bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects on net fluid transport of noxious stimulation of jejunal mucosa in anaesthetized rats
Authors: Peregrin A. Timar , Svensson  , Ahlman  , Jodal  , Lundgren
Published: March 2003

A major aim of the present study was to investigate whether exposing the jejunal mucosa to a noxious stimulus induces a net fluid secretion by activating the enteric nervous system (ENS) and, if so, to what extent an axon reflex was involved. Net fluid transport was measured in vivo with a gravimetric method. The intestinal mucosa was exposed to an isotonic solution with an unphysiologically low pH (1.0). This evoked a fluid secretion, which was markedly attenuated by giving hexamethonium (nicotinic receptor antagonist) i.v. or exposing the intestinal serosa to lidocaine (local anaesthetic). Atropine (muscarinic receptor antagonist) had no effect. Luminal acid evoked a fluid secretion of the same magnitude in acutely denervated segments and in segments denervated about 3 weeks prior to the experiments. Luminal capsaicin (1.6–16 m
M) did not influence jejunal net fluid transport. A second aim of the study is to investigate the effect of nifedipine (Ca channel blocker of L‐type) on the acid‐induced fluid secretion. Nifedipine markedly attenuated acid‐induced fluid secretion. In contrast to cholera toxin‐evoked secretion, the nifedipine effect was not mediated via 5‐hydroxytryptamine (5‐HT) as judged by measurements of 5‐HT release into the intestinal lumen and the lack of effect of granisetron (5‐HT3 receptor antagonist). It is concluded that the net fluid secretion evoked by hydrochloric acid in the small intestine is mainly mediated via an intramural reflex in the ENS. No experimental evidence was obtained for the involvement of an axon reflex. The site of action of the calcium channel blocker is tentatively discussed.
Mechanisms for activation of aortic baroreceptor C‐fibres in rabbits and rats
Authors: Thoren  , Munch  , Brown
Published: March 2003

In an earlier study, we examined the pressure–response characteristics of rat aortic baroreceptors with C‐fibre (non‐medullated) afferents. Compared with aortic baroreceptor fibres with A‐fibre (medullated) afferents, the C‐fibres were activated at higher pressures and discharged more irregularly when stimulated with a steady level of pressure. Here we examine the relationship between discharge and the aortic diameter in these two types of afferents in rats and rabbits. An in vitro aortic arch/aortic nerve preparation was used to record single‐fibre activity simultaneously with aortic arch pressure and diameter. Diameter was measured using a highly sensitive non‐contact photoelectric device. Baroreceptor discharge was characterized by stimulating the nerve endings with either slow pressure ramps from subthreshold to 200–250 mmHg, at a rate of rise of 2 mmHg s−1, or pressure steps from subthreshold to suprathreshold levels, at amplitudes of 110–180 mmHg. In response to these inputs, C‐fibres in rabbits (conduction velocities= 0.8–2.2 m s−1) behaved much like those in rats. The C‐fibres had significantly higher pressure thresholds (95 ± 3 mmHg vs. 53 ± 2 mmHg; mean ± SEM), lower threshold frequencies (2.4 ± 0.5 vs. 27.7 ± 1.8 spikes s−1), lower maximum discharge frequencies (22.7 ± 2.3 vs. 65 ± 5.8 spikes s−1) and more irregular discharge in response to a pressure step when compared with A‐fibres (conduction velocities of 8–16 m s−1). When plotted against diameter, C‐fibre ramp‐evoked discharge increased gradually at first, and then rose steeply at increasingly higher ramp pressures where aortic diameter became relatively constant. In contrast, A‐fibre discharge was linearly related to diameter over a wide range of pressure. These results suggest two interpretations: (1) The relation between stretch and C‐fibre discharge is highly non‐linear, with a marked increase in sensitivity at large diameters. (2) C‐fibres are stimulated by changes in intramural stress rather than stretch.
Physiological and morphological effects of perfusing isolated rat kidneys with hyperosmolal mannitol solutions
Authors: Lindström  , Rönnstedt  , Jaremko  , Haraldsson
Published: March 2003

Recently, we were able to modify the glomerular charge barrier using perfusates with low and normal ionic strengths keeping the osmolality unchanged. The concentration of fixed charges was reversibly reduced from 35 to 12 mEq L–1 as the solution with low content of NaCl was introduced with no apparent effect on the size selectivity. It can be argued however, that the mannitol used for maintenance of osmolality may induce changes in glomerular permeability per se. To explore this possibility, isolated kidneys were perfused at 8° with hyperosmolal mannitol solutions (560 mOsm) and compared with those perfused with standard albumin solutions (295 mOsm). The vascular resistance (PRU100) fell from 0.14 ± 0.01 to 0.11 ± 0.01 mmHg min 100 g mL–1 as the mannitol solution was introduced (P < 0.001). As the blood pressure should remain unchanged, the flow was increased from 8 to 11 mL min–1. The glomerular filtration rate (GFR) increased by 50% from 320 ± 40 to 490 ± 20 μL min−1 g–1 (P < 0.001). Despite these changes in haemodynamical parameters, there was no significant change in the fractional clearance for albumin. Kidneys perfused with the mannitol solution showed well‐preserved histology, while there was a conspicuous collapse of the cortical tissue and signs of tubular epithelial swelling with the standard perfusate. Moreover, all glomeruli were perfused in the mannitol group, as revealed by fluorescence of FITC dextran, while the distribution was uneven in the control kidneys. We conclude that perfusion of isolated kidneys with a hyperosmolal mannitol solution increased GFR by increasing the number of functionally active nephrons with no apparent effect on the glomerular barrier, a pattern differing from alteration of ionic strength.
Effects of oxytocin on the IGF‐axis and some gastrointestinal hormones in ad libitum fed and food‐restricted female rats
Authors: Sohlström  , Brismar  , Carlsson‐Skwirut  , Bang  , Uvnäs‐Moberg
Published: March 2003

