bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic Exocrine Secretions as a Source of Luminal Polyamines in Pigs
Authors: Loret Suzanne , Brolet Philippe , Pierzynowski Stefan , Gouders Isabelle , Klimek Monique , Danielson Viggo , Rosted Anne , Lesniewska Violetta , Dandrifosse Guy
Published: May 2004

The goal of the present study was twofold: (1) to detect the possible storage of dietary polyamines (PAs) in various tissues and (2) to investigate the role of dietary PAs in the differentiation of the pig intestinal epithelium. A first experimental series was designed to assess the accumulation of either milk PAs (mostly spermidine) or orally administered spermine (SPM) in piglet red blood cells (RBCs) and plasma, a preliminary stage in their distribution to growing and storage organs. Though PA concentrations of piglet RBCs and plasma were generally significantly higher than their sow counterparts, our experimental conditions failed to demonstrate that this increase could stem from ingested PAs. A second experimental series dealt with the determination of disaccharidase specific activities in proximal and distal parts of piglet gut on the 26th and 29th days after birth (preweaning time). In agreement with observations made previously on rat pups, we observed an increase in maltase specific activity (SA) at the end of the suckling period (the observed increase in sucrase SA was not significant). However, orally administered SPM did not affect this activity. Compared to the constant protein concentrations observed in both parts of the gut, the pancreatic protein content decreased sharply between the 26th and 29th postnatal days. At the same time pancreatic concentrations of spermidine (SPD) also decreased, suggesting that some pancreatic PAs were released as the organ secreted its proteins. In accordance with this hypothesis, we recorded SPM and SPD in pancreatic juice. The increases in PA concentrations seemed to follow the protein secretion pattern (i.e. PA concentrations reached a maximal value when the protein concentration was highest). The presence of PAs in pancreatic juice could be indicative of a control mechanism exerted by the pancreas on PA‐induced growth and differentiation of porcine intestinal epithelium.
Accumulation of cAMP Evoked by Acetylcholine Stimulation in Rat Submandibular Acinar Cells: Observation of Exocytosis, Fluid Secretion and [Ca2+]I
Authors: Nakahari Takashi , Ito Sigenori , Yoshida Hideyo , Furuya Eisuke , Imai Yusuke
Published: May 2004

The effects of cAMP accumulation evoked by acetylcholine (ACh) stimulation were studied in rat submandibular acinar cells by observing the exocytotic events, swelling of intercellular canaliculi (IC) and intracellular Ca2+ concentration ([Ca2+]i), which were monitored using an optical microscope. ACh stimulation evoked transient increases followed by sustained increases in the frequency of exocytotic events and IC swelling, while isoproterenol (isoprenaline; IPR) stimulation evoked sustained increases in these parameters. BAPTA treatment reduced the frequency of exocytotic events evoked by 5 μM ACh in the absence of extracellular Ca2+, and further addition of Rp‐cAMPS or H‐89 (protein kinase A (PKA) inhibitors) eliminated the remaining ACh‐evoked responses (50%). Addition of PKA inhibitors in the presence of extracellular Ca2+ reduced the frequency of exocytotic events evoked by 500 μM ACh in non‐BAPTA‐loaded cells. However, IC swelling evoked by 5 μM ACh was not affected by addition of PKA inhibitors, and was eliminated in BAPTA‐loaded cells perfused with Ca2+‐free solution. These results indicate that the IC swelling is regulated by [Ca2+]i and the frequency of exocytotic events is regulated by both [Ca2+]i and [cAMP]i during ACh stimulation. Addition of H‐89 inhibited the capacitative Ca2+ entry into ACh‐stimulated acinar cells. Biochemical analysis revealed that ACh stimulation increased the cAMP content in perfused submandibular glands. These results indicate that ACh stimulates the accumulation of cAMP in submandibular acinar cells and that this accumulation of cAMP modulates Ca2+‐regulated exocytosis.
Parasympathetic Non‐Adrenergic, Non‐Cholinergic‐Induced Protein Synthesis and Mitogenic Activity in Rat Parotid Glands
Authors: Ekström J. , Havel G. Engdahl , Reinhold A.‐C.
Published: May 2004

Electrical stimulation of the parasympathetic auriculo‐temporal nerve (40 Hz, 30 min), in the anaesthetized rat under α‐ and β‐adrenoceptor blockade, increased [3H]thymidine and [3H]leucine uptake into the parotid glands by 80 and 263%, respectively. The increase in response to parasympathetic stimulation was almost the same ([3H]thymidine 82% and [3H]leucine 283%) when atropine (2 mg kg‐1 I.P. or I.V.) was included in the pretreatment. Neither intravenous infusion of vasoactive intestinal peptide (0.5‐20 mg kg‐1 min‐1, 30 min) nor of bethanechol (10 mg kg‐1 min‐1, 30 min), under adrenoceptor blockade, increased the uptake of [3H]thymidine into the glands. However, these drugs increased [3H]leucine uptake, and in combination they interacted positively. Whereas vasoactive intestinal peptide is likely to be involved in the parasympathetic nerve‐evoked protein synthesis, the nature of the non‐adrenergic, non‐cholinergic component(s) involved in the mitogenic response is presently unknown.
Visual Signals in the Retina: From Photons to Synapses
Authors: Lagnado Leon
Published: May 2004

The ability to see the world around us is an immediate and striking example of the abilities of the nervous system, and perhaps for this reason, vision is one of the most intensively studied aspects of brain function (Hubel, 1995). This paper examines some of the earliest steps in vision occurring in the retina (Dowling, 1987; Rodieck, 1998).
Alteration in α‐ and β‐Adrenoceptor Profile of Rabbit Knee Joint Blood Vessels due to Acute Inflammation
Authors: Najafipour Hamid
Published: May 2004

