bluuebunny/crossref_metadata_2025 huggingface dataset:
Transepithelial transport and cell volume control in proximal renal tubules from the teleost Carassius auratus
Authors: KANLI H. , TERREROS D.A.
Published: October 2003

The objective of this work was to study cell volume regulation and transepithelial transport in renal proximal tubules. A modified stop‐flow technique in in vitro perfused renal proximal tubules of Carassius auratus was used. The rate of luminal fluid absorption and the epithelial thickness were measured. Isosmotic Na+ removal from the tubule lumen or addition of the Na+/glucose co‐transport blocker phloridzin (0.5 mM) to the lumen inhibited fluid absorption. Only minor effects on luminal absorption were observed following: (1) addition of the K+ channel inhibitor BaCl2 (1 mM); (2) addition of the Cl− channel inhibitor MK‐196 (1 mM); (3) lowering bath and perfusate HCO3− in the presence of 0.1 mM acetazolamide; or (4) addition of the leukotriene‐D4 receptor antagonist L‐660, 711 (20 μM). Isosmotic addition of 40 mM taurine to the bath inhibited the rate of fluid absorption. This effect could be partially overcome with the organic acid secretion inhibitors probenecid (1 mM) and bromcresol green (0.1 mM). Finally, administration of the 5‐lipoxygenase antagonist ETH 615–139 (20 μM) caused a significant reduction in the rate of luminal absorption. In summary, tubular reabsorption is, in this preparation, closely linked to sodium reabsorption. In the absence of luminal amino acids most of this sodium uptake seems to occur in co‐transport with glucose followed by osmotically obligated water. Eicosanoids from the 5‐lipoxygenase pathway appear to regulate this process. Finally, high concentrations of taurine in the bath opposed luminal fluid absorption, at least partially, by its secretion into the tubular lumen.
Glucagon‐like peptide‐1 reduces hepatic glucose production indirectly through insulin and glucagon in humans
Authors: LARSSON H. , HOLST J. J. , AHRÉN B.
Published: October 2003

The effect of glucagon‐like peptide‐1 (GLP‐1) on hepatic glucose production and peripheral glucose utilization was investigated with or without infusion of somatostatin to inhibit insulin and glucagon secretion in 13 healthy, non‐diabetic women aged 59 years. After 120 min 3‐3H‐glucose infusion, GLP‐1 was added (4.5 pmol kg−1 bolus + 1.5 pmol kg−1 min−1). Without somatostatin (n = 6), GLP‐1 decreased plasma glucose (from 4.8 ± 0.2 to 4.2 ± 0.3 mmol L−1, P = 0.007). Insulin levels were increased (48 ± 3 vs. 243 ± 67 pmol L−1, P = 0.032), as was the insulin to glucagon ratio (P = 0.044). The rate of glucose appearance (Ra) was decreased (P = 0.003) and the metabolic clearance rate of glucose (MCR) was increased during the GLP‐1 infusion (P = 0.024 vs. saline). Also, the rate of glucose disappearance (Rd) was reduced during the GLP‐1 infusion (P = 0.004). Since Ra was reduced more than Rd, the net glucose flow was negative, which reduced plasma glucose. Somatostatin infusion (500 μg h−1, n = 7) abolished the effects of GLP‐1 on plasma glucose, serum insulin, insulin to glucagon ratio, Ra, Rd, MCR and net glucose flow. The results suggest that GLP‐1 reduces plasma glucose levels mainly by reducing hepatic glucose production and increasing the metabolic clearance rate of glucose through indirectly increasing the insulin to glucagon ratio in healthy subjects.
Differential responses in intramuscular pressure and EMG fatigue indicators during low‐ vs. high‐level isometric contractions to fatigue
Authors: CRENSHAW A.G. , KARLSSON S. , GERDLE B. , FRIDÉN J.
Published: October 2003

This study investigated changes in intramuscular pressure (IMP) and surface electromyographic (EMG) parameters (mean frequency of the power spectrum, fmean; and signal amplitude denoted as root mean square, RMS) during contractions to fatigue at 25 and 70% of maximal voluntary contraction (MVC). Parameters were recorded simultaneously from the vastus lateralis muscle during knee extension. A significant decrease in fmean occurred with time at both contraction levels; however, the rate of decline (slope) was greater at 70% MVC. RMS increased throughout the contractions at both levels, with the relative increase being significantly greater for 25% MVC. IMP increased during 25% MVC but did not change during the 70% MVC contraction. IMP at rest was significantly higher post‐contractions than it was pre‐contractions at 25% MVC (21.1 vs. 8.0 mmHg, P < 0.01) and 70% MVC (13.7 vs. 8.6 mmHg, P < 0.01). Consequently, post‐contraction IMP was higher at 25% MVC than at 70% MVC (P < 0.01). IMP changes throughout the fatiguing contractions correlated negatively with fmean and positively with RMS at both MVC levels; however, these correlations were better at 25% MVC. The extent of intramuscular water accumulation is discussed as a major cause of the difference in IMP changes between 25% and 70% MVC. Significant differences in the rate of change for all parameters between high vs. low contraction levels may suggest a common mechanism governing changes in IMP and EMG fatigue indicators.
Acid‐induced increase in duodenal mucosal permeability is augmented by nitric oxide inhibition and vasopressin
Authors: HÄLLGREN A. , WILANDER E. , NYLANDER O.
Published: October 2003

