bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute mental stress but not enforced muscle activity transiently increases natural cytotoxicity in spontaneously hypertensive rats
Authors: JONSDOTTIR I. H. , JOHANSSON C. , ASEA A. , HELLSTRAND K. , HOFFMANN P.
Published: October 2003

The influence of acute mental stress and the effect of electrically induced skeletal muscle contractions on natural cytotoxicity in vivo was investigated in spontaneously hypertensive rats. Natural cytotoxicity in vivo was measured as the clearance of injected 51Cr‐labelled YAC‐1 lymphoma cells from the lungs, which are specifically lysed by natural killer cells. The mental stress consisted of an air jet directed towards the animals in their cage for 25 min. During the mental stress there was a significant increase in natural cytotoxicity. Thus, retained radioactivity in the lungs was decreased to 74±6% of the control levels which was set to 100% (P<0.01). This augmentation of YAC‐1‐cell clearance could be blocked with the β‐adrenergic receptor antagonist Timolol. Two hours after termination of the air stress, in vivo cytotoxicity had returned to control levels. In contrast, acute physical stress, consisting of electrically induced muscle contractions for 60 min, had no significant effects on in vivo cytotoxicity, either during the stimulation or 1, 2 or 24 h after the stimulation. Further, significantly increased plasma levels of adrenaline were seen after the air jet stress, but not after muscle stimulation. There were no significant changes in plasma noradrenaline levels either after air stress or muscle stimulation. These results indicate that changes in in vivo cytotoxicity after mild mental stress are dependent on increased plasma catecholamine levels while acute physical stress, without changes in catecholamine levels, does not influence in vivo cytotoxicity.
Endogenous nitric oxide as a physiological regulator of vascular tone in cat skeletal muscle during haemorrhage
Authors: EKELUND U. , MELLANDER S.
Published: October 2003

The problem whether endogenous nitric oxide (NO) may serve as a true physiological regulator of vascular tone in vivo was approached by testing its role during graded acute haemorrhage with the aid of the nitric oxide synthase (NOS) inhibitor l‐NAME. The study was performed on the vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of vascular resistance in the whole vascular bed (RT) and in its consecutive sections, the proximal arterial resistance (‘feeder’) vessels (>25 μm; Ra,prox), the small arterioles (<25 μm) and the veins. NO blockade by close‐arterial l‐NAME infusion in the control situation increased RT from 16.3 to 33.0 PRU (+102%), because of a selective increase in Ra,prox by 16.7 PRU. A 35% blood loss per se raised RT from 13.6 to 21.7 PRU. Superimposed NO blockade in this state caused a much stronger vasoconstriction than in the control situation, increasing RT to 60.9 PRU (+181%) and Ra,prox by 40.5 PRU, which indicated an ∼2.4‐fold increase (P< 0.001) in the NO dilator influence in the Ra,prox section above control. The effect was independent of autonomic nerves. The increased NO dilator influence during haemorrhage most likely was caused by an increased production of endothelium‐derived nitric oxide (EDNO). The constrictor response to l‐NAME was graded in relation to the blood loss (17.5 vs. 35%). The results indicate that EDNO functions as a physiological regulator of vascular tone in the arterial ‘feeder’ vessels during haemorrhage, serving to counterbalance to a significant extent the concomitant adrenergic constriction, and thereby preventing critical reduction of blood flow and untoward heterogeneous flow distribution within the tissue.
Neuromuscular adaptations during bilateral versus unilateral strength training in middle‐aged and elderly men and women
Authors: HÄKKINEN K. , KALLINEN M. , LINNAMO V. , PASTINEN U‐M. , NEWTON R. U. , KRAEMER W. J.
Published: October 2003

Twelve middle‐aged men and 12 middle‐aged women in the 50‐year‐old age group (M50; range 44–57 years; W50; 43–57), and 12 elderly men and 12 elderly women in the 70‐year‐old age group (M70; 59–75; W70; 62–75) volunteered as subjects in order to examine effects of 12‐week progressive heavy resistance strength training on electromyographic activity (EMG), muscle cross‐sectional area (CSA) of the quadriceps femoris and maximal concentric force in a one repetition maximum (1 RM) test of the knee extensor muscles. One half of the subjects in each group performed the knee extension (and flexion) exercises only bilaterally (BIL), while another half performed the exercises only unilaterally (UNIL). None of the subject groups demonstrated statistically significant changes in any of the 1 RM values during the 2 week control period with no training (between week ‐2 and 0) preceding the actual experimental training. However, the 12‐week training resulted in increases (P<0.05–0.001) in 1 RM values in each group so that the average relative increase of 19±12% (P<0.001) in bilateral 1 RM in all BIL trained subjects was greater (P<0.05) than that of 13±8% (P<0.001) recorded for all UNIL trained subjects. The average relative increases of 17±11% (P<0.001) and 14±14% (P<0.001) in unilateral 1 RM values of the right and left leg in all UNIL trained subjects were greater (P<0.05) than those of 10±18% (P<0.001) and 11±11% (P<0.001) recorded for all BIL trained subjects, respectively. The relative average increase of 19±19% (P<0.001) observed in the maximum averaged IEMG of both legs during the bilateral actions in all BIL trained subjects was greater (P<0.05) than that of 10±17% (P<0.05) recorded for all UNIL trained subjects. The relative increases of 14±12% (P<0.001) and 11±6% (P<0.001) recorded for the CSA in all BIL and UNIL trained subjects did not differ significantly from each others. The present findings suggest that progressive heavy resistance strength training leads to great increases in maximal dynamic strength of the trained subjects accompanied by both considerable neural adaptations and muscular hypertrophy not only in middle‐aged but also in elderly men and women. Both bilateral and unilateral exercises are effective to produce functional and structural adaptations in the neuromuscular system, although the magnitude of functional strength increase seems to be specific to the type of exercise used, further supporting the principle of specificity in the design of strength programmes.
Characteristics of fasting and fed myoelectric activity in rat small intestine: evaluation by computer analysis
Authors: BRÄNSTRÖM R. , HELLSTRÖM P. M.
Published: October 2003

