bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca2+ channels, ryanodine receptors and Ca2+‐activated K+ channels: a functional unit for regulating arterial tone
Authors: JAGGAR  , WELLMAN  , HEPPNER  , PORTER  , PEREZ  , GOLLASCH  , KLEPPISCH  , RUBART  , STEVENSON  , LEDERER  , KNOT  , BONEV  , NELSON
Published: March 2003

Local calcium transients (‘Ca2+ sparks’) are thought to be elementary Ca2+ signals in heart, skeletal and smooth muscle cells. Ca2+ sparks result from the opening of a single, or the coordinated opening of many, tightly clustered ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In arterial smooth muscle, Ca2+ sparks appear to be involved in opposing the tonic contraction of the blood vessel. Intravascular pressure causes a graded membrane potential depolarization to approximately −40 mV, an elevation of arterial wall [Ca2+]i and contraction (‘myogenic tone’) of arteries. Ca2+ sparks activate calcium‐sensitive K+ (KCa) channels in the sarcolemmal membrane to cause membrane hyperpolarization, which opposes the pressure induced depolarization. Thus, inhibition of Ca2+ sparks by ryanodine, or of KCa channels by iberiotoxin, leads to membrane depolarization, activation of
L‐type voltage‐gated Ca2+ channels, and vasoconstriction. Conversely, activation of Ca2+ sparks can lead to vasodilation through activation of KCa channels. Our recent work is aimed at studying the properties and roles of Ca2+ sparks in the regulation of arterial smooth muscle function. The modulation of Ca2+ spark frequency and amplitude by membrane potential, cyclic nucleotides and protein kinase C will be explored. The role of local Ca2+ entry through voltage‐dependent Ca2+ channels in the regulation of Ca2+ spark properties will also be examined. Finally, using functional evidence from cardiac myocytes, and histological evidence from smooth muscle, we shall explore whether Ca2+ channels, RyR channels, and KCa channels function as a coupled unit, through Ca2+ and voltage, to regulate arterial smooth muscle membrane potential and vascular tone.
Decline of the calcium response on successive stimulation of a rat brain endothelial cell P2U purinoceptor
Authors: NOBLES  , ABBOTT
Published: March 2003

A microfluorimetric method using Fura‐2 as calcium indicator was used to study the mechanism of desensitization of the calcium response evoked by activation of a brain endothelial cell P2U receptor. The study was mainly carried out on an immortalized rat brain endothelial cell line (RBE4), with some additional experiments on primary cultured rat brain microvascular endothelial cells. As previously described (
Nobles et al. 1995
), ATP (100 μM, 20 s) caused a transient increase in intracellular calcium levels ([Ca2+]i). This effect was dependent on the rate of filling of intracellular calcium stores, since a large inhibition of the ATP‐mediated response was seen in the presence of cyclopiazonic acid, an inhibitor of the store Ca2+‐ATPase. Application of repeated pulses of extracellular ATP led to a desensitization of the response, as measured by a decline in the release of intracellular calcium (
Nobles et al. 1995
). This desensitization was partially reversed after 300 s of incubation in agonist‐free medium. Extracellular phosphorylation of the purinergic receptor appeared not to be involved in the desensitization process, since a similar rate of desensitization was obtained with the non‐hydrolysable ATP analogue ATP gammaS. Oxidation of the purinergic receptor cannot account for the desensitization, since the decline of the ATP‐mediated response was unchanged in the presence of 3 m
M dithiothreitol. In the presence of ATP together with UTP, two equally potent activators of the P2U receptor, the desensitization was less than in the presence of only one of the agonists. The desensitization was greater when ATP was applied for longer (150 s) periods. Although these results do not exclude the participation of post‐receptor events in the desensitization process, they suggest that desensitization is governed at least in part by agonist–receptor interaction.
Increase in serum vascular endothelial growth factor levels during altitude training
Authors: ASANO  , KANEOKA  , NOMURA  , ASANO  , SONE  , TSURUMARU  , YAMASHITA  , MATSUO  , SUZUKI  , OKUDA
Published: March 2003

The present study was performed to evaluate the effects of physical exercise at altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight subjects underwent intensive swimming training for 21 days at 1886 m. After altitude training commenced, red blood cell (RBC) counts and erythropoietin levels increased, but both haemoglobin and haematocrit levels did not change significantly. The serum level of VEGF, measured by means of a highly sensitive chemiluminescence (ELISA), showed a transient decrease 10 days after start of the altitude training, thereafter increasing significantly to reach a peak level 19 days later, rising from 23.0 ± 5.3 to 46.0 ± 14.6 pg mL−1 (P < 0.05 vs. before). On return to low altitude in Japan, the level of VEGF decreased, and 1 month later had returned to initial levels. Endurance training at altitudes increases serum VEGF levels; this could be an adaptive reaction to hypoxic conditions. This result suggests that VEGF may provide a new physiological parameter for hypoxic stress imposed by high altitude training.
Jejunal permeability in humans invivo and rats insitu: investigation of molecular size selectivity and solvent drag
Authors: FAGERHOLM  , NILSSON  , KNUTSON  , LENNERNÄS
Published: March 2003

