bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of small intestinal water, sodium, and potassium transport and morphology in the pig
Authors: Leddin D. J.
Published: April 2011

The suitability of the young pig for studies of intestinal transport was investigated by determination of net water, sodium, and potassium absorption, and morphometry in jejunum and ileum. Active net absorption was seen in both jejunum and ileum. There was no difference in absorption between segments and there was a good correlation between water and electrolyte transport. Heart rate, arterial pressure, and absorption were constant with time. Villus height and width were similar to those of human, but crypt depth was greater, and the ratio of villus height to crypt depth less. The mucosa was partially permeable to polyethylene glycol 4000 and this marker is not suitable for studies of transport in young pigs.Key words: pig, intestinal transport, morphology, polyethylene glycol.
Study on the stereoselectivity of Inositol 1,4,5-trisphosphate recognition sites of bovine adrenal cortex
Authors: Luong Thanh-Truc , Boulay Guylain , Guillemette Gaétan
Published: April 2011

Inositol 1,4,5-trisphosphate (InsP3) is an intracellular messenger generated from the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C in response to Ca2+-mobilizing stimuli. InsP3 interacts with a specific receptor responsible for the release of sequestered Ca2+ from an intracellular store. The purpose of the present study was to evaluate the relative affinities of the naturally occurring D-isomer of InsP3 and that of its L-stereoisomer for the InsP3 receptor and the InsP3 metabolizing enzymes from bovine adrenal cortex. The InsP3 receptor recognized D- and L-isomers with respective affinities of 4.8 nM and 7.3 μM. This high degree of selectivity was also reflected in the capacity of both isomers to mobilize Ca2+ from the microsomal preparation. The partially purified InsP3 kinase preparation was also able to discriminate between the two stereoisomers. The activity of the kinase was half-maximally inhibited in the presence of 11 μM L-InsP3, a value much higher than the Km of the kinase for D-InsP3 (0.4 μM). Both stereoisomers exhibited equipotent affinities (around 17 μM) for the particulate preparation of InsP3 phosphatase. The enzyme, however, appeared to hydrolyze L-InsP3 at a much slower rate. These results demonstrated that the different recognition sites for InsP3 were expressing distinct levels of stereoselectivity. This property, which is an important aspect of ligand – receptor interaction, could be exploited for the design of new selective drugs interfering with InsP3 action and metabolism.Key words: inositol 1,4,5-trisphosphate (InsP3), InsP3 kinase, InsP3 phosphatase, InsP3 receptor, stereoselectivity, Ca2+ mobilization, adrenal cortex.
The superficial buffer barrier in vascular smooth muscle
Authors: Chen Qian , Cannell Mark , Breemen Cornelis van
Published: April 2011

Force development and fura-2 fluorescence were simultaneously measured in the rabbit inferior vena cava. Discharging SR Ca2+ with either caffeine or norepinephrine prior to stimulation of Ca2+ influx induced a delay of 30–70 s between the intracellular Ca2+ signal and development of force. This delay was abolished by the application of caffeine. These data support the superficial buffer barrier hypothesis, which holds that Ca2+ entry from the extracellular space proceeds via a restricted cytoplasmic region between the inner plasmalemmal surface and the peripheral sarcoplasmic reticulum (SR). Ca2+ accumulation by this SR fraction appears to be able to delay Ca2+ entry into the deeper myoplasm where it activates the myofilaments. Caffeine and thapsigargin elevated the steady-state [Ca2+]i, suggesting a contribution by the SR Ca2+ pump to Ca2+ extrusion from the cells. Norepinephrine enhanced myofilament Ca2+ sensitivity, while caffeine decreased it.Key words: smooth muscle, superficial buffer barrier, Ca2+ entry, Ca2+ extrusion, fura-2 fluorescence.
Role of corticosteroids in distal acidification of amiloride-treated rats
Authors: Ansaldo Martín , Damasco María Cristina , Lavallaz María Silvina de , Lantos Carlos Pedro , Malnic Gerhard
Published: April 2011

The role of amiloride-dependent sodium channels in the action of adrenal cortical steroids on urine–blood [Formula: see text] (U–B [Formula: see text]) differences was studied in bicarbonate-infused and amiloride-treated adrenalectomized rats. U–B [Formula: see text] was significantly reduced by amiloride in bicarbonate-infused control rats. Adrenalectomy further reduced U–B [Formula: see text] in amiloride-treated, bicarbonate-infused rats (from 27.9 ± 1.82 mmHg in sham-operated rats to 21.3 ± 1.58 mmHg in adrenalectomized (ADX) rats) (1 mmHg = 133.322 Pa). Acute administration of corticosterone and 18-hydroxycorticosterone (18-OH-B), but not of aldosterone, caused recovery of U–B [Formula: see text] to the level of sham-operated animals treated with amiloride. Aldosterone did not affect U–B [Formula: see text] in the presence of amiloride (21.9 mmHg ADX group vs. 20.98 mmHg aldosterone group). Results are compatible with aldosterone affecting distal H ion secretion mostly by a sodium and potential difference dependent mechanism, while corticosterone and 18-OH-B should act by other mechanisms (e.g., increased luminal buffer level).Key words: distal H ion secretion, corticosteroids, amiloride, adrenalectomy, aldosterone, corticosterone, 18-hydroxycorticosterone.
Central Peptidergic Mechanisms in Autonomic Control
Authors: Ferguson Alastair V.
Published: April 2011

