bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximal voluntary force of bilateral and unilateral leg extension
Authors: SCHANTZ P. G. , MORITANI T. , KARLSON E. , JOHANSSON E. , LUNDH A.
Published: December 2008

The aims were: (1) to investigate whether the 10–20% lower force during bilateral (BL) as compared to unilateral (UL) leg extension could be due to a general inability to activate fully a large number of muscles simultaneously, (2) to analyse the EMG signal of the quadriceps femoris during leg extensions, (3) to study the BL/UL force ratio in extension of the knee, and (4) to study the BL/UL leg extension force ratio in untrained and trained subjects. A 10% lower maximal voluntary isometric force was demonstrated during BL as compared to UL leg extension. This force discrepancy did not change when a total arm load of 250 N was applied simultaneously. Nor did the absolute force levels change, which indicates that the lower BL leg extension force is not due to a general mechanism of reduced activation with an increased number of muscles recruited in maximal voluntary contractions. Integrated EMG activity, mean power frequency and root mean square value of the EMG amplitude did not differ between UL and BL leg extensions. The knee extension force was slightly greater (4%) during BL than UL contractions. These findings are arguments against a reduced activation of the knee extensor muscles being the cause of the lower bilateral leg extension force. No differences in BL/UL force ratio were noted between groups of untrained and trained subjects despite the fact that several of the trained groups do different forms of BL leg extensions regularly. Thus, it does not appear that training readily affects the BL/UL leg extension force ratio.
Ground reaction forces at different speeds of human walking and running
Authors: NILSSON J. , THORSTENSSON A.
Published: December 2008

In this study the variation in ground reaction force parameters was investigated with respect to adaptations to speed and mode of progression, and to type of foot‐strike. Twelve healthy male subjects were studied during walking (1.0–3.0 m s‐1) and running (1.5–6.0 m s‐1). The subjects were selected with respect to foot‐strike pattern during running. Six subjects were classified as rearfoot strikers and six as forefoot strikers. Constant speeds were accomplished by pacer lights beside an indoor straightway and controlled by means of a photo‐electronic device. The vertical, anteroposterior and mediolateral force components were recorded with a force platform. Computer software was used to calculate durations, amplitudes and impulses of the reaction forces. The amplitudes were normalized with respect to body weight (b.w.). Increased speed was accompanied by shorter force periods and larger peak forces. The peak amplitude of the vertical reaction force in walking and running increased with speed from approximately 1.0 to 1.5 b.w. and 2.0 to 2.9 b.w. respectively. The anteroposterior peak force and mediolateral peak‐to‐peak force increased about 2 times with speed in walking and about 2–4 times in running (the absolute values were on average about 10 times smaller than the vertical). The transition from walking to running resulted in a shorter support phase duration and a change in the shape of the vertical reaction force curve. The vertical peak force increased whereas the vertical impulse and the anteroposterior impulses and peak forces decreased. In running the vertical force showed an impact peak at touch‐down among the rearfoot strikers but generally not among the forefoot strikers. The first mediolateral force peak was laterally directed (as in walking) for the rearfoot strikers but medially for the forefoot strikers.

Thus, there is a change with speed in the complex interaction between vertical and horizontal forces needed for propulsion and equilibrium during human locomotion. The differences present between walking and running are consequences of fundamental differences in motor strategies between the two major forms of human progression.
Intracellular ion exchange between cytoplasmic potassium and granule histamine, an integrated link in the histamine release machinery of mast cells*
Authors: UVNÄS B. , ÅBORG C.‐H. , LYSSARIDES L. , DANIELSSON L.‐G.
Published: December 2008

Rat peritoneal mast cells isolated by gradient centrifugation in Percoll were placed between two membrane filters in a Sartorius filter apparatus and superfused with isotonic balanced salt solutions or with deionized isotonic sucrose. Histamine was released according to ion exchange kinetics. Our explanation of the observed phenomena is as follows. The superfusion induces a flow of cytoplasmic K+ions across the histamine‐containing granules, resulting in an ion exchange K+←Hi+ions at the histamine binding sites. The concomitant equimolar outflow of histamine and potassium is considered to be due to a functional interplay between two histamine pools, a release and a donor pool. As the result of the K+←SHi+ion exchange at the histamine binding sites of the release pool, these sites become transiently occupied by K+ions only to be immediately reoccupied by Hi+ions from the donor pool. The observed equimolar outflows are consistent with a 1/1 molar ratio in the exchange between histamine and potassium ions.