Experiments were performed to investigate the nature of α‐ and β‐adrenoceptors in blood vessels supplying the posterior capsule of the acutely inflamed rabbit knee joint, and results were compared to findings from previous experiments on the normal joint, to assess any alteration which may occur in the adrenoceptor profile due to the inflammation process. Electrical stimulation of the posterior articular nerve resulted in vasoconstriction which was reversed to vasodilatation by phentolamine and yohimbine. The dose‐response curves to close intra‐arterial injection of α‐adrenoceptor agonists showed a rank‐order potency of: adrenaline = phenylephrine = clonidine. The adrenaline dose‐response curve was shifted to the right by administration of antagonists with a rank‐order potency of: phentolamine = yohimbine = prazosin. At this stage of the experiments there was an equal response of α1‐ and α2‐adrenoceptors in blood vessels of the acutely inflamed rabbit knee joint. In another group of animals the neurally mediated vasodilatation, which appeared after administration of phentolamine, was completely blocked by propranolol, and was reduced by about 50% by atenolol. The dose‐response curves to close intra‐arterial injection of β‐adrenoceptor agonists showed a rank‐order potency of: isoprenaline > salbutamol = dobutamine. The isoprenaline dose‐response curve was shifted to the right by administration of antagonists with a rank‐order potency of: propranolol > atenolol. These experiments also showed an almost equal response of β1‐ and β2‐adrenoceptors in blood vessels of the acutely inflamed rabbit knee joint. Overall, compared to previous experiments on the normal joint in which α2‐ and β1‐adrenoceptor responses predominated, acute inflammation resulted in a shift from α2‐ towards α1‐ and from β1‐ towards β2‐adrenoceptor responses.
Immunoglobulin a Secretion into Saliva During Dual Sympathetic and Parasympathetic Nerve Stimulation of Rat Submandibular Glands
Authors: Carpenter G. H. , Proctor G. B. , Anderson L. C. , Zhang X. S. , Garrett J. R.
Published: May 2004

Salivary secretion of proteins from rat submandibular glands was studied using graded stimulation of the parasympathetic nerve in isolation, and then at a fixed rate in combination with graded sympathetic nerve stimulation. Increasing the frequency of parasympathetic nerve stimulation per se caused a gradual increase in the secretion of peroxidase (from acini) but only small increases in proteinase (from ductal cells) and IgA outputs. Dual stimulations, with an increasing frequency of sympathetic nerve stimulation on a background of low frequency parasympathetic nerve stimulation, showed that maximal acinar secretion of peroxidase required only a low frequency of additional sympathetic stimulation, whereas ductal secretion of kallikrein was greatest with the highest frequency of additional sympathetic stimulation (20 Hz in bursts). IgA secretion also required high frequency additional sympathetic stimulation in bursts for greatest output. Although a synergism occurred with parasympathetic plus sympathetic nerve stimulation for the secretion of both peroxidase and kallikrein it was not evident for the secretion of IgA. This presumably reflects a difference for exocytosis of proteins stored in granules (e.g. peroxidase and kallikrein) compared to those proteins continuously transported across the plasma membrane in vesicles by transcytosis. This work confirms that vesicular movement of secretory IgA can be increased by both parasympathetic and sympathetic nerve stimulation, but the frequency parameters differ for each nerve.
Response of Isolated Ruminant Mammary Arteries to the Long R3 Analogue of Insulin‐Like Growth Factor I
Authors: Gow I. F.
Published: May 2004

Isolated mammary arteries from ruminants were used in a conventional organ bath system. Acetylcholine relaxed bovine but not ovine mammary arteries; both types responded to sodium nitroprusside. Noradrenaline (NA) caused a dose‐dependent increase in generated tension. An analogue of insulin‐like growth factor I (long R3‐IGF‐I) caused a rightward shift in the NA response curve in bovine vessels with intact endothelium (P < 0.02), and also in sheep arteries (P < 0.01). In bovine vessels, this effect was abolished when the endothelium was removed. The effect of long R3‐IGF‐I in bovine vessels was abolished by Nω‐nitro‐L‐arginine methyl ester (L‐NAME) an inhibitor of nitric oxide synthase, suggesting the effect of IGF‐I on mammary arteries in vitro requires NO generation.
Calcium and Fos Involvement in Brain‐Derived Ca2+‐Binding Protein (S100)‐Dependent Apoptosis in Rat Phaeochromocytoma Cells
Authors: Fulle Stefania , Pietrangelo Tiziana , Mariggiò Maria A. , Lorenzon Paola , Racanicchi Leda , Mozrzymas Jerzy , Guarnieri Simone , Zucconi‐Grassi Gigliola , Fanò Giorgio
Published: May 2004

Brain‐derived calcium‐binding protein S100 induces apoptosis in a significant fraction of rat phaeochromocytoma (PC12) cells. We used single cell techniques (patch clamp, videomicroscopy and immunocytochemistry) to clarify some of the specific aspects of S100‐induced apoptosis, the modality(ies) of early intracellular Ca2+ concentration increase and the expression of some classes of genes (c‐fos, c‐jun, bax, bcl‐x, p‐15, p‐21) known to be implicated in apoptosis of different cells. The results show that S100: (1) causes an increase of [Ca2+]i due to an increased conductance of L‐type Ca2+ channels; (2) induces a sustained increase of the Fos levels which is evident since the first time point tested (3 h) and remains elevated until to the last time point (72 h). All these data suggest that S100‐derived apoptosis in PC12 cells may be the consequence of a system involving an increase in L‐type Ca2+ channel conductance with consequent [Ca2+]i increase which up‐regulates, directly or indirectly, the expression of Fos.
Cardiovascular Effects of 8 h of Isocapnic Hypoxia with and without Beta‐Blockade in Humans
Authors: Clar Christine , Dorrington Keith L. , Fatemian Marzieh , Robbins Peter A.
Published: May 2004