The aims of this study were to investigate if administration of oxytocin to ad libitum fed and food‐restricted female rats affects weight gain, body fatness, the IGF‐axis, and some vagally mediated gastrointestinal hormones, such as gastrin, cholecystokinin (CCK) and somatostatin. Ad libitum fed and food‐restricted (receiving 70% of the food intake of the ad libitum fed group) female rats were injected subcutaneously, once a day, for 10 days, with saline (control) or oxytocin (1 mg kg–1 bodyweight). The animals were killed 5 days after the last injection. Oxytocin‐treated food‐restricted females had more body fat and lower plasma levels of IGF‐I, IGFBP‐1 and IGFBP‐3 compared with saline‐treated counterparts. Oxytocin‐treated ad libitum fed rats also had lower plasma levels of IGFBP‐1 but contained less body fat, compared with saline‐treated counterparts. There was no effect of oxytocin treatment on body weight or weight gain in either of the feeding groups. Except for gastrin, which was lower, there was no effect of oxytocin on the gastrointestinal hormones studied. The results indicate that oxytocin treatment influences fat deposition and the IGF‐axis in female rats, but that the results are dependent on the nutritional status of the animal.
Effects of [Na+]o, [Ca2+]o and cyclopiazonic acid on decline of post‐extrasystolic potentiation and twitch kinetics in guinea‐pig and human myocardial preparations
Authors: Ásgrimsson  , Wohlfart  , Brandt  , Jóhannsson
Published: March 2003

The decline of post‐extrasystolic potentiation was investigated in atrial and ventricular muscle of guinea‐pigs and in human atrial muscle. This decline is described in terms of the recirculation fraction (RF) for calcium in myocardial cells. Under control conditions, the mean values for RF were as follows: 0.61 ± 0.03 in the guinea‐pig atrium, 0.32 ± 0.05 in the guinea‐pig ventricle and 0.51 ± 0.10 in the human atrium. Upon increasing calcium concentrations within the range of 0.5–10 m M or decreasing the sodium to 70%, the steady‐state force and recirculation fraction increased concomitantly in all three types of muscles. Cyclopiazonic acid (CPA), in a 5–20 μM concentration, decreased force in the guinea‐pig preparations and decreased RF. The effects of CPA were great in atrial muscle, 20 μM CPA decreasing RF from 0.61 to 0.39. In ventricular muscle, this effect was small and not statistically significant. When changing calcium or sodium concentrations, increased force was accompanied by slower relaxation in atrial muscle, but an unchanged or slightly faster relaxation in ventricular muscle. In guinea‐pig myocardium, CPA (5–20 μM) prolonged the time to peak force (TPF), but it slowed relaxation only in the ventricle. Reducing the calcium outflow by Na/Ca exchange increased RF as expected, and reducing the SR calcium re‐uptake decreased RF. These interventions were also expected to reduce the rate of decline of intracellular calcium, but relaxation was not consistently prolonged. This indicates that factors other than the SR calcium pump and sarcolemmal Na/Ca exchange determine, or at least influence, the rate of relaxation.
Oxygen cost of dynamic leg exercise on a cycle ergometer: effects of gravity acceleration
Authors: Girardis  , Linnarsson  , Moia  , Pendergast  , Ferretti
Published: March 2003

A model of the metabolic internal power (Ėint) during cycling, which includes the gravity acceleration (ag) as a variable, is presented. This model predicts that Ėint is minimal in microgravity (0 g; g=9.81 m s–2), and increases linearly with ag, whence the hypothesis that the oxygen uptake (V˙O2) during cycling depends on ag. Repeated V˙O2 measurements during steady‐state exercise at 50, 75 and 100 W on the cycle ergometer, performed in space (0 g) and on Earth (1 g) on two subjects, validated the model. V˙O2 was determined from the time course of decreasing O2 fraction during rebreathing. The gas volume during rebreathing was determined by the dilution principle, using an insoluble inert gas (SF6). Average V˙O2 for subject 1 at each power was 0.99, 1.21 and 1.52 L min–1 at 1 g (n=3) and 0.91, 1.13 and 1.32 L min–1 at 0 g (n=5). For subject 2 it was 0.90, 1.12 and 1.42 L min–1 at 1 g, and 0.76, 0.98 and 1.21 L min–1 at 0 g. These values corresponded to those predicted from the model. Although resting V˙O2 was lower at 0 g than at 1 g, the net (total minus resting) exercise V˙O2 was still smaller at 0 g than at 1 g. This difference reflects the lower Ėint at 0 g.
Neuromuscular fatigue during repeated exhaustive submaximal static contractions of knee extensor muscles in endurance‐trained, power‐trained and untrained men
Authors: Pääsuke M. , Ereline J. , Gapeyeva H.
Published: March 2003