The mechanisms controlling rates and routes for intestinal absorption of nutrients and small compounds are still not fully clarified. In the present study we aimed to investigate the effect of solvent drag on intestinal permeability of compounds with different molecular sizes in humans and rats. The effective intestinal permeabilities (Peff) of hydrophilic compounds (MW 60–4000) were determined in the single‐pass perfused jejunum in humans in vivo and rats in situ under iso‐ and hypotonic conditions. The transport mechanism(s) of water and the importance of the solvent drag effect were investigated by the use of D2O. This is the first report in humans establishing the relation between in vivo measured jejunal Peff and molecular size for hydrophilic compounds. In addition, in rats we also found a molecular‐size selectivity for hydrophilic compounds similar to man. The jejunal Peff of water and urea (MW 60) in both species were several times higher than predicted from their physicochemical properties. In humans, the jejunal absorption of urea and creatinine (MW 113) was increased by solvent drag, while no effect was found for the other investigated compounds. In rats, Peff for urea and creatinine were unaffected. In conclusion, it is still unclear if solvent drag occurs mainly through the para‐ or transcellular route, although, results from this study further add to our earlier reports suggesting that the transcellular route is most important from a quantitative point of view regardless of physicochemical properties of the transported compounds.
Modulation of Na+ × H+ exchange by hydrostatic pressure in isolated bovine articular chondrocytes
Authors: Browning  , Walker  , Hall  , Wilkins
Published: March 2003

The effects of increased hydrostatic pressure on Na+ × H+ exchange activity in bovine articular chondrocytes have been characterized. Chondrocytes were isolated from the cartilage matrix and the cells were loaded with the pH‐sensitive fluorophore BCECF. Cells were acidified by ammonium rebound and the rate of recovery of pHi back to control levels was determined using cuvette fluorimetry. The application of hydrostatic pressure (1–300 atm) to cells within the fluorimeter was found to stimulate the rate of recovery from acidification, recorded as proton fluxes, in MOPS buffered media. This increase was dependent on the presence of extracellular Na+ ions and was inhibited by the Na+ × H+ exchange inhibitor EIPA. The pressure‐stimulated increase in H+ flux is therefore mediated completely by Na+ × H+ exchange. In addition, the stimulation could be abolished by the kinase inhibitor staurosporine, was not additive with the stimulation of Na+ × H+ exchange elicited by the addition of serum and was unaffected by low concentrations of the myosin light chain kinase inhibitor ML‐7. We therefore conclude that hydrostatic pressure activates Na+ × H+ exchange in this cell type by a pathway which involves direct phosphorylation of the transporter protein itself. This is the first demonstration of the activation of Na+ × H+ exchange by hydrostatic pressure and the relevance of this finding to the biology of cartilage tissue is discussed.
The role of astrocytes and noradrenaline in neuronal glucose metabolism
Authors: Fillenz  , Lowry  , Boutelle  , Fray
Published: March 2003

In the classical model the energy requirements during neuronal activation are provided by the delivery of additional glucose directly into the extracellular compartment that results from the increase in local cerebral blood flow (rCBF). The present review proposes that astrocytes play a key role in the response to neuronal activation. Arginine for the synthesis of NO, which has a major role in the increase in rCBF, is released from astrocytes in response to stimulation of astrocytic glutamate receptors. The increased delivery of glucose by the blood stream enters astrocytes, where some of it is converted to glycogen. During neuronal activation there is a decrease in extracellular glucose owing to increased utilization followed by a delayed increase; this results from stimulation of astrocytic β‐adrenergic receptors, which leads to a breakdown of glycogen and the export of glucose.
Contribution of satellite cells to IGF‐I induced hypertrophy of skeletal muscle
Authors: Barton‐Davis  , Shoturma  , Sweeney
Published: March 2003

Insulin‐like growth factor I (IGF‐I) is critical in promoting growth of skeletal muscle. When IGF‐I is introduced into mouse hindlimb muscles by viral‐mediated gene transfer, local overexpression of IGF‐I produces significant increases in muscle mass and strength compared with untreated controls ( Barton‐Davis et al. 1998
). We have proposed that this functional hypertrophy is primarily owing to the activation of satellite cells which leads to increased muscle regeneration. In order to test if satellite cells are essential in mediating the hypertrophic effects of IGF‐I, we used gamma radiation to destroy the proliferative capacity of satellite cells. The right hindlimbs of adult C57BL/6 male mice were subjected to one of the following treatments: (1) 2500 rad gamma radiation only, (2) viral‐mediated gene transfer of IGF‐I only, (3) 2500 rad gamma radiation plus viral‐mediated gene transfer of IGF‐I, or (4) no intervention as a control. Approximately 4 months after treatment, the extensor digitorum longus muscles (EDL) from both hindlimbs were removed for mechanical and morphological measurements. Treatment with gamma radiation significantly prevented normal growth of the muscle. When combined with IGF‐I treatment, approximately half of the IGF‐I effect was prevented by gamma radiation treatment. This suggests that the remaining half of IGF‐I induced hypertrophy is owing to paracrine/autocrine effects on the adult myofibres. Thus, these data are consistent with a mechanism by which IGF‐I induced muscle hypertrophy via a combination of satellite cell activation and increasing protein synthesis in differentiated myofibres.
An overview of carbohydrate–protein interactions with specific reference to myosin and ageing
Authors: Ramamurthy  , Höök  , Larsson
Published: March 2003

