bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Captopril in L‐Name‐Induced Hypertension on the Rat Myocardium, Aorta, Brain and Kidney
Authors: Bernátová Iveta , Pechánová Ol'Ga , Simko Fedor
Published: May 2004

Long‐term administration of NG‐nitro‐L‐arginine methyl ester (L‐NAME) induces development of hypertension and hypertrophy of the left ventricle in rats. The aim of the present study was to demonstrate the effect of chronic L‐NAME treatment on DNA and RNA concentration, and protein synthesis in the rat heart, aorta, brain and kidney and to determine the effect of angiotensin converting enzyme (ACE) inhibitor captopril on these potential alterations. Four groups of rats were investigated: control, L‐NAME (40 mg kg−1 day−1), captopril (100 mg kg−1 day−1), and L‐NAME (40 mg kg−1 day−1) + captopril (100 mg kg−1 day−1). NO synthase activity in the heart, aorta, brain and kidney was found to be decreased in the L‐NAME group. In the group of rats treated with L‐NAME + captopril, captopril did not affect NO synthase inhibition. Captopril, however, completely prevented development of hypertension and left ventricular hypertrophy in this group. In the L‐NAME group, DNA and RNA concentrations, as well as [14C]leucine incorporation, were significantly increased in all the tissues investigated. In the L‐NAME + captopril group, captopril completely prevented the enhancement of DNA and RNA concentrations and [14C]leucine incorporation in all tissues compared to the L‐NAME group. Moreover, a significant decrease in RNA concentration and [14C]leucine incorporation below control values was found in the captopril group as well as the L‐NAME + captopril group in all the tissues investigated. We conclude that captopril prevented the development of hypertension and increase in nucleic acid concentration and protein synthesis in the heart, aorta, brain and kidney in rats treated with L‐NAME + captopril. However, this protective effect of captopril was not associated with increased NO synthase activity in this model of hypertension.
Exhaled Nitric Oxide Increases During High Frequency Oscillatory Ventilation in Rabbits
Authors: Artlich Andreas , Adding Christofer , Agvald Per , Persson Magnus G. , Lönnqvist Per‐Arne , Gustafsson Lars E.
Published: May 2004

This study compared the effects of high frequency oscillatory ventilation (HFOV) and intermittent mandatory ventilation (IMV) on the homeostasis of nitric oxide (NO) in the lower respiratory tract of healthy rabbits. The mechanisms underlying a putative stretch response of NO formation in the airways were further elucidated. Male New Zealand White rabbits were anaesthetized, tracheotomized and ventilated with IMV or HFOV in random order. Total NO excretion increased from 9·6 ± 0·8 nl min−1 (mean ±s.e.m.) during IMV to 22·6 ± 2·7 nl min−1 during HFOV (P < 0·001). This increase was not explained by changes of functional residual capacity (ΔFRC). A similar increase in NO excretion during HFOV was seen in isolated buffer‐perfused lungs under constant circulatory conditions (P < 0·05, n= 4). Intratracheal mean CO2 and NO concentrations, measured at 2·5, 5, 7·5 and 10 cm below tracheostomy, increased significantly with increasing distance into the lung during both IMV and HFOV (P < 0·001 for each comparison). At every intratracheal location of the sampling catheter, particularly low in the airways, both CO2 and NO concentrations were significantly higher during HFOV than during IMV (P < 0·01 for each comparison). We conclude that HFOV increases pulmonary NO production in healthy rabbits. Increased stretch activation of the respiratory system during HFOV is suggested as a possible underlying mechanism. The increase in mean airway NO concentrations may have biological effects in the respiratory tract. Whether it can account for some of the benefits of HFOV treatment needs to be considered.
Actions of the Pro‐Inflammatory Cytokine Il‐1[beta] on Central Synaptic Transmission
Authors: O'Connor John J. , Coogan Andrew N.
Published: May 2004

Within the last decade huge advances have been made in the understanding of the interactions between the central nervous system (CNS) and the immune system. Foremost amongst these is the realization that cytokines, classically regarded as mediators and co‐ordinators of the inflammatory and immune responses, can exert a number of neuromodulatory effects within the CNS under both physiological and pathological conditions (for recent reviews see Rothwell & Hopkins, 1995; Rothwell et al. 1997; Rothwell, 1999). Consistent with this, it has been shown that many cytokines and their receptors are present in the brain (Hopkins & Rothwell, 1995). Much attention has focused on the pro‐inflammatory cytokine interleukin‐1 (IL‐1) especially the [beta] variant. IL‐1[beta] has been shown to be produced in the CNS in response to a number of stimuli including peripheral administration of lipopolysaccharide (LPS); traumatic brain injury; acute stress; anorexia and [beta]‐adrenoceptor agonist administration (e.g. Maruta et al. 1997). IL‐1 receptors have also been shown to be present in many brain regions, with high levels in the hippocampus and hypothalamus (Ban et al. 1991). Expression of IL‐1 receptors has also been shown to be upregulated in response to insult, e.g. kainic acid administration (Nishiyori et al. 1997) and expression is higher in aged animals (Murray & Lynch, 1998). However this review will concentrate on the effects of IL‐1[beta] on hippocampal synaptic transmission and long‐term potentiation (LTP), a process long thought to be an important underlying mechanism of learning and memory formation (for review see Bliss & Collingridge, 1993).
Temperature Effect on the Rates of Isometric Force Development and Relaxation in the Fresh and Fatigued Human Adductor Pollicis Muscle
Authors: de Ruiter C. J. , Jones D. A. , Sargeant A. J. , de Haan A.
Published: May 2004