The aim of the study was to determine if and by what mechanism(s) nitric oxide inhibition modulates the susceptibility of the duodenum to hydrochloric acid‐induced disturbances of mucosal integrity. A second aim was to investigate whether basal permeability is a determinant of epithelial acid barrier function. Using an in situ duodenal perfusion model, mucosal permeability, alkaline secretion and morphology were investigated in anaesthetized rats. Luminal perfusion with 50 mm hydrochloric acid increased duodenal mucosal permeability in the control animals. In animals receiving the nitric oxide synthase inhibitor N‐nitro‐l‐arginine methyl ester (l‐NAME 3 mg kg−1 and 1 mg kg−1 h−1) and in those receiving vasopressin (1 IU kg−1 h−1), however, the mean increase in permeability in response to acid was markedly higher. In rats treated with either hexamethonium (20 mg kg−1) or atropine (0.5 mg kg−1) l‐NAME failed to augment the acid‐induced increase in permeability. Perfusion with hypotonic saline (25 mm) increased basal permeability but did not influence the response to acid. Exposure of the duodenum to hydrochloric acid caused very subtle changes of duodenal morphology. It is concluded that both inhibition of endogenous nitric oxide synthesis and vasopressin treatment augment the acid‐induced increase in mucosal permeability. The mechanisms involved may be related to changes of Starling forces in the microcirculatory bed. Endogenous nitric oxide may protect the duodenal mucosa by regulating vascular permeability and interstitial fluid pressure.
Quantification of α2A and α2C adrenoceptors in the rat striatum and in different regions of the spinal cord
Authors: UHLÉN S. , LINDBLOM J. , TIGER G. , WIKBERG J. E. S.
Published: October 2003

The α2C‐adrenoceptor preferring radioligand [3H]‐MK912 was used for labelling α2A‐ and α2C‐adrenoceptors in the rat striatum, in the cervical, thoracic and lumbar parts of the spinal cord, and in the dorsal and ventral halves of the spinal cord. In addition, guanfacine was used as a tool to delineate the α2A‐ and α2C‐adrenoceptors. In the striatum the sites were 72% α2A‐ and 28% α2C‐adrenoceptors, while in all regions of the spinal cord the proportions of the sites were about 96% α2A‐ and 4% α2C‐adrenoceptors. A multi‐curve experimental design and computer analysis was used in order to enable the accurate quantification of the α2A‐ and α2C‐adrenoceptors in the striatum and spinal cord.
Supersensitivity in rat micro‐arteries after short‐term denervation
Authors: BENTZER P. , NIELSEN N. , ARNER M. , DANIELSEN N. , EKBLAD E. , LUNDBORG G. , ARNER A.
Published: October 2003

Contractile responses to phenylephrine and high‐K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short‐term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 μm) were obtained 10 days after surgery. Vessels from the non‐operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene‐related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high‐K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short‐term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic α‐receptors but also associated with changes in the cellular excitation‐contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
Glucocorticoid and ACTH regulation of rat peritoneal phagocyte chemiluminescence and nitric oxide production in culture
Authors: HAUGEN S. E. , WIIK P.
Published: October 2003

In order to study the adrenocortical regulation of monocyte/macrophage functions further, leucocytes from the rat peritoneum were incubated in vitro with glucocorticoid concentrations up to 10 μmol L−1 and with adrenocorticotropic hormone (ACTH) up to 100 μg mL−1. The monocyte/macrophage production of reactive oxygen molecules was measured by luminol amplified chemiluminescence, and the production of nitric oxide (NO) was measured as nitrite (NO2−). Dexamethasone in vitro in nanomolar concentrations inhibited monocyte/macrophage chemiluminescence and also nitric oxide production; the potency was dexamethasone > methylprodnisolone > prednisolone. ACTH enhanced both activated chemiluminescence and endotoxin‐induced nitric oxide production, but only at concentrations about 20–100 μg mL−1, and there was no significant effect of physiological concentrations. In summary, the results of the present study further confirm and substantiate that glucocorticoids in low pharmacological concentrations have a general inhibitory effect on monocyte/macrophage production of reactive oxygen molecules through the specific glucocorticoid receptors, while the stimulatory effect of ACTH is only observed by very high, non‐physiological concentrations. Furthermore, since low concentrations of glucocorticoids inhibited the production of these reactive oxygen molecules in vitro, indirect mechanisms involving hormones and other elements outside the immune system are not essential for the effect of glucocorticoids on monocytes/macrophages.
Assessment of renal function by 51Cr‐EDTA and endogenous creatinine clearances in the pig
Authors: PALNAES HANSEN C. , BIE P. , STADIL F.
Published: October 2003