Non‐enzymatic glycosylation (glycation), a post‐translational modification of proteins, results from the reaction of proteins with reducing sugars. Glycation is implicated in various pathologies like diabetes, Alzheimer’s disease and it has been suggested to play an important role in the ageing process. Research on protein glycation has primarily studied extracellular proteins such as albumin, haemoglobin and collagen. However, there is increasing evidence that intracellular proteins may also be affected by glycation, and glycation of myosin is reported to decrease myosin ATPase activity. Glycated adducts are detected by various techniques such as chromatography, electrophoresis, fluorescence and immunochemistry. Inhibition or removal of these adducts has been achieved by chemical compounds such as aminoguanidine (amG), β‐mercaptoethanol (bME) and N‐phenacylthiazolium bromide (PTB). In the present pilot study, using a novel in vitro motility assay, we have observed an attenuation in the motility speed of actin (≈13%) on myosin extracted from single muscle fibre segments after 15‐min glucose incubation. Addition of bME to the incubation medium maintained actin motility speed.
D1 Dopamine receptor signalling defect in spontaneous hypertension
Authors: Felder  , Eisner  , Jose
Published: March 2003

Dopamine modulates cardiovascular function by actions in the central and peripheral nervous system, by altering the secretion/release of prolactin, pro‐opiomelanocortin, vasopressin, aldosterone, and renin, and by directly affecting renal function. Dopamine produced by the renal proximal tubule exerts an autocrine/paracrine action via two classes of dopamine receptors, D1‐like (D1 and D5) and D2‐like (D2, D3, and D4), that are differentially expressed along the nephron. The autocrine/paracrine function of dopamine, manifested by tubular rather than by haemodynamic mechanisms, becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension. The molecular basis for the dopaminergic dysfunction in hypertension may involve an abnormal post‐translational modification of dopamine receptors.
Control of arterial blood pressure and renal sodium excretion by nitric oxide synthase in the renal medulla
Authors: Mattson  , Wu
Published: March 2003

Work in our laboratory has focused on the role of nitric oxide synthase (NOS) in the regulation of renal medullary function. Biochemical studies demonstrated that the renal medulla is enriched in immunoreactive NOS protein and NOS enzymatic activity when compared with the renal cortex. Further experiments showed large amounts of NOS activity in the inner medullary collecting ducts, while moderate NOS activity was found in glomeruli and vasa recta and minimal NOS activity was detected in other nephron segments examined. In subsequent functional studies, selective renal medullary infusion of NOS stimulators (bradykinin or acetylcholine) or inhibitors ( L‐NAME) preferentially altered medullary blood flow. The alterations in medullary flow were associated with parallel changes in sodium and water excretion. Similar to the effects observed in anaesthetized rats, chronic infusion of
L‐NAME directly into the renal medullary interstitial space of conscious, uninephrectomized SD rats selectively decreased renal medullary blood flow throughout a 5‐day
L‐NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension, and the effects were reversible. In contrast to the effects of chronic NOS inhibition, renal medullary infusion of NOS substrate
L‐arginine prevented the development of sodium‐sensitive hypertension in the Dahl salt‐sensitive rat placed on a high sodium diet. The data reviewed in this paper indicate that NOS isoforms expressed in the renal medulla have a potent influence on renal medullary tubular and vascular function with consequential effects on fluid and electrolyte homeostasis and arterial blood pressure.
Effect of hyperoxia on aerobic and anaerobic performances and muscle metabolism during maximal cycling exercise
Authors: Linossier  , Dormois  , Arsac  , Denis  , Gay  , Geyssant  , Lacour
Published: March 2003

The hyperoxia‐improved tolerance to maximal aerobic performance was studied in relation to exercising muscle metabolic state. Five students were submitted to four different tests on a cycle ergometer, each being conducted under normoxia and hyperoxia (60% FiO2) on separate days: Test 1, a progressive exercise until exhaustion to determine the maximal work load (W˙max) which was unchanged by hyperoxia; Test 2, an exercise at W˙max (287 ± 12 W) until exhaustion to determine the performance time (texh) which was elevated by 38% under hyperoxia but exhaustion occurred at the same arterial proton and lactate concentrations; Test 3 (S‐Exercise test) consisted of cycling at W˙max for 90% normoxic‐texh (4.8 ± 0.5 min under both O2 conditions) then followed by a 10‐s sprint bout during which the total work output (W˙tot) was determined; W˙tot was elevated by 15% when exercising under hyperoxia; Test 4 (M‐Exercise test) consisted also of cycling at W˙max for 4.8 ± 0.5 min with blood and muscle samples taken at rest and at the end of the exercise to compare the level of different metabolites. During hyperoxic M‐Exercise test, glycogen was twice more depleted whereas glucose‐6‐phosphate and lactate were less accumulated when compared with normoxia. No significant differences were observed for pyruvate, phosphocreatine and muscle/blood lactate ratio between the two conditions. Conversely to normoxia, levels of ATP, ADP and total NADH were maintained at their resting level under 60% FiO2. These data lead us to suppose a higher oxidation rate for pyruvate and NADH in mitochondria, thereby lowering the metabolic acidosis and allowing a better functioning of the glycolytic and contractile processes to delay the time to exhaustion.
On the direction and velocity of blood flow in the extradural intravertebral vein of harp seals (Phoca groenlandica) during simulated diving
Authors: Nordgarden  , Folkow  , Walløe  , Blix
Published: March 2003

