like immunoactivity (ACTH-LI) from perifused dispersed adenohypophyseal cells was examined under basal conditions and in response to various secretagogues. Frequent sampling of effluent perifusion medium and a variable stimulation format allowed us to discern differences in the effects of the secretagogues. The dye, dextran blue, was used to define the kinetics of flow intrinsic to the perifusion system, allowing a detailed analysis of the responses to secretagogues. Each agent had a time course of action which could be related to its supposed site and mode of action in these cells. A crude hypothalamic extract, a partially purified corticotrophin releasing factor preparation, 8-bromoadenosine 3′,5′-cyclic monophosphate (8Br-cAMP), and 3-isobutyl-1-methylxanthine all caused dose-related, repeatable increases of the release of ACTH-LI. A 10-fold elevation in the concentration of K+ in the perifusion medium (10K) caused a transient increase in the release of ACTH-LI which was reduced when repeated. These results suggest that 10K stimulates the release of ACTH-LI only from a "readily-releaseable pool." The other agents appear to affect the release process more profoundly, for example, by stimulating intracellular transport of the ACTH-LI.
Mechanical anisotropy of purified elastin from the thoracic aorta of dog and sheep
Authors: Sherebrin M. H. , Song S. H. , Roach Margot R.
Published: April 2011

Mechanical anisotropy was found in elastin from the wall of the thoracic aorta by testing digested vessels from seven mature dogs and five pregnant ewes. The elastin was purified by removing the muscle and collagen with 0.1 N NaOH at 75 °C for 5 h. Strips oriented circumferentially and longitudinally with respect to the vessel axis were cycled at increasing loads until failure. Combining the results for four dogs and three sheep the ultimate tensile strength was 405 × 103 ± 155 × 103 SDN/m2 circumferentially and 189 × 103 ± 85 × 103 SD N/m2 longitudinally. The difference is significant at p < 0.01. The ultimate strain was not significantly different, 1.19 ± 0.29 SD circumferentially and 1.01 ± 0.26 SD longitudinally. At 0.4 strain, the Young's modulus for four samples from four dogs was 404 × 103 ± 64 × 103 SD N/m2 circumferentially; the modulus for five samples from five dogs was 245 × 103 ± 60 × 103 SD N/m2 longitudinally. The difference is significant at p < 0.05. At 0.7 strain, the Young's modulus for four dogs was 486 × 103 ± 82 × 103 SD N/m2 circumferentially and 343 × 103 ± 62 × 103 SD N/m2 longitudinally. The difference is significant at p < 0.05. The reasons for the anisotropy in terms of the structure are not obvious from preliminary studies using the scanning electron microscope with stretched samples.
Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock
Authors: Vadas Peter , Hay John B.
Published: April 2011

This study examined the role of plasma phospholipase A2 (PLA2) in the mediation of the hypotension associated with experimental endotoxin shock in rabbits. Endotoxin shock was induced in rabbits, and mean arterial blood pressure and plasma PLA2 levels were monitored. Serial plasma PLA2 determinations over 5 h showed an 11-fold increase in circulating enzyme activity, and the rise in circulating enzyme activity was directly related to the fall in mean arterial blood pressure. Pretreatment of rabbits with glucocorticoids abrogated the hypotensive effect of endotoxin, and also inhibited a rise in plasma PLA2 activity. To determine if the rise in PLA2 activity was simply a mechanistically unrelated epiphenomenon, the effect of infusion of exogenous PLA2 (purified from the blood of rabbits in endotoxin shock) was investigated. Infusion of the exogenous enzyme into normal rabbits caused a fall in mean arterial blood pressure, and the rate of fall of blood pressure paralleled that induced by endotoxin itself. Treatment of the PLA2-active fraction, prior to infusion with the PLA2 inhibitor, p-bromophenacyl bromide, protected against this hypotensive effect. These data are consistent with the postulate that the endotoxin-induced release of massive amounts of PLA2 into the systemic circulation in rabbits contributes significantly to the hypotension associated with septic shock.
Changes in responsiveness of rat granulosa cells to prostaglandin E2 and follicle-stimulating hormone during culture
Authors: Goff A. K. , Armstrong D. T.
Published: April 2011