Evaluation of gastrointestinal myoelectric activity has been limited by the assessment techniques and the complexity of the recorded myoelectric signal. Commonly, myoelectric activity is evaluated as motor patterns, which only gives a semiquantitative measure of myoelectric events within the bowel wall. Using myoelectric recordings from the proximal small intestine in rats, a computerized system for acquisition, storage, display and calculation of characteristics for the myoelectric activity was developed. The software was tested in myoelectric recordings from nine rats in fasting and fed states. All migrating myoelectric complexes (MMCs) during fasting and fed myoelectric patterns were recognized in both digital and analog recordings. Reproduction of myoelectric recordings by the computerized system was indistinguishable from that of the analog system. Employing an appropriate cut‐off trigger level and a high sampling frequency, spike potentials were recorded in the proximal jejunum with 0.4 (0.3–0.5) spikes 10 s‐1 during phase 1 of MMC, 19.5 (15.1–23.9) (P<0.001) during phase 2, and 103.8 (97.2–110.5) (P<0.001) during phase 3. In fasted state, MMCs were most frequent in the proximal jejunum whereas fewer were found in the duodenum and distal jejunum. To achieve stable values for MMC cycle length at least four MMCs had to be calculated. After feeding in phase 1, the myoelectric activity increased to 23.8 (13.6–33.9) spikes 10 s‐1 (P< 0.001), whereafter the spiking activity decreased over a period of 2 h until a fasting motor pattern was resumed. It is concluded that computerized technology enables evaluation not only of myoelectric patterns, but also of spiking activity per time unit, i.e. the intensity of myoelectric activity in the gut.
Sustained forearm vasodilation in humans during mental stress is not neurogenically mediated
Authors: LINDQVIST M. , DAVIDSSON S. , HJEMDAHL P. , MELCHER A.
Published: October 2003

To evaluate the possible neurogenic influence on forearm vasodilation during mental stress (Stroop's colour word conflict test), haemodynamic and catecholamine responses were registered in 12 healthy men after axillary blockade. Forearm blood flow was measured with venous occlusion plethysmography and forearm vascular resistance was calculated, with intra‐arterial blood pressure data. Blood samples for arterial and venous adrenaline and noradrenaline determinations were collected. Basal forearm blood flow increased markedly after axillary blockade, but the relative responses of forearm blood flow and forearm vascular resistance to mental stress were the same as in previously studied unblocked individuals (about +125% and about ‐40%, respectively). There was no increase in noradrenaline overflow from the forearm during mental stress in the nerve blocked arm. Heart rate and arterial systolic pressure responses as well as catecholamine responses to mental stress were augmented in the nerve blocked group, presumably due to a certain arousal caused by the experimental procedure. Increases in forearm blood flow and decreases in forearm vascular resistance during infusion of adrenaline were similar in the nerve blocked and in the control arm. In conclusion, vasodilation in the forearm during mental stress occurs in the absence of nervous control of the vascular bed. The reactivity of the vascular bed to an exogenous vasodilator (adrenaline) remains unchanged after axillary blockade.
Comparative study of the effects of nitric oxide synthase and cyclo‐oxygenase inhibition on duodenal functions in rats anaesthetized with inactin, urethane or a‐chloralose
Authors: SABABI M. , NYLANDER O.
Published: October 2003

This study was undertaken to investigate the effects of a cyclo‐oxygenase and a nitric oxide synthase (NOS) inhibitor on duodenal mucosal alkaline secretion (DMAS), motility and mucosal permeability in inactin‐, urethane‐ and α‐chloralose anaesthetized rats. Proximal duodenum was perfused with a 150 mm NaCl solution and DMAS was determined by back titration. Mucosal permeability was assessed by measuring blood to lumen clearance of 51Cr‐EDTA and duodenal motility by measuring intraluminal pressure. Mean arterial blood pressure and mucosal permeability were significantly lower in urethane‐ than in inactin‐ or α‐chloralose anaesthetized rats (urethane: 90±2 mm Hg and 0.15±0.02 mL min‐1 100 g‐1; inactin: 112±5 mm Hg and 0.62±0.15 mL min‐1 100 g‐1; α‐chloralose: 111±4 mm Hg and 0.61±0.06 mL min‐1 100 g‐1, respectively). Basal (pre‐drug) DMAS was significantly lower in urethane rats (6.2±1.0 μmol  cm‐1 h‐1) than in α‐chloralose (9.3±1.2 μmol cm‐1 h‐1), but not different from that in inactin‐anaesthetized rats (7.5±0.8 μmol cm‐1 h‐1). No or very few spontaneous duodenal contractions occurred under the control (pre‐drug) conditions in any group. All animals responded to the cyclo‐oxygenase inhibitor indomethacin or the NOS inhibitor N‐nitro‐l‐arginine‐methyl‐ester (l‐NAME) with induction of duodenal motility and an increase in DMAS. The effect of indomethacin or l‐NAME on mucosal permeability was similar in all anaesthetic groups except that l‐NAME induced a transient increase in the inactin and α‐chloralose groups but a sustained increase in urethane‐anaesthetized animals. It is concluded that inactin‐ and α‐chloralose anaesthetized rats do not differ regarding the studied basal values. Urethane‐anaesthetized animals differed from rats given the other two anaesthetics in that basal mucosal permeability and mean arterial blood pressure were lower. Endogenous prostaglandins and NO contribute to the postoperative ileus and the low rate of DMAS also in urethane‐ and α‐chloralose anaesthetized rats.
Skeletal muscle and heart antioxidant defences in response to sprint training
Authors: ATALAY M. , SEENE T. , HÄNNINEN O. , SEN C. K.
Published: October 2003