The neural and muscular changes during fatigue produced in repeated submaximal static contractions of knee extensors were measured. Three groups of differently adapted male subjects (power‐trained, endurance‐trained and untrained, 15 in each) performed the exercise that consisted of 10 trials of submaximal static contractions at the level of 40% of maximal voluntary contraction (MVC) force till exhaustion with the inter‐trial rest intervals of 1 min. MVC force, reaction time and patellar reflex time components before and after the fatiguing exercise and following 5, 10 and 15 min of recovery were recorded. Endurance‐trained athletes had a significantly longer holding times for all the 10 trials compared with power‐trained athletes and untrained subjects. However, no significant differences in static endurance between power‐trained athletes and untrained subjects were noted. The fatigue test significantly prolonged the time between onset of electrical and mechanical activity (electromechanical delay) in voluntary and reflex contractions. The electromechanical delay in voluntary contraction condition for power‐trained and untrained subjects and in reflex condition for endurance‐trained subjects had not recovered 15 min after cessation of exercise. No significant changes in the central component of visual reaction time (premotor time of MVC) and latency of patellar reflex were noted after fatiguing static exercise. It is concluded, that in this type of exercise the fatigue development may be largely owing to muscle contractile failure.
The role of the L‐arginine/nitric oxide pathway in myocardial ischaemic and reperfusion injury
Authors: Pernow  , Wang
Published: March 2003

Myocardial ischaemia followed by reperfusion (I/R) is associated with impaired endothelial function including diminished release and/or effects of nitric oxide (NO) which may contribute to the development of I/R injury. The aim of the present study was to investigate the role of the L‐arginine/NO pathway in myocardial I/R injury. In isolated rat hearts subjected to global ischaemia followed by reperfusion
L‐arginine and the NO donor S‐nitroso‐N‐acetyl‐
D,
L‐penicillamine (SNAP), but not
D‐arginine, significantly enhanced the recoveries of mycardial performance and coronary flow, and reduced the area of no‐reflow and creatine kinase outflow. The NO synthase inhibitor NG‐nitro‐
L‐arginine (
L‐NNA) abolished the protective effects of
L‐arginine. Endothelium‐dependent vasodilatation after I/R was preserved in
L‐arginine treated but not in vehicle hearts. Following I/R Ca2+‐dependent NO synthase activity was reduced by 90% in comparison with non‐ischaemic hearts.
L‐arginine but not
D‐arginine significantly increased NO synthase activity. In anaesthetized pigs,
L‐arginine given by local coronary venous retroinfusion reduced myocardial infarct size induced by 45 min of coronary artery ligation and 4 h of reperfusion to 35% of the area at risk from 76% in controls. The protective effect of
L‐arginine was blocked by
L‐NNA. Acetylcholine‐induced coronary vasodilatation following I/R was attenuated in controls but not in
L‐arginine treated pigs. It is concluded that
L‐arginine or the NO donor SNAP reduces I/R‐induced myocardial and endothelial injury. The protective effect of
L‐arginine seems to be mediated through maintained production of NO by preserving the function of Ca2+‐dependent NO synthase in the heart.
The effects of exercise duration on adrenal HSP72/73 induction in rats
Authors: Demirel  , Powers  , Naito  , Tumer
Published: March 2003

This study investigated the effects of varying durations of exercise training on heat shock proteins 72 and 73 (HSP72/73) induction in the rat adrenal gland. Female Sprague–Dawley rats (120 days old) were assigned to either a sedentary control group (C) or one of the three endurance exercise training groups. Trained animals ran on a treadmill at ≈75% VO2max for 10 weeks (4–5 days week–1) at one of the three different exercise durations (30 min day–1=T30, 60 min day–1=T60, or 90 min day–1=T90). All durations of exercise training resulted in an increase in the HSP72 levels (P < 0.0001). The magnitude of the training‐induced elevation in the HSP72 levels in the adrenal gland increased as a function of the training duration (≈60‐fold increase in T90; ≈40‐fold increase in T60; and ≈15‐fold increase in T30). Longer exercise durations (>60 min day–1), also resulted in small but significant increase in HSP73 level (≈1.2‐fold increase in both T60 and T90; P < 0.05). These results demonstrate that the physiological stress created by chronic treadmill running can induce both HSP72 and HSP73 in rat adrenal gland. Increased levels of adrenal HSP72/73 expression during rigorous exercise, may be one of the adaptive mechanisms of the adrenals to cope with an increased dose of stress.
The influence of thyroid hormone on myosin isoform composition and shortening velocity of single skeletal muscle fibres with special reference to ageing and gender
Authors: Yu  , Degens  , Larsson
Published: March 2003

This review summarizes the effects of altered thyroid hormone levels on the expression of myosin isoforms and contractility in single muscle fibres from fast‐ and slow‐twitch muscles from young and old male and female rats. The differences between male and female hyperthyroid soleus muscles are suggested to be related to an interaction of thyroid hormones and sex hormones in the regulation of myosin gene expression. Additionally, the mismatch between the protein and mRNA levels of MyHCs between male and female hyperthyroid extensor digitorum longus (EDL) muscles raises the possibility of a gender‐related difference in post‐transcriptional, translational or post‐translational regulation of MyHC isoforms by T3.
Sarcoplasmic reticulum in aged skeletal muscle
Authors: Margreth  , Damiani  , Bortoloso
Published: March 2003