Since the recognition in the 1970s that peptides may play more diverse physiological roles than suggested by their original recognition as circulating hormones, there has been an explosion of information regarding the potential central nervous system actions of these substances. Pharmacological binding studies have described an extensive distribution of many different groups of peptidergic receptors suggesting potential sites of action for specific peptides within the brain. Many of these receptor localizations were found within the blood brain barrier indicating that these substances were released locally and perhaps acted as neurotransmitters. Over the years, experiments demonstrating physiological effects of locally administered peptides in regions where receptors for that molecule are localized have added credibility to such a hypothesis. The explosion of interest in the peptides as potential chemical messengers within the brain has since led to the description of multiple peptidergic neuronal systems within the brain. In addition, there are now many different reports of postsynaptic effects of exogenous administration of peptides on single neurons. Similarly, many studies have reported more broad-based physiological effects resulting from actions of peptides within the central nervous system.The manuscripts that follow summarize presentations in a symposium to examine the "Central Peptidergic Mechanisms in Autonomic Control," which was part of the program at the Canadian Federation of Biological Sciences annual meeting held at Queen's University in Kingston in July of 1991. The express purpose of this symposium in its inception was to provide a forum for consideration of the CNS actions of peptides in the context of a systems physiology approach. We hoped to consider our current knowledge of the roles of peptides in the brain as they relate to the control of specific physiological systems. Therefore rather than presenting a consideration of individual peptides, and each one's multitude of potential roles, the manuscripts presented in the following section have addressed what is known of central peptidergic involvement in the physiological control of reproductive function (W. K. Samson), cardiovascular regulation (A. V. Ferguson), thermoregulatory control (Q. J. Pittman), and drinking (M. Evered).I should like to take this opportunity to thank all who contributed to this symposium, in particular the speakers without whose cooperation it would not have been possible. I am also indebted to the sponsors of the symposium: Merck Frosst, Warner Lambert, Sandoz, the Canadian Physiological Society, and the Faculty of Medicine at Queen's University, whose generous support permitted such a highly qualified group of invited speakers to attend.
Investigating the role of angiotensin II in thirst: Interactions between arterial pressure and the control of drinking
Authors: Evered Mark D.
Published: April 2011

Several lines of evidence suggest that angiotensin II plays a physiological role in the control of thirst. Establishing that, however, has been surprisingly difficult, given our current knowledge about the renin–angiotensin systems in the circulation and the brain and the variety of techniques available to measure and manipulate them. A major problem is that stimulating or blocking the renin–angiotensin system affects several physiological variables simultaneously. Since several of these variables also influence the controls of water intake directly or indirectly, the interpretation of the effect on drinking becomes more difficult. To illustrate the problem and recent developments, this paper describes some of the interactions between the effects of angiotensin II on arterial pressure and thirst, and it shows how they have contributed to the controversy over the physiological role of the peptide.Key words: renin–angiotensin system, thirst, arterial pressure.
Monophasic and biphasic effects of angiotensin II and III on norepinephrine uptake and release in rat adrenal medulla
Authors: Vatta M. S. , Bianciotti L. G. , Locatelli A. S. , Papouchado M. L. , Fernández B. E.
Published: April 2011

Angiotensin II and III have hypertensive effects. They induce vascular smooth muscle constriction, increase sodium reabsorption by renal tubules, stimulate the anteroventral third ventricle area, increase vasopressin and aldosterone secretions, and modify catecholamine metabolism. In this work, angiotensin II and III effects on norepinephrine uptake and release in rat adrenal medulla were investigated. Both angiotensins decreased total and neuronal norepinephrine uptake. Angiotensin II showed a biphasic effect only on evoked neuronal norepinephrine release (an earlier decrease followed by a later increase), while increasing the spontaneous norepinephrine release only after 12 min. On the other hand, angiotensin III showed a biphasic effect on evoked and spontaneous neuronal norepinephrine release. Both angiotensins altered norepinephrine distribution into intracellular stores, concentrating the amine into the granular pool and decreasing the cytosolic store. The results suggest a physiological biphasic effect of angiotensin II as well as angiotensin III that may be involved in the modulation of sympathetic activity in the rat adrenal medulla.Key words: angiotensin II, angiotensin III, norepinephrine uptake, norepinephrine release, adrenal medulla.
Chronic low frequency stimulation reduces myosin phosphorylation in rabbit fast twitch muscle
Authors: Klug G. A. , Biedermann M. , Houston M. E. , Stuart D. , Mumby M. , Stull J. T.
Published: April 2011