The essential role of cytoplasmic potassium in the histamine release mechanism is a new and important observation with possible implications not only as to histamine release in general (including so‐called ‘spontaneous’ histamine release) but also as to the release of biogenic amines and other positively charged substances stored in granules in ionic linkage to the matrix.
Effects of adrenaline and prior exercise on the release of alanine, glutamine and glutamate from incubated rat skeletal muscle
Authors: NIE Z. T. , WALLBERG‐HENRIKSSON H. , JOHANSSON S. , HENRIKSSON J.
Published: December 2008

Catecholamines have been proposed as important regulators of the rate of amino acid release from skeletal muscle. In the present study, we have investigated the influence of adrenergic action and its possible interaction with exercise on muscle release and tissue content of alanine, glutamine and glutamate. For this purpose epitrochlearis muscles were dissected from resting and exercised (1 and 2 h) rats and incubated for 1 h in the presence or absence of adrenaline. In addition, muscles from water‐immersed resting rats were included to separate the influence of the stress involved in the swimming exercise from that of muscle contractile activity per se. In muscles from untreated resting rats, the release, tissue content and total amount (released amount + tissue content) of the three amino acids were not influenced by 10‐7 M adrenaline; when the adrenaline concentration was raised to 10‐5 M only the tissue content of glutamate was significantly changed (– 50%, P < 0.001). However, in muscles of rats subjected to 2 h prior exercise or water immersion, 10‐7 M adrenaline significantly increased the release of glutamine (+ 48% and +34%, P <0.05) and glutamate (+ 38% and +27%, P < 0.05). Moreover, 1 h of water immersion resulted in a significant increase in muscle glutamine and glutamate compared to values from the exercised and control rats. The data suggest that adrenergic action is involved in the regulation of muscle amino acid transport during exercise and that the stress involved in exercise may mask the influence of contractile activity per se on formation of amino acids in skeletal muscle.
Comparative effects of the α‐adrenoceptor agonists noradrenaline, phenylephrine and clonidine in the human saphenous veinin vivoandin vitro
Authors: SJÖUBERG T. , NORGREN L. , ANDERSSON K.‐E. , STEEN S.
Published: December 2008

The α‐adrenoceptor‐mediated contractile effects of noradrenaline (αl+α2), phenylephrine (αl) and clonidine (α2) on human saphenous veins were investigatedin vivoandin vitro.By infusion (0.3 ml min‐1) of the drugs (increasing concentrations in the infused solution) into distended (40 mmHg) saphenous veins in six healthy subjects, local vasoconstriction was induced, measured by a photo‐electric device. The drugs induced dose‐dependent contractions in all subjects, and dose‐response curves were constructed. These were compared with concentration‐response curves based onin‐vitroresults. Macroscopically normal saphenous veins, taken at saphenousectomies, were used, and the preparations were contracted isometrically in organ baths by the agonists. From the curves obtainedin vivoandin vitro, the relative potencies of phenylephrine and clonidine (in relation to noradrenaline) were calculated and compared. The relative potencies of phenylephrinein vivo(76%) andin vitro(82%) did not differ significantly. However, the relative potency of clonidine was significantly (P < 0.05) lowerin vivo(90%) thanin vitro(99%). Thus, it is concluded that there are differences between the results obtainedin vivoandin vitro, stressing the importance of comparativein vivo‐in vitrostudies.
On the regulatory functions of neuropeptide Y (NPY) with respect to vascular resistance and exocrine and endocrine secretion in the pig pancreas
Authors: HOLST J. J. , ØRSKOV C. , KNUHTSEN S. , SHEIKH S. , NIELSEN O. V.
Published: December 2008