A decrease in muscle mass and strength and a slowing of muscle contraction are common features of the ageing process. Recent advances in basic biochemical knowledge have provided new insights into pathogenetic mechanisms underlying age‐related changes in the excitation–contraction coupling process, Ca2+‐transients and isometric twitch‐contraction time. Sarcoplasmic reticulum (SR) Ca2+‐pumps are not basically altered in physiological ageing, but several aspects of the Ca2+‐transport system remain controversial, regarding phosphorylation‐dependent regulation in slow‐twitch muscles, in particular. It seems that conflicting reports and divergent interpretations concerning the effect of ageing on SR Ca2+‐release arise from the type of muscle, the stage of the ageing process and the animal species. A cause–effect relationship between the decrease in dihydropyridine receptors and in muscle strength is strongly suggested by studies in transgenic mice, but is unsupported by our studies with fast‐twitch and slow‐twitch muscles of old rats. Our experimental evidence also seems to exclude the occurrence of age‐related changes in the number and in the functional behaviour of Ca2+‐release channels/ryanodine receptors (RyR1), based on [3H]‐ryanodine binding studies. There is emerging, although only suggestive evidence, so far, that modulation of RyR1 by SR luminal protein calsequestrin, or the functional coupling of RyRs by FKBP‐12, may be altered in ageing skeletal muscle.
Sequential changes of [3H]forskolin, [3H]cyclohexyladenosine and [3H]PN200‐110 binding sites in the brain of 6‐hydroxydopamine‐lesioned rats
Authors: Araki  , Tanji  , Kato  , Imai  , Mizugaki  , Itoyama
Published: March 2003

Receptor autoradiographic technique was studied to investigate sequential changes in adenylyl cyclase, adenosine A1receptors andL‐type calcium channels in the striatum and substantia nigra 1–8 weeks after unilateral 6‐hydroxydopamine injection of the medial forebrain bundle in rats. [3H]Forskolin, [3H]cyclohexyladenosine (CHA) and [3H]PN200‐110 were used to label adenylyl cyclase, adenosine A1receptors andL‐type calcium channels, respectively. The degeneration of the nigrostriatal pathway caused a significant increase in [3H]forskolin binding in the striatum of both the ipsilateral and contralateral sides from 2 to 4 weeks post‐lesion. The ipsilateral substantia nigra showed a transient increase in [3H]forskolin binding 4 weeks post‐lesion. In contrast, [3H]CHA binding showed no significant change in most brain areas after lesioning. On the other hand, a conspicuous decrease in [3H]PN200‐110 binding was observed in the dorsolateral striatum of ipsilateral side 4 weeks post‐lesion. Thereafter, the striatum of both the ipsilateral and contralateral sides showed a significant decrease in [3H]PN200‐110 binding 8 weeks post‐lesion. These results demonstrate that unilateral 6‐hydroxydopamine into the medial forebrain bundle of rats can experimentally cause a significant increase in adenylyl cyclase binding sites in the striatum and substantia nigra, whereas no conspicuous change in adenosine A1receptors is observed in these areas during post‐lesion. In contrast,L‐type calcium channels were progressively damaged in the striatum after unilateral 6‐hydroxydopamine treatment. These findings suggest that adenylyl cyclase and calcium system may contribute to the degeneration processes of the dopaminergic neurones.
Deficits in nitric oxide production after tetanic stimulation are related to the reduction of long‐term potentiation in Schaffer‐CA1 synapses in aged Fischer 344 rats
Authors: Mori  , Togashi  , Matsumoto  , Yoshioka
Published: March 2003

In the present study, we investigated whether nitric oxide (NO) production after tetanic stimulation is involved in long‐term potentiation (LTP) in Schaffer‐CA1 synapses in both young adult and aged rats. The changes in both the population spike amplitude and NO metabolites, nitrite (NO2–) and nitrate (NO3–), in the CA1 region were simultaneously determined before and after tetanic stimulation. Increases in NOx (NO2– plus NO3–) levels in the CA1 region were observed after tetanic stimulation in young adult rats as well as increase in the population spike amplitude. In aged rats, LTP was significantly inhibited compared with that in young adult rats. No increase in NOx level after tetanic stimulation was observed in aged rats. These findings directly demonstrated that NO production might be involved in the process of LTP formation in Schaffer‐CA1 synapses of the rat hippocampus, and that the deficiency of hippocampal NO production might be responsible for reduction of LTP formation in aged rats.
Oxygen tension and content in the regulation of limb blood flow
Authors: Calbet J.A.L.
Published: March 2003

During submaximal exercise, muscle blood flow increases when arterial oxygen content (CaO2) is reduced. The increase in blood flow is brought about by elevating cardiac output (CO) and enhancing leg vascular conductance. Conversely, increased CaO2 elicits lower limb blood flow (LBF) and CO. During maximal exercise, the influence of CaO2 on muscle blood flow is modulated depending on the amount of muscle mass recruited. When a small muscle mass is activated and the pumping capacity of the heart is not limited, changes in CaO2 barely influence the level of blood flow attained at peak exercise. However, when a large muscle mass is engaged in the exercise, as occurs for example during cycling and running, muscle blood flow is decreased if maximal CO is reduced, as happens during exercise in severe hypoxia. In contrast, maximal muscle blood flow and CO are maintained at peak exercise when CaO2 is increased. As such, exercise intensity, muscle mass and CaO2 appear to be the critical factors determining muscle blood flow during exercise.
The distribution of rest periods affects performance and adaptations of energy metabolism induced by high‐intensity training in human muscle
Authors: PARRA J. , CADEFAU J.A. , RODAS G. , AMIGÓ N. , CUSSÓ R.
Published: March 2003