The purpose of the present study was to investigate the effect of temperature on the rates of isometric force development and relaxation in electrically activated fresh and fatigued human adductor pollicis muscle. Following immersion of the lower arm for 20 min in water baths of four different temperatures, muscle temperatures were approximately 37, 31, 25 and 22°C. Maximal isometric force was reduced by 16.8 ± 1.5% at 22°C. The stimulation frequency‐force and ‐rate of force development relationships were shifted to the left at lower temperatures. Q10 values for the maximal rates of force development and relaxation, and the times for 100 to 50% and 50 to 25% force relaxation, were about 2.0 between 37 and 25°C and about 3.8 between 25 and 22°C. However, the time for 50 to 25% force relaxation had a relatively high Q10 value between 25 and 22°C (6.9) and this parameter also appeared to be more sensitive to fatigue compared to the other indices of relaxation. Nevertheless, the effect of fatigue on all parameters decreased with cooling over the entire (37‐22°C) temperature range.
Bidirectional Neurones in the Cervical Enlargement of the Cat Spinal Cord with Axons Descending to Sacral Segments and Ascending to the Cerebellum and the Lateral Reticular Nucleus
Authors: Grottel K. , Krutki P. , Mrówczynski W.
Published: May 2004

Neurones located in cervical segments (C6/C7) of the spinal cord were investigated electrophysiologically in cats deeply anaesthetized with α‐chloralose. Extracellular recordings of antidromic action potentials were performed in order to establish whether long descending propriospinal neurones projecting to sacral segments could have collateral axonal branches ascending to supraspinal centres. The effects of stimulation of the lateral reticular nucleus (LRN) and the inferior cerebellar peduncle (restiform body, RB), as well as the thirteenth thoracic (Th13) and sacral (S1/S2) segments of the spinal cord were tested in 93 cells. Two main groups of cells were identified: 54% of the total sample were classified as purely propriospinal and 46% as bidirectional neurones. Various patterns of projections, as well as the ipsi‐, contra‐ or bilateral courses of axons in the lateral funiculi of the spinal cord, enabled several types of neurones to be distinguished within the above groups. Comparison between particular types showed no significant difference with respect to location in the grey matter (predominantly Rexed's laminae VII‐VIII) and the conduction velocities of descending axons. However, the mean axonal conduction velocities of branches ascending to LRN and/or RB were significantly lower in comparison to those measured for spinal collaterals. The hypothetical function of the neurones examined is discussed. Since the same information can be conveyed simultaneously by these branching neurones to lower spinal segments and supraspinal centres, an integrative role in the system of motor control is suggested.
Adrenocortical Response Profiles to Corticotrophin‐Releasing Hormone and Adrenocorticotrophin Challenge in the Chronically Catheterized Adult Guinea‐Pig
Authors: Liu Li , Matthews Stephen G.
Published: May 2004

The guinea‐pig has been used extensively to investigate adrenal steroidogenesis. However, very little is known about adrenocortical responses to corticotrophin‐releasing hormone (CRH) and adrenocorticotrophin (ACTH) in this species, in vivo. In the present study, we have developed a stress‐free sampling system, in the chronically catheterized adult guinea‐pig, that has allowed us to investigate basal and activated adrenocortical activity. Indwelling carotid artery and jugular vein catheters were surgically implanted into female guinea‐pigs (n= 5). Each animal was treated with vehicle, human CRH (0·2 or 2 μg kg−1) and ACTH1‐24 (0·2 or 2 μg kg−1), and serial plasma samples removed for analysis of ACTH and cortisol concentrations by radioimmunoassay. There was no effect of serial sampling on pituitary‐adrenocortical activity, indicating that the animals remain in an unstressed state. Basal plasma ACTH and cortisol concentrations were 703·9 ± 24·5 pg ml−1 and 117·9 ± 5·2 ng ml−1, respectively. Both CRH and ACTH significantly increased adrenocortical activity in a dose‐dependent manner. ACTH (2 μg kg−1) was the most potent activator leading to plasma cortisol concentrations of 647 ± 116 ng ml−1. In conclusion, we have shown that basal plasma cortisol concentrations in the guinea‐pig are low compared to those obtained in previous studies by cardiac puncture or following decapitation. However, plasma ACTH concentrations are high compared to other species. We have also shown that human CRH and ACTH1‐24 act as potent activators of the guinea‐pig pituitary‐adrenocortical axis, leading to response profiles consistent with mild cortisol resistance.
Membrane Oestrogen Receptors on Rat Pituitary Tumour Cells: Immuno‐Identification and Responses to Oestradiol and Xenoestrogens
Authors: Watson Cheryl S. , Campbell Celeste H. , Gametchu Bahiru
Published: May 2004

Our laboratory has identified plasma membrane oestrogen receptors on a GH3/B6 rat pituitary tumour cell line and several sublines which produce rapid (within minutes), non‐genomic responses to oestrogens. Oestrogen receptors have been identified by their binding to nine different antibodies (Abs) which together recognize at least seven epitopes on the oestrogen receptor‐α. GH3/B6/F10 cells, a membrane oestrogen receptor‐enriched subline, elevate intracellular calcium levels in response to 10 nM oestradiol. Prolactin release in these cells is triggered by both 1 pM and 1 nM oestradiol and diethylstilbestrol (DES). A membrane oestrogen receptor‐α immunocyto‐chemical signal rapidly disappears (at 3 min) and reappears (at 12‐15 min) when 1 nM oestradiol, 10 nM diethylstilbestrol, or 10 nM nonylphenol is applied to the cells. This suggests that both oestrogens and xenoestrogens can utilize this alternative pathway for oestrogenic action. Xenoestrogens, which have so far shown weak effects in genomic assay systems, should now be retested for activity in eliciting membrane‐initiated oestrogenic responses.
Renal Interstitial Hydrostatic Pressure and Urinary Sodium Excretion in Rats with Angiotensin‐Converting Enzyme Inhibitor‐Induced Papillary Atrophy
Authors: Nilsson Annika B. M. , Guron Gregor S. , Adams Michael A. , Friberg Peter
Published: May 2004