This study seeks to confirm the progressive changes in cardiac output and heart rate previously reported with 8 h exposures to constant hypoxia, and to examine the role of sympathetic mechanisms in generating these changes. Responses of ten subjects to four 8 h protocols were compared: (1) air breathing with placebo; (2) isocapnic hypoxia (end‐tidal PO2 = 50 mmHg) with placebo; (3) isocapnic hypoxia with beta‐blockade; and (4) air breathing with beta‐blockade. Regular measurements of heart rate and cardiac output (using ultrasonography and N2O rebreathing techniques) were made with subjects seated in the upright position. The sensitivity of heart rate to rapid variations in hypoxia (GHR) and heart rate in the absence of hypoxia were measured at times 0, 4 and 8 h. No significant progressive effect of hypoxia on cardiac output was detected. There was a gradual rise in heart rate with hypoxia of 11 ± 2 beats min‐1 in the placebo protocol and of 10 ± 2 beats min‐1 in the beta‐blockade protocol over 8 h, compared to the air breathing protocols. The rise in heart rate was progressive (P < 0.001) and accompanied by progressive increases in both GHR (P < 0.001) and heart rate measured in the absence of hypoxia (P < 0.05). No significant effect of beta‐blockade was detected on any of these progressive changes. We conclude that sympathetic mechanisms that act via beta‐receptors play little role in the progressive changes in heart rate observed over 8 h of moderate hypoxia.
Renin and Heart Rate Responses to Haemorrhage are Age Dependent in Conscious Lambs
Authors: Smith Francine G. , Basati Raghmeet , Sener Alp , Abu‐Amarah Isam
Published: May 2004

The present experiments were carried out in conscious lambs (1‐2 weeks old, n= 9) and older sheep (11‐12 weeks old, n= 11) to determine whether the cardiovascular and endocrine responses to 0, 10 and 20% haemorrhage were developmentally regulated. The major novel finding of our study is that throughout the first 3 months of postnatal life, there is a similar decrease in mean arterial pressure and a similar restoration of pressure to pre‐haemorrhage levels, for the same degree of blood loss, yet the mechanisms used to restore pressure appear to be age dependent as follows. In lambs, but not in older sheep, heart rate increased for 1 h after 20% haemorrhage. Activation of the renin‐angiotensin system was also greater and more prolonged in lambs than in older sheep following haemorrhage, and occurred at a lesser degree of blood loss. Plasma arginine vasopressin responses to haemorrhage were, however, similar in both age groups. These data provide new information that some of the mechanisms used to restore arterial pressure following blood volume depletion appear to be age dependent.
Cyclic Amp‐Mediated Inhibition of Noradrenaline‐Induced Contraction and Ca2+ Influx in Guinea‐Pig vas Deferens
Authors: Kato Kenichi , Furuya Kishio , Tsutsui Izuo , Ozaki Tsuyoshi , Yamagishi Shunichi
Published: May 2004

The relaxation effects of forskolin and methylxanthines on noradrenaline (NA)‐induced contractions were investigated by measuring isotonic contraction and intracellular calcium concentration ([Ca2+]i) in the epididymal side of guinea‐pig vas deferens. NA (100 μM) and high K+ (55 mM) induced a biphasic contraction; fast, transient (phasic) and slow, sustained (tonic) phases. Both phases in either NA or high K+ stimulation were abolished in Ca2+‐free solution. Pretreatment with 10 μM nifedipine, an L‐type Ca2+ channel blocker, reduced both phasic and tonic contractions induced by high K+. In the case of NA‐induced contraction, however, nifedipine reduced the phasic contraction but not the tonic contraction. The nifedipine‐insensitive tonic contraction was relaxed by the application of polyvalent cations (Mn2+, Co2+, Cd2+ and La3+). These findings indicate that NA‐induced biphasic contraction is mainly due to nifedipine‐insensitive Ca2+ influx, especially in the tonic phase. Cyclic AMP‐increasing agents such as forskolin (0.5‐10 μM), IBMX (5‐500 μM) and caffeine (1‐20 mM) relaxed the NA‐induced contraction extensively in a concentration‐dependent manner. However, these agents only partially relaxed the high K+‐induced contraction. Forskolin (10 μM) and IBMX (100 μM) reduced the [Ca2+]i response to NA, but had no effect on the [Ca2+]i response to high K+. These results suggest that an increase in intracellular cAMP may relax the NA‐induced contraction by attenuating a nifedipine‐insensitive Ca2+ influx and by a mechanism independent of a reduction in [Ca2+]i.
Hypotonic Swelling Increases L‐Type Calcium Current in Smooth Muscle Cells of the Human Stomach
Authors: Hee Kim Chun , Rhee Poong‐Lyul , Chul Jong , Kim Yong‐Il , So Insuk , Whan Kim Ki , Park Myoung Kyu , Uhm Dae‐Yong , Mook Kang Tong
Published: May 2004