The changes in responsiveness of granulosa cells to either FSH or prostaglandin E2 (PGE2), during culture of the cells, have been examined. In freshly isolated cells, FSH and PGE2 stimulated both cyclic AMP and progesterone production in a dose–dependent manner. In these cells, FSH stimulated cyclic AMP production to a greater extent than did PGE2. After the cells had been cultured for 2 days, neither FSH nor PGE2 stimulated progesterone production to any detectable extent. In these cells the ability of FSH to stimulate cyclic AMP was decreased, and that of PGE2 was increased markedly, such that PGE2 was far more effective than FSH in stimulating cyclic AMP. After culture of the cells for a further 2 days (4 days total), the FSH stimulation of cyclic AMP returned to that seen in freshly isolated cells, whereas the stimulation by PGE2 remained elevated. The acute stimulation of progesterone production could be restored by chronic exposure of the cells to either FSH or PGE2. These results demonstrate that dramatic changes in responsiveness of granulosa cells take place during culture. The results also suggest that some stimulating factor must be present to maintain the steroidogenic capabilities of the cells. Without this, although the cells are able to produce cyclic AMP in response to FSH, they cannot produce progesterone.
Chronopharmacological studies of phenylbutazone in the rat
Authors: Labrecquf G. , Bélanger P. M. , Doré F. M.
Published: April 2011

Temporal variations in the anti-inflammatory action and in the ulcerogenic and lethal effects of phenylbutazone were studied in rats. The results indicate that small doses of the drug produced a larger reduction of paw edema in the morning than in the evening. At 0900, doses of 10, 30, and 100 mg/kg of phenylbutazone reduced the carrageenan-induced paw edema by 23, 44, and 66%, respectively. At 2000, the same doses of the drug decreased the paw edema by 9, 22, and 62%, respectively. No circadian variation was observed in the ulcerogenic effect of phenylbutazone. The mean lethal dose (LD50) of the drug was larger in the morning than in the evening and the values obtained were 710 ± 24 (SE) mg/kg at 0900 in comparison to 525 ± 38 (SE) mg/kg at 2000.
Enkephalinergic control of somatostatin secretion from the perfused rat stomach
Authors: McIntosh C. H. S. , Kwok Y. N. , Mordhorst T. , Nishimura E. , Pederson R. A. , Brown J. C.
Published: April 2011

A role for the enkephalins in the regulation of gastric somatostatin (SLI) secretion has been investigated in an isolated perfused rat stomach model. Both methionine- and leucine-enkephalins caused a dose-dependent inhibition of gastric inhibitory polypeptide (GIP) stimulated SLI secretion. Leu-enkephalin was one order of magnitude less potent than met-enkephalin: 50% inhibition by met-enkephalin was at 4 × 10−9 M and with leu-enkephalin 3.5 × 10−8 M. Naloxone (100 nM) had no effect on basal secretion but blocked the inhibitory action of met-enkephalin (1 nM or 1 μM). Vagal stimulation (7 V, 10 Hz, 5 ms) inhibited GIP-stimulated SLI release. Administration of naloxone partially reversed this inhibition, suggesting that endogenous opioids were at least partially responsible for vagally induced inhibition. A number of possible pathways by which endogenous enkephalins may modulate SLI release have been proposed.
Specific binding of vasoactive intestinal peptide to human circulating mononuclear cells
Authors: Ottaway C. A. , Bernaerts C. , Chan B. , Greenberg G. R.
Published: April 2011