The effect of the distribution of rest periods on the efficacy of interval sprint training is analysed. Ten male subjects, divided at random into two groups, performed distinct incremental sprint training protocols, in which the muscle load was the same (14 sessions), but the distribution of rest periods was varied. The `short programme' group (SP) trained every day for 2 weeks, while the `long programme' group (LP) trained over a 6‐week period with a 2‐day rest period following each training session. The volunteers performed a 30‐s supramaximal cycling test on a cycle ergometer before and after training. Muscle biopsies were obtained from the vastus lateralis before and after each test to examine metabolites and enzyme activities. Both training programmes led to a marked increase (all significant, P < 0.05) in enzymatic activities related to glycolysis (phosphofructokinase – SP 107%, LP 68% and aldolase – SP 46%, LP 28%) and aerobic metabolism (citrate synthase – SP 38%, LP 28.4% and 3‐hydroxyacyl‐CoA dehydrogenase – SP 60%, LP 38.7%). However, the activity of creatine kinase (44%), pyruvate kinase (35%) and lactate dehydrogenase (45%) rose significantly (P < 0.05) only in SP. At the end of the training programme, SP had suffered a significant decrease in anaerobic ATP consumption per gram muscle (P < 0.05) and glycogen degradation (P < 0.05) during the post‐training test, and failed to improve performance. In contrast, LP showed a marked improvement in performance (P < 0.05) although without a significant increase in anaerobic ATP consumption, glycolysis or glycogenolysis rate. These results indicate that high‐intensity cycling training in 14 sessions improves enzyme activities of anaerobic and aerobic metabolism. These changes are affected by the distribution of rest periods, hence shorter rest periods produce larger increase in pyruvate kinase, creatine kinase and lactate dehydrogenase. However, performance did not improve in a short training programme that did not include days for recovery, which suggests that muscle fibres suffer fatigue or injury.
Differential activation of mitogen‐activated protein kinase signalling pathways by isometric contractions in isolated slow‐ and fast‐twitch rat skeletal muscle
Authors: Wretman  , Widegren  , Lionikas  , Westerblad  , Henriksson
Published: March 2003

Activation of mitogen‐activated protein (MAP) kinases has been implicated in the signal transduction pathways linking exercise to adaptive changes of muscle protein expression. In the present study, we investigated whether contractions of isolated muscles induced phosphorylation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2) and p38 MAPK in a fibre‐type dependent manner. Slow‐twitch (soleus) and fast‐twitch (epitrochlearis, extensor digitorum longus) rat skeletal muscles were exposed to intermittent tetanic stimulation. Compared with the contralateral non‐stimulated muscle, contractions increased ERK1/2 phosphorylation to the same extent in fast‐ and slow‐twitch muscles. Significant increase in phosphorylation of p38 MAPK was observed in the fast‐twitch muscles only. The total amount of ERK1/2 and p38 MAPK proteins was higher in the slow‐twitch soleus muscle. In conclusion, MAP kinase signalling pathways are differentially activated and expressed in slow‐ and fast‐twitch muscles. In addition, this activation is owing to muscle contraction per se and do not demand additional external influence.
Central AT1 and AT2 receptors mediate chronic intracerebroventricular angiotensin II‐induced drinking in rats fed high sodium chloride diet from weaning
Authors: Camara A. K. S. , Osborn J.
Published: March 2003

Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT1 and AT2 receptors in mediating chronic ICV AII‐induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10–12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min−1) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT1 receptor antagonist, losartan (0.25 μg min−1) or the AT2 receptor blocker, PD 123319 (0.50 μg min−1) blocked chronic ICV AII‐induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII‐mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT1 and AT2 receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT1 receptors.
Caffeine‐induced depolarization in amphibian skeletal muscle fibres: role of Na+/Ca2+ exchange and K+ release
Authors: Kotsias B. A. , Venosa R. A.
Published: March 2003

Caffeine (4 mM) produces a depolarization of about 10 mV in frog muscle fibres (Leptodactylus ocellatus). The aim of this work was to study the mechanisms of this effect. An approximately threefold rise in membrane resistance [Cl−‐free (SO42–) medium] substantially increased, and both Na+‐free medium and Ni2+ (5 mM) reduced, the caffeine‐induced depolarization. In voltage‐clamped (–60 mV) short fibres from lumbricalis muscle of the toad (Buffo arenarum), caffeine generated an inward current of 4.13 ± 0.48 μA cm–2. This caffeine‐induced current was reduced by 60% in Na+‐free medium, 44% in the presence of 5 mM amiloride and 48% by 5 mM Ni2+, suggesting that the activation of the Na+–Ca2+ exchanger in its forward mode may play a role in the observed electrical effects of the drug. Caffeine also produced a marked release of K+. Net K+ efflux increased from 3.5 ± 0.2 (control) to 22.1 ± 2.3 pmol s–1 cm–2 (caffeine). It is shown that in the presence of the drug, [K+] in the lumen of the T tubules may well increase to levels which could produce, in part, both the observed depolarization and the caffeine‐induced current under voltage clamp conditions. The caffeine‐induced K+ efflux was not reduced by 5 mM Ni2+. At a holding potential of 30 mV the caffeine‐induced current was reversed (outward) and roughly halved by 5 mM Ni2+. The Ni2+‐sensitive fraction of the caffeine‐induced current, assumed to represent the Na+–Ca2+ exchanger current, had an estimated reversal potential close to 12 mV ([Na+]o=115 mM; [Ca2+]o=1 mM). In conclusion, the depolarizing effect of caffeine described here would be produced by two mechanisms: (a) an inward current generated by the activation of the Na+–Ca2+ exchanger in its forward mode, and (b) the rise of the external [K+] in restricted spaces like the T tubules.
Mechanisms of hypotensive effects of a posture change from seated to supine in humans
Authors: Pump B. , Kamo T. , Gabrielsen A. , Norsk P.
Published: March 2003