Ronald et al. (1977
) suggested that blood flow in the caudal/lumbar sections of the extradural intravertebral vein (EIV) of seals changes direction from running towards the head before diving, to the opposite during diving. The possible advantage would be that the oxygen‐depleted venous effluent from the brain is routed via the EIV to the posterior parts of the hepatic sinuses and the inferior caval vein and, hence, is prevented from mixing with the more oxygen‐rich venous blood in their anterior parts. We have re‐examined this hypothesis by use of Doppler flowmetry. A catheter‐tip flow probe was introduced into the EIV of two similar‐sized juvenile harp seals, and flow direction and rate determined before, during and after simulated dives lasting for 5 min, at three positions (caudal, lumbar and thoracic) along the EIV. Regardless of probe position, blood was mainly flowing towards the head in 11 of 13 experiments prior to diving, in 8 of 13 experiments during diving and in 11 of 13 experiments during recovery after diving (and away from the head in the remaining experiments). Flow direction was most variable in the caudal position. Mean blood velocity in the EIV was substantially lower during diving (0.10 ± 0.22 cm s–1 (n=5) in thoracic position) than in the pre‐dive (3.98 ± 3.32 cm s–1 [n=5]) and post‐dive (5.75 ± 4.07 cm s–1 [n=5]) situations. Thus, the direction and rate of flow in the EIV was variable, particularly during diving, as is to be expected in a system of anastomosing, valveless veins. We conclude that the hypothesis of
Ronald et al. (1977
) most likely is false.
Electrically evoked eccentric and concentric torque–velocity relationships in human knee extensor muscles
Authors: Seger  , Thorstensson
Published: March 2003

The torque–velocity relationship, obtained during in situ conditions in humans, demonstrates a levelling‐off of eccentric torque output at the isometric torque level, at least for knee extensor actions. In contrast, the in vitro force–velocity relationship for animal muscle preparations is characterized by a sharp rise in eccentric force from isometric maximum. A force‐regulating ‘protective’ mechanism has been suggested during maximal voluntary high‐tension eccentric muscle actions. To investigate this phenomenon, maximal voluntary and three different levels of submaximal, electrically induced torques were compared during isometric and low velocity (10, 20 and 30° s–1) isokinetic eccentric and concentric knee extensor actions in 10 healthy, moderately trained subjects. Eccentric torque was higher than isometric during electrically evoked, but not during maximal voluntary muscle actions. In contrast, concentric torque was significantly lower than isometric for both maximal voluntary and submaximal, electrically evoked conditions. Comparisons of normalized torques (isometric value under each condition set to 100%) demonstrated that the maximal voluntary eccentric torque had to be increased by 20%, and the isometric by 10% in order for the maximal voluntary torque–velocity curve to coincide with the electrically stimulated submaximal ones. These results support the notion that a tension‐regulating mechanism is present primarily during eccentric maximal voluntary knee extensor actions.
The red blood cell as an oxygen sensor: what is the evidence?
Authors: Ellsworth M.L.
Published: March 2003

The matching of oxygen supply with demand requires the existence of a mechanism within the tissue capable of both sensing tissue oxygen need and inducing alterations in vascular perfusion necessary to meet that need. Historically, localized sites within the tissue and the vessels themselves have been investigated with the sensor site failing to be determined. Within the last decade, studies have focused on the red blood cell, the efficient carrier of oxygen, as a possible candidate. The red blood cell is clearly capable of sensing oxygen levels, as its extent of haemoglobin desaturation (decrease in oxygen content) is intimately tied with tissue oxygen demand. In addition, numerous studies have indicated that the red blood cell is capable of releasing increased amounts of adenosine 5′‐triphosphate (ATP) as oxygen content falls and its haemoglobin becomes desaturated. Within the vasculature, intraluminal ATP has been shown to induce a vasodilator response which is conducted along the vessels resulting in augmentation of tissue perfusion. While details of the red blood cell’s role are still under investigation, evidence presented here supports the intriguing idea that the mobile red blood cell may itself be able to augment blood flow and oxygen delivery wherever and whenever the need might arise. Such a mechanism eliminates the requirement for a diverse network of sensing sites throughout the vasculature and should provide a more efficient means of appropriately matching oxygen supply with demand.
Interaction of nitric oxide and reactive oxygen species on rat diaphragm contractility
Authors: Lawler  , Hu
Published: March 2003

Growing evidence indicates that reactive oxygen species (ROS) as well as nitric oxide (NO) have a profound influence on contractile function of skeletal muscle possibly through modulation of excitation–contraction coupling. We hypothesized that if NO and xanthine oxidase (XO) interact at key sites in excitation–contraction coupling, the effects of XO with nitric oxide synthase (NOS) inhibitors and NO donors on contractile function of the unfatigued diaphragm would not be additive. Diaphragm fibre bundles were extracted from 4‐month Fischer‐344 rats and placed in Krebs solution bubbled with 95% O2, 5% CO2. Baseline twitch tension, tension at 20 Hz (low‐frequency), and maximal tetanic tension (Po) at 120 Hz were then measured (PRE). In Experiment 1 diaphragm fibre bundles were exposed to Krebs with 200 μM hypoxanthine as a control (CON); 0.02 U mL–1 XO + 200 μM hypoxanthine; 1 m
M of the NOS inhibitor N‐nitro‐
L‐arginine (
L‐NNA) or
L‐NNA + XO. Five minutes were allowed for equilibration, and a second set of contractile measures was taken (POST). In Experiment 2 we exposed diaphragm fibre bundles to one of the following four solutions: CON, XO, 100 μM of the NO donor sodium nitroprusside (SNP) and XO + SNP, and evaluated contractile function as described above. In Experiment 3 we tested to determine if peroxynitrite production from the reaction of superoxide anion and NO affected the above results for SNP using 30 μM ebselen as a peroxynitrite quencher. Xanthine oxidase resulted in a significant potentiation of diaphragm twitch tension and tension at 20 Hz (+29%) without affecting Po.
L‐NNA also significantly increased 20 Hz tension but did not alter Po. However, the combination of XO + L‐NNA did not further increase low‐frequency contractility. Sodium nitroprusside alone did not affect diaphragm contractility, but did attenuate XO‐induced potentiation in the XO + SNP group. Ebselen did not alter the impact of SNP on XO in the diaphragm. These data support the hypothesis that XO and NO interact or compete at similar sites of action that modulate contractility of the unfatigued diaphragm.
Intramuscular pressure and electromyographic responses of the vastus lateralis muscle during repeated maximal isokinetic knee extensions
Authors: Crenshaw A.G. , Gerdle B. , Heiden M. , Karlsson S. , FridÉn J.
Published: March 2003