The interaction of the neuropeptide vasoactive intestinal peptide with human circulating mononuclear cells has been studied. Mononuclear cells were able to bind radiolabelled vasoactive intestinal peptide; the binding was rapid, reversible, saturable, and specific for vasoactive intestinal peptide. A fragment of vasoactive intestinal peptide (10–28) was 25-fold less effective than intact peptide as a competitor for the binding of the tracer. Secretin was 100-fold less effective as a competitor and glucagon competed poorly even at concentrations 10 000 times greater than that of the tracer molecule. In tracer dilution studies, the binding suggested a single class of binding sites with an apparent dissociation constant (Kd) of 2.4 × 10−10 M and a capacity of 2 000 sites per cell. In the presence of vasoactive intestinal peptide, there was a dose-dependent augmentation of cyclic AMP in the mononuclear cells. The concentration of vasoactive intestinal peptide which produced a half-maximal effect was the same as the Kd for the peptide binding. We conclude that mononuclear cells have specific high-affinity binding sites for vasoactive intestinal peptide. Interactions between mononuclear cells and vasoactive intestinal peptide may be an important mechanism modulating local immune responses within tissues innervated by vasoactive intestinal peptide containing neurons.
Modulation of ovine myometrial activity by estradiol-17β. The possible involvement of prostaglandins
Authors: Lye S. J. , Sprague Cher L. , Challis J. R. G.
Published: April 2011

Administration of estradiol-17β (E2; 50 μg s.c. per day) to nonpregnant ewes results in a cyclic pattern of uterine activity; periods of high activity (6- to 8-h duration) alternating with periods of low activity or quiescence (2–3 h). To examine the role of prostaglandins (PG) in this pattern five nonpregnant, bilaterally ovariectomized ewes were treated in turn with corn oil injected s.c. (control), E2 (50 μg s.c), and E2 (50 μg s.c.) plus 600 μg/min meclofenamic acid (MFA) i.v. Intrauterine pressure (IUP) and uterine electromyographic (EMG) activity were recorded continuously. Samples of blood from the inferior vena cava and abdominal aorta were collected every 30 min for one period of 16 h during each treatment. Following corn oil injection, uterine activity remained at the low level and there was no correlation between PG concentrations and uterine activity. After administration of E2, plasma E2 concentrations rose fivefold from basal values by 3.5 h after injection and returned to basal levels by 13 h. Administration of E2 resulted in the appearance of a cyclical pattern of uterine activity. Vena cava concentrations of 13,14-dihydro-15-keto PGF2α were positively correlated to the frequency (five out of five ewes), and the maximum amplitude (four out of five ewes) of IUP cycles, and were significantly elevated during high activity compared with low activity periods. Venous PGE concentrations did not show a consistent relation with uterine activity parameters. MFA reduced plasma PG concentrations below other treatments and also abolished the cyclical pattern of activity. These data suggest that PG's may play a role in the cycles of myometrial activity resultant upon E2 treatment of the ewe.
Noradrenergic modulation of neuronal transmission in the offspring of amphetamine-treated rats
Authors: Ramírez Oscar A. , Carrer Hugo F.
Published: April 2011

The model of noradrenergic modulation of synaptic transmission between the entorhinal cortex and dentate gyrus was used to investigate the function of catecholaminergic neurones in the offspring of rats injected with dl-amphetamine during pregnancy (0.5 mg∙kg−1∙day−1; s.c). A conditioning train of pulses applied to the locus coeruleus produces an increase in the amplitude of the population spike evoked in the granule layer of the gyrus dentatus by perforant path stimulation. Results show that, in the offspring of amphetamine-treated rats, the potentiating effect of locus coeruleus stimulation was two to three times greater than in control animals (151 ± 30 vs. 66 ± 20%; p < 0.05). This effect may be due to the changes in catecholamine metabolism and (or) catecholamine receptors observed in these animals and could help explain the behavioral alterations caused by amphetamine exposure in utero.
Chronic ethanol treatment alters the biosynthesis of β -endorphin by the rat neurointermediate lobe
Authors: Gianoulakis Christina , Chan John S. D. , Kalant Harold , Chrétien Michel
Published: April 2011

Tolerance to ethanol was induced in male Sprague–Dawley rats (225 – 250 g) by chronic feeding with a liquid diet containing 6.5% ethanol (v/v). Control rats were pair-fed with a liquid diet in which the ethanol was replaced by an equicaloric concentration of sucrose. Immediately following sacrifice of the animals the neurointermediate lobes (NIL) were removed and incubated with [3H]phenylalanine. The biosynthesized proopiomelanocortin (POMC), β-lipotropin β-LPH), and β-endorphin (β-EP) were purified by immunoprecipitation with an antiserum to β-EP and analyzed by sodium dodecyl sulfate poly-acrylamide disc gel electrophoresis. Alcohol treatment for 3 days had no effect on the degree of incorporation of [3H]phenylalanine into POMC, β-LPH, and β-EP but treatment for either 15 or 21 days increased the incorporation of [3H]phenylalanine into all three peptides. Ethanol treatment also increased the β-endorphinlike immunoreactivity (β-EPLIR) found in the incubation medium, but no significant change was observed in the β-EPLIR extracted from the NIL either immediately after sacrifice or after 3 h of incubation of the NIL. However, a significant decrease of β-EPLIR was found in the anterior lobes of rats treated with ethanol for 21 days. Furthermore, the β-EPLIR in the serum of alcohol-treated rats was significantly higher than in the serum of their corresponding controls. These results indicate an effect of ethanol on the endorphin system and are consistent with the suggestion that endorphins may be mediators of some of the ethanol effects.
Cyclic AMP phosphodiesterase activity in the hearts of trained rats
Authors: Palmer Warren K. , Doukas Sylvia
Published: April 2011

Running exercise trained rats at either 60 or 76% of their [Formula: see text] caused myocardial cyclic AMP phosphodiesterase (PDE) activity to be increased above control levels for at least 24 h following work. Neither training nor the exercise had any effect on the total concentration of calmodulin in heart tissues. The affinity of PDE for cyclic AMP was not changed by the exercise or training. The chelating agent, EGTA, had the same influence on PDE activity regardless of whether it was present in assays of control or exercised heart extract. Km and EGTA results suggest that calcium-bound calmodulin does not account for the higher PDE activity in the hearts of exercised rats. Supernatants from hearts homogenized in the presence of charcoal, to remove nucleotides from the extract, did not eliminate the exercise-associated increase in PDE activity. These results suggest that the elevated activity was not caused by an in vitro nucleotide activation. Preincubation of the enzyme from exercised and control rat hearts with snake venom activated PDE when assays were performed with the low concentration of cyclic AMP (1 μM). Moreover, the activity reached in the extract of exercisers (23.3 pmol∙100 μL−1∙min−1) was significantly greater than the activity found in control hearts (17.59 pmol∙100 μL−1∙min−1). Exercise increases PDE activity in the myocardium of trained rats. The results presented suggest that the increased PDE activity resulting from exercise is not dependent upon exercise intensity when the work is in excess of 60% of [Formula: see text]. In addition, the data obtained using indirect probes suggest that the increased enzyme activity was not caused by metabolites, endogenous nucleotides, or calmodulin changes in the hearts of exercised animals.
Polychlorinated benzene and phenol congeners as inducers of rat hepatic drug-metabolizing enzymes in immature male Wistar rats
Authors: Denomme M. A. , Leece B. , Gyorkos J. , Homonko K. , Safe S.
Published: April 2011

The effects of the higher chlorinated benzene and phenol congeners as inducers of the hepatic microsomal drug-metabolizing enzymes have been determined in the immature male Wistar rat by comparing the enzymic, electrophoretic, and spectral properties of the microsomes. 3,4,5-Trichiorophenol, 1,2,4,5-tetrachlorobenzene, 1,2,3,5-tetrachlorobenzene, 1,2,4-trichlorobenzene, and pentachlorobenzene induced 4-dimethylaminoantipyrine (DMAP) N-demethylase, an enzyme induced by phenobarbitone (PB) and several PB-type inducers. Hexachlorobenzene induced DMAP N-demethylase and aldrin epoxidase, two PB-inducible enzymes, and benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase, two enzymes induced by 3-methylcholanthrene (MC). This mixed-type induction pattern has been previously reported for hexachlorobenzene. The remaining higher chlorinated benzene and phenol congeners were inactive as inducers of the drug-metabolizing enzymes in the immature male Wistar rats.
Increase in ventricular fibrillation threshold following blockade of atrioventricular conduction
Authors: Reynolds A. Keith , Dresel Peter E.
Published: April 2011