The effect of 1 – 12 days of electrical stimulation (10 Hz) on the ability to phosphorylate the P-light chain of myosin was studied in rabbit tibialis anterior muscle. Myosin phosphorylation was induced by exposure of the stimulated muscle and that of the contralateral leg to a single conditioning stimulus train (5 Hz) for 25 s via the motor nerve. Isometric tension was measured as were the myosin light chain composition and the activities of the enzymes responsible for phosphorylation and dephosphorylation. A computer simulation of the potential effect of a stimulation-induced disruption of Ca2+ metabolism on phosphorylation was also performed. Chronic stimulation for as little as 1 day eliminated light chain phosphorylation and reduced the myosin light chain kinase activity by approximately 36%. Conversely, phosphatase activity and light chain composition were unaffected. The model demonstrated that a slight depression in the magnitude of the Ca2+ transient could potentially attenuate phosphorylation. The data suggest that phosphorylation of myosin is extremely sensitive to prolonged muscle activity. Furthermore, it appears more likely that this sensitivity is related to regulation of intracellular free Ca2+ than to the other elements of the calmodulin-dependent system for myosin phosphorylation examined.Key words: myosin phosphorylation, muscle, contraction, stimulation.
Improved sensitivity of the mouse interstitial cell testosterone assay with the addition of forskolin
Authors: Debertin Werner J. , Pomerantz David K.
Published: April 2011

Modification of the mouse interstitial cell testosterone assay by the addition of 1.5 μM forskolin to the incubation medium has improved the sensitivity of this luteinizing hormone bioassay from approximately 100 to 3 pg/tube of NIH rLH RP-2. Luteinizing hormone can be clearly detected in 1 μL of serum from rats castrated 1 week previously and 5 μL of serum from intact rats. Parallelism was noted between dilution curves of serum from intact and castrated rats, and the luteinizing hormone standard curve. Luteinizing hormone detected in serum samples from 30 intact rats by the improved bioassay and by radioimmunoassay was significantly correlated (r = 0.85). Secretion patterns of circulating luteinizing hormone in individual rats were similar when detected by either bioassay or radioimmunoassay. Thus, with the addition of forskolin, the mouse interstitial cell testosterone assay has been improved so that luteinizing hormone can be detected in small volumes of serum or plasma from male rats.Key words: luteinizing hormone, bioassay, rat serum/plasma, forskolin.
Histochemical and contractile responses of rat medial gastrocnemius to 2 weeks of complete disuse
Authors: Gardiner Phillip F. , Favron Michèle , Corriveau Pierre
Published: April 2011

We studied the histochemical and in situ contractile changes in a rat ankle extensor, medial gastrocnemius, in which activation of muscle fibres by motoneurones was blocked for 14 days, using the sodium channel blocker tetrodotoxin applied to the sciatic nerve. Muscles were atrophied and showed slower twitch responses, greater fusion at subtetanic frequencies of stimulation, and higher twitch/tetanic ratios. Tetanic force/mm2 of fibre area and fatiguability were unchanged. Type II fibres were more atrophied and showed greater decreases in mitochondrial succinate dehydrogenase activity than type I fibres. The contractile changes resulting from complete disuse do not occur in models in which weight-bearing alone has been removed (space flight, hindlimb suspension), suggesting that the residual motoneurone activity reported in models of weightlessness is sufficient to prevent these responses. Similarly, the finding of a greater type II fibre susceptibility to complete disuse, which differs from the pattern seen in models of weightlessness, suggests that this residual motoneurone activity in the latter influences atrophic responses in a manner that is variable among motor unit types, to produce the reported preferential type I atrophy characteristic of removal of weight-bearing.Key words: disuse, atrophy, fibre types, succinate dehydrogenase, contractile properties.
Role of spleen in ANF-induced reduction in plasma volume
Authors: Kaufman Susan
Published: April 2011

Atrial natriuretic factor (ANF) causes an increase in hematocrit that cannot be accounted for by urinary losses. The mechanism behind this phenomenon was studied in intact and splenectomized rats. Rat ANF 99–126 was infused i.v. for 30 min into conscious rats at rates of 0 (saline control), 0.05, or 0.1 μg/min. Plasma volume was then determined by dilution of the dye, Evan's Blue. In one group of rats, red cell volume was determined using 51Cr-labelled erythrocytes. ANF infusion was continued uninterrupted throughout the experiments. In the intact rats, ANF (0.10 μg/min) caused hematocrit to increase from 38.9 ± 0.5 to 41.2 ± 0.4% (p < 0.005). Splenectomy so attenuated this response to ANF that it failed to reach significance. Similarly, ANF (0.10 μg/min) caused plasma volume to fall from 5.1 ± 0.1 to 4.5 ± 0.1 mL/100 g body wt. (p < 0.005) in the intact rats, but did not affect plasma volume in the splenectomized rats. As a result, blood volume was significantly reduced by ANF in the intact rats, but remained unchanged in the splenectomized rats. Red cell volume did not change in response to infusion of ANF, nor did ANF affect the rate of clearance of Evan's Blue out of the plasma. It is concluded that the spleen is an important site of movement of protein-poor fluid out of the vasculature, and that this exchange is influenced by ANF.Key words: spleen, ANF, blood volume, hematocrit.
Whole-cell chloride conductances in cultured brushed human nasal epithelial cells
Authors: Grygorczyk Ryszard , Bridges Michael A.
Published: April 2011