The purpose of the present study was to characterize the Ca2+ channels in smooth muscle cells from human stomach and to examine the effects of osmotic swelling on the channel activity. Ca2+ channel current with either Ca2+ or Ba2+ as charge carrier was recorded from freshly isolated smooth muscle cells using the conventional whole‐cell patch clamp technique. The degree of cell swelling as a result of hypotonic challenge was monitored using a video image analysis system. The changes in intracellular Ca2+ concentration ([Ca2+]i) were measured by microfluorimetry. The pharmacological and voltage activation profile suggests a typical dihydropyridine‐sensitive L‐type Ca2+ current. Cell swelling, induced by hypotonic challenge, enhanced the amplitude of currents through L‐type Ca2+ channels without significant effects on steady‐state voltage dependency. After treatment with the L‐type Ca2+ channel agonist Bay K 8644 (0.1‐2 μM), no further significant increase in calcium channel current or corresponding [Ca2+]i transients were provoked by the swelling. The above results demonstrated that the presence of L‐type Ca2+ current in smooth muscle cells of the human stomach and the augmentation of the current are closely associated with the volume increase resulting from hypotonic swelling.
Changes in Chemoreflex Characteristics Following Acute Carbonic Anhydrase Inhibition in Humans a Rest
Authors: Vovk Andrea , Duffin James , Kowalchuk John M. , Paterson Donald H. , Cunningham David A.
Published: May 2004

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (ACZ, 10 mg kg‐1 I.V.) on the peripheral and central chemosensitivity and breathing pattern was investigated in four women and three men aged 25 ± 3 years using a modified version of Read's rebreathing technique. Subjects were exposed to dynamic increases in CO2 in hypoxic and hyperoxic backgrounds during control conditions and following acute CA inhibition. All manoeuvres were repeated twice and averaged for data analysis. The central chemoreflex sensitivities, estimated from the slopes of the ventilatory response to CO2 during hyperoxic rebreathing, increased following acute CA inhibition (control vs. ACZ treatment: 1.87 ± 0.66 vs. 4.07 ± 1.03 l min‐1 (mmHg CO2)‐1, P < 0.05). The increased slope was reflected by an increase in the rate of rise of tidal volume and breathing frequency. Furthermore with ACZ, there was a left‐ward shift of the ventilation vs. end‐tidal PCO2 curve during hyperoxic hypercapnia but not hypoxic hypercapnia. The peripheral chemoreflex sensitivity was isolated by subtracting the hyperoxic slope (central only) from the hypoxic slope (central and peripheral). Following ACZ administration, the peripheral chemosensitivity was blunted (control vs. ACZ treatment: 3.66 ± 0.92 vs. 1.33 ± 0.46 l min‐1 (mmHg CO2)‐1, P < 0.05). In conclusion, acute CA inhibition enhanced the central chemosensitivity to CO2 but diminished the peripheral chemosensitivity.
Power Output of Fast and Slow Skeletal Muscles of MDX (Dystrophic) and Control Mice After Clenbuterol Treatment
Authors: Lynch Gordon S. , Hinkle Richard T. , Faulkner John A.
Published: May 2004

The mdx mouse is the most commonly used animal model for Duchenne muscular dystrophy. We tested the null hypothesis that 20 weeks of clenbuterol treatment (∼2 mg kg−1 day‐1) of mdx and control mice would have no effect on the absolute and specific force (Po, kN m−2) and absolute and normalised power output (W kg−1) of extensor digitorum longus (EDL) and soleus muscles. For mdx and control mice, clenbuterol treatment produced modest increases in the mass of the two muscles but did not increase absolute or specific force or normalised power output. For absolute power output, only the EDL muscles of mdx mice showed a difference following treatment, with the power output of treated mice being 118% that of the untreated mice. The modest effects of clenbuterol treatment on the dynamic properties of skeletal muscle provide little support for any improvement in muscle function for the dystrophic condition.
Influence of the Extent of Haemoglobin Hydrolysis on the Digestive Absorption of Haem Iron in the Rat. an in Vitro Study
Authors: Vaghefi N. , Nedjaoum F. , Guillochon D. , Bureau F. , Arhan P. , Bouglé D.
Published: May 2004

This study was designed to assess the haem‐peptide interactions which occur during progressive haemoglobin hydrolysis by digestive enzymes and their relationship with haem iron digestive absorption. The behaviour of different haemoglobin hydrolysates was studied using the Ussing chamber model. Hydrolysates were produced from enzyme digestion of bovine haemoglobin at pH 3 by pepsin and at pH 10 by subtilisin. Samples with increasing degrees of hydrolysis (0‐15%) were studied. Biochemical assays (pyridine haemochromogen method and UV absorption spectra) were used to follow haem solubility and haem‐peptide interactions in samples. Increasing the hydrolysis level of haemoglobin was associated with an enhanced iron uptake; the highest uptake rate was reached between 8 and 11% of globin hydrolysis, whichever enzyme was used. The mechanisms rendering iron soluble and available differ between the two enzymes. The comparison between biochemical and absorption data suggests that the formation of soluble peptide‐haem complexes was not sufficient to enhance haem iron absorption, since globin‐bound iron is poorly absorbed; an efficient absorption occurred only when haem was loosely bound to low molecular weight peptides.
Contractile Properties, Fatigue and Recovery are not Influenced by Short‐Term Creatine Supplementation in Human Muscle
Authors: Jakobi J. M. , Rice C. L. , Curtin S. V. , Marsh G. D.
Published: May 2004