The purpose of the study was to investigate changes in intramuscular pressure (IMP) (maximal during contraction – peak IMP, and between contraction, relaxation IMP – RxIMP) and surface electromyographic activity (EMG) parameters [mean frequency of the power spectrum (fmean), and signal amplitude, root mean square (RMS)] throughout 100 repetitive isokinetic contractions for six healthy subjects. Parameters were recorded simultaneously from the vastus lateralis muscle during maximal knee extension. Regression analyses revealed significant decreases for peak IMP and fmean, and an increase in RxIMP; RMS, however, did not change. All parameters demonstrated trends of change throughout the contractions that were non‐linear. Details and inter relations for RxIMP and fmean were highlighted to express intramuscular fluid accumulation and fatigue development, respectively. Individual regression analyses for RxIMP revealed significant positive correlations for all subjects (range of r=0.62 to 0.89). At group level, mean RxIMP increased from 6.0 mmHg for the 1st contraction to 14.0 mmHg for the 100th contraction. For fmean, individual regressions were significantly negative for all subjects (r=–0.75 to –0.89). Fmean decreased from 89.2 Hz for the 1st contraction to 63.3 Hz for the 100th contraction. When the data were delineated between the fatigue (contractions 1–40) and endurance phases (41–100), the slopes of increase for RxIMP, and of decrease for fmean were significantly greater during the fatigue phase. RxIMP throughout the 100 contractions correlated negatively with fmean for each subject (r=–0.54 to –0.78); when delineated, the correlation between parameters was significantly greater for the fatigue as compared with the endurance phase. Relaxation IMP trends are mainly attributed to intramuscular water accumulations during repetitive contractions. In spite of consistent correlations between RxIMP and fmean a causal association could not be established. It may be suggested that a common factor occurring during the fatiguing process governs changes in RxIMP and fmean.
Enhanced intestinal motility influences absorption in anaesthetized rat
Authors: Sababi M. , Bengtsson U. Hultkvist
Published: March 2003

The subject of this investigation was to study influence of the intestinal motility on absorption of 3‐o‐methyl‐D‐glucose (3‐OMG), mannitol and polyethylene glycol (PEG 4000), used as absorption route markers, while monitoring cardiovascular parameters in an intestinal in situ model in rats. Rats were anaesthetized with Inactin® and Rapinovet®. A segment of duodenum, approximately 10 cm, was perfused single‐pass with saline containing unlabelled and radioactive 3‐OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost completely in the intestinal perfusate suggesting an intact mucosal integrity. Most animals exhibited an intestinal contractile activity resembling fed motility except seven out of 19 given Rapinovet®, which showed a ‘burst‐type’ pattern resembling migrating motor complex (MMC). Absorption of 3‐OMG in rats with MMC‐like motility appears to be lower than in rats with fed‐like motility, while no such difference was seen for mannitol. Moreover, there was a positive correlation (r 2=0.75) between intestinal activity (fed) and absorption of 3‐OMG, but not with absorption of mannitol. The carrier‐mediated absorption of 3‐OMG was not only influenced by intestinal motility, but also by its pattern. This was not observed with mannitol, which is passively absorbed.
Effect of 10‐day cast immobilization on sarcoplasmic reticulum calcium regulation in humans
Authors: Thom J. M. , Thompson M. W. , Ruell P. A. , Bryant G. J. , Fonda J. S. , Harmer A. R. , De Jonge X. A. K. Janse , Hunter S. K.
Published: March 2003

This study investigated the effects of 10‐day lower limb cast immobilization on sarcoplasmic reticulum (SR) Ca2+ regulation. Muscle biopsies were analysed in eight healthy females for maximal rates of SR Ca2+ release, Ca2+ uptake and Ca2+ ATPase activity at control, during immobilization at day 3 (IM 3), day 6 (IM 6) and day 10 (IM 10). Quadriceps muscle cross‐sectional area (CSA) and 1‐repetition maximum (1RM) leg extension strength were measured to determine the extent of muscle size and strength adaptations. Muscle CSA and strength decreased following 10 days of immobilization (11.8 and 41.6%, respectively, P < 0.01). A decrease in SR Ca2+ uptake rate (analysed per g wet wt) was found at IM 3 (13.2%, P=0.05), with a further decrease at IM 10 (19.8% from control, P < 0.01). At IM 10, a decrease in SR Ca2+ uptake rate (per mg protein) also occurred (19.9%, P < 0.01). Sarcoplasmic reticulum Ca2+ ATPase activity and rate of Ca2+ release were not altered with 10 days of immobilization. This study observed a decrease in SR Ca2+ uptake rate, muscular atrophy and strength loss over 10 days of immobilization in humans.
Differential effects of diminished oestrogen and androgen levels on development of skeletal muscle fibres in hypogonadal mice
Authors: Sciote J. J. , Horton M. J. , Zyman Y. , Pascoe G.
Published: March 2003