Human airway epithelial cells were obtained by nasal brushing, thus avoiding the use of proteolytic enzymes for cell isolation. Whole-cell Cl− conductances were studied in these cells by means of the patch-clamp technique. During whole-cell recordings, cell swelling activated a Cl− conductance that was blocked by indanyloxyacetic acid (48 ± 10% inhibition at 50 μM). The swelling-induced current outwardly rectified and showed inactivation at depolarizing voltages (≥ +60 mV) and activation at hyperpolarizing voltages (≤ −30 mV). The voltage sensitivity of current activation was approximately twice that of inactivation. Another Cl− current with different kinetics was observed when nonswollen airway cells were stimulated with ionomycin (2 μM) in the presence of 1 mM Ca2+. The Ca2+-induced current exhibited activation during depolarizing voltage steps (≥ +40 mV) and inactivation during hyperpolarizing voltage steps (≤ −40 mV). In contrast to the swelling-induced current, the activation of Ca2+-induced current was less sensitive to voltage compared with its inactivation. Tail current analysis suggested that Cl− channels having a linear current–voltage relation mediate the response to Ca2+. This study indicates that brushed human nasal epithelial cells possess Cl− conductances that are regulated by cell swelling and Ca2+ and that they represent a useful in vitro model for studying ion transport in epithelia.Key words: chloride channels, epithelia, airway, patch clamp.
Regional intercostal activity during coughing and vomiting in decerebrate cats
Authors: Iscoe Steve , Grélot Laurent
Published: April 2011

Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours.Key words: diaphragm, abdominal muscles, intercostal muscles.
Role of sodium and water excretion in the antihypertensive effect of vasopressin in the spontaneously hypertensive rat
Authors: Chiu E. K. Y. , Wang H. , McNeill J. R.
Published: April 2011

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (μmol∙kg−1∙min−1), and urine flow (μL∙kg−1∙min−1) were measured in conscious unrestrained spontaneously hyptertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng∙kg−1∙min−1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 ± 6.2 to 137 ± 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 ± 3 mmHg (29 ± 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague–Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion. Because the infusions of phenylephrine were associated with either a similar or greater natriuresis and diuresis than the infusions of vasopressin, it is unlikely that the large fall in arterial pressure that occurred following the withdrawal of the vasopressin infusion (the "withdrawal-induced antihypertensive phenomenon") was related to the preceding natriuresis and diuresis.Key words: vasopressin, spontaneously hypertensive rat, sodium excretion, water excretion, renal function, phenylephrine.
Recovery of rat tibialis anterior motor unit properties following partial denervation
Authors: Bell Gordon J. , Ayer Kathy , Gordon Tessa , Devashayam Suresh , Martin Thomas P.
Published: April 2011

The recovery of selected mechanical, morphological, and metabolic properties of rat tibialis anterior fast motor units was determined following partial denervation (n = 7) or partial denervation and hemispinal cord transection (n = 5) and compared with age-matched control units (n = 7). Following 1–12 months of recovery, the mechanical properties of each unit were measured and the fibres depleted of glycogen by using standard ventral root filament stimulation techniques. Quantitative histohemical techniques were used to determine cross-sectional area and the activities of succinate dehydrogenase and α-glycerolphosphate dehydrogenase in individual unit fibres. Partial denervation increased the mean fibre area but decreased α-glycerolphosphate dehydrogenase activity. Succinate dehydrogenase was unchanged in the denervated groups. The variability in area and enzymatic activities among the unit fibres was unchanged. However, the interrelationship between the enzymes was altered by both denervation procedures. Succinate dehydrogenase activity was directly related to fatigue resistance and inversely related to tetanic tension across the units. These findings suggest that a motor unit reestablishes many of its properties despite marked changes to the composition of the unit brought about by partial denervation. In addition, a reduction in the neuromuscular activity of units during reorganization had a limited effect on recovery.Key words: motor unit, succinate dehydrogenase, α-glycerolphosphate dehydrogenase, spinal cord hemisection.
Muscle metabolism in track athletes, using 31P magnetic resonance spectroscopy
Authors: McCully Kevin K. , Vandenborne Krista , DeMeirleir Kenny , Posner Joel D. , Leigh Jr. John S.
Published: April 2011