There have been several studies on the effect of short‐term creatine (Cr) supplementation on exercise performance, but none have investigated both voluntary and stimulated muscle contractions in the same experiment. Fourteen moderately active young men (19‐28 years) were randomly assigned, in a double blind manner, to either a creatine (Cr) or placebo (P) group. The subjects supplemented their regular diet 4 times a day for 5 days with either 5 g Cr + 5 g maltodextrin (Cr group), or 5 g maltodextrin (P group). Isometric maximal voluntary contraction (MVC), muscle activation, as assessed using the modified twitch interpolation technique, electrically stimulated contractile properties, electromyography (EMG), endurance time and recovery from fatigue were measured in the elbow flexors. The fatigue protocol involved both voluntary and stimulated contractions. Following supplementation there was a significant weight gain in the Cr group (1.0 kg), whereas the P group did not change. For each group, pre‐supplementation measures were not significantly different from post‐supplementation for MVC, twitch and tetanic tensions at rest, time to peak tension, half‐relaxation time and contraction duration. Prior to Cr supplementation time to fatigue was 10 ± 4 min (mean ± S.E.M.) for both groups, and following supplementation there was a non‐significant increase of 1 min in each group. MVC force, muscle activation, EMG, stimulated tensions and durations were similar for the Cr and P groups over the course of the fatigue protocol and did not change after supplementation. Furthermore, recovery of MVC, stimulated tensions and contractile speeds did not differ as a result of Cr supplementation. These results indicate that short‐term Cr supplementation does not influence isometric elbow flexion force, muscle activation, stimulated contractile properties, or delay time to fatigue or improve recovery.
Activation of Human Leukocytes by Acute Hypoxia
Authors: Sanidas Dimitris , Garnham Andrew , Mian Rubina
Published: May 2004

Exposure of human leukocytes to 12% and 6% O2in vitro resulted in striking ultrastructural and morphological changes. These changes included the appearance of crater‐like holes, a reduction in granular size and disruption of the cellular membrane. The implications of these findings is discussed.
Differences in the Calcium‐Handling Response of Isolated Rat and Guinea‐Pig Cardiomyocytes to Metabolic Inhibition: Implications for Cell Damage
Authors: Williams Helen , Kerr Paul M. , Suleiman M.‐Saadeh , Griffiths Elinor J.
Published: May 2004

Species differences in response to hypoxic damage have been observed in studies using whole hearts. The aims of this study were to determine whether (i) species differences in response to simulated hypoxia could be detected at the level of the single myocyte, and (ii) there were any interspecies differences in the Ca2+ handling properties of the cells. Ventricular myocytes were isolated from hearts of adult rats and guinea‐pigs and electrically stimulated on the stage of a fluorescence microscope. Cell length was measured using an edge‐tracking device, and total intracellular [Ca2+] ([Ca2+]i) determined using indo‐1. Cells were exposed to metabolic inhibition (MI) (2.5 mM NaCN and no glucose) to simulate hypoxia followed by washout of CN and re‐addition of glucose (‘reperfusion’). Following exposure to MI, rat cells underwent rigor contracture in 18.8 ± 0.8 min (n = 80 cells), whereas the time was longer for guinea‐pig cells (32.9 ± 1.2 min, n = 83) (P < 0.001). If cells were reperfused after 1‐5 min in rigor, then rat cells showed improved morphological recovery compared with guinea‐pig cells (P < 0.05); thereafter recovery decreased with increasing time spent in rigor, and was similar in both groups. In indo‐1 loaded cells, [Ca2+]i was significantly increased in cells from both species at the end of MI; however, the actual increase was much higher in guinea‐pig cells. Upon reperfusion, [Ca2+]i recovered fully in rat cells, but in guinea‐pig cells there was no significant decrease. The restoration of [Ca2+]i to normal levels in rat cells following MI was associated with improved contractile recovery compared with guinea‐pig cells. We conclude that rat cells are more resistant to effects of MI than are guinea‐pig cells; this may be related to species differences in Ca2+ handling during and following exposure to MI.
Left Ventricular Diastolic Filling and Cardiovascular Functional Capacity in Older Men
Authors: Petrella Robert J. , Cunningham David A. , Paterson Donald H.
Published: May 2004

We investigated anaerobic threshold (thetaL) gas exchange kinetics and maximal oxygen uptake (V̇O2,max) among older men with reduced left ventricular end‐diastolic filling (LVDF). Ten men (mean age, 73 years) with LVDF impairment and low fitness, but without other cardiovascular dysfunction were studied. Treatments compared to control included: 5 days, high intensity exercise training protocol; 5 days, calcium channel blockade (240 mg verapamil); 21 days, detraining/washout; and 5 days, combined treatments. Results indicated no changes in resting left ventricular systolic function with any treatment. Significant resting diastolic function changes included increased early:late flow velocity (control, 0.87; training, 1.28; verapamil, 1.32), and a decreased isovolumic relaxation time (control, 0.10 s; training, 0.08 s; verapamil, 0.08 s). The combined treatments were not additive. Sub‐threshold oxygen uptake kinetics (tauVO2, s) were significantly faster following either training or verapamil (tauVO2,control, 62 ± 12; tauVO2,training, 44 ± 9; tauVO2,verapamil, 48 ± 10) and combined treatments (tauVO2, 41 ± 8). V̇O2,max (ml kg‐1 min‐1) was significantly increased (control, 21.8 ± 2.2; training, 27.3 ± 2.2; verapamil, 25.2 ± 3.4; combined treatments, 26.9 ± 2.3). Increasing ventricular preload with either exercise training or calcium channel blockade was coincident with faster tauVO2 and increased V̇O2,max.
Nitric Oxide, cGMP and cAMP Modulate Nitrobenzylthioinosine‐Sensitive Adenosine Transport in Human Umbilical Artery Smooth Muscle Cells from Subjects with Gestational Diabetes
Authors: Aguayo Claudio , Sobrevia Luis
Published: May 2004