The hypothesis tested was that the hydrostatic stimulation of carotid baroreceptors is pivotal to decrease mean arterial pressure at heart level during a posture change from seated to supine. In eight males, the cardiovascular responses to a 15‐min posture change from seated to supine were compared with those of water immersion to the xiphoid process and to the neck, respectively. Left atrial diameter and cardiac output (rebreathing) increased similarly during the posture change and water immersion to the xiphoid process and further so during neck immersion. Mean arterial pressure decreased by 12 ± 2 mmHg during the posture change, by 5 ± 1 mmHg during xiphoid immersion, and was unchanged during neck immersion. Arterial pulse pressure increased by 12 ± 3 mmHg during the posture change (P < 0.05) and less during xiphoid and neck immersion by 7 ± 3 mmHg (P < 0.05). Total peripheral vascular resistance decreased similarly during the posture change and neck immersion and slightly less during xiphoid immersion (P < 0.05). In conclusion, the hydrostatic stimulation of carotid baroreceptors combined with some additional increase in arterial pulse pressure, which also stimulates aortic baroreceptors, accounts for more than half of the hypotensive response at heart level to a posture change from seated to supine.
Exercise‐induced muscle damage and inflammation: fact or fiction?
Authors: Malm C.
Published: March 2003

Physical exercise is necessary for maintaining normal function of skeletal muscle. The mechanisms governing normal muscle function and maintenance are vastly unknown but synergistic function of hormones, neurosignalling, growth factors, cytokines and other factors, is undoubtedly important. Because of the complex interaction among these systems the lack of complete understanding of muscle function is not surprising. The purpose of exercise‐induced changes in muscle cell function is to adapt the tissue to a demand of increased physical work capacity. Some of the approaches used to investigate changes in skeletal muscle cell function are exercise and electrical stimulation in animals and human models and isolated animal muscle. From these models, it has been concluded that during physical exercise, in an intensity and duration dependent manner, skeletal muscle is damaged and subsequently inflamed. The purpose of the inflammation would be to repair the exercise‐induced damage. Because of the design and methods used in a majority of these studies, concerns must be raised, and the question asked whether the paradigm of exercise‐induced muscle inflammation in fact is fiction. In a majority of conducted studies, a non‐exercising control group is lacking and because of the invasive nature of the sampling methods used to study inflammation it does not appear impossible that observed inflammatory events in human skeletal muscle after physical exercise are methodoligical artefacts.
The role of Ca2+ and calmodulin in insulin signalling in mammalian skeletal muscle
Authors: Bruton J. D. , Katz A. , Westerblad H.
Published: March 2003

The role of Ca2+ in mediating effects of insulin on skeletal muscle has been widely debated. It is believed that in skeletal muscle Ca2+ has a permissive role, necessary but not of prime importance in mediating the stimulatory actions of insulin. In this review, we present evidence that insulin causes a localized increase in the concentration of Ca2+. Specifically, insulin induces a rise in near‐membrane Ca2+ but not the bulk Ca2+ in the myoplasm. The rise in near‐membrane Ca2+ is because of an influx through channels that can be blocked by L‐type Ca2+ channel inhibitors. Calcium appears to exert some of its subsequent effects via calmodulin‐dependent processes as calmodulin inhibitors block the translocation of glucose transporters and other enzymes as well as the insulin‐stimulated increase in glucose transport.
Apoptosis and changes in contractile protein pattern in the skeletal muscle in heart failure
Authors: Vescovo G. , Ambrosio G. B. , Libera L. Dalla
Published: March 2003

Chronic heart failure is characterized as a clinical disorder by exercise intolerance. There are two factors that are independently responsible for the reduced exercise capacity: (a) a shift from myosin heavy chain 1 (MHC1) to MHC2a and MHC2b and (b) muscle atrophy. We have demonstrated, both in experimental models of heart failure and in man, that the more severe the heart failure, the greater the magnitude of skeletal muscle apoptosis. In the monocrotaline treated rat, that develops a severe right‐sided heart failure, the increased number of apoptotic nuclei was paralleled by increasing levels of circulating TNFα. In agreement with some recent observations showing that sphingolipids can mediate programmed cell death, we found that in animals with heart failure and high number of apoptotic nuclei, circulating levels of sphingosine were significantly increased. In a study conducted in patients with heart failure we found a correlation between exercise capacity limitation and skeletal myocytes apoptosis. There was also a correlation between degree of muscle atrophy and magnitude of apoptosis. The shift in MHCs, although with a different mechanism, is also responsible for the reduced exercise capacity in these patients. In fact there is a strong correlation between indices of severity of CHF and MHC composition. Muscle fatigue, appears earlier in patients that have a greater skeletal muscle expression of ‘fast’ MHCs. We have also demonstrated that MHCs shift and apoptosis can be prevented by using angiotensin II converting enzyme inhibitors and angiotensin II receptor blockers.
Harnessing the potential of dystrophin‐related proteins for ameliorating Duchenne’s muscular dystrophy
Authors: Krag T. O. B. , Gyrd‐Hansen M. , Khurana T. S
Published: March 2003