Androgen and oestrogen hormones influence skeletal muscle size and the characteristics of skeletal muscle fibre types. These effects have typically been assessed by producing acute shortages (castration/ovariectomy) or by hormone supplementation. Little evidence exists, however, on how sex hormone shortages affect muscle development from early stages through to adulthood. Using the hypogonadal mouse model (hpg) we examined the effects of diminished androgen and oestrogen upon muscle size and fibre type composition in murine gastrocnemius and soleus muscles. Hypogonadal male soleus muscle was significantly smaller than normal males, and approximated the normal and hypogonadal females weight and fibre type characteristics. The hypogonadal male gastrocnemius muscle, however, was significantly small in comparison with normal and hypogonadal female gastrocnemius muscles, with the type IIB fibre diameters decreased most markedly. The hypogonadal female soleus muscle approximated the normal female phenotype, but the gastrocnemius muscle was larger than the normal female, approximating the size of the normal male gastrocnemius muscle. Here too, the type IIB fibres showed the most alteration, with greatly increased fibre diameters. Appropriate amounts of androgens were necessary for gender‐specific patterns of growth in male muscles, whilst similar amounts of oestrogen were necessary for female gastrocnemius muscle growth, but not for female soleus muscle. Hypogonadism in this murine model generally retards muscle development in males, but has no apparent influence or enhances muscle development in females. Type IIB fibres are most dependent upon sex hormones for appropriate development, but this relationship is muscle‐specific.
Mitogen‐activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contraction
Authors: Widegren U. , Ryder J. W. , Zierath J. R.
Published: March 2003

Exercise has numerous growth and metabolic effects in skeletal muscle, including changes in glycogen metabolism, glucose and amino acid uptake, protein synthesis and gene transcription. However, the mechanism(s) by which exercise regulates intracellular signal transduction to the transcriptional machinery in the nucleus, thus modulating gene expression, is largely unknown. This review will provide insight on potential intracellular signalling mechanisms by which muscle contraction/exercise leads to changes in gene expression. Mitogen‐activated protein kinase (MAPK) cascades are associated with increased transcriptional activity. The MAPK family members can be separated into distinct parallel pathways including the extracellular signal‐regulated kinase (ERK) 1/2, the stress‐activated protein kinase cascades (SAPK1/JNK and SAPK2/p38) and the extracellular signal‐regulated kinase 5 (ERK5). Acute exercise elicits signal transduction via MAPK cascades in direct response to muscle contraction. Thus, MAPK pathways appear to be potential physiological mechanisms involved in the exercise‐induced regulation of gene expression in skeletal muscle.
Platelet‐derived growth factor receptors expressed in response to injury of differentiated vascular smooth muscle in vitro: effects on Ca2+ and growth signals
Authors: Lindqvist A. , Nilsson B.‐O. , Ekblad E. , Hellstrand P.
Published: March 2003

Vascular smooth muscle cells (VSMCs) in the intact vascular wall are differentiated for contraction, whereas the response to vascular injury involves transition towards a synthetic phenotype, with increased tendency for proliferation. Platelet‐derived growth factor (PDGF) is thought to be important for this process. We investigated expression and functional coupling of PDGF receptors (PDGFRs) α and β in rat tail arterial rings kept in organ culture, in order to capture early events in the phenotypic transition. In freshly dissected rings no PDGFR immunoreactivity was found in medial VSMCs, whereas PDGFR α was detected in nerve fibres. After organ culture for 1–4 days PDGFR α and β as well as phospholipase Cγ2 (PLCγ2), known to couple to PDGFR, were expressed in VSMCs within 100 μm of the cut ends. Calponin, a marker for the contractile phenotype, was decreased near the injured area, suggesting that cells were in transition towards synthetic phenotype. In these cells, which showed functional Ca2+‐release from the sarcoplasmic reticulum, PDGF‐AB (100 ng mL–1) had no effect on [Ca2+]i, whereas cultured VSMCs obtained from explants of rat tail arterial rings responded to PDGF‐AB with an increase in [Ca2+]i. However, PDGFR within the cultured rings coupled to growth signalling pathways, as PDGF‐AB caused a tyrphostin AG1295‐sensitive activation of extracellular signal‐regulated kinases 1 and 2 and of [3H]‐thymidine incorporation. Thus, early expression of PDGFR in VSMC adjacent to sites of vascular injury coincides with signs of dedifferentiation. These receptors couple to growth signalling, but do not activate intracellular Ca2+ release.
Palmitate oxidation in rat hepatocytes is inhibited by foetal calf serum
Authors: Sleboda J. , Bremer J. , Horn R. S.
Published: March 2003

The rate of oxidation of fatty acids in mammals is minimal prior to birth. In this study, we have shown that foetal calf serum (FCS) inhibits oxidation of palmitate while serum from newborn calves is almost without effect. Foetal calf serum was also found to increase fatty acid synthesis from acetate. Uptake of laurate in mitochondria is partially dependent upon the carnitine palmitoyltransferase (CPT) I/CPT II system, while octanoate transport occurs without its participation. Comparison of the effects of FCS on the oxidation of palmitate, laurate and octanoate supports the view that the observed actions of FCS result from regulation of CPT I activity. The material in FCS that affects fatty acid metabolism has a molecular weight <3 kDa, as determined by dialysis and ultra‐filtration studies.
Inhibition of human α1E subunit‐mediated Ca2+ channels by the antipsychotic agent chlorpromazine
Authors: McNaughton N. C. L. , Green P. J. , Randall A. D.
Published: March 2003