Although endurance training enhances the antioxidant defence of different tissues, information on the effect of sprint training is scanty. We examined the effect of sprint training on rat skeletal muscle and heart antioxidant defences. Male Wistar rats, 16–17 weeks old, were sprint trained on a treadmill for 6 weeks. Total glutathione levels and activities of glutathione peroxidase, glutathione reductase, glutathione S‐transferase and superoxide dismutase in heart and various skeletal muscles were compared in trained and control sedentary animals. Lactate dehydrogenase and citrate synthase enzyme activities were measured in muscle to test the effects of training on glycolytic and oxidative metabolism. Sprint training significantly increased lactate dehydrogenase activity in predominantly fast glycolytic muscles and enhanced total glutathione contents of the superficial white quadriceps femoris, mixed gastrocnemius and fast‐glycolytic extensor digitorum longus muscles. Oxidative metabolic capacity increased in plantaris muscle only. Compared with the control group, glutathione peroxidase activities in gastrocnemius, extensor digitorum longus muscles and heart also increased in sprint trained rats. Glutathione reductase activities increased significantly in the extensor digitorum longus muscle and heart. Glutathione S‐transferase activity was also higher in the sprint trained extensor digitorum longus muscle. Sprint training did not influence glutathione levels or glutathione‐related enzymes in the soleus muscle. Superoxide dismutase activity remained unchanged in skeletal muscle and heart. Sprint training selectively enhanced tissue antioxidant defences by increasing skeletal muscle glutathione content and upregulating glutathione redox cycle enzyme activities in fast and mixed fibre leg muscles and heart.
The effect of endothelin receptor blockade on the development of the Sephadex‐induced inflammation in the rat lung
Authors: ANDERSSON S. E. , HEMSÉN A. , LUNDBERG J. M.
Published: October 2003

The non‐peptide ET‐receptor antagonist Bosentan was used to investigate the role of endogenous endothelin‐1 (ET‐1) in the development of the Sephadex‐induced lung inflammation in the rat. Intratracheal instillation of Sephadex caused a 60‐fold rise in endothelin‐1‐like‐immunoreactivity (ET‐1‐LI) in bronchoalveolar lavage fluid (BALF) concomitant with development of lung oedema, an influx of inflammatory cells into the airways and a rise in the protein content in BALF. The ET‐1‐LI level in lung homogenate was not significantly affected. Pre‐treatment with Bosentan reduced ET‐1‐LI content in the lung parenchyma but increased ET‐1‐LI levels in BALF, possibly indicating an effective displacement of ET‐1 from its receptors. In Bosentan‐treated animals there was an enhancement of the lung oedema formation following Sephadex instillation, but no significant change in the number of leucocytes or protein concentration in BALF. The present data thus do not support the hypothesis that endogenous ET‐1 mediates oedema formation or leucocyte influx in this model. If anything, Bosentan enhanced the oedema formation in parallel with increased ET‐1‐LI in BALF.
Differences in mouth occlusion pressure and breathing pattern between arm and leg incremental exercise
Authors: RAMONATXO M. , PRIOUX J. , PREFAUT C.
Published: October 2003

The aim of the study was to compare breathing pattern, mouth occlusion pressure, mean inspiratory flow and the ratio of mouth occlusion pressure to mean inspiratory flow at the same power output and carbon dioxide output during arm and leg incremental exercise. Mouth occlusion pressure was used as an index of inspiratory neuromuscular activity and its ratio to mean inspiratory flow as an index of the ‘effective’ impedance of the respiratory system. Eight normal subjects performed two incremental exercise tests, one with arms, the other with legs, on different weeks and in randomized order, and on two identical cycle ergometers. The power output was increased by steps of 25 W for arms and 50 W for legs every 4 min until exhaustion. At the same power output, oxygen consumption, carbon dioxide output, ventilation, mean inspiratory flow, mouth occlusion pressure, ‘effective’ impedance (P<0.001) and respiratory frequency (P<0.01) were higher during arm exercise than during leg exercise, whereas inspiratory time (P<0.05) and expiratory time (P<0.01) were lower. At the same carbon dioxide output, mouth occlusion pressure, ventilation, ‘effective’ impedance (P<0.001) and respiratory frequency (P<0.01) were higher and expiratory time (P<0.05) was lower during arm exercise. In conclusion, the higher inspiratory neuromuscular activity and impedance of the respiratory system during arm exercise and the differences observed in ventilation and breathing pattern at equal carbon dioxide output seem related to the differences in exercising muscle afferents and the presence of an increased load due to contraction of rib cage muscles to stabilize posture.
Prostaglandin E2 inhibits antidiuretic hormone induced transepithelial sodium transport and cAMP production in frog skin epithelium (Rana esculenta)
Authors: RYTVED K. A. , ANDERSEN H. , NIELSEN R.
Published: October 2003