The threshold for electrically induced ventricular fibrillation was determined in anesthetized open-chest dogs, before and after blockade of atrioventricular (A-V) conduction. Without exception, the threshold was significantly elevated after creation of the block. The precise mechanism of this effect is not known at this time. However, it is apparent that when ventricular fibrillation thresholds are being determined, the functional status of A-V conduction should be established and maintained throughout the study.
Prostaglandin synthesis by human amnion is dependent upon extracellular calcium
Authors: Olson David M. , Opavsky Mary Anne , Challis John R. G.
Published: April 2011

Prostaglandin (PG) E and F output was studied in collagenase-dispersed amnion cells to determine the effect of extracellular Ca2+ upon PG synthesis. In the presence of 2.5 mM CaCl2, PGE and PGF output (picograms per 105 cells per 3 h) by cells obtained at term prior to labour following elective cesarean section (CS) was 183 ± 39 and 127 ± 23, respectively. This increased to 435 ± 111 (p < 0.025) and 241 ± 49 (p = 0.056) from cells obtained after spontaneous labour and delivery at term (SL). Exclusion of CaCl2 from the medium (plus 0.1 mM EGTA) significantly reduced (p < 0.025) PGE output in CS and SL cells (83 ± 22 and 183 ± 47, respectively) and PGF output in CS cells (70 ± 17). PGE output in both CS and SL cells was unchanged when CaCl2 concentrations in the medium were decreased from 2.5 to 0.25 mM, but significantly attenuated (p < 0.01) when extracellular CaCl2 was decreased from 0.25 to 0 mM. The voltage-sensitive Ca2+ channel blocker, D-600, decreased PGE output in the presence of (2.5 mM) CaCl2 to levels observed in the absence of CaCl2. Ionophore A23187 restored PGE output in the presence of D-600 and Ca2+. PGF output from CS amnion cells was stimulated by A23187 and elevated extracellular K+ (40 mM). In each case, exclusion of CaCl2 from the medium eliminated the response. These, results suggest that PG output by human amnion is dependent, in part, upon the presence of extracellular Ca2+ and that Ca2+ may enter the cell via a potential-sensitive mechanism.
Forskolin potentiates calcium-dependent amylase secretion from rat pancreatic acinar cells
Authors: Heisler Seymour
Published: April 2011

The cellular and molecular effects of forskolin, a direct, nonhormonal activator of adenylate cyclase, were assessed on the enzyme secretory process in dispersed rat pancreatic acinar cells. Forskolin stimulated adenylate cyclase activity in the absence of guanyl nucleotide. It promoted a rapid and marked increase in cellular accumulation of cyclic AMP alone or in combination with vasoactive intestinal peptide (VIP) but was itself a weak pancreatic agonist and did not increase the secretory response to VIP or other cyclic AMP dependent agonists. Somatostatin was a partial antagonist of forskolin stimulated cyclic AMP synthesis and forskolin plus cholecystokinin-octapeptide (CCK-OP) induced amylase release. Forskolin potentiated amylase secretion in response to calcium-dependent agonists such as CCK-OP, carbachol and A-23187, but did not affect the ability of CCK-OP and (or) carbachol to mobilize 45Ca from isotope preloaded cells; forskolin alone did not stimulate 45Ca release. In calcium-poor media, the secretory response to forskolin and CCK-OP was reduced in a both absolute and relative manner. The data suggests that calcium plays the primary role as intracellular mediator of enzyme secretion and that the role of cyclic AMP may be to modulate the efficiency of calcium utilization.
Pancreatic insulin response in relation to exercise training
Authors: Richard Denis , LeBlanc Jacques
Published: April 2011

The present study was undertaken to measure the effects of exercise training on pancreatic insulin secretion in response to glucose and nonglucose stimuli. Wistar female rats with an initial body weight of approximately 180 g were divided into trained and sedentary groups. After a period of 10 weeks of training, glucose-, tolbutamide-, and arginine-tolerance tests were performed in vivo in both trained and untrained animals. The tests were done in nonanesthetized animals 40 h after the last exercise bout. It was found that exercise training leads to a diminution of plasma insulin levels after either glucose, tolbutamide, or arginine administration. These results present direct evidence that exercise training reduces plasma insulin response not only to glucose but also to nonglucidic secretagogues.
Effect of a potassium-deficient diet on arterial blood pressure, plasma and tissue cations, and tissue norepinephrine in the hypertensive dog
Authors: Garcia Raul , Constantopoulos Georges , Gutkowska Jolanta , Genest Jacques
Published: April 2011

Chronic potassium deficiency in one-kidney one-clip hypertensive dogs significantly reduces blood pressure and plasma potassium, with a simultaneous increase in plasma renin activity. Tissue potassium concentration was decreased and tissue sodium concentration was increased in striated muscle and adrenal glands, which may suggest that the sodium-potassium pump was inhibited. In myocardium the sodium concentration was higher but the potassium concentration was not significantly lower than in control hypertensive dogs on normal diets. Arterial cation concentrations in the potassium-deficient group were not significantly different from those in the control group. Tissue norepinephrine concentration was higher in arteries from potassium-deficient animals, significantly so in the mesenteric and femoral arteries. The conclusion is that potassium deficiency may decrease blood pressure in the one-kidney one-clip hypertensive dogs by impairing the release of norepinephrine.
Inhibition of fast axonal transport in vitro by the local anesthetics prilocaine, mepivacaine, and bupivacaine
Authors: Lavoie P.-A.
Published: April 2011

The aim of the present study was to establish the concentrations of prilocaine, mepivacaine, and bupivacaine which are effective at blocking fast axonal transport, to determine whether prilocaine and mepivacaine offer a better prospect of dissociating conduction block and transport block in vivo than does lidocaine and whether bupivacaine offers a better prospect than etidocaine in the same context. Fast axonal transport of [3H]leucine-labeled proteins was studied in vitro in bullfrog spinal nerves and quantitated by liquid scintillation counting. Exposure of spinal nerves to 14 mM prilocaine reduced the quantity of 3H-labeled proteins which accumulated at a ligature by 86%, and exposure to 14 mM mepivacaine reduced it by 70%; 10 mM prilocaine reduced this same parameter by 54%, a degree of inhibition close to the 44% reduction caused by 14 mM lidocaine. The D(−) and L(+) stereoisomers of mepivacaine each reduced transport to the ligature by approximately 50% at a concentration of 14 mM. Bupivacaine reduced the accumulation of 3H-labeled proteins at the ligature by 49% at a 10 mM concentration (pH 6.2); its potency is close to that found for etidocaine in a previous study. Since prilocaine and mepivacaine are at least as potent as lidocaine as transport inhibitors and at blocking impulse conduction, these two anesthetics offer no advantage over lidocaine to achieve dissociation of conduction block from transport block in vivo. Bupivacaine appears to offer no advantage over etidocaine in the same context, as the two agents have a similar potency as local anesthetics and a similar potency as inhibitors of fast axonal transport.
Methylmercury distribution, metabolism, and neurotoxicity in the mouse brain
Authors: Vandewater Laurie J. S. , Racz William J. , Norris Albert R. , Buncel Erwin
Published: April 2011