In anaesthetized pigs, clearances of 51Cr‐EDTA (EDTA) and endogenous creatinine were compared with renal clearance of inulin measured during constant infusion after bolus injection. Creatinine was determined by enzymatic (Kodak Ektachem) as well as conventional (Jaffé) methods. In saline‐loaded pigs, renal clearance of constantly infused EDTA was 97.0 ± 6.7 mL min−1 and identical to the clearance of inulin (94.1 ± 9.1 mL min−1). There was good agreement between individual clearances. The extraction fractions of the two markers were indistinguishable (0.26 ± 0.02 and 0.28 ± 0.03, respectively). In other experiments the clearance of EDTA calculated from the first 4 h of the time course of the plasma concentration after single injection was 64.4 ± 3.7 mL min−1, correlating well with inulin clearance (63.0 ± 1.2 mL min−1). When calculated only from the monoexponential phase of the disappearance curve (`slope clearance'), significantly higher results were obtained (+33%, P < 0.001). Renal clearance of EDTA after single injection was 7.5 ± 1.5 mL min−1 (∼12%) lower than inulin clearance (P < 0.001). Values of creatinine clearances determined by the two analytical methods showed a poor agreement with inulin clearance. It is concluded that, in pigs, glomerular filtration rate may be estimated by the clearance of EDTA using constant infusion or single injection of EDTA and that the renal clearance of endogenous creatinine is a less useful a measure of GFR.
The activation pattern in normal humans during suppression, imagination and performance of saccadic eye movements
Authors: LAW I. , SVARER C. , HOLM S. , PAULSON O.B.
Published: October 2003

The distribution of activated cerebral regions was examined in nine normal subjects during four different eye movement‐related conditions: (1) fixation – fixation on a central light emitting diode; (2) saccadic suppression – fixation on a diode in the presence of flashing lateral targets; (3) reflexive/volitional saccades – performance of overt eye movements to two laterally lit targets and back to the centre; and (4) imagined saccades – imagining, but not performing, the same eye movements. The regional neural activity was measured indirectly using repetitive bolus injections of oxygen‐15‐labelled water and positron emission tomography (PET) to yield time‐integrated images of the normalized count distribution. These were aligned and anatomically normalized to a standard stereotactic space and the averages of each condition were analysed categorically using statistical parametric mapping. Compared to central fixation, reflexive/volitional saccades significantly activated regions in the classically known cortical oculomotor regions. The most notable activation during the saccade suppression task, compared to central fixation alone, was a bilateral activation of the parietal cortex with a right‐sided preponderance, activation of the supplementary eye field/caudal cingulate regions, and activation of frontal regions close to the frontal eye fields. Imagined performance of eye movements without overt eye movements activated the supplementary eye field and frontal eye fields identically to regions involved in overt eye movements, thus demonstrating that overt eye movements are not a prerequisite of the activation of these regions in normal humans.
Metabolite accumulation increases adenine nucleotide degradation and decreases glycogenolysis in ischaemic rat skeletal muscle
Authors: WELSH D.G. , LINDINGER M.I.
Published: October 2003

Adenine nucleotides and glycogen are degraded in skeletal muscle during no‐flow ischaemia. Past investigations have ascribed these metabolic changes to the severe energetic stress which arises with the removal of exogenous substrates (principally oxygen). We tested this hypothesis by measuring the high‐energy phosphagen and glycogen contents of stimulated rat hindlimb muscles (1 twitch s−1) prior to and following 40 min of no‐flow ischaemia or hypoxic perfusion without glucose (Pao2 = 4.6 ± 0.1 torr, plasma glucose = 0.3 ± 0.1 mmol L−1). Both experimental protocols eliminated exogenous substrate supply; however, the maintenance of flow during hypoxic perfusion ensured the removal of metabolic by‐products. A period of forty minutes of skeletal muscle ischaemia was characterized by reductions in the total adenine nucleotide pool, phosphocreatine and glycogen in the slow oxidative soleus, fast oxidative‐glycolytic plantaris and the fast glycolytic white gastrocnemius. Compared to ischaemia, the total adenine nucleotide pool was higher (by 7.2–13.3 μmol g−1 dry wt) and the glycogen content lower (by 10.0–16.6 μmol g−1 dry wt) in skeletal muscle exposed to hypoxic perfusion without glucose. The ability of hypoxic perfusion to attenuate TAN degradation and augment glycogenolysis can be attributed to metabolic by‐product removal. By limiting muscle lactate and PCO2 accumulation, hypoxic perfusion without glucose attenuates cellular acidification; this could in turn limit AMP deaminase activation and glycogen phosphorylase inhibition. We conclude that the ischaemia‐induced alterations in adenine nucleotide and glycogen metabolism arise in response to the elimination of exogenous substrates and to the accumulation of metabolic by‐products.
The adrenal medulla as a wet sponge: a role for the intramedullary venous vasculature?
Authors: LØNNING K. , CARMICHAEL S.W. , HELLE K.B.
Published: October 2003

Synchronous contractions in the intramedullary venous vasculature have been postulated to assist in the discharge of hormones from the stimulated adrenal medulla in a manner analogous to the squeezing of a wet sponge. This study reports on two experimental approaches to support the hypothesis that contractions in the venous vasculature may contribute to the hormonal efflux. Firstly, the bovine adrenal medulla was perfused retrogradely via the bovine central adrenomedullary vein and changes in the vascular volume were assessed as changes in wet weight of the perfused tissue. Stimulation with acetylcholine and carbachol resulted in repetitive, transient weight losses, suggesting cholinergically mediated reductions in the vascular volume. Secondly, the contractile properties of the longitudinal layers of smooth muscle cells in the intramedullary venous system were characterized, using the bovine central adrenomedullary vein as a model. The results showed that the longitudinal layers of this vein were, similarly to the circular layers, selectively contracted by endothelin‐1 via an ETA‐like receptor, by neuropeptide Y and by membrane depolarization (high K+). However, the vein was insensitive to electrical stimulation, acetylcholine and carbachol, as well as to catecholamines. These results suggest neuropeptide Y, released from the cholinergically stimulated chromaffin cells, as the most likely mediator of stimulus‐evoked synchronous contractions of the venous vasculature in the bovine adrenal medulla. Together, these experiments provide support for the `wet sponge' hypothesis for hormonal discharge from the adrenal gland.
Can reactive oxygen species precondition the isolated rat heart against arrhythmias and stunning?
Authors: TAKESHIMA S. , VAAGE J. , VALEN G.
Published: October 2003

Ischaemic preconditioning has cardioprotective effects. Reactive oxygen species may be possible mediators. The present study investigated whether low doses of exogenous hydrogen peroxide could mimic preconditioning in isolated, Langendorff‐perfused rat hearts. Hearts were subjected to two episodes of 3 min global ischaemia and 5 min reperfusion (n = 17), or were given 10 (n=15), 20 (n=10), 30 (n=20), 40 (n=18), 80 (n=17) or 160 μM (n=10) hydrogen peroxide for 10 min, followed by 10 min recovery, before 25 min global ischaemia and 60 min reperfusion, and compared with ischaemic controls of matching perfusion time (n=17 and n=23). Cardiac performance was assessed by heart rate, left ventricular systolic, end‐diastolic and developed pressures, and coronary flow. Severe reperfusion arrhythmias occurred frequently in control hearts, and was attenuated by ischaemic preconditioning. All hearts pretreated with 160 μM hydrogen peroxide had severe arrhythmias throughout reperfusion, while these were not seen in any heart perfused with 20 μM hydrogen peroxide (P< 0.01 compared to controls). Ischaemia and reperfusion induced a minor decrease in heart rate, left ventricular systolic and developed pressures, and increased end‐diastolic pressure. Ischaemic preconditioning attenuated the decrease of heart rate and the increase of end‐diastolic pressure, and increased coronary flow, while hydrogen peroxide did not significantly attenuate these changes. In conclusion, a low dose of exogenous hydrogen peroxide before global ischaemia inhibited severe reperfusion arrhythmias, but had no other protective effects. The present work does not suggest that reactive oxygen species are important mediators of the preconditioning effects on stunning and arrhythmias in the rat heart.
Effect of alveolar hypoxia on segmental pulmonary vascular resistance and lung fluid balance in dogs
Authors: WELLING K.‐L. K. , SANDER M. , RAVN J. B. , LARSEN B. , ABILDGAARD U. , AMTORP O.
Published: October 2003

In a biventricular bypass preparation with constant‐flow perfusion, pulmonary arterial pressure (Ppa), average pulmonary capillary pressure (Ppc), venous pressure (Pv), extravascular lung water volume (EVWd) and capillary permeability‐surface area product for urea (PS) were determined in control animals and in animals subjected to alveolar hypoxia. During hypoxia, Ppa increased in a biphasic manner, the site of hypoxic pulmonary vasoconstriction being located in the arterial upstream segment. At baseline, Ppc values were identical in control and experimental animals (3.4 ± 0.4 vs. 3.6 ± 0.2 mmHg). During 150 min of airway hypoxia, the rise in Ppc (5.1 ± 0.3mmHg) did not exceed the rise in Ppc (4.9 ± 0.5mmHg) recorded in control animals at same time interval during normoxic ventilation. EVWd increased during hypoxia to values significantly higher than those obtained in control animals (0.559 ± 0.036 vs. 0.466 ± 0.027 mL water g−1 lung). PS remained unchanged at baseline level throughout experiments in both groups of animals. Present data suggest that lung oedema formation during alveolar hypoxia may be caused by increased transcapillary fluid loss preferentially through transcellular hydraulic pathways in capillary endothelial cells.
Intramuscular EMG from the hip flexor muscles during human locomotion
Authors: ANDERSSON E.A. , NILSSON J. , THORSTENSSON A.
Published: October 2003

The purpose was to investigate the activation pattern of five major hip flexor muscles and its adaptation to changing speed and mode of progression. A total of 11 healthy subjects performed walking and running on a motor‐driven treadmill at speeds ranging from 1.0 to 6.0 m s−1. Intramuscular fine‐wire electrodes were used to record myoelectric signals from the iliacus, psoas, sartorius, rectus femoris and tensor fascia latae muscles. The basic pattern, with respect to number of activation periods, remained the same irrespective of speed and mode of progression. However, differences in the relative duration and timing of onset of activation occurred between individual muscles. Over the speed range in walking, a progressively earlier onset was generally seen for the activation period related to hip flexion. Changes in EMG amplitude were measured in the iliacus and psoas muscles and showed a marked increase and difference between walking and running at speeds above 2.0 m s−1. Thus, the alternating flexion–extension movements at the hip during locomotion appear to be governed by a rather fixed `neural program' which normally only needs minor modulations to accomplish the adjustments accompanying an increase in speed of progression as well as a change from walking to running.
Importance of nitric oxide in hepatic arterial blood flow and total hepatic blood volume regulation in pigs
Authors: GRUND F. , SOMMERSCHILD H. T. , WINECOFF A. , UJHELYI M. R. , TØNNESSEN T. , KIRKEBØEN K. A. , RUTLEN D. L. , ILEBEKK A.
Published: October 2003

The importance of nitric oxide in regulating basal arterial blood flow has been examined in several different vascular beds by intra‐arterial infusion of inhibitors of nitric oxide synthesis, but not in the arterial vascular bed of the liver. In the present study, NG‐nitro‐L‐arginine (L‐NNA), in a dose of 0.5 and 1.0 μmol mL−1 of hepatic arterial blood flow, was infused for 5 min into the hepatic artery in seven pigs anaesthetized with pentobarbital sodium. The haemodynamic effects observed by the first infusion were not further enhanced by the second infusion. Hepatic arterial resistance increased by 143 ± 38% and hepatic arterial blood flow declined by 38 ± 10%. A systemic effect due to `spillover' was observed, as evidenced by an increase in mean aortic blood pressure of 24 ± 4 mmHg. However, no significant increase in arterial mesenteric resistance was observed and total liver blood flow remained unchanged. Hepatic arterial vasodilation in response to occlusion of the portal vein, the arterial buffer response, remained intact after inhibition of nitric oxide synthesis. Liver lobe thickness, measured by an ultrasonic technique,was not found to change with inhibition of arterial nitric oxide synthesis, excluding a significant direct effect of arterial nitric oxide on liver capacitance. In conclusion, nitric oxide is an important regulator of hepatic arterial resistance, but does not mediate the hepatic arterial buffer response and was not found to play any significant role in total hepatic capacitance regulation.
Time‐dependent effects of ischaemia on neuropeptide Y mechanisms in pig renal vascular control in vivo
Authors: MALMSTRÖM R.E. , LUNDBERG J.M.
Published: October 2003

We have investigated the effects of ischaemia on neuropeptide Y (NPY) mechanisms involved in sympathetic vascular control of the pig kidney in vivo. Reperfusion after 2 h of renal ischaemia was associated with local overflow of noradrenaline (NA) but not of NPY‐like immunoreactivity (‐LI). Renal sympathetic nerve stimulation 10 min into reperfusion evoked markedly reduced vasoconstrictor effects and significantly less overflow of NA (reduced by 70% from the pre‐ischaemic conditions), whereas NPY‐LI overflow was unaltered. Renal vasoconstrictor responses to exogenous peptide YY (PYY), phenylephrine and angiotensin II were strongly attenuated after this ischaemic period, while vasoconstriction to α,β‐methylene ATP was maintained to a larger extent. The renal vascular responses and NA overflow had become partially normalized within a 2 h recovery period. In contrast, the renal vasoconstrictor response and the overflow of NPY‐LI upon sympathetic nerve stimulation were enhanced after 15 min of renal ischaemia. In parallel, the PYY‐evoked renal vasoconstriction was selectively and markedly prolonged after the 15 min of ischaemia. In the presence of the NPY Y1 receptor antagonist BIBP 3226, the augmented vascular response to nerve stimulation was significantly attenuated. We conclude that reperfusion after 2 h of renal ischaemia is associated with local overflow of NA, whereas the sympathetic nerve‐evoked release of NA and the reactivity of the renal vasculature to vasoconstrictor stimuli are reversibly reduced. Furthermore, possibly due to an impaired local degradation, the role of neurogenically released NPY in renal sympathetic vasoconstriction is enhanced after short‐term (15 min) ischaemia compared with control conditions.
Enzyme adaptations of human skeletal muscle during bicycle short‐sprint training and detraining
Authors: LINOSSIER M.‐T. , DORMOIS D. , PERIER C. , FREY J. , GEYSSANT A. , DENIS C.
Published: October 2003

The effect of sprint training and detraining on supramaximal performances was studied in relation to muscle enzyme adaptations in eight students trained four times a week for 9 weeks on a cycle ergometer. The subjects were tested for peak oxygen uptake (V˙O2 peak), maximal aerobic power (MAP) and maximal short‐term power output (W˙max) before and after training and after 7 weeks of detraining. During these periods, biopsies were taken from vastus lateralis muscle for the determination of creatine kinase (CK), adenylate kinase (AK), glycogen phosphorylase (PHOS), hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and its isozymes, 3‐hydroxy‐acyl‐CoA dehydrogenase (HAD) and citrate synthase (CS) activities. Training induced large improvements in W˙max (28%) with slight increases (3%) in V˙O2 peak} (P < 0.10). This was associated with a greater glycolytic potential as shown by higher activities for PHOS (9%), PFK (17%) and LDH (31%) after training, without changes in CK and oxidative markers (CS and HAD). Detraining induced significant decreases in V˙O2 peak (4%), MAP (5%) and oxidative markers (10–16%), while W˙max and the anaerobic potential were maintained at a high level. This suggests a high level in supramaximal power output as a result of a muscle glycogenolytic and glycolytic adaptation. A long interruption in training has negligible effects on short‐sprint ability and muscle anaerobic potential. On the other hand, a persistent training stimulus is required to maintain high aerobic capacity and muscle oxidative potential. This may contribute to a rapid return to competitive fitness for sprinters and power athletes.
Changes in maximal exercise ventilation and breathing pattern in boys during growth: a mixed cross‐sectional longitudinal study
Authors: PRIOUX J. , RAMONATXO M. , MERCIER J. , GRANIER P. , MERCIER B. , PREFAUT C.
Published: October 2003

The aim of this mixed cross‐sectional longitudinal study covering a total age range of 11–17 years, i.e. the entire pubertal growth period, was (1) to specify the changes in maximal breathing pattern during incremental exercise; (2) to determine what parts of the changes are due to anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength; and (3) to determine if the role of these variables is identical before, during and after pubertal growth spurt. This study was conducted in 44 untrained schoolboys separated into three groups, with an initial age of 11.2 ± 0.2 years for group A, 12.9 ± 0.25 years for group B, and 14.9 ± 0.26 years for group C. These children were subsequently followed for 3 years, during the same time period each year. The maximal inspiratory and expiratory pressures (PI max and PE max) were used as an index of the respiratory muscle strength. During an incremental exercise test, maximal ventilation (V˙E max), tidal volume (VT max), breathing frequency (fmax), inspiratory and expiratory times (tI max and tE max) and mean inspiratory flow (VT/tI max) were measured at maximal oxygen uptake (V˙O2max). Our study showed that there was a marked increase with age in V˙E max, VT max, and VT/tI max , and no significant changes in fmax, tI max and tE max. PI max and PE max showed a general trend towards an increase between 11 and 17 years. The study of the linear correlations between maximal breathing pattern and the anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength showed that, in the three groups of children, (1) lean body mass was the major determinant of V˙E max, VT max and VT/tI max and the relationships were significantly different before, during and after the pubertal growth spurt; (2) physical fitness was the main determinant of tI max, tE max and fmax before and after the pubertal growth spurt; and (3) maximal respiratory strength did not play a significant role. In conclusion, this mixed cross‐sectional longitudinal study showed, at maximal exercise, a significant increase in V˙E max during growth due only to a significant increase in VT max and VT/tI max, and that the relationships of anthropometric characteristics and physical fitness with maximal breathing pattern change during growth.
Differential titin isoform expression in human skeletal muscle
Authors: FRY A.C. , STARON R.S. , JAMES C.B.L. , HIKIDA R.S. , HAGERMAN F.C.
Published: October 2003

Mammalian skeletal muscle expresses at least two isoforms of the cytoskeletal protein titin (connectin; MW ≈ 3000 kDa). These isoforms are associated with different passive force curves, and thus may affect physical performance. To study the distribution of titin and its possible influence on performance in humans, muscle biopsies were obtained from 15 males (X± SE; age = 25.4 ± 2.9 years, height = 177.7 ± 1.8 cm, weight = 76.5 ± 2.2 kg). Two biopsies were obtained on separate occasions from both the right and left vastus lateralis, and one biopsy each from the lateral head of the right gastrocnemius and the right soleus, with all biopsies handled identically. Fibre type analyses were performed via mATPase histochemistry. Expression of titin and myosin heavy chain isoforms were determined by SDS‐PAGE. Titin bands in the resulting gels were highly repeatable and were verified by migration patterns, as well as Western blot analysis. Two groups of subjects were identified: group 1 (n=10) expressed only one titin isoform (titin‐1) in all biopsies, and group 2 (n=5) expressed two titin isoforms (titin‐1 and titin‐2) in all biopsies. No significant differences (P> 0.05) between groups were observed for percentage fibre types, percentage fibre type areas, fibre type cross‐sectional areas, and percentage myosin heavy chain expression when comparing individual muscles, sampling times or bilateral comparisons. This is the first report of differential titin isoform expression in healthy, mature human skeletal muscle, but it is not clear why this occurs or what influence this may have on performance.
Lysosomal and cytosolic pH as regulators of exocytosis in mouse macrophages
Authors: SUNDLER R.
Published: October 2003

Lysosomal secretion in macrophages may be triggered by any agent that causes a rise in lysosomal pH, i.e. lysosomotropic amines, H+‐ionophores or inhibitors of vacuolar type H+‐ATPase. Rises in lysosomal pH and secretion are also triggered upon interaction with yeast‐derived zymosan particles. The molecular mechanism for this latter lysosomal alkalinization is not known. Lysosomal secretion is also modulated by changes in cytosolic pH, being somewhat enhanced by cytosolic alkalinization and severely inhibited by cytosolic acidification. These effects are not mediated via changes in lysosomal pH. In addition, a critical, permissive effect on the secretory response is exerted by a protein phosphorylation cascade mediated via protein kinase C. Even its basal activity appears to exert a permissive effect, but stimulation by phorbol ester leads to a synergistic increase in lysosomal secretion. Also, the potent inhibition of lysosomal secretion that develops over many hours of exposure to dexamethasone appears to be due to attenuated signalling via protein kinase C and is partly overcome by phorbol ester stimulation.
The effect of angiotensin AT1 receptor blockade in the brain on the maintenance of blood pressure during haemorrhage in sheep
Authors: MATHAI M.L. , PENNINGTON G.L. , MCKINLEY M.J.
Published: October 2003

The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT1 receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg−1 body wt). Losartan (1 or 0.33 mg h−1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 ± 0.84 mL kg−1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h−1 caused an early onset of the decompensation phase after only 9.8 ± 0.8 mL kg− 1 of blood loss compared with control. Intravenous infusion of losartan (1 mg h−1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 ± 1.0 mL kg−1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT1 receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h−1 caused an early onset of the decompensation phase during haemorrhage at 11.06 ± 0.91 mL kg−1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT1‐receptor‐mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.
Effects of adenosine on ex vivo filtragometry platelet aggregation in relation to plasma levels
Authors: JONZON B. , KARLBERG K. E. , QUERROL‐FERRER V. , SYLVÉN C.
Published: October 2003

The aim of the present study was to investigate the concentration effect of adenosine on unstimulated platelet aggregation in humans. Adenosine infusion was given intravenously to 12 volunteers in the antecubital vein with infusion rates increasing from 20 to 100 μg kg−1 min−1. Filtragometry measurements were obtained from the contralateral antecubital vein before and during 100 μg kg−1 min−1 or during maximal tolerable infusion rate. In another set of experiments with 10 volunteers, basal filtragometry measurements were obtained before and after infusion of various concentrations of adenosine into the filtragometer test unit. With intravenous infusion aggregation time tended to increase from 333±42 to 418±8 s (mean±SEM) and increased the venous plasma adenosine concentration from 0.42±0.09 μM to 1.52±0.38 μM. Adenosine infusion into the filtragometer tubing system dose‐dependently inhibited aggregation (P<0.05). Adenosine was rapidly eliminated with a half‐life of adenosine in the filtragometry tubing system calculated to be about 6 s. These data extend our knowledge from an in vitroto an ex vivo situation that adenosine dose‐dependently has a platelet antiaggregatory effect.
Skeletal muscle of trained and untrained paraplegics and tetraplegics
Authors: SCHANTZ P. , SJÖBERG B. , WIDEBECK A.‐M. , EKBLOM B.
Published: October 2003

The effect of physical conditioning on skeletal muscle of individuals with spinal cord injuries (SCI) has been investigated. The anterior portion of the deltoid muscle (active in wheel‐chair propulsion) of untrained and endurance‐trained paraplegics and tetraplegics, as well as that of untrained able‐bodied subjects, was studied. The characterization involved fibre type distribution, capillarization, fibre areas and also oxidative and glycolytic enzyme levels. A general trend towards a successively higher proportion of type I fibres and lower proportion of type IIB fibres was noted in the order of able‐bodied subjects (type I, 42%; type IIB, 41%, n=8), paraplegics (type I, 57%; type IIB, 13%, n=13) and tetraplegics (type I, 74%; type IIB, 4.5%, n=11). The trained SCI groups had significantly higher levels of the citric acid cycle marker enzyme citrate synthase (34% and 63%) than the untrained SCI groups and able‐bodied subjects, respectively. The glycolytic marker enzyme 6‐phosphofructokinase was 32% lower in the tetraplegic groups than in the other groups. In contrast, the fatty acid oxidation marker enzyme 3‐hydroxyacyl‐CoA dehydrogenase was markedly higher in the tetraplegic group than in the able‐bodied subjects (58%) and tended to be higher (21%, P<0.1) than in the paraplegic group. The trained SCI groups displayed significantly higher (28%) levels of capillaries per fibre than the untrained SCI groups, which had about the same levels as the untrained able‐bodied subjects. It is concluded that several of the findings are in line with normal muscular adaptation, whereas others are unexpected and support a hypothesis that some of the findings might be due to differences between the groups in, for instance, hormone levels or in types of muscular load.
Stimulation‐induced calcium signalling and ion transport in rat pancreatic acini
Authors: GROMADA J. , JØRGENSEN N. K. , NAUNTOFTE B. , DISSING S.
Published: October 2003

In the present study we have characterized receptor‐mediated Ca2+ signalling patterns as well as Ca2+‐mediated ion transport mechanisms in collagenase isolated rat pancreatic acini. Measurements of the initial Ca2+ response to maximal carbachol stimulation revealed a rapid increase in [Ca2+]i, which, in general, occurred synchronously throughout the cells. Less frequently, not all cells in the acinus responded to carbachol, but did respond to subsequent stimulation with bombesin, indicating that not all cells possess receptors for all the applied agonists. In view of the heterogeneity in the agonist‐evoked Ca2+ responses, ionomycin was used to assess the role of Ca2+ in activating K+, Na+ and Cl‐ transport mechanisms. Ionomycin induced a rise in [Ca2+]i, thereby increasing Cl‐ permeability as well as stimulating K+ efflux, probably through non‐specific cation channels. However, the resting K+ efflux was insensitive to blockers of non‐specific cation channels, indicating the existence of a selective resting K+ conductance. Ionomycin also stimulated influx of Na+, which in part was mediated by non‐specific cation channels. The changes in ion fluxes measured in the present study revealed that when [Ca2+]i is raised in rat pancreatic acini, they gain Na+ and Cl‐ and lose K+, with non‐specific cation channels being essential for this process.
Lung distension and carbon dioxide affect pulmonary nitric oxide formation in the anaesthetized rabbit
Authors: STRÖMBERG S. , LÖNNQVIST P. A. , PERSSON M. G. , GUSTAFSSON L. E.
Published: October 2003

Positive end‐exspiratory pressure (PEEP) and nitric oxide (NO) can influence lung VA/Q‐matching and pulmonary vascular resistance, and application of PEEP can increase exhaled NO in animals. To obtain a better understanding of these mechanisms, we examined how different types of ventilation or changes in CO2 affect the formation of endogenous NO. Exhaled NO in pentobarbital‐anaesthetized rabbits was monitored by chemiluminescence. The animals were enclosed in a chamber and subjected to various modes of positive as well as negative pressure ventilation which was adjusted to induce similar changes in functional residual capacity (FRC) with maintained ventilatory rate and tidal volume. In addition, stepwise increase in FiCO2 (1.0–10%) was studied. Negative extrathoracic end‐exspiratory pressure during negative extrathoracic pressure ventilation produced an increase in NO production similar to that of positive end‐exspiratory pressure during positive pressure ventilation, the increase consisting of an initial peak followed by a plateau. The faster the FRC was increased, the higher was the initial peak in NO. The greater the increase in FRC, the higher was the plateau NO concentration. Increased FiCO2 caused a dose‐dependent reduction in exhaled NO. The observations of lung distension effects on exhaled NO suggest the possibility of stretch‐receptors or ‐receptive mechanisms coupled to NO formation within the lung. In addition, NO formation in the lung is influenced by CO2 in a reciprocal fashion.
Effects of 1,1‐dimethylguanidine administration on blood pressure, heart rate and renal sympathetic nerve activity in normotensive and spontaneously hypertensive rats
Authors: ZHANG W. , PETTERSSON A. , THORÉN P. , HEDNER T.
Published: October 2003