We compared the effects of electrical stimulation of the splanchnic nerves and infusions of neuropeptide Y, noradrenaline or a combination of the two on pancreatic vascular resistance and exocrine and endocrine secretion. For these studies we used isolated perfused pig pancreas with preserved splanchnic nerve supply. The exocrine secretion was stimulated with physiological concentrations of secretin and cholecystokinin octapeptide. Noradrenaline and NPY at 10‐8M both increased pancreatic perfusion pressure. Their effects were additive and similar in magnitude to that of electrical stimulation of the splanchnic nerves at 4–8 Hz. Nerve stimulation as well as NPY and noradrenaline infusions inhibited exocrine secretion, but an additive effect could not be demonstrated. Neither NPY nor noradrenaline could reproduce the stimulatory effect of nerve stimulation on glucagon secretion, nor the weak inhibitory effect on somatostatin secretion. NPY alone had no effect on insulin secretion and did not influence the inhibitory effect of noradrenaline. It is concluded that NPY is likely to cooperate with noradrenaline in the control of pancreatic blood flow, whereas its role in the control of pancreatic secretion is likely to be of minor importance, if any.
The effect of amiloride and benzimidazoleguanidine added to the inside medium on electrolyte pathways in the frog skin glands
Authors: ESKESEN K. , USSING H. H.
Published: December 2008

Serosal amiloride inhibits Na+, K+and Cl‐efflux and reduces short‐circuit current and transepithelial conductance in noradrenaline‐stimulated frog skin in which the sodium channels in the apical membrane are blocked by amiloride. BIG (benzimidazoleguanidine) inhibits Na+and K+efflux and reduces the short‐circuit current. In some skins BIG decreased and in others it increased Cl‐efflux and conductance. The variable response appears to be due not only to inhibition of salt extrusion from the gland cells but also to activation of Cl‐transport through the mitochondria‐rich cells, since it was shown that BIG could increase Cl‐efflux in gland‐free preparations. Different target mechanisms in the gland cells where the two substances may exert their effect are discussed.
Physical exercise and brain monoamines: a review
Authors: CHAOULOFF F.
Published: December 2008

A review of the literature on the relationship of exercise to mental health strongly suggests that the two are closely linked. Thus, physical activity has been reported to reduce depression symptoms and anxiety, and to improve coping with stress. Logically, many investigators have then tried to determine the physiological mechanisms that are responsible for this mood‐elevating effect of exercise. Among the current hypotheses, those regarding the endorphin and the monoamine systems have received a great deal of attention. On that basis, the respective effects of physical exercise on brain dopamine, noradrenaline and serotonin transmission are reviewed herein. In addition, suggestions are advanced for future research in this field.
Sarcoplasmic reticulum of human skeletal muscle: age‐related changes and effect of trainirig
Authors: KLITGAARD H. , AUSONI S. , DAMIANI E.
Published: December 2008

The effect of ageing on human skeletal muscle was investigated using needle biopsies from young and aged subjects and from aged subjects trained with different activity patterns. Histochemical staining for myofibrillar ATPase of ageing m. vastus lateralis demonstrated an unchanged fibre type distribution but a selective atrophy of type IIa and type IIb fibres. Analysis of myosin heavy chain (MHC) composition showed that type I MHC increased with ageing (P<0.05). The relative content of the MHC isoforms correlated with the relative area of the respective fibre types. Sarcoplasmic reticulum (SR) proteins were investigated in muscle extracts by electrophoretic and immunoblotting techniques. When compared to a young control group (28 0.1 years old,n =7) blots of post‐myofibrillar supernatant proteins probed with polyclonal antibodies to the rabbit fast SR Ca‐ATPase, a marker of extrajunctional SR, showed that the content of Ca‐ATPase was significantly lower (P< 0.05) in the old control group (68 ± 0.5 years old,n= 8). On the other hand the content of calsequestrin (CS), the major intraluminal protein of SR terminal cisternae (TC), and of the 350‐kDa ryanodine‐binding protein, which is localized in the junctional regions of TC, did not show a concomitant decrease. These results suggest that ageing differentially affects extrajunctional and junctional SR of human skeletal muscle. These age‐related changes were not observed within a group of old strength‐trained subjects.
A model for the fast 4‐aminopyridine effects on amphibian myelinated nerve fibres. A study based on voltage‐clamp experiments
Authors: ÅRHEM P. , JOHANSSON S.
Published: December 2008

The effect of eaminopyridine (4‐AP) on the potassium currents in the node of Ranvier in myelinated nerve fibres was investigated with the voltage‐clamp technique. The potential and time dependence of the currents in solutions with a high potassium concentration (114.5 mm) were studied. The block of the tail current was found to be less than that of the corresponding current during a potential step. Also, the time‐course of the tail current was modified. In order to explain these findings, kinetic models of the 4‐AP action were constructed and analysed numerically. A simple four‐state model, in which 4‐AP interacts only with open channels and where the binding is diphasically potential dependent, was found to account for the effects.
Effects of sympathetic stimulation on C‐fibre responses in rabbit
Authors: SHYU B. C. , OLAUSSON B. , HUANG K. H. , WIDERSTRÖM E. , ANDERSSON S. A.
Published: December 2008