The stimulation of transepithelial sodium transport by arginine vasotocin (AVT) and the ability of prostaglandin E2 (PGE2) to inhibit the AVT dependent sodium transport was examined on pieces of frog skin taken from different regions of the frog. The basal sodium transport was of the same magnitude in the abdominal, thoracal and upper and lower dorsal region. In all regions the sodium transport could be stimulated by AVT, though the stimulation was highest in the abdomen. Subsequent addition of PGE2 caused a significant inhibition of the AVT dependent sodium transport in the abdomen but had only minor effects on the other parts of the skin. Therefore, pieces of skin from the abdomen were selected for the remaining experiments. Addition of PGE2 to skin pieces in the presence of AVT resulted in a hyperpolarization of the cellular potential and a decrease in the transepithelial sodium transport, indicating a decreased apical sodium permeability. This was correlated with a decrease in cellular cAMP contents. We conclude that frog skin exhibits large regional differences in sensitivity to AVT and that PGE2 only modulates the natriferic effect of AVT in the abdomen.
Phosphate and cyclic AMP excretion decreases during less than 12 hours of hypoxia in conscious rats
Authors: MIMURA Y.
Published: October 2003

Hypocapnia is known to have an antiphosphaturic effect that overcomes the phosphaturic effect of hypoxia. The objective of this study was to examine whether conscious rats exposed to acute hypoxia show a decrease in phosphate excretion due to the concomitant hypocapnia. Wistar rats weighing 200 g were exposed to hypoxia (inspired oxygen fraction=0.10) or normoxia (inspired oxygen fraction=0.21) for 6 h; and rats were alternately exposed to hypoxia or normoxia every 12 h for a total 36 h. Renal clearance and hormone studies were performed. Rats exposed to 6 h of hypoxia (n = 11) showed significant hypophosphaturia and decreases in absolute and fractional excretion of phosphate (0.38±0.10 μg min‐1, mean ±SE, P<0.0001 and 0.59±0.15%, P<0.0001) as compared with normoxic rats (n = 11, 3.91±0.68 μg min‐1 and 5.62±0.85%). In addition, nephrogenous adenosine 3′,5′‐cyclic monophosphate level per glomerular filtrate was significantly decreased (‐0.87±0.64 nmol dL GF‐1, P<0.05) and plasma parathyroid hormone level was unchanged (45.2±9.5 pg mL‐1) after 6 h of hypoxia as compared with normoxic rats (4.03±1.83 nmol dL GF‐1 and 54.3±10.4 pg mL‐1). A parallel increase in urinary noradrenaline and a decrease in dopamine excretion was observed in rats after 6 h of hypoxia. The decreased phosphate and adenosine 3′,5′‐cyclic monophosphate excretion during acute hypoxia were restored to normoxic levels by reoxygenation with 21% oxygen in the study of 12‐h intermittent hypoxia. In summary, (1) hypoxia produced by inhalation of 10% oxygen for 12 h or less causes reduced phosphate and adenosine 3′,5′‐cyclic monophosphate (cAMP) excretion by spontaneously breathing rats; (2) these effects are reversed by reoxygenation and (3) hypoxia elicits a parallel increase in noradrenaline excretion and a decrease in dopamine excretion. These data suggest that renal adrenergic and dopaminergic systems play important roles in hypophosphaturia during acute hypoxia in conscious rats.
Endogenous opioid mechanisms in hypothalamic blood flow autoregulation during haemorrhagic hypotension and angiotensin‐induced acute hypertension in cats
Authors: KOMJÁTI K. , VELKEI‐HARVICH M. , TÓTH J. , DALLOS G. , NYÁRY I. , SÁNDOR P.
Published: October 2003

The influence of naloxone‐induced general opiate receptor blockade on hypothalamic blood flow autoregulation was investigated in anaesthetized, artificially ventilated, temperature controlled cats. In order to study the changes of the hypothalamic blood flow (H2‐gas clearance technique) at the lower limit of autoregulation systemic arterial pressure was reduced in a stepwise manner to 100, 80, 60 and 40 mmHg, by haemorrhage. Autoregulatory mechanisms of the hypothalamic vessels remained effective and hypothalamic blood flow showed no significant reduction until the arterial pressure was reduced to 60 mmHg in the vehicle‐treated control cats. General opiate receptor blockade by 1 mg kg‐1 mL‐1 i.v. injected naloxone resulted in a significant reduction of the autoregulatory capacity of the hypothalamic vessels: the blood flow followed passively the arterial pressure fall already from 100 mmHg mean arterial pressure. The effect of opiate receptor blockade on the upper limit of the autoregulation was studied during acute arterial hypertension, induced by angiotensin‐II infusion (25 μg 0.1 mL‐1 min‐1 i.v.). Hypothalamic blood flow remained remarkably steady following angiotensin‐II infusion in the saline‐treated control animals. Naloxone pretreatment (1 mg kg‐1 mL‐1 i.v.), however, induced a significant downward shift of the upper limit of the autoregulation, and hypothalamic blood flow started to increase in the 125–145 mmHg arterial pressure range. The narrowing of the autoregulatory range following general opiate receptor blockade suggests an important role of endogenous opioid peptides in hypothalamic blood flow autoregulatory mechanisms both in hypotensive and in hypertensive conditions.
Neonatal pre‐ganglionic sympathectomy affects morphometrically defined architecture in rat cerebral arteries
Authors: KÅHRSTRÖM J. , HARDEBO J. E. , NORDBORG C. , OWMAN C.
Published: October 2003