The importance of angiotensin type‐1 (AT1) receptor stimulation during renal development has recently been established in both pharmacological and knockout models. We have previously reported irreversible and progressive papillary atrophy and a reduced baseline renal interstitial hydrostatic pressure (RIHP) after neonatal angiotensin‐converting enzyme (ACE) inhibition. The aim of the present study was to investigate the consequences of these abnormalities on urinary sodium excretion during acute extracellular sodium loading. Rats were treated neonatally with enalapril (10 mg kg−1 day−1) or saline control from days 3 to 23 after birth. Urinary sodium excretion was assessed in relation to mean arterial pressure (MAP) and RIHP responses in adult anaesthetised rats during moderate (1·5 and 3% body weight) and severe (9% body weight) saline‐induced volume expansion. Control rats responded to the moderate volume expansion by increasing MAP by 16 ± 6% and RIHP by 40 ± 23%, respectively. In neonatally enalapril‐treated rats, however, MAP and RIHP remained unchanged and were associated with a smaller increase in sodium excretion (44 ± 11% of the total amount infused versus 71 ± 16% for controls, P < 0·05). In contrast, severe volume expansion resulted in marked pressure rises in both the enalapril‐treated group (36 ± 12 and 112 ± 48% of baseline for MAP and RIHP, respectively) and the control group (34 ± 21 and 130 ± 34% of baseline for MAP and RIHP, respectively). Moreover, the increases in MAP and RIHP were associated with complete excretion of the severe sodium challenge within 60 min in both treatment groups. We conclude that a RIHP response appears to be a prerequisite for adequate urinary sodium excretion in this model of papillary atrophy. Hence, an intact renal medulla is not mandatory in the renal handling of sodium during extracellular loading.
Salivary Secretion of Highly Concentrated Chromogranin a in Response to Noradrenaline and Acetylcholine in Isolated and Perfused Rat Submandibular Glands
Authors: Kanno Tomio , Asada Naoto , Yanase Haruko , Iwanaga Toshihiko , Ozaki Tsuyoshi , Nishikawa Yasuko , Iguchi Kazuaki , Mochizuki Tohru , Hoshino Minoru , Yanaihara Noboru
Published: May 2004

Chromogranin A (CgA) is a member of a family of highly acidic proteins, chromogranins, which are co‐stored in the adrenergic neurons and paraneurons and co‐released with adrenaline and noradrenaline (NAd) in response to adequate stimulation. The present study provides novel evidence that CgA‐like immunoreactivity (IR) is stored in the exocrine cells in the granular convoluted tubule, and is secreted into saliva by stimulation with NAd and acetylcholine (ACh) in the isolated and perfused rat submandibular gland. NAd at 1 μM produced maximum secretion of CgA‐like IR (<< 0.9 mM) and a marked increase in salivary flow. Further increases in NAd concentration (10 or 100 μM) yielded concentration‐dependent decreases in both responses. ACh at 1 μM produced maximum salivary flow and a slight elevation of CgA‐like IR secretion (6 μM); 100 μM ACh decreased the salivary flow but increased the CgA‐like IR secretion (0.6 mM). Electron microscopic examination showed vigorous compound exocytosis of secretory granules in the cells of the granular convoluted tubule when the submandibular gland was stimulated with 1 μM NAd. These results provide an experimental basis for the view that the salivary CgA‐like IR secretion may be a sensitive and quantitative index of the activity of the sympathetic nervous system innervating the gland.
The Influence of Erythropoietin on the Vascular Responses of Rat Resistance Arteries
Authors: Wu Xiao Chun , Richards Nicholas T. , Johns Edward J.
Published: May 2004

This study examined the effect of erythropoietin (EPO) on resting tension and on the responses of rat mesenteric and renal arcuate arteries in vitro to a number of agonists as a possible cause of its blood pressure elevating properties when used therapeutically. Noradrenaline and potassium chloride induced concentration‐dependent vasoconstrictions in both vessel types but the basal tension, maximum tension, and the ‐log concentration producing half‐maximal response (pEC50) were altered in the presence of 0·1 or 20 U ml−1 EPO. The thromboxane A2 receptor agonist U46619 induced a constriction of the renal arcuate arteries which was enhanced by EPO at 20 U ml−1, from 1·68 ± 0·34 to 2·64 ± 0·39 mN mm−1 (P < 0·01), but which was unchanged by NG‐nitro‐L‐arginine methyl ester (10−4 m). Serotonin (10−9‐10−5 M) caused a concentration‐related vasoconstriction in renal arcuate arteries which was shifted to the right in the time control study (P < 0·001) but this was abolished by both 0·1 and 20 U ml−1 of EPO. Acetylcholine induced a relaxation of precontracted mesenteric arteries, by 95·4 ± 1·64% with an EC50 of 7·08 ± 0·08 M which was reduced (P < 0·001) by 20 U ml−1 EPO to 81·7 ± 3·56% and 6·10 ± 0·11 M, respectively. The sodium nitroprusside‐induced relaxations were unaffected by EPO. The acetylcholine‐mediated relaxations in renal arcuate arteries were unchanged by EPO. Bradykinin‐induced relaxations in mesenteric and renal arcuate arteries were unaffected by both EPO concentrations. Together these data showed that EPO over a large concentration range had only minor effects on basal tension and the vascular responsiveness of both mesenteric and renal arcuate arteries. The mechanism whereby EPO causes a chronic elevation in blood pressure is unlikely to be due to acute interactions with agonist‐mediated responses.
Nucleus Tractus Solitarii: Integrating Structures
Authors: Paton Julian F. R.
Published: May 2004