Duchenne’s muscular dystrophy (DMD) is a fatal disease caused by mutations in the DMD gene that lead to quantitative and qualitative disturbances in dystrophin expression. Dystrophin is a member of the spectrin superfamily of proteins. Dystrophin itself is closely related to three proteins that constitute a family of dystrophin‐related proteins (DRPs): the chromosome 6‐encoded DRP or utrophin, the chromosome‐X encoded, DRP2 and the chromosome‐18 encoded, dystrobrevin. These proteins share sequence similarity and functional motifs with dystrophin. Current attempts at somatic gene therapy of DMD face numerous technical problems. An alternative strategy for DMD therapy, that circumvents many of these problems, has arisen from the demonstration that the DRP utrophin can functionally substitute for the missing dystrophin and its overexpression can rescue dystrophin‐deficient muscle. Currently, a promising avenue of research consists of identifying molecules that would increase the expression of utrophin and the delivery of these molecules to dystrophin‐deficient tissues as a means of DMD therapy. In this review, we will focus on DRPs from the perspective of strategies and issues related to upregulating utrophin expression for DMD therapy. Additionally, we will address the techniques used for anatomical, biochemical and physiological evaluation of the potential benefits of this and other forms of DMD therapy in dystrophin‐deficient animal models.
Regulation of synthesis of fibrillar collagens in rat skeletal muscle during immobilization in shortened and lengthened positions
Authors: Ahtikoski A. M. , Koskinen S. O. A. , Virtanen P. , Kovanen V. , Takala T. E. S.
Published: March 2003

Immobilization has been shown to cause muscle atrophy and decreased total collagen synthesis in skeletal muscle. These changes can be counteracted by stretch. The purpose of this study was to find out the early effects of immobilization in shortened and lengthened positions on expression of type I and III collagen at pre‐ and post‐translational level. The mRNA levels of type I and III collagen, prolyl 4‐hydroxylase activity, total collagen concentration and the proportions of type I and III collagens were analysed in soleus (SOL), gastrocnemius (GM), extensor digitorum longus and tibialis anterior (TA) muscles during immobilization in shortened and lengthened positions for 1, 3 and 7 days. The mRNA levels for type I and III collagens decreased during 3–7 days in all muscles, except TA. In shortened GM and SOL, the mRNA level of type I collagen was lower than in the corresponding lengthened muscles. Prolyl 4‐hydroxylase activity decreased in all muscles during 3–7 days. The activity in shortened GM was 30–37% lower than in the lengthened one during 3–7 days. Total collagen concentration and proportions of type I and III collagen showed no change during the 7&‐ thinsp;‐day immobilization period. The present study suggests that immobilization results in rapid down‐regulation of total muscular collagen synthesis and that the timing and degree is roughly similar in type I and III collagens. Stretch seems to partially counteract these effects. Immobilization effect and the partially preventive effect of stretch on down‐regulation of gene expression of prolyl 4‐hydroxylase and fibrillar collagens during immobilization seems to be greater in weight‐bearing SOL and GM than ankle joint dorsiflexors.
GABA and chloride permeate via the same channels across single plasma membranes microdissected from rabbit Deiters’ vestibular neurones
Authors: Rapallino M. V. , Cupello A.
Published: March 2003

The permeation of labelled γ‐aminobutyric acid (GABA) across single microdissected Deiters’ membranes has been studied in a microchamber system. The GABA permeation is via pores which are blocked by 4,4′‐diisothiocyanato stilbene‐2‐2′disulphonic acid (DIDS). As this substance blocks as well chloride permeation across these membranes we tested whether GABA and chloride permeate across the same pores. Membrane pre‐treatment with different doses of corticotropin releasing factor (CRF), a membrane permeant cyclic AMP analogue and phalloidin parallelly block the permeation of the two substances. Thus, it is most probable that GABA and chloride pass across the same pores. These pores may be swelling activated ones, opened by the mechanical stress on the membranes in the microchamber system. The passage of GABA across these pores may be of physiological importance in the termination of GABA inhibitory action on the vestibular Deiters’ neurones.
Halothane differentially decreases 5‐hydroxytryptamine‐induced contractions in normal and chronic hypoxic rat pulmonary arteries
Authors: De Crescenzo V. , Dubuis E. , Constantin S. , Rebocho M. , Girardin C. , Bonnet P. , Vandier C.
Published: March 2003

The mechanism of action of halothane is not fully understood in pulmonary circulation and especially in chronic hypertension models. As the 5‐hydroxytryptamine (5‐HT) pulmonary vasoconstrictor response increases in chronic hypoxic rat, halothane could differentially attenuate this vasoconstriction response on normoxic and chronic hypoxic rats. The effect of halothane on 5‐HT‐induced contractions on pulmonary arteries isolated from normoxic and chronic hypoxic rats was compared. Rings dissected from proximal pulmonary artery without endothelium were attached to a force transducer to record tone and placed in an organ chamber gassed either by air or air + halothane (1–5%). Contractions induced by (10–4 M) 5‐HT were used to test the effect of halothane on rings isolated from normoxic and chronic hypoxic rats. 5‐Hydroxytryptamine‐mediated contractions were more sensitive to external calcium in normoxic than chronic hypoxic rings. In calcium‐free solution, with verapamil or cadmium the amplitude of remaining 5‐HT‐induced contractions were greater in chronic hypoxic rings. Halothane (1–5%) decreased 5‐HT‐mediated contractions in normoxic and chronic hypoxic rings. The effect occurred with no change of pD2 for 5‐HT and was more pronounced in normoxic rings. The effect of halothane on both rings was abolished in the absence of external calcium or in the presence of verapamil. In the presence of cadmium, 5% halothane had no effect on normoxic rings but still decreased the remaining 5‐HT contraction on chronic hypoxic rings. The findings suggested that halothane decreased sarcolemmal calcium entry in pulmonary artery rings by a cadmium‐sensitive pathway in normoxic rats and by a cadmium‐insensitive pathway in chronic hypoxic rats.
Atrial distension, haemodilution, and acute control of renin release during water immersion in humans
Authors: GABRIELSEN A. , PUMP B. , BIE P. , CHRISTENSEN N. J. , WARBERG J. , NORSK P.
Published: March 2003

We tested the hypothesis that atrial distension (stimulation of cardiopulmonary baroreceptors) is not the single pivotal stimulus for the acute suppression of renin release during water immersion in humans and that immersion‐induced haemodilution constitutes an important additional stimulus. In nine healthy male subjects, identical increases in atrial distension were induced by two immersion procedures (of 30 min each); one without (WI) and one with attenuation (WI + cuff) of the concomitant haemodilution (estimated from changes in plasma protein concentration) by inflating thigh cuffs during immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P < 0.05) by 5.5 ± 0.4 mmHg and 4.6 ± 0.5 mm, respectively, and plasma protein concentration and plasma renin activity (PRA) progressively decreased (P < 0.05) by 4.8 ± 0.5 g L–1 and 1.6 ± 0.2 ng mL–1 h–1 (to 49 ± 4% of baseline values), respectively. The WI + cuff caused similar atrial distension as WI (CVP and LAD increased by 6.9 ± 0.5 mmHg and 5.5 ± 0.5 mm, respectively), attenuated haemodilution (plasma protein concentration decreased by 1.9 ± 0.4 g L–1, P < 0.05 vs. WI), and markedly inhibited suppression of PRA, which decreased by 0.4 ± 0.1 ng mL−1 h−1 (to 87 ± 4% of baseline values, P < 0.05 vs. WI). Differences in renin release could not be accounted for by differences in mean arterial pressure. In conclusion, baroreceptor stimulation induced by atrial distension is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion‐induced suppression of renin‐angiotensin system activity.
Interaction of exercise and diet on GLUT‐4 protein and gene expression in Type I and Type II rat skeletal muscle
Authors: LEE J. S. , BRUCE C. R. , TUNSTALL R. J. , CAMERON‐SMITH D. , HÜGEL H. , HAWLEY J. A.
Published: March 2003

We determined the interaction of exercise and diet on glucose transporter (GLUT‐4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty‐eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high‐fat (FAT, n=24) or high‐carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill running (4 sessions week–1 of 1000 m @ 28 m min–1, RUN, n=16). Eight trained rats were killed after their final exercise bout for determination of GLUT‐4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT‐4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT‐4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet–training interaction on GLUT‐4 mRNA, such that expression was increased in both the soleus (100% ↑P < 0.05) and EDL (142% ↑P < 0.01) in CHO‐fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL (↓ 45%, P < 0.05) but not the soleus (↓ 14%, NS). We conclude that exercise training in CHO‐fed rats increased both GLUT‐4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT‐4 mRNA in muscles from fat‐fed animals, exercise‐induced increases in GLUT‐4 protein were largely preserved, suggesting that control of GLUT‐4 protein and gene expression are modified independently by exercise and diet.
Does nitric oxide act as a cellular messenger in muscarinic endometrial secretion in the guinea‐pig?
Authors: MÖRLIN B. , HAMMARSTRÖM M. , EHREN I. , SJÖSTRAND N. O.
Published: March 2003

Uterine secretory cells receive a sympathetic cholinergic secremotor innervation. Nitric oxide (NO) has been suggested to be a second messenger of neurogenic modulated glandular secretion of the seminal vesicle. Thus a similar pattern for nervous induced carbohydrate secretion of the endometrium was assumed. The nitric oxide synthase (NOS) activity was estimated via formation of L‐citrulline from L‐arginine and histochemically with the nicotinamide‐adenine dinucleotide phosphate diaphorase (NADPH‐d) nitro blue technique. The carbohydrate secretion from everted uterine horns placed in organ baths was estimated. A calcium dependent formation of citrulline was found in the uterine horn suggesting an NOS activity. Strong NADPH staining cells were found in the glandular ducts of the endometrium and in the epithelial linings of the oviduct. Carbachol induced carbohydrate secretion of the endometrium while N‐nitro L‐arginin (L‐NNA) and N‐nitro L‐arginin methyl ester (L‐NAME) inhibited the carbachol induced secretion. The isomer D‐NAME had no effect on carbachol induced secretion. When L‐arginine was administered together with L‐NNA no inhibitory effect on carbachol induced secretion was seen. L‐arginine only had no effect on carbohydrate secretion. The NO donor glyceryl tritrate increased carbohydrate secretion but no synergistic effect was seen in combination with carbachol. The results suggest that glandular NO production is a prerequisite for muscarinic carbohydrate secretion of the endometrium.