In order to clarify further the nature of the long‐term influence on the cerebral vasculature by the sympathetic nerves, a bilateral cervical pre‐ganglionic denervation was performed in 1‐week‐old rats. Four weeks later, morphometric determinations of the vascular dimensions revealed diminished media cross‐sectional areas and luminal radii in the middle cerebral and posterior cerebral arteries, whereas these parameters were unaffected in the basilar artery. In the latter artery, however, a 40% increase in the cross‐sectional area of the internal elastic membrane was found. No re‐innervation of the denervated ganglia occurred during the course of the experiment. The results suggest that the long‐term effect exerted by the sympathetic nerves is associated with the nerve activity, rather than being a true trophic influence.
Neonatal chronic sympathectomy in normotensive rats affects pial arteries: enhanced stiffness and reduced capacity to dilate
Authors: KÅHRSTRÖM J. , HARDEBO J. E. , OWMAN C.
Published: October 2003

The functional implication of previously shown effects on pial wall morphology by sympathectomy was tested. Following either ganglionic or pre‐ganglionic denervation in 1‐week‐old rats the passive arterial compliance was reduced in basal cerebral arteries of 20‐week‐old normotensive, but not of hypertensive animals. The magnitude of the denervation induced stiffness was similar to the alteration seen in spontaneously hypertensive rats when compared with normotensive animals. No difference was seen between the two types of denervation. Following ganglionic sympathectomy in 1‐week old normotensive rats – and examined 19 weeks later – the increase in cerebral blood flow (measured with the [14C]butanol sampling technique) induced by high arterial CO2 concentration was attenuated compared with control, whereas basal cerebral blood flow of 20‐week‐old animals was not different from control. The results indicate a long‐term role by the sympathetic nerves not only on vessel wall composition, but also on the regulatory capacity of the cerebral circulation.
Effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin in humans
Authors: STØA‐BIRKETVEDT G. , WALDUM H.L. , VONEN B. , FLORHOLMEN J.
Published: October 2003

STØA‐BIRKETVEDT, G., WALDUM, H. L.,VONEN, B. & FLORHOLMEN, J. 1997. Effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin in humans. Acta Physiol Scand159, 321–325. Received 12 June 1996, accepted 8 November 1996. ISSN 000–6772. Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Physiological Laboratory, University School of Medicine, 6000 Trondheim and Department of Surgery, University Hospital of Tromsø, 9037 Tromsø, Norway.

Cimetidine reduces the appetite and weight in healthy overweight subjects. Gastrointestinal regulatory peptides such as cholecystokinin (CCK) have been proposed to mediate the satiety signal from gut to brain. Therefore, the effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin was studied. After an overnight fast, 12 healthy volunteers were given cimetidine (400 mg) on day 1, breakfast on day 2, and cimetidine 20 min before breakfast on day 3. Plasma concentrations of cholecystokinin and gastrin were measured by radioimmunoassay. Plasma cholecystokinin concentration increased with one major peak observed 30 min and one smaller peak observed 120 min after intake of cimetidine. The meal induced an increase in the plasma concentration of cholecystokinin, while cimetidine prior to the meal elicited a sustained postprandial cholecystokinin response. Cimetine had no effect on the basal plasma concentration of gastrin. The meal induced an increase in the plasma concentration of gastrin, while cimetidine prior to the meal elicited a sustained postprandial gastrin response. In conclusion, cimetidine increases the basal concentration of plasma cholecystokinin and elicits a sustained postprandial response of both cholecystokinin and gastrin. At least the cholecystokinin response may be one mechanism by which cimetidine reduces the appetite.
Laser‐Doppler measurements of concentration and velocity of moving blood cells in rat cerebral circulation
Authors: BARFOD C. , AKGÖREN N. , FABRICIUS M. , DIRNAGL U. , LAURITZEN M.
Published: October 2003

In brain cortex all capillaries are perfused with plasma at anyone time while the flow of blood cells is heterogenous. Increased blood flow is associated with increased number of moving erythrocytes in the microcirculation, while capillary recruitment in its classical anatomical sense appears not to exist in the brain. Modulation of the concentration of flowing erythrocytes may influence the oxygen supply to the tissue. Therefore, we examined the possibility that laser‐Doppler flowmetry (LDF) could be used to quantify changes in the microvascular concentration of moving blood cells (CMBC) and blood cell velocity (< v >) by comparing LDF measurements with electromagnetic flow measurements in vitro, and confocal laser‐scanning microscopy in vivo in the brain of anaesthetized male Wistar rats. In vitro measurements showed that CMBC was affected by changes in haematocrit, while < v > correlated almost linearly with blood cell velocity measured electromagnetically within a relevant physiological range. In vivo studies during hypercapnia (Paco2 from 39 ± 4 to 66 ± 5 mmHg) with confocal laser scanning microscopy disclosed a 39 ± 10% increase of cortical capillary erythrocytes, while CMBC measured with LDF increased by 37 ± 5%. Erythrocyte flow velocity in brain cortex capillaries increased by 65 ± 17% with confocal microscopy as compared to 72 ± 8% with LDF. Local electrical stimulation of cerebellar cortex, and application of adenosine or sodium‐nitroprusside, increased CMBC and < v > simultaneously, while during hypercapnia the < v > increase preceded the CMBC increase by 30 s. The CMBC rise rapidly reached a steady state in response to all types of stimulation, while < v > continued to increase during the major part, or the entire stimulation period. In conclusion, our data support the hypothesis that LDF may be useful for haemodynamic studies of brain microcirculation.
The effects of enalapril on the natriuretic response evoked by an oral sodium load in sodium deprived normotensive and hypertensive rats
Authors: MU J.Y. , JOHANSSON M. , LUNDGREN O.
Published: October 2003