Chlorpromazine is a neuroleptic antipsychotic agent with a long history of clinical use. Its primary mode of action is thought to be through modulation of monoaminergic inter‐neuronal communication; however, its side‐effect profile indicates substantial activities in other systems. Recent work has begun to uncover actions of this compound on ion channels. In this light we have investigated the actions of chlorpromazine on the recombinant α1E subunit‐encoded voltage‐sensitive Ca2+ channel (VSCC) that is believed to encode drug‐resistant R‐type currents found in neurones and other cells. Chlorpromazine produced a dose‐dependent antagonism of these channels that was reversed on drug removal. The mean IC50 was close to 10 μM. At this concentration, the level of antagonism observed was dependent on the membrane potential, with greater inhibition being observed at more negative test potentials. Furthermore, chlorpromazine induced substantial changes in the steady‐state inactivation properties of α1Eβ3‐mediated currents, although it was not seen to elicit a corresponding change in inactivation kinetics. These results are discussed with regard to the possible clinical mechanisms of chlorpromazine actions.
Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects
Authors: Rawson E. S. , Clarkson P. M. , Price T. B. , Miles M. P.
Published: March 2003

This study compared the effects of short‐term creatine supplementation on muscle phosphocreatine, blood and urine creatine levels, and urine creatinine levels in elderly and young subjects. Eight young (24 ± 1.4 years) and seven old (70 ± 2.9 years) men ingested creatine (20 g day–1) for 5 days. Baseline muscle phosphocreatine measurements were taken pre‐ and post‐supplementation using nuclear magnetic resonance spectroscopy (NMR). On the first day of supplementation subjects had blood samples taken immediately before and hourly for 5 h following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine levels was conducted. Twenty‐four hour urine collections were conducted for 2 days prior to the supplementation period and for 5 days during supplementation. Old subjects had significantly higher baseline plasma creatine levels than young subjects (68.5 ± 12.5 vs. 34.9 ± 4.7 μmol L–1; P < 0.02). There were no significant differences between groups in plasma creatine pharmacokinetic parameters (i.e. area under the curve, elimination rate constant, absorption rate constant, time to maximum concentration, and maximum concentration) following the 5 g oral creatine bolus. Urine creatine, assessed pre and on 5 days of supplementation, increased (P < 0.001), with no difference between groups. Urine creatinine did not change as a result of creatine supplementation. Young subjects showed a significantly greater increase in muscle phosphocreatine compared with old subjects, and post‐supplementation muscle phosphocreatine levels were greater in young subjects (young 27.6 ± 0.5; old 25.7 ± 0.8 mmol kg–1 ww) (P=0.02). There were no differences in blood or urine creatine between groups in response to supplementation, but old subjects had a relatively small increase (young 35% vs. old 7%) in muscle phosphocreatine after supplementation.
Effect of induced metabolic alkalosis on sweat composition in men
Authors: Patterson M. J. , Galloway S. D. R. , Nimmo M. A.
Published: March 2003

To determine whether induced metabolic alkalosis affects sweat composition, 10 males cycled for 90 min at 62.5 ± 1.3% peak oxygen uptake, on two separate occasions. Subjects ingested either empty capsules (placebo) or capsules containing NaHCO3– (0.3 g kg–1 body mass; six equal doses) over a 2‐h period, which commenced 3 h prior to exercise. Arterialized‐venous blood samples were drawn prior to and after 15, 30, 60 and 90 min of exercise. Sweat was aspirated at the end of exercise from a patch located on the right scapula region. NaHCO3– ingestion elevated blood pH, [HCO3–] and serum [Na+], whereas serum [Cl–] and [K+] were reduced, both at rest and during exercise (P < 0.05). Sweat pH was greater in the NaHCO3– trial (6.24 ± 0.18 vs. 6.38 ± 0.18; P < 0.05), whereas sweat [Na+] (49.5 ± 4.8 vs. 50.2 ± 4.3 mEq L–1), [Cl–] (37.5 ± 5.1 vs. 39.3 ± 4.2 mEq L–1) and [K+] (4.66 ± 0.19 vs. 4.64 ± 0.34 mEq L–1) did not differ between trials (P > 0.05). Sweat [HCO3–] (2.49 ± 0.58 vs. 3.73 ± 1.10 mEq L–1) and [lactate] (8.92 ± 0.79 vs. 10.51 ± 0.32 mmol L–1) tended to be greater after NaHCO3– ingestion, although significance was not reached (P=0.07 and P=0.08, respectively). These data indicate that induced metabolic alkalosis can modify sweat composition, although it is unclear whether the secretory coil, reabsorptive duct, or both are responsible for this alteration.
Effect of exercise on concentrations of free amino acids in pools of type I and type II fibres in human muscle with reduced glycogen stores
Authors: ESSÉN‐GUSTAVSSON B. , BLOMSTRAND E.
Published: March 2003

A few animal studies have shown that some amino acid concentrations vary between different muscle fibre types. In the present study, amino acid concentrations were measured in separate pools of different fibre types in human skeletal muscle, with reduced glycogen stores, before and after sustained exercise. Five subjects exercised at a submaximal work rate for 60 min and then at a maximal rate for 20 min. Biopsy samples were taken from the vastus lateralis muscle before and after exercise; they were freeze‐dried and individual fibres were dissected out. Fragments of these fibres were stained for myosin‐adenosine triphosphatase (ATPase) and identified as type I or type II fibres. The concentrations of free amino acids were measured by high performance liquid chromatography (HPLC) in perchloric acid (PCA) extracts containing pools of either type of fibre. After exercise, glycogen was decreased in type I fibres (53%) and in four subjects also in type II fibres. The concentrations of most amino acids were similar in the two fibre types before exercise, but the glutamate, aspartate and arginine levels were 10% higher in type II than in type I fibres. After exercise, the glutamate concentration was decreased by 45% in both fibre types and the branched‐chain amino acids (BCAA) were decreased in type II fibres (14%). Exercise caused an increase by 25–30% in tyrosine concentration in both type I and type II fibres. The results show that amino acids can be measured in pools of fibre fragments and suggest that amino acid metabolism play an important role in both type I and type II fibres during exercise.
Effects of transient muscle contractions and stretching on the tendon structures in vivo
Authors: KUBO K. , KANEHISA H. , FUKUNAGA T.
Published: March 2003

This study compared the effects of static stretching (ST) and repeated muscle contractions (CON) on the viscoelastic properties of tendon structures in vivo. Eight male subjects performed ST (passively flexed to 35 of dorsiflexion) for 5 min and 50 repetitions of isometric maximum voluntary contraction (MVC) for 3 s each with 3 s relaxation. Before and after each task, the elongation of the tendon and aponeurosis of the medial gastrocnemius muscle (MG) was directly measured by ultrasonography, while the subjects performed ramp isometric plantar flexion up to MVC, followed by a ramp relaxation. The relationship between the estimated muscle force (Fm) and tendon elongation (L) during the ascending phase was applied to a linear regression, the slope of which was defined as stiffness of the tendon structures. The percentage of the area within the Fm–L loop to the area beneath the curve during the ascending phase was calculated as an index representing hysteresis. The ST protocol significantly decreased the stiffness (–8%) and hysteresis (29%)., respectively. In contrast, the CON protocol significantly decreased the stiffness, but not the hysteresis. These results suggested that the stretching and repeated contractions would make the tendon structures more complaint, and further decreased the hysteresis of the tendon structures.
Intrauterine growth restriction reduces nephron number and renal excretory function in newborn piglets1
Authors: Bauer R. , Walter B. , Bauer K. , Klupsch R. , Patt S. , Zwiener U.
Published: March 2003

To examine the effects of intrauterine growth restriction on nephron number, renal circulation, and renal excretory functions in newborns, studies were conducted on 1‐day‐old anaesthetized piglets, divided into normal weight (n = 6) and intrauterine growth restricted (n = 6) piglets. Renal blood flow was measured by coloured microspheres, glomerular filtration rate was measured by inulin clearance, and osmotic clearance and fractional sodium excretion were calculated. In addition, an estimation of the nephron number was performed by counting representative glomerular numbers in microscopic sections. Newborn intrauterine growth restricted piglets exhibited a reduced glomerular filtration rate and osmotic clearance (P < 0.05), whereas renal blood flow and the filtration fraction as well as fractional sodium excretion were similar in normal weight and intrauterine growth restricted piglets. The nephron number was markedly reduced in intrauterine growth restricted piglets even if the nephron number was related to body weight (P < 0.01). There was a positive correlation between nephron number and glomerular filtration rate (r = 0.69, P < 0.05). Reduced glomerular filtration rate of newborn intrauterine growth restricted piglets is associated with a reduced nephron number. Thus, at birth, compensatory response of renal function due to nephron deficit does not exist in intrauterine growth restricted piglets.
Plasticity of leaf traits and insect herbivory in Solanum incanum L. (Solanaceae) in Nguruman, SW Kenya
Authors: Gianoli Ernesto , Hannunen Salla
Published: March 2003

Plasticity of leaf traits of Solanum incanum was evaluated by comparing its expression in three sites differing in soil moisture (dry, intermediate, humid) in Nguruman, SW Kenya. Leaf size and shape, and leaf traits related to defence against herbivores, varied significantly among sites. The relationship between leaf traits showing among‐site variation and insect herbivory was evaluated at a within‐site scale. Leaf thickness was correlated with the level of foliar herbivory by a flea beetle (Epitrix sp.). This correlation was negative at the dry site and positive at the humid site. No relationship was found at the intermediate site. Interestingly, leaf thickness and toughness were positively and significantly correlated at the dry site, but not elsewhere. Finally, overall patterns of herbivory by the flea beetle and unidentified defoliators differed among sites. The importance of scale when evaluating plant plasticity is discussed.
Notes on sitatunga in The Gambia
Authors: Starin E. D.
Published: March 2003

Opportunistic sightings were made of an introduced, free‐ranging population of sitatunga (Tragelaphus spekei gratus) in the Abuko Nature Reserve for 5.5 years. The sitatunga used more habitat types than the sympatric bushbuck (T. scriptus), were most active during the coolest times of the day, retreated into shade during the hottest times of the day and their diet consisted mostly of mature leaf parts. In terms of social behaviour, the sitatunga spent most of the time on their own, females gave birth during the dry season, and males engaged in horn wrestling and vegetation horning. Today, this population has disappeared and the wild Senegambian population has never been studied or surveyed. The numbers are probably dwindling throughout the area.