We tested whether preferred running event in track athletes would correlate with the initial rate of phosphocreatine (PCr) resynthesis following submaximal exercise. PCr recovery was measured in the calf muscles of 16 male track athletes and 7 male control subjects following 5 min of repeated plantar flexion against resistance. Pi, PCr, and pH were measured using phosphorus magnetic resonance spectroscopy (31P MRS) with an 8-cm surface coil in a 1.8-T magnet. During exercise, work levels were gradually increased to deplete PCr to 50–60% of the initial value. No drop in pH was seen in any of the subjects during this exercise. The areas of the PCr peaks following exercise were fit to monoexponential curves. Two or three tests were performed on each subject and the results averaged. Athletes were divided into three groups based on their primary event: sprinters running 400 m or less, middle-distance athletes running 400–1500 m, and long-distance athletes running farther than 1500 m. The maximal rates of PCr resynthesis (mmol∙min−1∙kg−1 muscle weight) were 64.8 ± 8.6, for long-distance runners; 41.4 ± 11, for middle-distance runners; 32.0 ± 7.0, for sprinters; and 38.6 ± 10, for controls (mean ± SE). The faster PCr recovery rates seen in long-distance runners compared with sprinters indicate greater oxidative capacity, which is consistent with the known differences between athletes in these events.Key words: exercise recovery, human, phosphocreatine.
Effects of acute swimming exercise on muscle and erythrocyte malondialdehyde, serum myoglobin, and plasma ascorbic acid concentrations
Authors: Koz Mitat , Erbaş Deniz , Bilgihan Ayşe , Aricioğlu Aysel
Published: April 2011

Acute exercise may induce free-radical production in mitochondria during basal metabolism of aerobic cells. Ascorbic acid is a strong antioxidant agent, whereas myoglobin is known to act as an oxygen reservoir. The purpose of this study was to investigate the effects of acute exercise on malondialdehyde levels in gastrocnemius, vastus medialis, and triceps brachi muscles and erythrocytes. In addition, we investigated the ascorbic acid levels and serum myoglobin concentrations in rats, following acute swimming exercise. We found that the levels of muscle malondialdehyde and serum myoglobin increased and the levels of plasma ascorbic acid decreased, in proportion to the duration of exercise; however, the levels of erythrocyte malondialdehyde did not change.Key words: lipid peroxidation, malondialdehyde, myoglobin, ascorbic acid, acute swimming exercise.
Impact of enalapril therapy on in vitro coronary artery responsiveness in pacing-induced heart failure
Authors: Forster Christine , Larosa Giulia , Armstrong Paul W.
Published: April 2011

In vitro coronary artery responsiveness to angiotensin I, angiotensin II, noradrenaline, phenylephrine, BHT 920, and potassium chloride together with functional relaxation to acetylcholine was investigated in dogs with pacing-induced heart failure treated with enalapril (oral administration of 10 mg∙day−1) for a mean duration of 26 days. Although maximal responses generated to both angiotensin I and angiotensin II were unaltered in the enalapril-treated group, angiotensin II became more potent following enalapril treatment: the EC50 for angiotensin II following placebo treatment was 2.4 (0.6–5.8; 95% confidence limits) nM and following enalapril treatment was 0.03 (0.007–0.1; 95% confidence limits) nM. In addition to the above changes, coronary artery rings from dogs treated with enalapril developed significantly less tension to noradrenaline, phenylephrine, and BHT 920. In contrast, responses to potassium chloride were unaltered following enalapril treatment. However, the relaxation to acetylcholine was enhanced from 38.9 ± 3.0 to 50.4 ± 3.5% (placebo versus enalapril, p < 0.05). These findings indicate that enalapril may possess α-blocking properties and enhance the relaxation response to acetylcholine through an endothelial-dependent mechanism in addition to inhibiting converting enzyme.Key words: congestive heart failure, converting enzyme inhibitors, α-agonists, angiotensin, endothelium.
Effects of chronic hypoxia on the whole-body insulin action in rats
Authors: Fushiki T. , Kano T. , Ito K. , Hirofuji C. , Inoue K. , Moritani T. , Sugimoto E.
Published: April 2011

The effect of chronic hypoxia on the whole-body insulin action in rats was investigated. Rats were kept in a hypobaric hypoxia chamber maintained at a simulated altitude of 4000 m for 10 weeks. At the end of the experimental period, the mean body weight of the hypoxic rats was significantly lower than that of the control rats. The muscle weight to body ratio of the quadriceps muscle in hypoxic rats was larger than that in control rats, but those of the gastrocnemius, soleus, and extensor digitorum longus muscles did not differ between the control and hypoxic rats. On the other hand, the epididymal fat pads of hypoxic rats were markedly smaller than those of the control rats. The results of a euglycemic clamp experiment with infusions of 14 and 3.6 mU insulin∙kg−1∙min−1 indicated that the steady-state glucose infusion rate was not statistically different between hypoxic and control rats. It is suggested that chronic hypoxia did not influence the whole-body insulin action on glucose transport activity.Key words: hypoxia, insulin action, glucose clamp.
Aminergic and peptidergic elements and actions in a cardiac parasympathetic ganglion
Authors: Konopka Lukasz M. , Merriam Laura A. , Hardwick Jean C. , Parsons Rodney L.
Published: April 2011

Correlated histochemical, immunocytochemical, and electrophysiological experiments have been undertaken to identify putative neurotransmitter–neuromodulator substances in cells and fibers in the parasympathetic cardiac ganglion of the mudpuppy, Necturus maculosus, and to determine the action of these agents on the properties of the parasympathetic postganglionic neurons. The mudpuppy cardiac ganglion contains two neuron types: large parasympathetic postganglionic neurons and smaller intrinsic neurons initially identified as small intensely fluorescent cells. We have shown that the postganglionic neurons contain both acetylcholine and a galanin-like neuropeptide. Also, we have demonstrated that the intrinsic neurons contain a number of different biogenic amines such as dopamine and serotonin, as well as neuropeptides including a substance P-like peptide and a galanin-like peptide. The results of these studies indicate that the anatomical and histochemical organization of the mudpuppy cardiac ganglion is more complex than that seen in other amphibians and is very similar to that found in most mammalian species. Previously, we showed that galanin has actions that make it of interest as a potential inhibitory neurotransmitter in the mudpuppy cardiac ganglion. Galanin hyperpolarizes and decreases membrane excitability in most parasympathetic neurons. Here we show that galanin initiates membrane hyperpolarization by activating a voltage- and time-dependent potassium conductance. We also present the initial results of ongoing studies which indicate that calcitonin gene-related peptide can depolarize some of the parasympathetic neurons as well as evidence that serotonin initiates depolarization in many parasympathetic neurons. This serotonin-induced depolarization consists of an initial transient depolarization followed by a longer, more slowly developing depolarization. Action potential activity is stimulated during the initial period of depolarization, but depressed during the later, slow depolarization. The results of these electrophysiological experiments suggest that many of the bioactive substances that have been identified in the different cells and nerve fibers within the cardiac ganglion affect the excitability of the postganglionic neurons. In conclusion, we suggest that the results of the studies summarized in this review demonstrate that the cardiac ganglion in the mudpuppy is not simply a relay station. Rather, the cardiac ganglion has a complex organization and exhibits a diversity of physiological responses, indicating that it very likely is another site of integration for control of cardiac function.Key words: parasympathetic neurons, cardiac ganglion, neuropeptides, biogenic amines, galanin, serotonin.
Energy Metabolism and Effects of Energy Depletion or Exposure to Glutamate
Authors: Sokoloff Louis
Published: April 2011

The entire program of the first day of the IBRO satellite meeting entitled Ions, Water, and Energy in Brain Cells was devoted to the subject of energy. There were three sessions on the topics of energy metabolism, activation, and development and pathological conditions, followed by a final general discussion on the contents of the day's topics. During this general discussion there were spirited exchanges on the role of glycogen in the energy metabolism of the brain, on the metabolic source of the energy consumed by functional activity, e.g., glycolytic or oxidative energy metabolism, and on the sources of the acid-equivalents that are responsible for the tissue acidosis accompanying cerebral hypoxia. Despite the arguments pro and con presented on all of the issues that were discussed, it is doubtful that a consensus was achieved on most of the issues.Key words: glycogen, glycolysis, oxidative metabolism, acidosis, energy metabolism.
Oxidative metabolism in neuronal and non-neuronal mitochondria
Authors: Lai James C. K.
Published: April 2011

Methodological advances have allowed the isolation of two populations of synaptic (SM and SM2) and two populations of nonsynaptic (A and B) mitochondria from rat forebrain. All four populations of brain mitochondria are metabolically active and essentially free from nonmitochondrial contaminants. They (SM, SM2, A, and B) can oxidize a variety of substrates; the best substrate is pyruvate. With pyruvate as the substrate, the respiratory control ratios (i.e., state 3/state 4) in all four populations are routinely >6. Results from numerous enzyme activity measurements provide strong support for the hypothesis that brain mitochondria are very heterogeneous with respect to their enzyme contents and that the enzymatic activities in a particular population of mitochondria, be they synaptic or nonsynaptic, differ from those in another population of mitochondria derived from either the same or another brain region. The major methodological advances in brain mitochondrial isolation greatly facilitate metabolic studies. For example, we have demonstrated that the K+ stimulation of brain mitochondrial pyruvate oxidation is mediated through a K+-induced elevation of the activation state of the pyruvate dehydrogenase complex and the K+ stimulation of the flux through the pyruvate dehydrogenase complex. Our previous and ongoing studies using primary cultures of hypothalamic neurons and astrocytes are consistent with the proposal that brain cells are heterogeneous with respect to their capabilities in energy metabolism. I can envisage that in the not-so-distant future, one could adapt these preparations of cells as the starting material for the isolation of mitochondria of known cellular origin for metabolic studies.Key words: heterogeneity of brain mitochondria, regulation of intermediary metabolism.
Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies on retina
Authors: Ames III Adelbert
Published: April 2011

CNS tissue is well known to have large energy requirements. However, because of the difficulty of measuring rates of energy usage, relatively little is known about which cell types and which neurophysiological functions are the principal energy users. In experiments performed on rabbit retina in vitro, it was possible to measure O2 consumption and lactate production with the retinas under resting conditions and in different states of physiological activity. Resting energy consumption was large, as has been previously reported, and there were increases of up to 2.3 times with activity. Under some circumstances, the demands appeared to exceed the energy available. It was calculated that less than 5% of the energy generated by the retina was used for "vegetative metabolism" (i.e., for the anabolic reactions essential for viability), so that even in the resting state, the great majority of the energy usage appeared to be for function-related processes. This conclusion received further support from the finding that 50% of the energy generated was used for Na+ transport. The data obtained on retina are compared with published data on brain, which also suggest that a large fraction of the energy generated is used for function-related processes. It seems reasonable to conclude that by reversibly blocking the energy-demanding processes responsible for neurophysiological functioning, it would be possible to eliminate most of the energy requirements of CNS tissue and to reduce markedly its vulnerability to hypoperfusion.Key words: energy metabolism, oxygen consumption, glycolysis, neurophysiological function, sodium transport, ischemia.
Anoxia-induced extracellular ionic changes in CNS white matters: the role of glial cells
Authors: Ransom Bruce R. , Philbin Jr. Daniel M.
Published: April 2011

The rapid changes in brain extracellular ion concentrations that occur with anoxia are important in understanding the pathophysiology of anoxic – ischemic brain injury. While previous studies have focused on the ionic changes that occur in gray matter areas of the brain, white matter (WM) is also damaged by anoxia. We describe the changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) that accompany anoxia in WM, and present new results indicating that glial cells directly contribute to the observed fluctuations of these ions. Anoxia-induced changes in [K+]o and pHo were measured with ion-selective microelectrodes in the isolated rat optic nerve, a typical WM tract. To assess the contribution of glial cells, recordings were also made in optic nerves that contained only glial cells (produced by neonatal enucleation). Anoxia in WM produced less extreme changes in [K+]o and pHo than are known to occur in gray matter; in WM during anoxia, the average maximum [K+]o was 14 ± 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 ± 0.07 pH unit. These extracellular ionic changes were accompanied by rapid shrinkage of extracellular space volume. The ability of optic nerve axons to conduct action potentials was lost in temporal association with the increase in [K+]o. Increasing bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 ± 0.08 pH unit) and a smaller average increase in [K+]o (9.2 ± 2.6 mM). The increased glucose concentration presumably enhanced anaerobic metabolism, leading to extracellular lactate accumulation and a greater acid shift. More ATP would be available for operation of ion pumps, including the sodium pump, and this would result in less dramatic changes in [K+]o. The optic nerve showed significantly less irreversible damage after 60 min of anoxia in the presence of 20 mM glucose compared with 10 mM glucose. In the pure glial nerve, anoxia caused a 1.2 ± 1.1 mM increase in [K+]o and a 0.10 ± 0.04 unit decline in pHo, with time courses similar to the analogous changes in intact nerves. The small magnitude of these anoxia-induced changes in the glial preparation probably results in part from technical factors having to do with the small size of the pure glial nerves. The magnitude of the changes in the pure glial nerves was influenced by bath glucose concentration, with anoxia in 0 mM glucose producing a 1.7 ± 0.4 mM increase in [K+]o, and a 0.05 ± 0.06 unit decrease in pHo. We conclude that glial cells directly contribute to the ionic changes observed during anoxia in WM.Key words: ions, ischemia, glucose, optic nerve, compound action potential, ion-selective electrodes.
Overlapping and diverse distribution of Na–K ATPase isozymes in neurons and glia
Authors: Sweadner Kathleen J.
Published: April 2011

The Na–K ATPase is the plasma membrane enzyme that catalyzes the active uptake of K+ and extrusion of Na+, thereby establishing ion concentration gradients between the inside and outside of the cell. It consumes a large fraction of the energy used in the brain. The enzyme is present in both neurons and glia. Studies of ion flux and of the properties of membrane-associated ATPase activity have suggested that there is more than one functional type of Na–K ATPase in the central nervous system. Molecular cloning has demonstrated that there are three different genes encoding catalytic (α) subunits and at least two genes encoding glycoprotein (β) subunits; all are expressed in the brain. This brief review summarizes the current understanding of Na–K ATPase isozyme distribution and properties. Both neurons and glia can express different isoforms in a cell-specific manner.Key words: Na–K ATPase, monoclonal antibody, immunofluorescence, central nervous system, retina, in situ hybridization.
Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV)
Authors: Yuen Violet G. , Orvig Chris , Thompson Katherine H. , McNeill John H.
Published: April 2011