Unmyelinated C‐fibre responses to electrical stimulation were recorded in common peroneal, sural and tibial nerves of rabbits. Three distinct C elevations, here called C1, C2 and C3, were recorded. C2 is prohbly of somatic origin because it was depressed due to collision by peripheral stimulation of cutaneous receptors. The conduction velocity of C3 corresponded to that of sympathetic post‐ganglionic fibres. During sympathetic trunk stimulation the A‐fibre responses were not significantly changed while C responses, especially C2, were reduced in amplitude and slightly delayed. The C‐fibre responses were also influenced by intra‐arterial infusion of noradrenaline. In most cases, the latency of the response was increased. The effect of sympathetic stimulation was completely blocked by hexamethonium, and partly blocked by phentolamine, an adrenergic a‐receptor blocking agent which also blocked the effect of noradrenaline. The findings suggest that there are adrenergic receptors distributed along unmyelinated somatic afferent fibres. Sympathetic activity may release noradrenaline in the peripheral nerve, resulting in changed conductive properties in unmyelinated fibres transmitting sensory information.
Omeprazole: inhibitor of both acid formation and translocation in gastric mucosa
Authors: EKBLAD E. B. M.
Published: December 2008

Ekblad, E. B. M. 1989. Omeprazole: inhibitohd of both acid formation and translocation in gastric mucosa.Acra Physiol Scand137, 223–230. Received 15 March 1989, accepted 2 June 1989. ISSN 0001–6772. Cardiovascular Research Institute, University of California, San Francisco, and Nephrology, Veterans Administration Medical Center, San Francisco, CA, USA.

Omeprazole, believed to inhibit H+, K+‐ATPase, was used to study acid secretion dynamics in isolated gastric mucosa. Tissue was mounted in a chamber and continuously supplied with both fresh nutrient and secretory solution (flow‐through). Acid secretion was monitored on and recorded by a pH‐stat microprocessor set‐up. In spontaneously secreting mucosa the continuous presence of omeprazole causes a monotonic decline in secretion rate to a new lower steady state. The relationship between the inhibited steady‐state acid secretion rate and omeprazole concentration is expressed by the sum of two hyperbolic functions withK1s differing by a factor of more than 100. When omeprazole is removed, the secretion rate always recovers. The amount of acid suppressed depends uniquely on omeprazole exposure: it is proportional to the exposure at low exposure and disproportionate (logarithmic) at high exposure. The index of conservation declines with omeprazole exposure, i. e. the inhibition by omeprazole ranges from conservative (no net loss of acid) to non‐conservative (net loss of acid). Dithiothreitol causes the inhibition by omeprazole to be conservative (index of conservation = 0) at even higher omeprazole exposure. The index of conservation was introduced to allow for numerical evaluation of both inhibitory and stimulatory effects regardless of the magnitude of the effect. It is concluded that omeprazole acts at two different sites, possibly with inhibition by sulphoxide derivatives on the formation step and sulphide derivatives on the translocation step.,
Cardiovascular responses to intravenous calcitonin gene‐related peptide (CGRP) in the albino rabbit
Authors: ANDERSSON S. E.
Published: December 2008

The regional sensitivity of different vascular beds to i. v. CGRP was investigated in the albino rabbit by using the microsphere method. Experiments were performed without pre‐treatment on both conscious and pentobarbital‐anaesthetized animals. In addition, in one series on conscious animals, rabbits were pre‐treated with indomethacin in order to reduce the formation of prostaglandins. In another series, anaesthetized rabbits were subjected to ganglionic blockade with hexamethonium bromide in order to abolish reflexes involving the autonomic nervous system. 120 pmol kg‐1of CGRP was given to all the animals, the conscious animals receiving the peptide in one infusion lasting 4 min. In the anaesthetized animals, the dose was divided into first a 5‐min infusion of 30 pmol kg‐1followed some minutes later by a 3‐min infusion of 90 pmol kg‐1.