Adenosine transport was characterized in human umbilical artery smooth muscle cells isolated from non‐diabetic and diabetic pregnant subjects. Transport of adenosine was mediated by a Na+‐independent transport system inhibited by nanomolar concentrations of nitrobenzylthioinosine (NBMPR) in both cell types. Diabetes increased adenosine transport, an effect that was associated with a higher maximal velocity (Vmax) for NBMPR‐sensitive (es) saturable nucleoside transport (18 ± 2 vs. 61 ± 3 pmol (μg protein)‐1 min‐1, P < 0.05) and the maximal number of binding sites (Bmax) for specific [3H]NBMPR binding (74 ± 4 vs. 156 ± 10 pmol (μg protein)‐1, P < 0.05), with no significant changes in the Michaelis‐Menten (Km) and dissociation (Kd) constants, respectively. Adenosine transport was unaltered by inhibition of nitric oxide (NO) synthase (with 100 μM NG‐nitro‐L‐arginine methyl ester, L‐NAME) or protein synthesis (with 1 μM cycloheximide), but was increased by inhibition of adenylyl cyclase activity (with 100 μM, SQ‐22536) in non‐diabetic cells. Diabetes‐induced adenosine transport was blocked by L‐NAME and associated with an increase in L‐[3H]citrulline formation from L‐[3H]arginine and intracellular cGMP, but with a decrease in intracellular cAMP compared with non‐diabetic cells. Expression of inducible NO synthase (iNOS) was unaltered by diabetes. Dibutyryl cGMP (dbcGMP) increased, but dibutyryl cAMP (dbcAMP) decreased, adenosine transport in non‐diabetic cells. dbcGMP or the NO donor S‐nitrosoacetylpenicillamine (SNAP, 100 μM) did not alter the diabetes‐elevated adenosine transport. However, activation of adenylyl cyclase with forskolin (1 μM), directly or after incubation of cells with dbcAMP, inhibited adenosine transport in both cell types. Our findings provide the first evidence that adenosine transport in human umbilical artery smooth muscle cells is mediated by the NBMPR‐sensitive transport system es, and that its activity is upregulated by gestational diabetes.
Selective Long‐Term Electrical Stimulation of Fast Glycolytic Fibres Increases Capillary Supply but not Oxidative Enzyme Activity in Rat Skeletal Muscles
Authors: Egginton S. , Hudlická O.
Published: May 2004

Glycolytic fibres in rat extensor digitorum longus (EDL) and tibialis anterior (TA) were selectively activated, as demonstrated by glycogen depletion, by indirect electrical stimulation via electrodes implanted in the vicinity of the peroneal nerve using high frequency (40 Hz) trains (250 ms at 1 Hz) and low voltage (threshold of palpable contractions). This regime was applied 10 times per day, each bout being of 15 min duration with 60 min recovery, for 2 weeks. Cryostat sections of muscles were stained for alkaline phosphatase to depict capillaries, succinate dehydrogenase (SDH) to demonstrate oxidative fibres, and periodic acid‐Schiff reagent (PAS) to verify glycogen depletion. Specific activity of hexokinase (HK), 6‐phosphofructokinase, pyruvate kinase, glycogen phosphorylase and cytochrome c oxidase (COX) were estimated separately in homogenates of the EDL and the predominantly glycolytic cortex and oxidative core of the TA. Stimulation increased the activity of HK but not that of oxidative enzymes in fast muscles. Comparison of changes in oxidative capacity and capillary supply showed a dissociation in the predominantly glycolytic TA cortex. Here, COX was 3.9 ± 0.68 μM min‐1 (g wet wt)‐1 in stimulated muscles compared with 3.7 ± 0.52 μM min‐1 (g wet wt)‐1 in contralateral muscles (difference not significant), while the percentage of oxidative fibres (those positively stained for SDH) was also similar in stimulated (14.0 ± 2.8%) and contralateral (12.2 ± 1.9%) muscles. In contrast, the capillary to fibre ratio was significantly increased (2.01 ± 0.12 vs. 1.55 ± 0.04, P < 0.01). We conclude that capillary supply can be increased independently of oxidative capacity, possibly due to haemodynamic factors, and serves metabolite removal to a greater extent than substrate delivery.
Oscillations in Stroke Volume and Cardiac Output Arising from Oscillatory Ventilation in Humans
Authors: Davies L. Ceri , Francis D. P. , Crisafulli A. , Concu A. , Coats Andrew J. S. , Piepoli Massimo
Published: May 2004

Oscillations in the cardiovascular system have been observed in patients with periodic breathing. It is not clear whether these are driven by primary oscillations in the respiratory system or whether an intrinsic cardiovascular instability is required, as previous studies with subjects performing voluntary periodic breathing have failed to produce the cardiovascular oscillations. We investigated whether cardiovascular oscillations occurred in healthy controls performing voluntary periodic breathing. Six healthy subjects performed voluntary periodic breathing with guidance from a real‐time computer display. We measured ventilation, end‐tidal partial pressures of O2 (PO2) and CO2 (PCO2), heart rate, blood pressure (BP), arterial oxygen saturation and stroke volume and cardiac output by transthoracic impedance cardiography. Fourier analysis was used to quantify the size and phase of the periodic breathing‐induced oscillations in these parameters. Periodic breathing (amplitude 30% of mean ventilation) induced oscillations in end‐tidal PO2 (amplitude 0.8 kPa), end‐tidal PCO2 (amplitude 0.3 kPa), R‐R interval (amplitude 32.6 ms), systolic BP (amplitude 3 mmHg), diastolic BP (amplitude 3 mmHg), stroke volume (amplitude 8.0 ml, mean 79.5 ml) and cardiac output (amplitude 0.6 1, mean 5.9 l min‐1). The oscillations in stroke volume and cardiac output were nearly in phase with ventilation, with their peaks occurring 5.6 and 6.1 s, respectively, after the peak in ventilation. An oscillatory ventilatory pattern entrains the cardiovascular system in healthy controls into fluctuations, not only in heart rate and BP, but also in stroke volume and cardiac output.
A Novel Background Potassium Channel in Rat Atrial Cells
Authors: Shui Z. , Boyett M. R.
Published: May 2004