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin‐angiotensin‐aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar‐Kyoto (WKY) rats, inbred hypertension‐prone (SS/Jr) and hypertension‐resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three‐ to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin‐angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.
Rigorous swim training impairs mitochondrial function in post‐ischaemic rat heart
Authors: LEICHTWEIS S.B. , LEEUWENBURGH C. , PARMELEE D. J. , FIEBIG R. , JI L. L.
Published: October 2003

The effect of rigorous swim training (6 h day−1, 5 days week−1 for an average of 191 h) on mitochondrial respiratory function was investigated in rat heart subjected to in vivo ischaemia reperfusion (I‐R). Mitochondria was isolated from the risk region of the left ventricle subjected to 60 min occlusion of the main left coronary artery followed by 30 min reperfusion. Heart weight and heart‐to‐body weight ratio was increased by 21 and 28% (P < 0.01), respectively, in the trained (T, n = 15) vs. control rats (C, n = 20). I‐R per se showed minimal effect on heart mitochondria regardless of training status. In sham, state 4 respiration rate was 26 and 32% (P < 0.05) lower in T vs. C rats, using malate‐pyruvate (M‐P) and 2‐oxoglutarate (OG) as substrates, respectively. Training also reduced state 3 respiration by 28% (M‐P) and 50% (OG) (P < 0.01). The respiratory control index (RCI) was unaltered in T with M‐P, but decreased with OG (P < 0.01). In vitro exposure to superoxide radicals severely reduced state 4 and 3 respiration and RCI, but T hearts showed greater reductions of state 4 and 3 rates than C. Mitochondria from T hearts also revealed a greater state 4 inhibition by H2O2 and HO• compared with C. A lower glutathione content and a higher γ‐glutamyl transpeptidase activity (P < 0.05) was observed in T vs. C. It is concluded that rigorous swim training impairs heart mitochondrial function, making them more susceptible to in vivo and in vitro oxidative stress, and that this damaging effect may be related to a diminished glutathione reserve.
Influence of ingested fluid volume on physiological responses during prolonged exercise
Authors: McCONELL G. K. , BURGE C. M. , SKINNER S. L. , HARGREAVES M.
Published: October 2003

The effect of different rates of fluid ingestion on heart rate, rectal temperature, plasma electrolytes, hormones and performance was examined during prolonged strenuous exercise conducted at 21 °C. Seven well‐trained males (24 ± 1 yr; 68.6 ± 2.9 kg; Vo2 peak = 4.69 ± 0.17 L min−1; mean ± SEM) cycled for 2 h at 69 ± 1% Vo2 peak while receiving either no fluid replacement (NF), a volume of water estimated to prevent body weight loss (FR‐100 = 2.32 ± 0.10 L 2 h−1) or 50% of this volume (FR‐50 = 1.16 ± 0.05 L 2 h−1). The 2‐h exercise bout was followed by a ride to exhaustion at a workload estimated to be 90% Vo2 peak. After 2 h of exercise, NF was associated with a 3.2 ± 0.1% weight loss, while FR‐50 and FR‐100 resulted in losses of 1.8 ± 0.1 and 0.1 ± 0.1%, respectively. Compared with FR‐100, heart rate and rectal temperature were elevated (P < 0.05) during the second hour of exercise in NF, with FR‐50 intermediate. Reductions in plasma volume during exercise were greater in NF and FR‐50, compared with FR‐100 and plasma sodium concentration was elevated in NF, decreased slightly in FR‐100, with FR‐50 intermediate. Plasma renin activity, aldosterone and atrial natriuretic peptide increased to similar extents in the three trials. Plasma vasopressin remained unchanged for FR‐100, increased for NF, with intermediate values for FR‐50. Exercise time to exhaustion at 90% Vo2 peak was longer in FR‐100 (328 ± 93 s) than NF (171 ± 75 s) with FR‐50 (248 ± 107 s) not significantly different from either FR‐100 or NF. In conclusion, the responses of heart rate, rectal temperature, plasma sodium, and vasopressin during, and performance following, prolonged cycling exercise conducted at 21 °C are related to the amount of fluid ingested (i.e. the degree of dehydration).
Effect of bovine serum albumin on the calcium release channel of sarcoplasmic reticulum from rabbit skeletal muscle
Authors: CATINOT M.P. , BASTIDE B. , MONTEL V. , SUAREZ‐KURTZ G. , MOUNIER Y.
Published: October 2003

The effect of bovine serum albumin (BSA) on the activity of the calcium release channel of the sarcoplasmic reticulum from rabbit skeletal muscle was investigated using both tension recording from skinned fibres and electrophysiological recording of unitary channel currents from planar lipid membranes. BSA had no effect on the Ca2+ affinity of the contractile proteins, elicited no tension per se in Ca2+‐loaded skinned fibres, but potentiated caffeine‐induced tension. Maximum potentiation was observed with 0.05–0.5% BSA. BSA (0.1%) had no detectable effect on the basal activity of the Ca2+‐release channel incorporated in lipid bilayer. However, channel stimulation elicited by either caffeine (2 mM) or ATP (60 μM) was further enhanced by BSA (0.1%), as indicated by significant increases in Po, the open probability of the channel. These results suggest that BSA can modulate the response of the skeletal muscle SR Ca2+‐release channel to different activators such as caffeine and ATP.
Brachial arterial blood flow during static handgrip exercise of short duration at varying intensities studied by a Doppler ultrasound method
Authors: KAGAYA A. , HOMMA S.
Published: October 2003