Methylmercury distribution, biotransformation, and neurotoxicity in the brain of male Swiss albino mice were investigated. Mice were orally dosed with [203Hg]methylmercury chloride (10 mg/kg) for 1 to 9 days. Methylmercury was evenly distributed among the posterior cerebral cortex, subcortex, brain stem, and cerebellum. The anterior cerebral cortex had a significantly higher methylmercury concentration than the rest of the brain. The distribution of methylmercury's inorganic mercury metabolite was found to be uneven in the brain. The pattern of distribution was cerebellum > brain stem > subcortex > cerebral cortex. The order of the severity of histological damage was cerebral cortex > cerebellum > subcortex > brain stem. There was no correlation between methylmercury distribution in the brain and structural brain damage. However, there was a relationship between the distribution of methylmercury's inorganic mercury metabolite and structural damage in the anterior cerebral cortex (positive correlation) and the anterior subcortex (negative correlation). There was also a positive correlation between the fraction of methylmercury's metabolite of the total mercury present and structural brain damage in the anterior cerebral cortex. This study suggests that biotransformation may have a role in mediating methylmercury neurotoxicity.
Inhibition by cinnarizine of the responses of smooth muscle from spontaneously hypertensive and normotensive rats
Authors: Nghiem C. , Swamy V. C. , Triggle D. J.
Published: April 2011

A comparison was made of the inhibition by cinnarizine, a calcium antagonist, of the contractile responses of aortic, carotid, and iliac arterial strips and vasa deferentia from 15- to 17-week-old spontaneously hypertensive rats (SHR) and their normotensive counterparts, Wistar Kyoto (WKY) rats. KCl-induced responses of the aorta from both strains of rats and carotid arteries from WKY only were more sensitive to inhibition than were responses to norepinephrine. No significant differences were observed in the inhibition of tissue responses from the two strains of rats with the exception of the K+-induced responses of carotid arterial strips from SHR which were significantly less sensitive to inhibition when compared with carotid strips from WKY.
Differential sensitivity of Dahl salt-sensitive and Dahl salt-resistant rats to the hypotensive action of acute nifedipine administration
Authors: Sharma J. N. , Fernandez P. G. , Laher I. , Triggle C. R.
Published: April 2011

The calcium antagonist, nifedipine, was intravenously administered in a cumulative fashion, from 0.5 to 12 mg/kg, to Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats which had been maintained on a high (8.0%) or low (0.4%) salt (NaCl) diet. We observed, compared with the DR rats, dose-related and significant (P < 0.001) falls in the systolic (SBP) (72 ± 3 and 60 ± 9%, respectively) and diastolic blood pressure (DBP) (67 ± 2 and 62 ± 6%) of the DS rats maintained either on the low (0.4%) or high (8.0%) salt diets. In contrast, nifedipine therapy comparatively produced only moderate changes in the SBP and DBP of the DR rats (36 ± 12, 27 ± 9, 31 ± 10, and 30 ± 11%, respectively). We hypothesize that this differential sensitivity of the DS and DR rats to the hypotensive action of nifedipine may reflect a significantly more important role for a high resting Ca2+ influx, through nifedipine sensitive channels, in the maintenance of the blood pressure of the DS rat.
Hormonal regulation of acid cholesterol ester hydrolase activity: effects of triiodothyronine and 17α-ethynylestradiol
Authors: Severson David L. , Hayden L. Joseph , Fletcher Thea
Published: April 2011

Cholesterol ester hydrolase activity was measured in isolated rat hepatocytes and adipocytes. Administration of triiodothyronine to rats resulted in a specific and selective increase in lysosomal acid (pH 4.5) cholesterol ester hydrolase activity in hepatocytes. Since the majority of lipoprotein degradation occurs in liver parenchymal cells (hepatocytes), the stimulation of liver (hepatocyte) acid cholesterol ester hydrolase activity by triiodothyronine could contribute to the hypocholesterolemie action of thyroid hormones. Treatment of rats with 17α-ethynylestradiol to increase the hepatic degradation of lipoproteins did not change acid cholesterol ester hydrolase activity in liver, indicating that the thyroid hormone induced stimulation of acid cholesterol ester hydrolase activity in hepatocytes is not a secondary effect owing to the increased hepatic catabolism of low density lipoproteins (LDL). In contrast to the results with hepatocytes, hyperthyroidism did not increase acid cholesterol ester hydrolase activity in rat adipocytes.