A K+ channel activated by intracellular ATP has been observed in inside‐out patches from rat atrial cells. The channel has a slope conductance of 130 ± 5 pS in symmetrical 140 mM K+ solution, and is almost independent of voltage over the range from ‐80 to +80 mV. There is no detectable inactivation during application of ATP over a few minutes. In the presence of 3 mM intracellular ATP, channel openings occur as bursts with a mean open time of 1.7 ms, a mean closed time of 0.4 ms, a mean burst duration of 18 ms and a mean burst interval of 41 ms. Kinetic analysis suggests that ATP mainly affects the burst duration and the burst interval of the channel. Based on the properties above, the channel differs from other known K+ channels in cardiac cells and may contribute to background K+ current.
Stimulation of Ventilation by Normobaric Hyperoxia in Exercising Dogs
Authors: Haouzi P. , Allioui E. M. , Gille J. P. , Bedez Y. , Tousseul B. , Chalon B.
Published: May 2004

In order to describe the factors which, during hyperoxic exercise, can counteract the chemoreceptor‐mediated inhibition of ventilation by O2, minute ventilation (VE) and the pulmonary gas exchange were studied breath‐by‐breath in four dogs running on a treadmill (5 km h‐1) for 10 min during and following exposure to O2 of different durations. We found that a brief inhalation of O2 applied during the steady state of the VE response provoked a reduction in VE by 6.5 ± 0.9 l min‐1 whereas hyperoxia applied 2 min before the onset of exercise and maintained for 2.5 min during the running tests had a significantly weaker effect on VE (‐1.8 ± 0.2 l min‐1, P < 0.05). The rise in pulmonary CO2 output (VCO2) during the prolonged O2 exposure was less than in normoxic exercise leading to a deficit of CO2 eliminated by the lungs of 181 ml. The return to air breathing provoked a rise in VE, which reached within 73 s a much higher level than the control tests (22.9 ± 3.6 vs. 19.5 ± 2.2 l min‐1, P < 0.05); VE then subsided to control levels with a long exponential decline. The CO2 deficit during O2 breathing, was fully compensated after recovery in air within 6 min. No stimulatory effect on ventilation was observed at rest at the cessation of a similar exposure to O2 despite a higher end‐tidal PCO2 (+4 ± 1 mmHg) than in exercise. In conclusion, the stimulatory effect of O2 during exercise can be clearly revealed after recovery in air and seems to operate through a more complex mechanism than that thought to be involved at rest. We propose that the changes in CO2 stores in the exercising muscles could contribute to O2‐induced stimulation during exercise, possibly through stimulation of muscle afferents responding to local circulatory changes. Finally, the observation that during continuous dopamine (DA) infusion (5 μg kg‐1 min‐1) the VE response to recovery in air was only a slow decrease, suggests that the arterial chemoreceptors potentiate O2‐induced hyperventilation, or that the vascular actions of DA counteract part of the effects provoked by CO2 accumulation in the exercising muscles.
Doppler Sonography to Monitor Flow in Different Cerebral Arteries in the Rabbit
Authors: Roatta Silvestro , Roncari Silvia , Micieli Giuseppe , Bosone Daniele , Passatore Magda
Published: May 2004

Most of the transcranial Doppler (TCD) experimental studies on cerebral haemodynamics have been performed in the rabbit because of the similarity between its Willis circle and that of the human, but these studies have mainly been limited to the basilar artery. The present study was aimed at extending the use of TCD sonography to all other large cerebral arteries. In anaesthetised rabbits, these arteries were insonated from three different recording sites, i.e. top‐cranial, suboccipital and orbital, using a two‐channel pulsed Doppler device equipped with 4 and 8 MHz probes. First, discrimination between intra‐ and extracranial arteries was achieved through a standard ‘rebreathing’ test (hypercapnic‐hypoxic stimulation). The distinctive blood velocity response patterns, reflecting the different extents of metabolic reactivity in intra‐ and extracranial territories, are described and discussed. Intracranial arteries were then identified on the basis of their response to ipsi‐ and contralateral common carotid artery occlusion. This procedure allowed recording from the following arteries: anterior common trunk, anterior cerebral, internal carotid, middle cerebral and basilar; the latter could be simultaneously monitored with any of the others. This study provides an experimental model allowing investigation of regional differences in the haemodynamic response to neurogenic and pharmacological stimuli.
Effects of Resalination on Intestinal Glucose Transport in Chickens Adapted to Low Na+ Intakes
Authors: Garriga Carles , Moretó Miquel , Planas Joana M.
Published: May 2004

In chickens, we have shown that intestinal absorption of glucose via apical SGLT1 and basolateral GLUT2 transport systems is affected by dietary Na+; low‐Na+ adapted birds show a dramatic reduction of glucose transporters in both membranes in the rectum, an intermediate response in the ileum and no effects in the jejunum. We have now studied the effect of resalination of low‐Na+ adapted chickens on glucose kinetics across SGLT1 (using α‐methyl‐D‐glucoside as substrate) and GLUT2 (using D‐glucose) and on the specific binding of phlorizin and cytochalasin B, respectively. Twelve‐week‐old male Leghorn chickens were fed wheat and barley with drinking water containing either 150 mM NaCl (high‐Na+ group) or 0.015 mM (low‐Na+ group) for 14 days (serum aldosterone: 242 ± 6 pg ml‐1 in the low‐Na+ and 46 ± 4 pg ml‐1 in the high‐Na+ group). On day 14, the low‐Na+ group was either resalinated with an oral dose of NaCl (9 g (kg body wt)‐1) or switched to the high‐Na+ condition, for 1 week. Serum aldosterone measured 4 h, 1 day and 7 days after the change in NaCl intake fell to between 30 and 39 pg ml‐1. The changes in apical α‐methyl‐D‐glucoside and basolateral D‐glucose transport observed in the ileum and rectum of low‐Na+ adapted animals were completely reversed by resalination within 4 h of NaCl administration to the level of values observed for high‐Na+ adapted birds. The good correlation between the α‐methyl‐D‐glucoside and D‐glucose Vmax and the SGLT1 and GLUT2 density, respectively, supports the view that the increase in apical and basolateral hexose transport found in the ileum and rectum of both groups of resalinated birds is due to an increase in the number of protein transporters. The rapid changes in the number of glucose transporters observed suggest that the target of the regulatory signal(s) involved are the mature enterocytes present in the villi rather than the developing enterocytes in the crypt.
Albumin Clearance from Human Skeletal Muscle During Prolonged Steady‐State Running
Authors: Havas Eino , Lehtonen Mika , Vuorela Juha , Parviainen Tapani , Vihko Veikko
Published: May 2004