The purpose of this study was to determine forearm blood flow changes during static handgrip exercise at different intensities in relation to heart rate and blood pressure. Seven active women performed static handgrip exercise at intensities of 10, 30, 50 and 70% maximum voluntary contraction (MVC) in a supine position for 1 min. During exercise at different intensities, the brachial arterial blood flow (Doppler ultrasound method), calculated from vessel diameter, flow velocity and heart rate (measured by ECG), increased to a similar level (137.3 ± 20.2 – 160.9 ± 26.1 mL min−1) from pre‐exercise control value (87.5 ± 14.1 mL min−1). These increases at the lower intensities were attributable to increased in‐flow during one cardiac cycle, whereas at the higher intensities, they were due to increased heart rate. Both systolic and diastolic blood pressure (Finapres) changes increased from 10% MVC (16.1 ± 3.4, 9.0 ± 1.7 mmHg) up to 50% MVC (33.8 ± 6.7, 25.0 ± 4.9 mmHg), but were disproportionately more elevated at 70% MVC (46.1 ± 7.9, 42.9 ± 8.9 mmHg), suggesting neural vasoconstriction had occurred. Immediate post‐exercise hyperaemia, used as an indicator of poor blood supply, became greater as the exercise intensity increased. These results suggest that the brachial arterial blood flow was maintained at a similar level during 60‐s static handgrip exercise at different intensities by elevating the blood pressure and heart rate, which probably counteracted the increased intramuscular pressure and neural vasoconstriction occurring at the higher exercise intensity. The magnitude of the post‐exercise hyperemic response increased as exercise level increased despite increased blood flow to the arm during exercise. This suggests a worsening imbalance in oxygen delivery in forearm muscles at higher levels of exercise.
The cGMP pathway is not responsible for the blunted hypoxic vasoconstriction in rat lungs after altitude exposure
Authors: ASANO K. , YANAGIDAIRA Y. , YOSHIMURA K. , SAKAI A.
Published: October 2003

To examine the contribution of the cyclic guanosine monophosphate (cGMP) pathway in changes in pulmonary vasoconstriction during the initial days of altitude exposure, we tested the effects of LY83583 (an inhibitor of guanylate cyclase activation) and those of NG‐monomethyl‐l‐arginine (an inhibitor of nitric oxide synthesis) on airway hypoxia‐ (3% O2) and angiotensin II‐ (AII, 0.2 μg) induced vasoconstrictions in lungs from the rats exposed to either moderate altitude (MA, 570 torr) or high altitude (HA, 430 torr). At 2 days' exposure, hypoxic response was significantly blunted compared with the response in low‐altitude (LA, 710 torr) lungs in an altitude‐dependent manner. At 7 days' exposure, the response was recovered fully in MA lungs but partially in HA lungs. AII response was not significantly blunted at 2 days' exposure, but was significantly augmented in an altitude‐dependent manner at 7 days' exposure. LY83583 (10 μmol L−1) potentiated both responses in LA lungs but did not significantly potentiate either response in any altitude‐exposed lungs. NG‐monomethyl‐l‐arginine (10 μmol L−1) potentiated both responses in LA lungs but did not significantly potentiate either response in HA lungs at 2 days' and 7 days' exposure. Thus the cGMP pathway is not responsible for either the change in hypoxic vasoconstriction or the change in AII vasoconstriction in rat lungs during the initial 7 days of altitude exposure.
Effect of the inhibitor of NO synthase, N G‐nitro‐L‐arginine methyl ester, on histamine‐induced bronchospasm in the rabbit
Authors: DEWACHTER P. , VASSILIOU M. , SAUNIER C.G. , HARTEMANN D. , PESLIN R. , LAXENAIRE M.‐C.
Published: October 2003

New Zealand male rabbits were anaesthetized with thiopental, tracheotomized, curarized by vecuronium bromide and mechanically ventilated. Six rabbits received L‐NAME 10 mg kg−1 i.v., six rabbits L‐NAME 15 mg kg−1 iv, and six rabbits received saline i.v. (controls), 5 min before a histamine aerosol (2% solution during 5 min). Six others rabbits received an injection of L‐NAME 15 mg kg−1 iv, 5 min before the histamine aerosol, followed by an infusion of L‐arginine over a 60‐ min period. Total respiratory resistance (Rrs) and elastance (Ers) were derived by least square analysis of the relationship between tracheal pressure and flow, and computed every minute before and over a 1‐h period after the histamine aerosol. Oxygen free radicals (OFR) were measured with a luminometer, in microsomes from lung homogenates at the end of the experiment. Compared with the histamine response of the control group, the Rrs response in the L‐NAME 10 group was slightly less, while Ers changes were the same in the two groups. In contrast, L‐NAME 15 was responsible for an increased Rrs response, the difference being significant (P < 0.05) only between 15 and 40 min after the aerosol (+114% vs. + 85% in controls at the 20th min). The increase in Ers with L‐NAME 15 was stronger and significantly larger (+71% vs. +42% in controls at the 20th min after the histamine aerosol, P < 0.001). The relatively greater effect of L‐NAME on Ers than on Rrs suggests that NO predominantly modulates the response to histamine of the peripheral lung rather than that of the large airways. Furthermore, the effect of L‐NAME on Rrs was completely abolished by L‐arginine, while its effect on Ers was only partially reversed. This suggests that the changes in Ers are partly related to a hardly reversible phenomenon. Possibly, the mechanical changes are linked with the rise of OFR in the lung parenchyma, which were significantly higher in the L‐NAME 15 group compared to the control group (P < 0.05).
Effect of noradrenaline on tail arteries of SHR and WKY under perfusion at constant flow and constant pressure
Authors: MACHKOV V. V. , TARASOVA O. S. , TIMIN E. N. , RODIONOV I. M.
Published: October 2003

Vasoconstrictor effects of noradrenaline were compared in 6‐ to 7‐month‐old spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. A cylindrical segment was dissected from the proximal part of tail artery, cannulated at both ends and perfused alternately either at constant flow or constant pressure. Two series of experiments were performed. In the first series, vessels were perfused/superfused with Krebs‐Henseleit solution. In the second one a modified salt solution was used, in which NaCl was totally replaced by an equimolar amount of KCl. Under constant flow conditions noradrenaline evoked a more prominent resistance increase in SHR compared with WKY independently of the composition of solution (normal or high‐K+) used. At constant pressure perfusion with normal solution, the vasoconstrictor response to noradrenaline was more prominent in WKY. Under application of high‐K+ solution, vasoconstriction at constant pressure in SHR became more pronounced than that in WKY. We suggest that there is greater wall thickness:lumen diameter ratio in SHR vessels and thus different contribution of distension‐activated myogenic response is of primary importance for the data obtained.
Effects of topical platelet activating factor on the guinea‐pig tracheobronchial mucosa in vivo
Authors: GREIFF L. , ERJEFÄLT I. , ERJEFÄLT J.S. , WOLLMER P. , SUNDLER F. , PERSSON C.G.A.
Published: October 2003

Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway‐lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea‐pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I‐albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc‐DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro‐tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc‐DTPA from the airways as an index of mucosal absorption. PAF produced dose‐dependent mucosal exudation of plasma up to 20‐fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve‐like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
Inhaled carbon dioxide inhibits lower airway nitric oxide formation in the guinea pig
Authors: BANNENBERG G. L. , GIAMMARRESI C. , GUSTAFSSON L. E.
Published: October 2003

The present study addressed the effect of inhaled carbon dioxide on lower airway nitric oxide formation in normoxic anaesthetized guinea pigs. Ventilation with carbon dioxide (1.5, 3, 6, 9 and 12%) induced a concentration‐dependent decrease in the basal concentration of nitric oxide in exhaled tracheal air. A maximal reduction in exhaled nitric oxide of ≈25% was induced by 12% carbon dioxide in inhaled air. Ventilation with positive end‐expiratory pressure (7 cmH2O) increased the concentration of exhaled nitric oxide. Inhalation of carbon dioxide had a larger, concentration‐dependent, inhibitory effect (maximally 60%) on the lower airway nitric oxide formation induced by ventilation with positive end‐expiratory pressure, as compared with the effect on the basal concentration of nitric oxide. The results show that inhaled carbon dioxide suppresses lower airway nitric oxide excretion in the guinea pig. Endogenous carbon dioxide might exert effects through regulation of endogenous nitric oxide formation, for example in the regulation of airway tone or in ventilation–perfusion matching.
Alloxan diabetes abolishes the increased negativity of interstitial fluid pressure in rat trachea induced by vagal nerve stimulation
Authors: WOIE K. , K.REED R.
Published: October 2003

Increased negativity of interstitial fluid pressure (Pif) occurs concomitantly with oedema formation in acute airway inflammation. This observation is principally important because the loose connective tissues become `active' and provide the driving force for the rapid oedema formation via Pif. The present study reports Pif in acute airway inflammation in alloxan diabetic rats. The basis for the study was, firstly, that inflammation is important in the pathogenesis of asthma. Secondly, that clinically there is almost a mutual exclusion between diabetes and asthma and, lastly, that the inflammatory response is attenuated in alloxan diabetic rats. Pif was measured on the ventral side of the trachea with sharpened glass capillaries (3–6 μm) connected to a servocontrolled counterpressure system. Measurements and nerve stimulation were performed after circulatory arrest, since oedema formation associated with inflammation will increase Pif, causing an underestimation of a potentially increased negativity of Pif. Control or diabetic rats (alloxan 45 mg kg−1 i.v. 5 days earlier) received either the mast cell degranulating substance compound 48/80 (100 μg), dextran 70 (60 mg) i.v. or vagal nerve stimulation. After dextran, Pif was −4.7 ± 0.9 (SD) mmHg (n = 6) and −1.3 ± 0.3 mmHg (n = 6) (P < 0.01) in normal and diabetic rats, respectively. Corresponding values after vagal nerve stimulation were −5.3 ± 1.8 mmHg (n = 5) and −0.7 ± 0.2 mmHg (P < 0.01). Insulin treatment restored the Pif response to dextran and vagal stimulation. Pif after Compound 48/80 did not differ between control and diabetic rats. Interstitial volume, total tissue water and transcapillary albumin extravasation increased significantly in controls after vagal nerve stimulation, but was attenuated in diabetic rats.