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 ± 0.07 μg/mL (16.8 μM) in CT rats and 0.76 ± 0.05 μg/mL (15.2 μM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 ± 3.0 μg/g (0.37 μmol/g) in CT and 26.4 ± 2.6 μg/g (0.53 μmol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and −dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.Key words: bis(maltolato)oxovanadium(IV), vanadium, diabetes, streptozotocin, myocardial dysfunction.
Cultured endothelial cells from distinct vascular areas show differential responses to agonists
Authors: Woodley N. , Barclay J. K.
Published: April 2011

Nous avons comparé la capacité des cellules endothéliales isolées de l'aorte, de la veine cave, de la chambre ventriculaire et du système microvasculaire pulmonaire du lapin de produire un ou des facteurs de relaxation en réponse à l'acetylcholine (ACh) et à la bradykinine (BK). Des anneaux aortiques de lapin dépouillés d'endothélium ont été précontractés avec 1 μM de phényléphrine et superfusés à 2 mL/min avec une solution tampon bicarbonatée de Krebs–Henseleit. Les anneaux ont été exposées à des épreuves témoins d'embols de 3 mL de 1 μM d'ACh ou 1 μM de BK. Les embols d'ACh et de BK ont été ajoutés à des cultures de cellules endothéliales qui avaient été incubées pendant 45 min dans des milieux contenant ou non 10 μM de NG-nitro-L-arginine (NNLA). La solution ainsi obtenue a été répandue sur les anneaux en moins de 8 s. Seules les cellules endothéliales ventriculaires gauches stimulées avec ACh et BK et les cellules endothéliales microvasculaires pulmonaires stimulées avec BK ont donné des produits qui ont relaxé les anneaux d'approximativement 6 ± 2%. L'incubation avec la NNLA a atténué ces relaxations. Nos résultats indiquent qu'il existe des différences dans la capacité des cellules endothéliales de divers sites anatomiques de libérer des facteurs de relaxation dérivés de l'oxyde nitrique en réponse à l'ACh et à la BK. Mots clés : facteur de relaxation dérivé de l'endothélium, aorte, dosage biologique in vitro, acétylcholine, bradykinine, superoxyde dismutase, nitroprussiate de sodium.[Traduit par la rédaction]
The basal endothelial inhibitory influence on vascular tone is not affected in nitroglycerin-tolerant rat aorta
Authors: Voorde J. Van de , Vyt S. , Vanheel B.
Published: April 2011

Prolonged exposure to nitrovasodilators produces tolerance and dependence. Nitrovasodilators exert their action on vascular smooth muscle cells by activation of guanylyl cyclase. Nitrates share this mechanism with endothelial NO, which exerts a continuous inhibitory influence on vascular tone. Whether the basal inhibitory endothelial influence might be affected in rat aorta exposed in vitro to a tolerance-inducing concentration of nitroglycerin was investigated in this study. It was found that the basal inhibitory influence, assessed as its inhibitory influence on norepinephrine-induced contraction, and as the contractile effect of N-nitro-L-arginine methyl ester or methylene blue, was the same in nitroglycerin-tolerant and control aortic rings. Our results give an indication that changes in basal inhibitory endothelial influence are not involved in the phenomena of nitrate tolerance and nitrate dependence.Key words: nitroglycerin, nitrates, tolerance, endothelium, nitric oxide.
Excitatory cardiovascular and respiratory effects of baclofen in intact rats
Authors: Trippenbach Teresa , Lake Norma
Published: April 2011

The rat has become the preferred animal model for study of the central control of the cardiorespiratory system. However, data in the literature suggest that the role of GABAB receptors in control of the respiratory timing may be different in rats from that in other species. Therefore in this study we investigated cardiorespiratory effects of repeated injections of 0.5 nM baclofen and 50 nM CGP35348, GABAB receptor agonist and antagonist, respectively, applied into the fourth ventricle of urethane-anesthetized intact, spontaneously breathing Wistar rats. Baclofen increased arterial blood pressure (ABP), heart rate, inspiratory time (Ti), and the rate of rise (Di/t) and peak amplitude of the integrated diaphragmatic EMG (Di). Expiration (Te) was unaffected. CGP35348 reversed the ABP and Di effects of baclofen and decreased Di/t and Te below their control values, whereas Ti remained prolonged. These excitatory effects of baclofen are consistent with previously reported effects of low i.v. doses of baclofen in cats, and suggest that GABAB receptors may modulate the depth and duration of inspiration. We conclude that the intact rat represents a suitable animal model for investigations of the integrated control of cardiorespiratory functions. To our knowledge this is the first investigation reporting excitatory effects of GABAB receptor stimulation on inspiratory activity in rats. The depressant effects of baclofen on the respiratory rhythm reported in the rat "isolated" brain in situ, and the neonatal rat brainstem – spinal cord in vitro seem to be unique for those specific preparations.Key words: baclofen, CGP35348, fourth ventricle, rat.