This study was designed to find out if the lymph flow, indicated as albumin clearance, from active skeletal muscle is maintained constant during a prolonged steady‐state exercise. 99mTc‐labelled albumin was injected bilaterally into the vastus lateralis muscles of eight endurance‐trained men. The radioactivity at the injection site was monitored by a gamma‐camera before, frequently during, and after a 2 h run at a controlled steady intensity of 69 ± 4% of the maximal heart rate. The fractional clearance rate of albumin was calculated for each monitoring interval, and was expressed as percentage clearance per minute (% min‐1). During the first 15 min of exercise the clearance rate was five times higher than at rest before the exercise (0.29 ± 0.12 vs. 0.06 ± 0.05% min‐1, P = 0.001). During the next 25 min of running the clearance rate fell to 0.19 ± 0.08% min‐1 (P = 0.02), from which level it was further attenuated, being 0.12 ± 0.04% min‐1 at the end of the exercise. After the exercise the clearance rate fell rapidly to the level of 0.04 ± 0.03% min‐1. The results showed that the albumin clearance from working muscles is not constant during steady‐state exercise, suggesting that lymph flow from exercising skeletal muscle may not be constant despite lymphatic pumping being assumed to be unchanged during the course of exercise (i.e. constant exercise intensity and running speed).
Carbohydrate Ingestion Prior to Exercise Augments the Exercise‐Induced Activation of the Pyruvate Dehydrogenase Complex in Human Skeletal Muscle
Authors: Tsintzas K. , Williams C. , Constantin‐Teodosiu D. , Hultman E. , Boobis L. , Greenhaff P.
Published: May 2004

This study examined the effect of pre‐exercise carbohydrate (CHO) ingestion on pyruvate dehydrogenase complex (PDC) activation, acetyl group availability and substrate level phosphorylation (glycogenolysis and phosphocreatine (PCr) hydrolysis) in human skeletal muscle during the transition from rest to steady‐state exercise. Seven male subjects performed two 10 min treadmill runs at 70% maximum oxygen uptake (V̇O2,max), 1 week apart. Each subject ingested 8 ml (kg body mass (BM))‐1 of either a placebo solution (CON trial) or a 5.5% CHO solution (CHO trial) 10 min before each run. Muscle biopsy samples were obtained from the vastus lateralis at rest and immediately after each trial. Muscle PDC activity was higher at the end of exercise in the CHO trial compared with the CON trial (1.78 ± 0.18 and 1.27 ± 0.16 mmol min‐1 (kg wet matter (WM))‐1, respectively; P 0.05) and this was accompanied by lower acetylcarnitine (7.1 ± 1.2 and 9.1 ± 1.1 mmol kg‐1 (dry matter (DM))‐1 in CHO and CON, respectively; P 0.05) and citrate concentrations (0.73 ± 0.05 and 0.91 ± 0.10 mmol (kg DM)‐1 in CHO and CON, respectively; P 0.05). No difference was observed between trials in the rates of muscle glycogen and PCr breakdown and lactate accumulation. This is the first study to demonstrate that CHO ingestion prior to exercise augments the exercise‐induced activation of muscle PDC and reduces acetylcarnitine accumulation during the transition from rest to steady‐state exercise. However, those changes did not affect the contribution of substrate level phosphorylation to ATP resynthesis.
Stretch Reflexes in the Rectus Abdominis Muscle in Man
Authors: Myriknas S. E. , Beith I. D. , Harrison P. J.
Published: May 2004

The spinal reflex circuitry of the rectus abdominis (RA) muscle in man was investigated by the application of a mechanical tap to the muscle. Electromyographic recordings were made in ten healthy subjects, performing a series of manoeuvres, using pairs of surface electrodes placed bilaterally. The reflex responses elicited largely depended on the amount of tonic (postural) activity of the trunk. When standing in the upright position, no reflex activity was recorded in response to the tap. Reflex activity due to mechanical tap was readily recorded when the muscle became tonically active. Moderate, backward trunk extension introduced short‐latency reflexes at 18.8 ± 1.9 ms (mean ± S.D.) ipsilaterally and 20.8 ± 1.8 ms contralaterally. Excitatory reflex activity of longer latency was also recorded contralaterally in all subjects (latency 45.1 ± 4.3 ms) and ipsilaterally in five of the ten subjects (latency 47.2 ± 2.6 ms). Vibration of the tapped muscle produced a reduction in the amplitude of the early reflex responses, whilst increasing the amplitude of the late responses. Moreover, the early reflexes were facilitated by the Jendrassik manoeuvre. Such observations are consistent with the early responses being mediated, at least partly, monosynaptically, and the late responses being of polysynaptic nature. This implies that muscle spindle afferents from rectus abdominis monosynaptically activate motoneurones contralaterally.
Possible Contribution of Central Gamma‐Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving Rats
Authors: Takemoto Yumi
Published: May 2004

Previous studies have shown that central administration of GABA (gamma‐aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co‐varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone.