bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelium‐dependent relaxation and effects of prostacyclin, endothelin and platelet‐activating factor in human hand veins and arteries
Authors: ARNER M. , HÖGESTÄTT E. D.
Published: December 2008

An altered release of endothelium‐derived vasoactive factors has been implicated in several vasospastic conditions. Since the functional role of the endothelium in the hand vasculature is largely unknown, we examined the effects of ‘endothelial removal’ on vascular reactivity, and the effects of some ‘endothelium‐associated’ substances in isolated human hand veins and arteries. Acetylcholine induced a large relaxation (Emax= 97±1 %) in precontracted hand arteries. The relaxation was abolished by endothelial removal. In hand veins, acetylcholine induced a small relaxation (Emax= 13 ± 4%), which was unaffected by endothelial removal. An endothelium‐dependent relaxation was, however, obtained with high concentrations ( 10‐6mol 1‐1) of the Ca2+ionophore A23187. Contractile responses to noradrenaline, serotonin and prostaglandin F2xdid not differ between vein segments with and without endothelium. Endothelin was a potent constrictor of both veins and arteries. The potency and maximum response did not differ between the two types of vessel. Indomethacin pretreatment of veins did not influence the endothelin‐induced contractions, suggesting that cyclo‐oxygenase products are not involved in the response. In endothelin‐contracted veins and arteries, the prostacyclin analogue iloprost elicited relaxation of similar potency and amplitude. The maximum relaxation in veins was, however, 3 times larger than that produced by prostacyclin itself. Platelet‐activating factor was devoid of contractile and relaxant effects in both veins and arteries. The present study indicates differences between human hand veins and arteries regarding endothelial‐dependent relaxation, and suggests that the modulatory role of endothelium‐derived relaxing factor(s) is small in hand veins. The contractile and relaxant effects of endothelin and iloprost, however, did not differ between veins and arteries.
Lesions of bulbo‐spinal serotonergic or noradrenergic pathways reduce nociception as measured by the formalin test
Authors: TJØLSEN A. , BERGE O.‐G. , HOLE K.
Published: December 2008

Intrathecal administration of the neurotoxins 5,6‐dihydroxytryptamine (5,6‐DHT) and 6‐hydroxydopamine (6‐OHDA) in rats selectively lesioned the descending spinal serotonergic and noradrenergic pathways, respectively. Four days after neurotoxin administration the behaviour was evaluated in the formalin test. Several behavioural variables were recorded. The statistical analysis of the results was supplemented using a multivariate statistical method (partial least squares projection to latent variables, PLS) in addition to traditional analysis of variance. The described methods for recording and statistical analysis of behaviour appear to be useful in describing druginduced differences in behavioural patterns in the formalin test. Both types of lesion reduced the pain‐related behaviour in the formalin test (protection of the paw, biting and licking). The results indicate that the descending monoaminergic pathways are parts of a network which maintains adequate nociceptive responses to a chemical stimulus, or to stimuli lasting several minutes, as in the formalin test.
Vascular smooth muscle sensitivity to noradrenaline is reduced during an infection with trypanosoma brucei in rats and rabbits
Authors: KHASAR S. , ORIOWO M. A.
Published: December 2008

α1‐adrenoceptor sensitivity to noradrenaline has been studied in some arterial smooth muscles of rats and rabbits infected withT. brucei. In rabbits, a decrease in sensitivity of the arterial smooth muscles to noradrenaline was observed in the thoracic aorta, central ear but not renal arteries. No change in the sensitivity of the smooth muscles to histamine was observed. In rats, noradrenaline potency was reduced in the aorta, renal but not tail arteries. In both species, affinity of noradrenaline for a,‐adrenoceptors was significantly (P< 0.05) reduced in arteries where the potency of noradrenaline was reduced. PrazosinKBvalues in infected animals were significantly (P< 0.05) lower than controls. These results are interpreted to suggest either an alteration in the structure of a,‐adrenoceptors during an infection, or accumulation of some factor(s) in the receptor microenvironment that modulated binding of agonists and antagonists to the receptors during an infection withT. brucei. The possible role of reduced α1‐adrenoceptor affinity in the hypotension observed during an infection withT. bruceiis discussed.
Effect of immobilization on carbonic anhydrase lll and myoglobin content in human leg muscle
Authors: VIRTANEN P. , VAANANEN H. K. , PASANEN L. , LÄHDE S. , PURANEN J. , TAKALA T. E. S.
Published: December 2008

Carbonic anhydrase III and myoglobin concentrations were measured from vastus medialis muscle samples before and 6 weeks after postoperative leg immobilization following knee ligament reconstruction. Seven patients were immobilized with conventional cast so that the knee joint was fixed at 20° flexion. Seven other patients used braces allowing a motion of 30–70°. The atrophy of the medial part of musculus quadriceps was estimated by computer tomography. No difference in carbonic anhydrase III and myoglobin concentrations or muscle atrophy between the cast and brace groups was observed. The cross‐sectional area of the medial part of musculus quadriceps decreased 38% during immobilization. The specific concentrations of carbonic anhydrase III and myoglobin remained unaltered. Due to the remarkable postoperative atrophy of the muscle the total carbonic anhydrase III and myoglobin contents, however, decreased significantly (37% and 31%, respectively). The results suggest that the net breakdown of carbonic anhydrase III and myoglobin during disuse atrophy occur at the same rate as the average net degradation of mixed muscle proteins and that the process is independent of the immobilization procedure.
Calcitonin gene‐related peptide (CGRP) and leg vascular resistance during head‐up tilt induced hypovolaemic shock in man
Authors: MATZEN S. , SCHIFTER S. , RADVANSKY J. , KNIGGE U. , WARBERG J. , SECHER N. H.
Published: December 2008

Calcitonin gene‐related peptide is a potent vasodilator and its distribution in perivascular nerves suggests a role in the regulation of vascular tone. We evaluated leg vascular resistance together with total peripheral resistance and the arterial plasma concentrations of calcitonin gene‐related peptide and catecholamines during 50° head‐up tilt induced hypotension in 7 males. During tilt mean arterial pressure, heart rate, total peripheral resistance, leg vascular resistance and plasma noradrenaline increased, while cardiac output and leg blood flow decreased. After 45±9min (mean ± SE) presyncopal symptoms appeared together with decreases in mean arterial pressure (81 ± 6 to 56 ± 9 mmHg), heart rate (97 ± 6 to 73 ± 8 beats min‐1), leg vascular resistance (158 ± 9 to 109 ± 8 mmHg min 1‐1) and total peripheral resistance (17 ± 3 to 10 ± 2 mmHg min 1‐1) (P< 0.01). Plasma calcitonin gene‐related peptide increased from 32 ± 3 to 35±3pmo111(P<0.01) and adrenaline from 1.1 ± 0.2 to 1.7±0.3 nmol 1‐1(P< 0.01), while noradrenaline did not change. The results indicate that presyncopal symptoms induced by head‐up tilt are associated with regional as well as total decreases in vascular resistance accompanied by moderate increases in arterial plasma concentrations of calcitonin gene‐related peptide and adrenaline.
Hypovolaemia inhibits acid‐induced alkaline transport in the rat duodenum via an alpha‐2 adrenergic mechanism
Authors: JÖNSON C. , HAMLET A. , FÄNDRIKS L.
Published: December 2008

Acid exposure of the duodenal mucosa is a well‐known stimulant of the mucosal alkaline secretion. We have previously reported that a minor blood loss inhibits this secretory increment via activation of the splanchnic nerves. In the present study the pharmacological characteristics of the splanchnic neural inhibition of the alkaline secretion were investigated. Duodenal HCO‐3secretion was measured byin‐situtitration in chloralose‐anaesthetized rats. Exposure of the duodenal mucosa to hydrochloric acid (0.01 m, 5 min) increased the secretion by approximately 60%. A 10% decrease in blood volume simultaneously to the luminal acidification abolished the secretory increase, as previously reported. Treatment with either guanethidine or yohimbine blocked the bleeding‐induced inhibition of the secretion after acid‐exposure. Neither prazosin nor propranolol did prevent such hypovolaemia‐induced inhibition of duodenal alkaline secretion. The present results suggest that the splanchnic neural inhibition of acid‐induced duodenal HCO‐3secretion is mediated via adrenergic nerve fibres and alpha‐2 adrenoceptors.
Cholecystokinin‐stimulated insulin secretion and protein kinase C in rat pancreatic islets
Authors: KARLSSON S. , AHRÉN B.
Published: December 2008

In isolated rat pancreatic islets, the possible involvement of protein kinase C in cholecystokinin‐8‐stimulated insulin secretion was investigated. In islets exposed for 24 hours to the phorbol ester 12‐O‐tetradecanoyl phorbol 13‐acetate (500 nmol l‐1), a procedure known to down‐regulate islet protein kinase C‐activity, the insulinotropic effect of cholecystokinin‐8 (10‐7 mol l‐1) was partially reduced (by 34 ± 8%, P < 0.001). In contrast the insulinotropic response to acute exposure to 12‐O‐tetradecanoyl phorbol 13‐acetate (10‐6 mol l‐1) was totally abolished (P < 0.001), whereas the insulin response to glucose (8.3 mmol 1‐l) was not affected. In normal islets, the protein kinase C‐inhibitor, staurosporine, inhibited 12‐O‐tetradecanoyl phorbol 13‐acetate‐ and glucose‐stimulated insulin secretion (P < 0.01), but was without effect on cholecysto‐kinin‐8‐stimulated insulin release. Furthermore, in normal islets, cholecystokinin‐8 had no effect on insulin release at a low glucose level (3.3 mmol l‐1). However, at this low glucose level, cholecystokinin‐8 clearly potentiated insulin release induced by acute exposure to 12‐O‐tetradecanoyl phorbol 13‐acetate (lo‐8— 10‐6 mol l‐1, P < 0.001). This potentiating effect was abolished by the removal of extracellular Ca2+.

It is concluded that the insulinotropic effect of cholecystokinin‐8 in rat islets is partially mediated by the protein kinase C pathway. Furthermore, the lack of effect of cholecystokinin‐8 on insulin secretion at a low glucose level might be explained by an insufficient activation of protein kinase C under these conditions.
Different metabolic regulation by adenosine in omental and subcutaneous adipose tissue
Authors: VIKMAN H.‐L. , RANTA S. , KIVILUOTO T. , OHISALO J. J.
Published: December 2008

Adenosine content was higher in omental adipose tissue (0.91±0.13nmol g‐1 of wet weight; mean ± S.E.M.) than in abdominal subcutaneous adipose tissue (0.42 ± 0.08 nmol g‐1 of wet weight) in rapidly frozen surgical biopsy samples taken from ten patients undergoing elective abdominal surgery. This difference was statistically significant (P < 0.002). The sensitivity of isoprenaline‐stimulated lipolysis to inhibition by N6‐(phenylisopropyl)adenosine was studied in omental and abdominal subcutaneous adipocytes isolated from nine patients. The effect of this adenosine R,‐site agonist was less pronounced in omental than in abdominal subcutaneous adipocytes which could be due to a desensitization phenomenon. This difference was statistically significant (P= 0.012). The ratio of the inhibitory guanine nucleotide binding proteins Gi1 and Gi2 to the corresponding stimulatory protein Gs was the same in plasma membranes prepared from omental and abdominal subcutaneous adipocytes. In conclusion, in omental adipose tissue, adenosine content is higher and the response to this nucleoside is less pronounced than in subcutaneous adipocytes. This difference cannot be explained by a different (Gi1 + Gi2)/Gs ratio.
GABA, receptor mediated fast synaptic inhibition in the rabbit brain‐stem respiratory system
Authors: SCHMID K. , BOHMER G. , GEBAUER K.
Published: December 2008

The involvement of GABA mediated neurotransmission in the central control of respiration was investigated by administration of the specific GABA, receptor agonist muscimol and the specific GABA, receptor antagonist bicuculline into the fourth cerebral ventricle of the rabbit. Cycle‐triggered averaging of the phrenic nerve activity (PNA) was used to quantify drug‐induced changes of the central respiratory pattern. Muscimol reduced the peak amplitude of PNA and increased the duration of the respiratory phases. High amounts of muscimol led to a long‐lasting but reversible central apnea.

Bicuculline very effectively blocked the effects of externally applied muscimol. Blockade of intrinsically active GABAergic neurotransmission by bicuculline resulted in a multitude of effects. Peak amplitude of PNA increased whereas the duration of both inspiration and expiration decreased. In this respect, effects of bicuculline and muscimol were complementary. Bicuculline reduced the slope of the inspiratory ramp, increased postinspiratory activity and induced an augmenting type of discharge activity in the last part of expiration resulting in a smooth transition between expiration and inspiration. In some cases the respiratory modulation was completely lost and PNA became perfectly tonic. This ‘apneustic’ type of respiratory pattern could be transformed into rhythmic breathing by increasing the respiratory drive.

We conclude that neurotransmission via GABA, receptors is important for the maintenance of respiratory rhythm as well as the generation of normal respiratory pattern.
Dependence of the mean power frequency of the electromyogram on muscle force and fibre type
Authors: GERDLE B. , HENRIKSSON‐LARSÉN K. , LORENTZON R. , WRETLING M.‐L.
Published: December 2008

The aim of this study was to investigate whether the mean power frequency of the electromyogram of the knee extensors was force and/or muscle fibre‐type dependent. Ten female subjects performed a gradually increasing static knee extension (5 seconds duration) using an isokinetic dynamometer. Electromyogram‐signals were obtained from the vastus lateralis, vastus medialis and the rectus femoris muscles. The torque signal and the three electromyogram signals were recorded on a tape recorder. From the electromyogram recordings the mean power frequency and the signal amplitude were determined. Muscle biopsies were later obtained from the right vastus lateralis and stained for alkaline and acid mATPase for the determination of fibre‐type proportion and areas.

Both the mean power frequencies and the signal amplitudes of the three knee extensors were positively torque dependent. Furthermore it was found that the fibre type proportion and the regression coefficient of the torque (%)‐mean power frequency relationship were positively correlated. Also a negative correlation existed between the type‐1 (%) proportion and the intercept of the individual torque (%)‐mean power frequency relationships. In contrast to proposed models of the electromyogram signal no correlation was found between the mean power frequency and the fibre area.
Recurrent and reciprocal inhibition of the human monosynaptic reflex shows opposite changes following intravenous administration of acetylcarnitine
Authors: SCHIEPPATI M. , GRITTI I. , ROMANO‘ C.
Published: December 2008

A long‐latency, long‐lasting increase in the recurrent inhibitory effect on the coleus monosynaptic (Hoffmann, H) reflex was induced after intravenous administration of L‐acetylcarnitine, a substance known to possess central cholinergic activity. This effect was paralleled by disappearance of the H reflex inhibition (functionally disinhibition) induced by stimulation of Ia afferent fibres from the tibialis anterior (reciprocal inhibition) and gastrocnemius medialis muscle. Magnitude and time course of the L‐acetylcarnitine‐induced effects were significantly correlated. The data suggest that (1) the L‐acetylcarnitine depression of the reciprocal inhibition is mediated by excitation of Renshaw cells impinging on la interneurones (INs), and (2) the inhibitory effect of GM Ia afferents onto Sol is mediated by INs subjected to Renshaw inhibition. The results point to the similarity in the wiring of the ‘output stage’ circuit between cat and humans, and provide a method for testing this network in man.
Contribution of galanin to stress‐induced impairment of insulin secretion in swimming mice
Authors: DUNNING B. E. , SON S. KARLS , AHRÉN B.
Published: December 2008

This study examines the potential role of the neuropeptide, galanin, in stress‐induced inhibition of insulin secretion in swimming mice. Firstly, the pancreatic and adrenal content of galanin‐like immunoreactivity was determined in mice after swimming stress. It was found that pancreatic content was significantly lower in stressed mice than in resting controls, both after 2 (P < 0.05) and 6 (P < 0.025) minutes of swimming, suggesting partial release of pancreatic galanin during stress. In contrast, the adrenal content of galanin‐like immunoreactivity did not change during the swimming stress. Gel filtration of tissue extracts indicated that (1) mouse pancreas contains two forms of galanin‐like immunoreactivity; one co‐eluting with synthetic porcine galanin (centred on Kav of 0.70) and another with a larger molecular weight (centred on Kav, of 0.30), and (2) mouse adrenal contains a small void volume‐peak and a larger peak of immunoreactivity, the latter co‐eluting with synthetic galanin. Secondly, the effects of swimming stress on plasma glucose and insulin levels were compared in mice that received high titre rabbit anti‐galanin serum with those in mice receiving normal rabbit serum. In normal rabbit serum‐pretreated swimming mice, glucose‐induced insulin levels were only 50% of resting controls (P < 0.01). Immunoneutralization of galanin with specific antiserum abolished this swimming stress‐induced inhibition of glucose‐stimulated insulin levels. This was accompanied by a modestly enhanced rate of glucose disappearance. These findings suggest that pancreatic galanin is released during swimming stress in mice and that endogenous galanin makes a major contribution to stress‐induced impairment of insulin secretion.
Pulmonary, hepatic and splenic sequestration of technetium‐99m labelled autologous rabbit granulocytes: scintigraphic cell distributions after intravenous and intraarterial injections, exsanguination and intraarterial injection of cells passed through an intermediary host
Authors: FARSTAD B. S. , SUNDREHAGEN E. , OPDAHL H. , BENESTAD H. B.
Published: December 2008

In man, about half the intravascular granulocytes are not freely circulating, but temporarily sequestered (‘marginated’), so that they cannot be retrieved by bleeding. Where and how the sequestration occurs is not settled and is the subject of the present report. Isolated autologous rabbit granulocytes, labelled with two different 99mTc methods, were reinjected and followed with external scintigraphy.

Intraarterial as well as intravenous injection led to rapid accumulation of radioactivity over the lungs. This finding was corroborated and extended by similar experiments, where the labelled cells had firstly been passed through an intermediary rabbit host to remove altered cells, i. e. cells damaged, ‘primed’ (pre‐activated), or activated. In the final autologous host about two thirds of the label rapidly localized to the lungs and liver, and a few per cent to the spleen (which is very small in the rabbit). Even though more than half of the intermediary rabbit's calculated blood volume was removed, the blood sample contained only a few per cent of the rabbit's radioactivity; consequently, many of the labelled leucocytes had marginated during the bleeding. The proportional distribution of radioactivity over lungs, spleen, kidneys, and the rest of the intermediary animal was not markedly changed by this exsanguination, but there was a 4–20% decrease over the liver.

Taken together, our findings indicate that normal granulocytes marginate in lungs, liver, and spleen ‐ apparently explicable by the effects of cell size, vessel diameter, cell stiffness (visco‐elastic properties) and size of the arterio‐venous hydrostatic pressure difference. The liver and spleen seemed to play additional roles, since radioactivity over these organs decreased much slower than expected from reported blood half‐times of intact and slightly damaged rabbit granulocytes. This led to a suggestion that macrophages exposed to blood normally phagocytose apoptotically dying granulocytes.
Evaluation of the impression technique by measuring interstitial oedema in rat testis
Authors: LINDAHL O. , BERGH A. , DAMBER J.‐E. , ANGQUIST K.‐A.
Published: December 2008

The impression method for assessment of subcutaneous oedema was evaluated in a rat testis model where the testicular interstitial fluid volume was changed both artificially by infusion of rat plasma and pharmacologically by administration of human chorionic gonadotrophin. Both the integral value and the impression force value, as measured with the impression method, changed with infused volume, and changes as small as 16,μl (approximately 7% of the total interstitial fluid volume in a testis) could be detected. Rats were treated with a single injection of 100 i. u. human chorionic gonadotrophin in order to induce changes in the volume of interstitial fluid in the testis. Both the integral value and the impression force value seemed to reveal information on testicular interstitial fluid volume in rats treated with human chorionic gonadotrophin that was similar to data revealed by measuring the actual fluid content in the testis. Interstitial fluid volume measured morphometrically in the contralateral testis in human chorionic gonadotrophin‐treated rats was significantly correlated to the impression force value (r= 0.75) and the integral value (r= 0.52). This rat testis model proved to be an interesting experimental set‐up for evaluation of the impression technique.
Tissue osmolality in intestinal villi of four mammals in vivo and in vitro
Authors: HALLBÄCK D.‐A. , JODAL M. , MANNISCHEFF M. , LUNDGREN O.
Published: December 2008

Using a freezing point depression method osmolality in the intestinal tissue of four mammals (gerbils, guinea‐pigs, rabbits and rats) was estimated in vivo, during fluid transport from an isotonic electrolyte‐glucose solution. Net fluid transport was also measured. In gerbils, guinea‐pigs and rabbits tissue osmolality was also estimated during in vitro conditions. A marked hyperosmolality was observed in vivo in the upper parts of the villi of all four mammals studied. The tissue osmolality was significantly higher than that seen in the same species during in vitro conditions. A villus hyperosmolality was observed also in species which exhibited a net fluid secretion (guinea‐pig, rabbit ileum), indicating that the fluid secretion emanated from the intestinal crypts. Based on the results of the present experiments and on observations made in earlier experiments performed on the cat, it is proposed that the villus hyperosmolality is created by a countercurrent multiplier present in the intestinal villus. The hyperosmolar compartment in the villus tissue creates the force that drives fluid from lumen to tissue.
Resiniferatoxin‐, capsaicin‐ and CGRP‐evoked porcine coronary vasodilatation is independent of EDRF mechanisms but antagonized by CGRP(8–37)
Authors: FRANCO‐CERECEDA A.
Published: December 2008

In the present study the effects of activation of capsaicin‐sensitive C‐fibre afferents by resiniferatoxin and capsaicin as well as the effects of the co‐stored peptides calcitonin gene‐related peptide substance P and neurokinin A on porcine coronary vascular tonein vitrowas investigated.

Resiniferatoxin, capsaicin, calcitonin gene‐related peptide and neurokinin A all evoked a sustained, concentration‐dependent vasodilatation of potassium (60 mm)‐precontracted arteries. Substance P also caused vasodilatation of the precontracted arteries but this effect was transient and tachyphylaxis developed rapidly upon repeated administration. Incubation with the calcitonin gene‐related peptide fragment (8–37) did not influence the vascular tone per se but markedly attenuated the dilatory effect of calcitonin gene‐related peptide and totally abolished the vasodilatation induced by resiniferatoxin and capsaicin while leaving the effect of neurokinin A and substance P unaltered. Incubation with methylene blue, an inhibitor of endothelium‐derived relaxing factor mechanisms, which completely blocked the substance P‐evoked vasodilatation, as well as substance P‐tachyphylaxis, did not influence the vasodilator response to resiniferatoxin, capsaicin or calcitonin gene‐related peptide. The neurokinin A‐evoked vasodilatation was most likely mediated through activation of neurokinin 1‐receptors since it remained unchanged in the presence of the neurokinin 2‐receptor antagonist dactinomycin and (Nle10)‐neurokinin A (4–10), which selectively activates neurokinin 2‐receptors, had only a minor dilatory effect on the precontracted arteries.

It is concluded that RTX, capsaicin and CGRP share several characteristic features with regard to coronary vasodilatation and the present study provides evidence that cardiac vasodilatation upon activation of C‐fibre afferents by both RTX and capsaicin is mediated by CGRP.
Muscle lactate transport studied in sarcolemmal giant vesicles: dependence on fibre type and age
Authors: JUEL C. , HONIG A. , PILEGAARD H.
Published: December 2008

Lactate transport was studied in sarcolemmal giant vesicles obtained from rat or rabbit skeletal muscle. With this technique it is possible to obtain quantitative information on sarcolemmal transport characteristics. In equilibrium exchange experiments with 10, 30 and 60 mm lactate, vesicles from ‘red’ rat muscles had a 50% higher lactate transport capacity than vesicles from ‘white’ muscles. Giant vesicles made from rabbit red muscles had a 39% higher lactate transport capacity than vesicles from white muscles. These differences probably reflect a different number of lactate transporters, whereas the lactate affinity in red and white muscles are identical.

Lactate transport capacity decreased with age. Sarcolemmal giant vesicles made from 22‐month‐old rats had a 28% lower transport capacity than vesicles from 2‐month old rats. In absolute terms, the initial exchange flux with 30 mm lactate was 92 and 127 pmol cm‐2 sec‐1 for old and young rats, respectively. In supplementary studies in which microelectrode measurements were made in single mouse muscle fibres, it was shown that the cellular acidification rate due to lactate incubation, was 38% lower in fibres from 18‐month old mice than in fibres from 2‐month old mice.
Characterization, localization and actions of endothelins in umbilical vessels and placenta of man
Authors: HEMSÉN A. , GILLIS C. , LARSSON O. , HAEGERSTRAND A. , LUNDBERG J. M.
Published: December 2008

Endothelin‐like immunoreactivity was observed in the endothelial lining of umbilical vein and artery as well as in the epithelium of the amniotic membrane. High levels of endothelin‐like immunoreactivity (0.4–1.4 pmol g‐1) were detected in human amniotic membrane, umbilical vessels and placenta. The concentration of endothelin‐like immunoreactivity in the amniotic fluid was much higher (77 pmol l‐1) than in umbilical cord plasma (10 pmol l‐1). Characterization by reverse phase HPLC revealed that most of the endothelin‐like immunoreactivity eluted in the position of synthetic endothelin‐1 or oxidized endothelin‐1.

Specific, high affinity binding sites for endothelin‐1 were present in placenta and umbilical artery. Endothelin binding sites were also found in cultured smooth muscle cells from the umbilical artery and vein. In the placenta, endothelin‐1 and ‐3 were almost equipotent as competing ligands for endothelin‐1 binding sites, whereas in the umbilical artery endothelin‐3 was much less potent than endothelin‐1. Scatchard analysis of the binding for placental membranes displayed a straight line (r=–0.994) indicating a single class of endothelin receptors with a Kd‐value of 80 pmol l‐1 and Bmax of 113 fmol mg‐1. Endothelin‐1 caused potent contractions of umbilical arteries and veins with threshold effects at 10 pmol l‐1 while endothelin‐3 had no contractile effect up to 10‐7 mol l‐1.

It is concluded that endothelin‐1 predominates over other endothelins in umbilical vessels, amnion and placenta, and high levels of endothelin‐1 was observed in foetal circulation and amniotic fluid. Endothelin‐receptors seem to be of different types in placenta (ETB type) and umbilical vessels (ETA type).
Effects of bradykinin and papaverine on renal autoregulation and renin release in the anaesthetized dog
Authors: BUGGE J. F. , STOKKE E. S. , KIIL F.
Published: December 2008

The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 ± 3 and 58 ± 3 mmHg, respectively. Renin release increased from 0.3±0.1 to 22±4μg AI min‐1, and sodium excretion decreased from 99 +29 to 4.6 ± 3.3μmol min‐1when renal arterial pressure was reduced from 122±6 to 44±2 mmHg. Infusion of bradykinin (50 ng kg‐1min‐1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min‐1increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94±6 and 93±6 mmHg, respectively. Sodium excretion increased sixfold at control renal arterial pressure and was still as high as the initial control values at low renal arterial pressure (97±27μmol min‐1) accompanied by only a small increase in renin release (1.4±0.3 to 6±2μg AI min‐1). We conclude that bradykinin does not influence autoregulatory pressure limits of renal blood flow and glomerular filtration rate nor the accompanying increase in renin release during reductions in renal arterial pressure. Papaverine on the other hand maintains high sodium chloride delivery to macula densa at low renal arterial ressure, suppressing renin release and impairing autoregulation through effects on the tubulo‐glomerular feedback mechanism.
Effect of prior exercise in Pi/PC ratio and intracellular pH during a standardized exercise. A study on human muscle using [31P]NMR
Authors: LAURENT D. , AUTHIER B. , LEBAS J. F. , ROSSI A.
Published: December 2008

Seven subjects underwent a standard localized exercise of calf muscles in order to investigate whether the metabolic exercise‐induced steady‐state, as revealed by the evaluation of inorganic phosphate/phosphocreatine ratio, depends on the conditioning of the muscle just prior to the exercise. The experimental protocols consisted of two separate experiments using first [31P]nuclear magnetic resonance spectroscopy and second (on 3 subjects) infrared oxyphotometry to respectively follow variation of energy metabolism and tissular deoxygenation. The exercise consisted of 240 successive plantar flexions (0.5 Hz frequency) against a high load equivalent to SO% of the maximal voluntary contraction. This exercise was accomplished before cold exercise and after warm exercise, a warming‐up period bringing to approximately 50% of Vo2max. The results showed that: (1) steady‐state level of phosphate/phosphocreatine and intracellular acidosis was significantly lowered by warming‐up; (2) cold and warm exercise steady‐state of calculated adenosine diphosphate values were not significantly different; (3) cold exercise rapidly induced a high tissular deoxygenation that is not observed during warm exercise; and (4) time‐constant of phosphocreatine resynthesis is lowered after warm exercise but the initial slope of time‐evolution is not modified. Parallel experiments also showed that phosphate/phosphocreatine steady‐state was not modified in comparison with warm exercise when the same power of exercise was reached by stepwise incrementation of the charge. From these results we postulate that a better tissue oxygenation due to a global or localized warming‐up allows to reach the same mechanical performance with a lower decrease of PCr content, owing to a faster adjustment of oxidative metabolism during the transitional period. However the aerobic pathway flux during the steady‐state is probably the same before and after the warming‐up despite different values of phosphate/phosphocreatine. As a consequence it can be assumed that this ratio is not a good indicator of the rate of muscle oxidative metabolism during the steady‐state phase of the exercise.
Reversal by Concanavalin A of the inhibitory effects of extracellular Ca2+ on pinocytosis in Amoeba proteus
Authors: JOHANSSON P. , COBBOLD P. H. , JOSEFSSON J.‐O.
Published: December 2008

When Concanavalin A, 1–20 μg ml‐1 binds to the surface of Amoeba proteus the cell's response to Ca2+ and to cationic inducers of pinocytosis is strikingly altered. Separately, Concanavalin A and Ca2+ are weak inducers but their combined effects are intense pinocytosis and suppression of the normal inhibitory effect of Ca2+ on cation‐induced pinocytosis. At high concentrations (> 25 μg ml‐l) the lectin increases cellular uptake and binding of 45Ca in the cell surface but the ionic permeability and the potential of the cell membrane are little changed by treatment with Concanavalin A. Subsequent addition of Ca2+ starts the pinocytic cycle and causes a fivefold increase of the membrane resistance without depolarizing the cell. Neither a rise of free intracellular calcium nor an influx of 45Ca preceeds formation of pinocytotic channels when Con A is applied to cells in the presence of calcium. All effects of Concanavalin A are blocked by α‐methylmannoside while succinyl‐Concanavalin A is without effects on pinocytosis. These findings suggest that crosslinking of cell surface carbohydrates reverses calcium inhibition of pinocytosis and increases the cell's pinocytotic response to cations without modifying either the bioelectrical effects or the intracellular free concentration of calcium.
Plasma immunoreactive atrial natriuretic peptide and vasopressin after ethanol intake in man
Authors: LEPPÄLUOTO J. , VUOLTEENAHO O. , ARJAMAA O. , RUSKOAHO H.
Published: December 2008

To study the mechanisms of alcohol‐induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg‐1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1‐l (mean ± SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280±10 to 340 ± 4 mosm kg‐1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P < 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance increased from ‐3.4 ± 1.4 to 2.8 ± 1.5ml min‐l in 2 h (P < 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng 1‐1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1‐1 at 6 and 12 h, respectively (P < 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng 1‐1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 ±2, 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in blood pressure were observed during the ingestion period, but the heart rate rose significantly from 70 min‐1 at 6 p.m. to 95 min‐1 at 12 p.m.

We conclude that ethanol intake in relation to serum ethanol levels caused in the first phase a rapid increase in osmolality which was associated with a decrease in plasma immunoreactive arginine vasopressin. This caused hypotonic diuresis and increased free water clearance followed by volume contraction which evidently led to decreased plasma immunoreactive atrial natriuretic peptide. Serum osmolality was significantly elevated during the whole experiment and serum sodium 1–2 h after the ethanol intake. This was associated with the return of plasma immunoreactive atrial natriuretic peptide to initial levels after 6 h, the increase in plasma immunoreactive arginine vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP is not responsible for the diuresis seen after the alcohol intake.
Age‐related changes of exercise‐induced plasma catecholamines and neuropeptide Y responses in normal human subjects
Authors: JENSEN E. WINTHER , ESPERSEN K. , KANSTRUP I.‐L. , CHRISTENSEN N. JUEL
Published: December 2008

Age‐related plasma noradrenaline and neuropeptide Y were evaluated in seven young (mean ± SD, 28 ± 3 years) and seven elderly (64 ± 8 years) normal subjects during rest and different work loads on a cycle ergometer. In the supine and the sitting position plasma noradrenaline and neuropeptide Y were almost identical in the two groups. Plasma neuropeptide Y did not increase during exercise at 100 W for 15 min. At this load plasma noradrenaline levels were higher in the older subjects (mean ± SEM, 0.97 ± 0.12 vs. 0.60 ± 0.09 ng ml‐l). There was a significant correlation between plasma noradrenaline and the relative work load at 100 W (r = 0.794, P = 0.0007). At 75% of maximal work load plasma noradrenaline and neuropeptide Y were higher in the young group (1.84 ± 0.16 vs. 1.26 ± 0.13 ng ml‐l (noradrenaline) and 38 ± 4 vs. 22 ± 5 pmol 1‐1 (neuropeptide Y)). In the elderly group plasma neuropeptide Y did not increase during exercise and showed a tendency to fall below basal level 5 min post‐exercise. It is concluded, that plasma noradrenaline does not increase more in older subjects during exercise when correcting for the generally lower physical fitness in this group compared to younger subjects, and that plasma neuropeptide Y does not increase during exercise in older subjects, suggesting an age‐reduced capacity in this system.
Glycogen breakdown in different human muscle fibre types during exhaustive exercise of short duration
Authors: VØILLESTAD N. K. , TABATA I. , MEDBØ J. I.
Published: December 2008

The rates of glycogen breakdown during exhaustive intense exercise of three different intensities were determined in type I and subgroups of type II fibres. The exercise intensity corresponded to 122 ±2, 150 ± 7 and 194 ± 7% of Vo2max. Muscle biopsies were taken from both legs before and immediately after exhaustion. Muscle lactate concentration increased by 27 ±1, 27 ± 1 and 20 ± 2 mmolkg‐1 wet wt during the exercise at 122, 150 and 194%Vo2max, respectively. The rates of glycogen depletion increased in all fibre types with increasing intensity, and the decline in type I fibres was 30–35% less than in type II fibres at all intensities. No differences were observed between the glycogen depletion rates in subgroups of type II fibres (IIA, IIAB and IIB). During the exercise at 194% Vo2max, the rates of glycogen breakdown were 0.35 ± 0.03 and 0.52 ± 0.05 mmol s‐1 kg‐1 wet wt in type I and type II fibres, respectively. For both fibre types, the rates were 32 and 69% lower during the exercise at 150 and 12296 VO2max. These data indicate that the glycolytic capacity of type I fibres is 30–35% lower than the capacity of type II fibres, in good agreement with the differences in phosphorylase and phosphofructokinase activities (Essén et al. 1975, Harris et al. 1976). The data also indicate that both fibre types contribute significantly to the anaerobic energy release at powers up till almost 200%Vo2max.
Human, tactile, directional sensibility and its peripheral origins
Authors: NORRSELL U. , OLAUSSON H.
Published: December 2008

Tactile directional sensibility is probably functionally important and deserves attention as it is known to be sensitive to many different disturbances of the somatosensory system. Therefore, the ability of healthy adults to determine the direction of motion of a light tactile stimulus travelling proximally or distally along a straight line on depilated, hairy skin of the forearm was examined with two‐alternative, forced‐choice technique. The aim was to investigate the relative importance of different types of afferent information which may be used for this purpose. A test was started with the moving stimulus covering a distance of no less than 2.5 mm, which was subsequently increased until the subject could report the direction of motion reliably.

Afterwards, the distance was decreased until the subject could no longer do so. Three different stimulation conditions were used and for a point stimulator touching the skin it was found that the necessary distance decreased to 2.5 mm after a moderate increase of the vertical contact load. No such decrease was found when a frictionless air‐stream point stimulator was used instead. The distances which had to be covered by the point stimulator touching the skin increased to values which were comparable to those obtained with the air‐stream stimulator after the lateral extensibility of the skin had been diminished. This was achieved by attaching a surgical sticky plaster around the stimulated skip area. The present findings consequently indicated that optimal, tactile, directional sensitivity depends on peripheral afferent messages which signal the direction of lateral stretching of the skin.
Intrathecal neurokinin A facilitates the spinal nociceptive flexor reflex evoked by thermal and mechanical stimuli and synergistically interacts with substance P
Authors: XU X.‐J. , WIESENFELD‐HALLIN Z.
Published: December 2008

The neuropeptide neurokinin A was injected intrathecally and its effect on the spinal nocifensive flexor reflex was examined. The reflex, which was evoked by electrical, thermal or mechanical stimulation of the foot and was recorded from the ipsilateral hamstring muscles, was substantially facilitated by 7 pmol intrathecally injected neurokinin A. The facilitatory effect of neurokinin A to thermal stimulation was, however, significantly stronger than to electrical or mechanical stimuli. Furthermore, co‐administration of neurokinin A with substance P induced a significant synergistic facilitation of the reflex. It is suggested that neurokinin A, like substance P, may be released in association with activation of polymodal C‐nociceptors.
Selective inhibition by dactinomycin of NANC sensory bronchoconstriction and [125I] NKA binding due to NK‐2 receptor antagonism
Authors: LOU Y.‐P. , DELAY‐GOYET P. , LUNDBERG J. M.
Published: December 2008

Y.‐P. Lou, P. Delay‐Goyet& J. M. Lundberg. 1991. Selective inhibition by dactinomycin of NANC sensory bronchoconstriction and [125I]NKA binding due to NK‐2 receptor antagonism.Acta Physiol Scand144, 221–231. Received 6 May 1991, accepted 13 September 1991. ISSN 0001–6772. Department of Pharmacology, Karolinska Institutet, Stockholm.

In the present study, dactinomycin (m)inhibited the non‐adrenergic, non‐cholinergic bronchoconstriction upon antidromic vagal nerve stimulation (1 Hz for 1 min) in the isolated perfused guinea‐pig lung by 84%. The release of calcitonin gene‐related peptide was unchanged, however, suggesting a postjunctional action. Dactinomycin (10‐5, 5 × 10‐5m)also reduced non‐adrenergic non‐cholinergic bronchial contractions (maximally by 75%) induced by electrical field stimulation or capsaicin, while the cholinergic component and non‐adrenergic non‐cholinergic relaxation remained intact. The neurokinin‐2 receptor antagonist l‐659 877(10‐6m)had a similar effect as dactinomycin, inhibiting the non‐adrenergic non‐cholinergic bronchial contractions by 69%, while the neurokinin‐1 receptor antagonist CP‐96,345 (10‐6m)had no effect. The bronchoconstriction evoked by neurokinin A, the selective neurokinin‐2 receptor agonist Nle10neurokinin A (4–10) and capsaicin was markedly inhibited by dactinomycin while the contraction induced by substance P (SP), the selective neurokinin‐1 receptor agonist Sar9Met(02)11SP, endothelin‐1 and acetyl‐choline was not affected. In autoradiographic experiments on guinea‐pig lung, [125I]neurokinin A‐labelled sections showed dense binding in the bronchial smooth muscle layer. Dactinomycin inhibited the specific binding of [251]neurokinin A in a concentration‐dependent manner (IC50= 6.3 × 10‐6m)and 66% of [125I]neurokinin A total binding was inhibited by 10‐4M dactinomycin. In the rat colon, [125I]neurokinin A binding to neurokinin‐2 sites on circular smooth muscle was inhibited by dactinomycin with an IC50value of 7.9 × 10‐6M. Dactinomycin failed to reduce increased nerve‐evoked contractions or those caused by Nle10neurokinin A (4–10)per sein the rat vas deferens, which are considered to be mediated by neurokinin‐2 receptor activation. In the rat portal vein, dactinomycin did not influence the contractions caused by the neurokinin‐3 selective agonist Pro7neurokinin B. In conclusion, dactinomycin selectively inhibited neurokinin‐2 receptor activation in guinea‐pig lung and rat colon, but not in rat vas deferens, which may depend on the existence of different neurokinin‐2 receptor subtypes. Neurokinin A is most likely the main endogenous excitatory non‐adrenergic non‐cholinergic transmitter in guinea‐pig bronchi.
Alpha2‐receptor‐mediated inhibition of intraluminal release of gastric somatostatin in anaesthetized rats
Authors: ALIÑO S. F. , GARCIA D. , UVNÄS‐MOBERG K.
Published: December 2008

Aliño, S. F., Garcia, D. & Uvnäs‐Moberg, K. 1992. Alpha2‐receptor‐mediated inhibition of intraluminal release of gastric somatostatin in anaesthetized rats.Acta Physiol Scand144, 233–238. Received 22 February 1991, accepted 11 October 1991. ISSN 00014772. Department of Pharmacology and Pharmaceutics, University of Valencia, Valencia, Spain, Department of Cell Biology and Morphology Science, University of Pais Vasco, Leioa, Spain and Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.

The aim of the present study was to investigate how the sympathetic nervous system affects the vagally induced intragastric release of somatostatin and gastrin. Experiments were performed on anaesthetized rats in which the stomach was perfused with a dextrane solution (pH ≅ 5.9) or dextrane buffer (pH 7.4). pH as well as gastrin and somatostatin levels were measured in the gastric perfusate when it had passed the stomach. Vagal stimulation caused a decrease in perfusate pH and an increase of the intraluminal output of gastrin and somatostatin when the stomach was perfused with the dextrane solution pH 5.9. Pretreatment with phentolamine (1 mg kg‐1) significantly increased and pretreatment with clonidine (60, ug kg‐1h‐1) significantly decreased somatostatin release caused by vagal stimulation, whereas gastrin levels remained largely unchanged. The effect of clonidine persisted in rats pretreated with indomethacin (5 mg kg‐1), whichper sepotentiates the vagally induced luminal somatostatin release. When the stomach was perfused with the dextrane buffer pH 7.4, basal gastrin levels were significantly higher than during perfusion with the solution pH 5.9, whereas somatostatin levels remained unchanged. Neither somatostatin nor gastrin levels increased following vagal stimulation during gastric perfusion with the dextrane buffer pH 7.4. However, following pretreatment with phentolamine somatostatin levels increased during these conditions.