Presently, many researchers have adopted a reductionistic approach to physiology. Specifically, this involves studies on acutely isolated or cultured cells. While this is essential for our understanding of important cellular and subcellular mechanisms, it should not be forgotten that physiology is about the function of an integrating body. One view point is that definitive interpretations can only be made by crossing boundaries of physiology from the molecular/ cellular to the systems/behavioural level. An aim of this lecture will stress the importance of a multidisciplinary approach to physiology, that is, ‘putting the cell back into the system’. The lecture attempts to demonstrate why this is important for enhancing the functional significance and relevance of physiological data as well as for validating predictions.
The Influence of Streptozotocin Diabetes and Metformin on Erythrocyte Volume and on the Membrane Potential and the Contractile Characteristics of the Extensor Digitorum Longus and Soleus Muscles in Rats
Authors: McGuire Michelle , MacDermott Mary
Published: May 2004

The effects of streptozotocin (STZ) diabetes and the antihyperglycaemic agent metformin on the contractile characteristics of the limb skeletal muscles and on erythrocyte volume were examined in rats. After 8 weeks of diabetes, the tetanic tension of the extensor digitorum longus (EDL) muscle decreased and the half‐relaxation time of the soleus muscle increased. Endurance decreased in both muscles. Metformin treatment of the diabetic rats did not prevent the development of these contractile changes. Diabetes induced depolarisation in the EDL and soleus muscles. Following exposure to insulin, both muscles repolarised. Metformin treatment of control rats induced depolarisation in the EDL and soleus muscles, but in the depolarised EDL and soleus muscles of the diabetic rats metformin treatment caused no further depolarisation. The muscles of metformin‐treated control and diabetic rats hyperpolarised in the presence of insulin. Diabetes caused an increase in the volume of the blood erythrocytes. This was prevented by metformin treatment.
Determination of an Optimal Axial‐Length Tension for the Study of Isolated Resistance Arteries on a Pressure Myograph
Authors: Coats P. , Hillier C.
Published: May 2004

The effects of longitudinal stretch on vasoreactivity were assessed in isolated, pressurised arteries from the rat mesentery, rat mid‐cerebral and human subcutaneous vascular beds. A stretch‐dependent increase in reactivity was observed only in rat third order mesenteric arteries. Longitudinal stretch >> 20% (force equal to 0.23 ± 0.04 mN) optimises vasoconstrictor responses to noradrenaline and phenylephrine in rat third order mesenteric arteries. Stretch did not affect the vasoconstriction response to depolarisation by 30 mM K+ PSS in any of the arteries studied. Similarly, stretch had no affect on pressure‐dependent myogenic responses in rat mid‐cerebral arteries. Endothelium‐independent and endothelium‐dependent mechanisms of vasorelaxation were unaffected by stretch in rat third order mesenteric arteries. Likewise, stretch did not affect vasoreactivity in rat mid‐cerebral and human subcutaneous resistance arteries. Our results show that longitudinal stretch in isobaric‐mounted rat third order mesenteric arteries is an important methodological consideration. Considering our results, we recommend that isobaric‐mounted rat third order mesenteric arteries are stretched >> 20% to provide optimal experimental conditions for pharmacological studies.
A Monocarboxylate Transporter MCT1 is Located at the Basolateral Pole of Rat Jejunum
Authors: Orsenigo M. N. , Tosco M. , Bazzini C. , Laforenza U. , Faelli A.
Published: May 2004

We have functionally expressed and identified a monocarboxylate transporter (MCT1) from rat jejunal enterocyte and we provide evidence for its basolateral localization. Poly(A)+ RNA isolated from rat jejunum was injected into Xenopus laevis oocytes and expression of a proton‐lactate symporter was investigated by means of L‐[14C]lactate uptake. The existence of an endogenous capacity for L‐lactate transport was demonstrated; when, however, oocytes were injected with jejunal mRNA, an expressed L‐lactate uptake was seen which differed from the endogenous transporter since it was significantly pH dependent. After sucrose density gradient fractionation, the highest expression of the pH‐dependent lactate uptake was detected with the mRNA size fraction of about 2‐3 kb in length. The substrate specificity, stereoselectivity and sensitivity to pCMBS (an organomercurial thiol reagent that modifies cysteine residues) of the expressed transport were in good agreement with results previously obtained using isolated jejunal basolateral membranes. Using the reverse transcriptase‐polymerase chain reaction, the presence of mRNA coding for the MCT1 isoform was demonstrated in jejunal enterocytes. These data, together with previous results, suggest that MCT1 is a major route for lactate efflux across the basolateral membrane of rat jejunum; this is in contrast to current opinion which restricts the presence of MCT1 to the apical membrane of the whole small intestine.
The Role of Nitric Oxide in Mediating Pancreatic Endocrine Responses to Insulin‐Induced Hypoglycaemia in the Conscious Calf
Authors: Edwards C. M. B. , Ghatei M. A. , Bloom S. R. , Edwards A. V.
Published: May 2004

The role of nitric oxide (NO) in mediating pancreatic endocrine responses to moderate hypoglycaemia has been investigated in conscious unrestrained calves. The synthesis of endogenous NO was inhibited by the administration of N‐nitro‐L‐arginine methyl ester (L‐NAME; 100 mg kg−1 I.A.), while sodium nitroprusside was infused continuously (2‐4 μg min−1 kg−1 I.V.) to mimic the tonic production of NO. This effectively abolished the rise in plasma pancreatic polypeptide (PP) concentration during moderate hypoglycaemia (0.7 nmol kg−1 insulin I.V.) and significantly reduced the response to more intense hypoglycaemia (2.0 nmol kg−1 insulin I.V.). In contrast, the glucagon response was not significantly affected in either group, although consistently higher plasma glucagon values were obtained in response to the higher dose of insulin following the administration of L‐NAME. It is concluded that, in the absence of L‐NAME, production of NO contributes to the PP response, but not the glucagon response to hypoglycaemia in this species under physiological conditions.
Motor Unit Discharge Characteristics during Voluntary Contraction in Patients with Incomplete Spinal Cord Injury
Authors: Smith Hazel C. , Davey Nick J. , Savic Gordana , Maskill David W. , Ellaway Peter H. , Frankel Hans L.
Published: May 2004

Synchronisation of motor unit discharges is commonly seen in hand muscles of normal man but is absent following neurologically complete spinal cord injury and reduced after stroke. These findings support the notion that some corticospinal inputs to motoneurones are shared and contribute to the observed synchrony of discharge. In this study we have examined motor unit discharge in hand muscles below the level of an incomplete spinal cord injury in an attempt to relate strength of synchrony to the integrity of the corticospinal tract. Eight patients with incomplete spinal cord injury (neurological level C3‐C7) and eight control subjects took part in the study. The patients had sustained injury 14‐191 weeks prior to the recordings and had since regained good motor function in their hands. Two concentric needle electrodes were inserted into the first dorsal interosseus muscle which subjects were instructed to contract weakly so that potentials from individual motor units could be reliably identified on both recordings. Synchrony was detected by constructing cross‐correlograms between the discharges of pairs of individual motor units. The amount of synchronous firing was determined from the magnitude of any peak in the cross‐correlogram, as the probability above chance (XP) of one motor unit firing with respect to the other and vice versa. The degree of synchrony was lower (P < 0.05) in the patient group (mean XP 0.06) than in the control group (mean XP 0.09). The incidence of significant synchrony was lower in the patient group (41.8%) than in the control group (92.9%). The mean (± S.E.M.) frequency of motor unit discharge was slightly lower (P < 0.05) in patients (9.7 ± 0.4 impulses s−1) than controls (10.8 ± 0.5 impulses s−1). The mean width of synchrony peaks was narrower (P < 0.05) in patients (11.4 ± 1.1 ms) than controls (13.2 ± 0.6 ms). We conclude that the weaker synchrony of motor unit discharge in incomplete spinal cord injury may reflect permanent damage to some corticospinal axons.
Icln, An Ion Channel‐Forming Protein Associated with Cell Volume Regulation
Authors: Gschwentner M. , Fürst J. , Ritter M. , Bazzini C. , Wöll E. , Dienstl A. , Jakab M. , König M. , Scandella E. , Rudzki J. , Botta G. , Meyer G. , Lang F. , Deetjen P. , Paulmichl M.
Published: May 2004

It is not resolved whether the anionic channel involved in volume regulation after cell swelling comprises one or more subunits. Moreover, it remains to be determined which of the different proteins cloned so far, for which an involvement in cell volume regulation has been postulated, is the ideal candidate. In this review, we consider the role of the ICln protein, cloned from MDCK cells, in cell volume regulation.
The Influence of Acute Hypoxia and Carotid Body Denervation on Thermoregulation During Non‐Rapid Eye Movement Sleep in the Developing Lamb
Authors: Symonds Michael E. , Andrews David C. , Johnson Paul
Published: May 2004

We investigated the influence of ambient temperature on the thermoregulatory response to hypoxia in developing lambs before (at 4 and 14 days of age) and after (17 and 30 days of age) carotid body denervation (CBD). Lambs were studied during non‐rapid eye movement sleep at thermoneutral (23‐15°C) and cool (10‐5°C) ambient temperatures, during normoxia and acute hypoxia (inspired oxygen content of 13%). Measurements of oxygen consumption, arterial partial pressures of O2 and CO2, colonic temperature, incidence of shivering and plasma concentrations of thyroid hormones, cortisol, insulin and glucose were made under each condition. Oxygen consumption was higher at cool compared with thermoneutral ambient temperatures and decreased during hypoxia during cooling at all stages. At 4 days of age, only one lamb shivered during cooling in normoxia, but 4 out of 12 lambs shivered during hypoxia and colonic temperature fell, significantly, by 0.2°C. At 14 days, 8 out of 12 lambs shivered during cooling, of which 6 continued to shiver during hypoxia but colonic temperature did not change significantly. Plasma triiodothyronine concentrations increased on cooling at 4 and 14 days, an affect that was inhibited by hypoxia at 4, but not 14 days of age. At 17 days of age, i.e. post‐CBD, plasma thyroid hormone concentrations and oxygen consumption were lower during cold exposure compared with intact lambs at 14 days of age. In CBD lambs, imposing further hypoxia resulted in colonic temperature falling 0.6°C during cooling, with only 2 out of 10 lambs shivering. Plasma glucose and insulin, but not cortisol, concentrations decreased during hypoxia, irrespective of age or CBD. It is concluded that hypoxia has an important influence on metabolism and thermoregulation, which is modulated by age and environmental conditions. Compromised carotid body function, in lambs older than 2 weeks of age, can result in severe hypoxia and thermoregulatory dysfunction even with modest environmental cooling.
Telemetry Facilitates Long‐Term Recording of Gastrointestinal Myoelectrical Activity in Pigs
Authors: Gacsalyi U. , Zabielski R. , Pierzynowski S. G.
Published: May 2004

A method of telemetric measurement of antroduodenal myoelectrical activity (EMG) in freely moving pigs has been developed. Silver bipolar electrodes were sutured on the antrum and duodenum and connected to a telemetry transmitter implanted extraperitoneally between the abdominal muscles. The EMG signals were collected by a receiver, filtered, amplified and archived by a computer. The telemetric EMG signal did not differ from that obtained with a conventional wire method. Substantial differences between day and night migrating myoelectric complex (MMC) patterns were found. The advantages of telemetric EMG recording make it a useful tool for long‐term recording of antroduodenal EMG.
Simultaneous Monitoring of Vascular Contractility, Intracellular Ph and Intracellular Calcium in Isolated Rat Mesenteric Arteries; Effects of Weak Bases
Authors: Otter Donna , Austin Clare
Published: May 2004

We report the first simultaneous measurements of pHi, [Ca2+]i and tension, upon alteration of pHi, in isolated rat mesenteric arteries loaded with both carboxy SNARF and indo‐1. In these vessels (pre‐contracted by 30 mM KCl) alterations of pHi, by addition and subsequent washout of weak bases, produced complicated effects on tone. Although the changes in contractility did not mirror the changes in pHi they were, at all times, accompanied by parallel changes in [Ca2+]i.
Human Ejaculatory Duct: Parameters of Smooth Muscle Motor Activity and Modulatory Role of Autonomic Drugs
Authors: Mancinelli R. , Usai P. , Vargiu R. , De Lisa A. , Scarpa R. M. , Usai E.
Published: May 2004

The contractile behaviour and effects of several autonomic drugs on the motor activity of human isolated ejaculatory ducts were investigated. Ejaculatory ducts exhibited spontaneous contractions characterised by an amplitude of 2.35 ± 0.28 mN, a duration of 62.9 ± 3.72 s and a frequency of 0.64 ± 0.014 waves min‐1. Acetylcholine (10‐5‐10‐4 m) induced a slight increase in basal tone and in the frequency of the contraction waves. These effects were suppressed by atropine (10‐4 m). Noradrenaline (norepinephrine) increased the basal tone and frequency of spontaneous contractions in a dose‐dependent manner. These responses were competitively inhibited by HEAT, a selective a1‐adrenoceptor antagonist. These preliminary functional findings, indicating the presence of spontaneous motor activity of human ejaculatory ducts and its possible control by adrenergic agonists, suggests a physiological role for human ejaculatory duct in the propulsion of semen from the seminal vesicle towards the urethra.
A Putative Alternatively Spliced Variant of the P2X1 Purinoreceptor in Human Bladder
Authors: Hardy L. A. , Harvey I. J. , Chambers P. , Gillespie J. I.
Published: May 2004

Activation of purinergic P2X receptors, putatively P2X1, may be important in the initiation of contraction in human detrusor. Purinergic transmission may be more important in muscle taken from patients with bladder instability. In this study the presence of the P2X1 receptor subtype was confirmed using RT‐PCR. In addition, the results indicate, at the mRNA level, the presence of a splice variant of P2X1 that is lacking part of the second transmembrane domain. It is therefore possible that human bladder expresses multiple isoforms of the P2X1 receptor which may be potential sites for modifying or regulating putative purinergic activation of the human bladder.
Human Muscle Power Generating Capability During Cycling at Different Pedalling Rates
Authors: Zoladz Jerzy A. , Rademaker Arno C. H. J. , Sargeant Anthony J.
Published: May 2004

The effect of different pedalling rates (40, 60, 80, 100 and 120 rev min−1) on power generating capability, oxygen uptake (V̇O2) and blood lactate concentration [La]b during incremental tests was studied in seven subjects. No significant differences in V̇O2,max were found (mean ± S.D., 5.31 ± 0.13 l min−1). The final external power output delivered to the ergometer during incremental tests (PI,max) was not significantly different when cycling at 60, 80 or 100 rev min−1 (366 ± 5 W). A significant decrease in PI,max of ∼60 W was observed at 40 and 120 rev min−1 compared with 60 and 100 rev min−1, respectively (P < 0.01). At 120 rev min−1 there was also a pronounced upward shift of the V̇O2‐power output (V̇O2‐P) relationship. At 50 W δV̇O2 between 80 and 100 rev min−1 amounted to +0.43 l min−1 but to +0.87 l min−1 between 100 and 120 rev min−1. The power output corresponding to 2 and 4 mmol l−1 blood lactate concentration (P[La]2 and P[La]4) was also significantly lower (> 50 W) at 120 rev min−1 (P < 0.01) while pedalling at 40, 60, 80 and 100 rev min−1 showed no significant difference. The maximal peak power output (PM,max) during 10 s sprints increased with pedalling rate up to 100 rev min−1. Our study indicates that with increasing pedalling rate the reserves in power generating capability increase, as illustrated by the PI,max/PM,max ratio (54.8, 44.8, 38.1, 34.6, 29.2%), the P[La]4/PM,max ratio (50.4, 38.9, 31.0, 27.7, 22.9%) and the P[La]2/PM,max ratio (42.8, 33.5, 25.6, 23.1, 15.6%) increases. Taking into consideration the V̇O2,max, the PI,max and the reserve in power generating capability we concluded that choosing a high pedalling rate when performing high intensity cycling exercise may be beneficial since it provides greater reserve in power generating capability and this may be advantageous to the muscle in terms of resisting fatigue. However, beyond 100 rev min−1 there is a decrease in external power that can be delivered for an given V̇O2 with an associated earlier onset of metabolic acidosis and clearly this will be disadvantageous for sustained high intensity exercise.
Decreased Response of Rat Knee Joint Blood Vessels to Phenylephrine in Chronic Inflammation: Involvement of Nitric Oxide
Authors: Badavi Mohammad , Khoshbaten Ali , Hajizadeh Sohrab
Published: May 2004

The effect of chronic inflammation induced by Freund's Complete Adjuvant (FCA) on rat articular blood vessels and knee joint diameter was investigated. Blood flow changes in response to phenylephrine (an α1‐adrenoceptor agonist) in FCA‐treated and contralateral knee joints were studied over a 40 day period, using the laser Doppler flowmetery (LDF) technique. Unilateral injection of FCA (0.2 ml) increased the injected knee diameter on all days examined post‐injection (P < 0.001) and its maximum increase (53 ± 2%) was reached on day 3. After this, the diameter decreased gradually but did not return to its initial value. In control animals, topical application of 10‐13‐10‐ 7 mol phenylephrine onto the exposed joint capsule decreased blood flow dose dependently (11.1 ± 4.4 to 58.2 ± 4.5%, respectively, P < 0.001). Unilateral injection with FCA attenuated the phenylephrine response in both ipsilateral and contralateral knees compared with the response of control animals (5.2 ± 1.6 to 48.3 ± 6.1% and 1.9 ± 2.2 to 45.3 ± 5.6%, respectively, P < 0.05). The reduction persisted for 3 weeks after FCA injection (ipsilateral for 21 days; contralateral for 30 days, P < 0.001). Subsequently the response returned towards normal. To avoid the influence of α2‐adrenoceptors, yohimbine (an α2‐adrenoceptor antagonist) was injected (0.5 mg kg‐1, I.P.) 30 min before phenylephrine application. Yohimbine blocked the vasoconstrictor effect of 10‐10‐10‐7 mol clonidine (an α2‐adrenoceptor agonist, topical application) by 44‐67.7% inhibition, respectively (P < 0.001). Prazosin (an α1‐adrenoceptor antagonist, 0.1 mg kg‐1, I.P.) blocked the vasoconstrictor effect of phenylephrine (10‐10‐10‐7 mol, topical application) effectively (42 to 69.8% inhibition, respectively, P < 0.001). To assess the role of nitric oxide (NO) on the observed responses, N G‐nitro‐L‐arginine methyl ester (L‐NAME, NO synthase inhibitor) was applied topically (0.2 μmol) 5 min before phenylephrine application. L‐NAME application at 7 and 14 days after FCA injection potentiated the vasoconstrictor response in the FCA‐treated knee (P < 0.001) but had no significant effect on the contralateral knee. Blood pressure monitoring during phenylephrine, clonidine and L‐NAME administration indicated that topical application of the drugs had no significant effect on the systemic blood pressure. These findings indicate that the vasoconstrictor response to phenylephrine was decreased in chronic inflammation and increased NO production could be involved.
Protein Kinase C‐Dependent Inhibition of K+ Currents in Noradrenaline‐Induced Depolarization of Smooth Muscle of Guinea‐Pig vas Deferens
Authors: Kamimura Noritaka , Suga Sechiko , Nakano Kyoko , Kanno Takahiro , Takeo Teruko , Wakui Makoto
Published: May 2004

Ionic mechanisms and signal transduction underlying noradrenaline (NA)‐induced depolarization in single smooth muscle cells of guinea‐pig vas deferens were studied. NA caused depolarization followed by action potentials through activation of α1‐adrenoceptors. In the presence of nifedipine, no action potential was generated, and the magnitude of the depolarization depended on the concentration of NA (0.1‐100 μm). NA, through α1‐adrenoceptor activation, reduced the magnitude of membrane currents in response to voltage ramp pulses from ‐90 to ‐30 mV in a concentration‐dependent manner. The reversal potential of the current inhibited by NA changed proportionally to the change in the equilibrium potential of K+, suggesting that NA inhibited K+ channel activity. Treatment of cells with GDPβS, an inhibitor of G proteins, or bisindolylmaleimide (BIM), a selective protein kinase C (PKC) inhibitor, prevented the NA inhibition of the currents. Application of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), an activator of PKC, mimicked the effect of NA. It is suggested that in the smooth muscle of guinea‐pig vas deferens, activation of α1‐adrenoceptors and the subsequent activation of PKC led to inhibition of K+ currents, which is responsible for the depolarization induced by NA.
Heat Shock Protein Expression is Increased in Cardiac and Skeletal Muscles of Fischer 344 Rats After Endurance Training
Authors: Samelman T. R.
Published: May 2004

Heat shock proteins (HSPs) are expressed when cells are exposed to various types of stress and they may provide protection against cellular insult. Previous data have shown increases in HSP expression following acute exhaustive exercise in rats (Locke et al. 1990, 1995; Salo et al. 1991) and humans (Liu et al. 1999); however, it is not known if chronic exercise will increase resting levels of HSPs. The purpose of this study was to determine if basal protein levels of HSP 72/73 and HSP 60 are increased in cardiac and skeletal muscle of endurance trained Fischer 344 rats. Heart, soleus (SOL) and lateral gastrocnemius (LG) muscles were removed and hearts were sectioned into left ventricle (LV), right ventricle (RV) and atria (AT). Endurance training improved myocardial citrate synthase activity by 88, 90 and 77% and cytochrome c oxidase activity by 58, 51 and 89% in LV, RV and AT, respectively. LV and RV oxidative enzyme activities were greater when compared to AT for both trained and untrained rats (P < 0.05). HSP 72/73 expression was significantly greater (P < 0.05) in LV, RV and SOL from endurance trained versus from control rats (26, 45 and 67%, respectively). HSP 60 was also increased (P < 0.05) in LV, RV and SOL in trained relative to untrained rats. HSP 72/73 and HSP 60 were unchanged in AT and LG after training. These results indicate that endurance training increases the basal expression of stress proteins and this observation is consistent with the hypothesis that endurance training may activate a protective mechanism to stress.
Heart Rate and its Variability Change After the Menopause
Authors: Brockbank C. L. , Chatterjee F. , Bruce S. A. , Woledge R. C.
Published: May 2004

Resting heart rate and heart rate variability of 33 postmenopausal women were compared with those of 50 premenopausal women of comparable activity level, none of whom had used hormone replacement therapy. Heart rate was measured as the mean of at least 600 consecutive R‐R intervals obtained from electrocardiograph (ECG) records, and its variability as the standard deviation of these intervals. Activity levels were assessed by a scale modified from the Allied Dunbar National Fitness Survey (1992). There was a significant reduction in both mean R‐R interval and the standard deviation in the postmenopausal women who had experienced their last menstrual period (LMP) 1 year or more prior to the observations being made, but no observable changes during the first year post menopause.
Protective Effect of HOE642, a Selective Blocker of Na+‐H+ Exchange, Against the Development of Rigor Contracture in Rat Ventricular Myocytes
Authors: Ruiz‐Meana Marisol , Garcia‐Dorado David , Juliá Margarita , Inserte Javier , Siegmund Berthold , Ladilov Yuri , Piper Michael , Tritto Francesco Paolo , González Miguel A. , Soler‐Soler J.
Published: May 2004

The objective of this study was to investigate the effect of Na+‐H+ exchange (NHE) and HCO3−‐Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re‐energization (Rx). The effects of perfusion of HCO3− or HCO3−‐free buffer with or without the NHE inhibitor HOE642 (7 μM) were investigated during MI and Rx. In HCO3−‐free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 ± 1% to 40 ± 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3− abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura‐2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3−‐dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.
Thermoregulation in Winter Swimmers and Physiological Significance of Human Catecholamine Thermogenesis
Authors: Vybíral S. , Lesná I. , Jansky L. , Zeman V.
Published: May 2004

Thermoregulation in control subjects and cold‐adapted winter swimmers was examined during 1 h of cold water immersion (13°C). It was found that the thermoregulatory functions of winter swimmers differ from those of non‐cold‐adapted subjects. As evident from the relationship between rectal temperature and the magnitude of cold thermogenesis, in controls a significant part of cold thermogenesis during the early phase of cooling was induced by changes in peripheral temperature input, while in the late phase of cooling it was the central temperature input which was mainly engaged in induction of cold thermogenesis. In winter swimmers the magnitude of cold thermogenesis was solely related to changes in rectal temperature, indicating the predominance of the central temperature input in activation of heat production mechanisms. The thermoregulatory threshold for induction of cold thermogenesis was lowered (by 0.34°C), but the apparent hypothalamic thermosensitivity was the same as in non‐cold‐adapted subjects. These differences are indicative of adaptation of thermoregulatory control centres. Additionally, the activity of thermoregulatory effectors was also changed. Shivering was induced later during cooling (after 40 min) in winter swimmers than in controls, which suggests an important participation of non‐shivering thermogenesis in the early thermogenic response. Winter swimmers also showed bradycardia and a greater reduction in plasma volume during cooling. The data indirectly indicate restriction of heat loss from the body. Only a non‐significant increase in quantity of subcutaneous fat was observed in winter swimmers. Thus, winter swimmers were able to survive a significantly greater temperature gradient between body and environment than non‐cold‐adapted subjects by modifying the sensory functions of hypothalamic thermoregulatory centres to lower heat loss and produce less heat during cold exposure. Additionally, the capacity of the total cold thermogenesis due to potentiation of non‐shivering heat production was also increased. Heat produced due to thermogenic action of adrenaline may represent more than a quarter of the total cold thermogenesis. In conclusion, the data suggest that winter swimmers exhibit metabolic, hypothermic and insulative types of cold adaptation.
Effect of Maternal Nutrient Restriction in Early Gestation on Responses of the Hypothalamic‐Pituitary‐Adrenal Axis to Acute Isocapnic Hypoxaemia in Late Gestation Fetal Sheep
Authors: Hawkins Paul , Steyn Clare , McGarrigle Hugh H. G. , Saito Tsukuru , Ozaki Takashi , Stratford Lori L. , Noakes David E. , Hanson Mark A.
Published: May 2004

Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic‐pituitary‐adrenal (HPA) axis responses to exogenous corticotropin‐releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114‐129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient‐restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114‐115, 120‐123 and 126‐129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114‐115 and 120‐123 dGA did not differ between C and R fetuses. At 126‐129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.