1,1‐dimethylguanidine (DMG) is an endogenous nitric oxide (NO) synthesis inhibitor. This study investigates the effects of exogenous DMG administration, in anaesthetized spontaneously hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY). Mean blood pressure (MBP), heart rate (HR) and renal sympathetic nerve activity (SNA) were recorded in 12‐ to 14‐week old, anaesthetized SHR and WKY. Each rat received increasing bolus injections of DMG intravenously (1.03, 2.05, 6.39, 20.45 and 51.15 mg kg‐1). In separate experiments, SHR received L‐arginine or D‐arginine in a dose of 300 mg kg‐1 followed by DMG at 6.39 mg kg‐1. Thirty minutes later they received the same doses of the respective arginines followed by DMG at 20.45 mg kg‐1. DMG induced dose‐dependant increases in MBP in SHR and WKY. In SHR, HR increased with increasing doses of DMG (except at the near‐toxic doses of 51.15 mg kg‐1), whereas in WKY, HR decreased with increasing doses of DMG. The net change of renal SNA ranged from ‐5±3 to ‐55±12% in SHR and from ‐6±8 to ‐66±8% in WKY. Pre‐treatment with L‐arginine in SHR partly inhibited the pressor effect and attenuated the inhibition of renal SNA induced by DMG, but had little effect on HR. Thus the administration of NO inhibitor DMG could alter cardiovascular function and sympathetic nerve activity, and subsequently resulted in tachycardia in SHR and bradycardia in WKY.
Mechanisms of cutaneous vasoconstriction during upright posture
Authors: VISSING S. F. , SECHER N. H. , VICTOR R. G.
Published: October 2003

The cutaneous circulation is thought to participate in the neurocirculatory adjustments during orthostatic stress, but the underlying mechanisms mediating such reflex cutaneous vasoconstriction are poorly understood. The aim of this study was to assess the relative importance of baroreceptor (cardiopulmonary and arterial) and positional (vestibular, exercise, veno‐arteriolar and myogenic) reflexes in triggering cutaneous vasoconstriction during upright posture.

First, hypotensive lower body negative pressure (LBNP) was compared with actual postural changes to assess the relative contributions of baroreceptor reflexes and positional reflexes. Then changes in body position were compared with changes in limb position in the absence or presence of proximal (axillary) or distal (local cutaneous) nerve blocks, to assess the relative contributions of vestibular, exercise, veno‐arteriolar and myogenic reflexes. Skin sympathetic nerve activity was determined by microneurography, and skin blood flow was determined by laser Doppler velocimetry.

LBNP of –50 mmHg (cardiopulmonary + arterial baroreceptors) had no effect on skin sympathetic nerve activity or skin vascular resistance. In contrast, an upright posture with the arms dependent (baroreceptor+vestibular+exercise+veno‐arteriolar reflexes) caused a two‐ to threefold increase in skin vascular resistance. In the supine position, passive movement of the arm into a dependent position to activate veno‐arteriolar reflexes alone evoked an increase in skin vascular resistance which approximated the response to normal upright posture.

Blocking central sympathetic nerve impulses by application of an axillary blockade did not influence the cutaneous vasoconstrictor response to an upright posture or changes in limb position. In contrast, application of a distal nerve block by local cutaneous surface anaesthesia completely blocked vasoconstrictor responses evoked by these manoeuvres.

In conclusion, these experiments in human subjects identify a primary role for veno‐arteriolar reflexes in triggering vasoconstriction in the cutaneous circulation during upright posture.
Long‐lasting coronary vasoconstrictor effects and myocardial uptake of endothelin‐1 in humans
Authors: PERNOW J. , AHLBORG G. , LUNDBERG J. M. , KAIJSER L.
Published: October 2003

The effect of intravenous administration of the endothelium‐derived vasoconstrictor peptide endothelin‐1 (ET‐1 0.2, 1 and 8 pmol kg−1 min−1) on coronary blood flow in relation to plasma ET‐1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET‐1 elevated arterial plasma ET 35‐fold, dose‐dependently increased mean arterial blood pressure from 95±5 mmHg to 110±6 mmHg (P<0.01) and reduced heart rate from 64±4 beats min−1 to 58±4 beats min−1 (P<0.05) at 8 pmol kg−1 min−1. Coronary sinus blood flow was reduced maximally by 23±4% (P<0.01) and coronary vascular resistance increased by 48±11% (P<0.01). Coronary sinus oxygen saturation decreased from 35±1% to 22±2% at 2 min after the infusion (P<0.01). A coronary constrictor response was observed at a 4‐fold elevation in plasma ET. The reduction in coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET‐1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24±3% over the myocardium (P<0.05). The results show that ET‐1 induces long‐lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4‐fold elevation in plasma ET‐1. Furthermore, there is a net removal of circulating ET‐1 by the myocardium.