Thde most pronounced vasodilatory effects were seen in thhd pancreas, gallbladder, stomach, duodenum, tongue, teeth and the conjunctiva/nictitating membrane. In some series marked effects were also seen in the dura mater, choroid plexus and some parts of the brain. In the anaesthetized animals almost no statistically significant effects on local blood flows were seen following the first, smaller, dose, but following the larger dose more pronounced effects were observed. Pre‐treatment with indomethacin did not to any great extent affect the responses, which contradicts the involvement of prostaglandins. The pattern of the responses was unaffected by the ganglionic blockade, but the variability of response was reduced.

In conclusion there are great regional variations in the sensitivity to circulating CGRP. The patterns shows a resemblance to that obtained in other species, but there are some marked differences, The tissues most susceptible to the peptide are those easily exposed to noxious stimuli and containing CGRP in the sensory nerve endings, observations in agreement with the proposed role for the peptide in neurogenic defence mechanisms.,
Interaction between sympathetic nerve fibres and epithelial transport in the rat jejunal mucosain vivo
Authors: HEMLIN M.
Published: December 2008

The aim of this study was to elucidate the mechanisms behind the absorptive response to mesenteric nerve stimulation (MNS). Segments of rat jejunum were mounted with intact blood circulation in an‘in‐vivochamber’, allowing parallel registration of net fluid transport rate (NFT) and electrical parameters of the tissue. All segments secreted fluid spontaneously, and the secretion rate was inversely correlated to the corresponding potential difference (PD) across the segment. The secretion was not inhibited by atropine. The nicotinic antagonist hexamethonium (Hx) inhibited the secretion and changed the relationship between PD and NFT. MNS reversed the secretion into an absorption (absorptive response) and decreased PD and short‐circuit current (SCC) (electrogenic response). Total tissue resistance (Rt) was not significantly changed. The absorptive response increased at high control secretion rates and the electrogenic response increased at high control PD levels. The electrogenic response was inversely related to the absorptive response; however, the presence of Hx reversed this correlation. Guanetbidine, a sympatholytic agent, eliminated all effects of MNS. Phentolamine eliminated the absorptive response but not the electrogenic response, and the remaining electrogenic response was not sensitive to propranolol (a β‐adrenergic antagonist). Hx induced similar but smaller effects than MNS, and after Hx treatment the MNS effects were reduced. We conclude:

Fluid secretion in our model involves a mechanism other than electrogenic Cl‐secretion.

MNS activates sympathetic nerve fibres, which enhance fluid absorption and decrease PD and SCC.

The absorptive and electrogenic responses involve partly separate transport mechanisms.

Both responses are partly due to the inhibition of intramural secretory nervous pathways.

Some sympathetic nerve fibres interact directly with the epithelium.
Neuromuscular actions of endothelin on smooth, cardiac and skeletal muscle from guinea‐pig, rat and rabbit
Authors: WIKLUND W. P. , ÖHLÉN A. , WIKLUND C. U. , CEDERQVIST B. , HEDQVIST P. , GUSTAFSSON L. E.
Published: December 2008

The peptide endothelin (human, porcine) was investigated for effects on basal muscle tone and on responses to transmural nerve stimulation in a series of smooth muscle preparations, as well as in guinea‐pig atrium and rat and guinea‐pig diaphragm. Endothelin lacked effect on basal tone or on spontaneous and electrically driven contractions in skeletal and atrial muscle. It contracted guinea‐pig ileum, pulmonary and femoral arteries, rat anococcygeus, vas deferens and urinary bladder and rabbit taenia coli, whereas guinea‐pig taenia was relaxed. Guinea‐pig urinary bladdcr and vas deferens and rabbit iris sphincter were unaffected up to 3 × 10‐‐8M. Endothelin thus has a unique pattern of smooth muscle effects, exhibiting mostly contractile hut also relaxing effects.

Endothelin modified contractile responses to transmural nerve stimulation, yielding marked and persistent enhancement, in guinea‐pig and rat vas deferens, and enhancement also in guinea‐pig pulmonary artery. In guinea‐pig and rat vas deferens the response to exogenous ATP was increased by endothelin, thus suggesting a strong post‐junctional enhancement of neurotransmission. In guinea‐pig ileum nerve‐induced responses were inhibited by endothelin, whereas exogenous acetylcholine was enhanced, an effect suggesting a simultaneous pre‐junctional inhibition and post‐junctional enhancement.

The Ca2+channel blocker felodipine counteracted the stirnulatory effects of cndothelin on tone and transmurally induced contractions. Tachyphylaxis to cndothelin action was sometimes evident, but the anococcygeus being less prone to this might be useful for studies on endothelin antagonism. Endothelin thus has prominent post‐junctional, and also probably pre‐junctional, effects, lcnding further support for a distinct biological role of this peptide.
Tissue distribution of 125I‐labelled carbonic anhydrase isozymes I, II and III in the rat
Authors: APPELGREN L.‐E. , ODLIND B. , WISTR P. J.
Published: December 2008

Carbonic anh!‐drase (CA) isozymes CA I and CA II were isolated from rat erythrocytes, and CA III from rat skeletal muscle. They were purified to homogeneity and labelled with 125I using the Bolton‐Hunter method. The tissue distrihution of these [125I]CA isozymes was studied in rats with whole‐hody autoradiograph! at various times after an intravenous injection. The distribution pattern showed a remarkable organ speciticity. CA I and CA III were to a great extent localized to the renal cortex. This is compatible with renal uptake, secondary to glomerular filtration, of these isozymcs. This would be expected from the renal handling of proteins with the following characteristics: molecular aeight of 29,000; iso‐electric points, pI, around 7.2 and 0.5 respectively. However, CA II of similar molecular shape and size, with a pI of 6.8, remained in the blood and was preferentially localized to the liver. Further studies are needed to clarify why such similar proteins are targeted to different organs.
Effects of N6, 2‘‐0‐dibutyryladenosine 3’,5‘‐cyclic monophosphate, adenosine, and of oxotremorine and 3‐isobutyl‐1‐methylxanthine on the electrically evoked [3H] acetylcholine secretion in the guinea‐pig ileum myenteric plexus
Authors: ALBERTS P.
Published: December 2008

The guinea‐pig ileum longitudinal muscle‐myenteric plexus preparation, pre‐incubated with [3H]choline, was mounted in an organ bath and superfused with Tyrode's solution. [3H]Acetylcholine secretion was evoked by 150 electrical shocks at 0.5 Hz.>N6,2′‐0‐Dibutyryladenosine 3′,5′‐cyclic monophosphate (dibutyryl cyclic AMP) enhanced the [3H]acetylcholine secretion in the presence of eserine and the adenosine receptor antagonist 8‐phenyltheophylline (10 μmol 1‐1). Conversely, in the absence of 8‐phenyltheophylline the [3H]acetylcholine secretion was reduced by dibutyryl cyclic AMP. In the absence and presence of 8‐phenyltheophylline(apparent KD= 12 μ.mol 1‐1), adenosine reduced the [3H]acetylcholine secretion to 33% of control (IC50= 8, μmol l‐1) and to 48% of control (IC50= 14 μmol l‐1) respectively. Neither butyrate, dibutyryl cyclic GMP nor guanosine altered the [3H]acetylcholine secretion.

Interaction experiments with 3‐isobutyl‐1‐methylxanthine and oxotremorine were done in the absence of eserine, i.e. when oxotremorine is effective. Oxotremorine depressed the fractional secretion of [3H]acetylcholine with a ‘maximal inhibition’ of 13% of control (IC50= 10 nmol l‐1). In the presence of 3‐isobutyl‐1‐methylxanthine (5 mmol l‐1) oxotremorine depressed the secretion to 2% of control with an apparent IC50) value of 0.9 μmol l‐13‐Isobutyl‐I‐methylxanthine (0.01–4 mmol l‐1) enhanced the fractional secretion of [3H]acetylcholine with a ‘maximal enhancement’ value of 232% of control (EC50= 0.19 mmol l‐1). The presence of oxotremorine (30 nmol l‐1) counteracted, and higher concentrations reversed, the enhancement caused by 3–isobutyl‐I‐methylxanthine.

The results are consistent with the suggestion that the presynaptic muscarinic acetylcholine receptor‐mediated control of the secretion of [3H]acetylcholine in the guinea‐pig ileum myenteric plexus may be mediated both by cyclic AMP and calcium ions.
Capsaicin and histamine antagonist‐sensitive mechanisms in the immediate allergic reaction of pig airways
Authors: ALVING K. , MATRAN R. , LACROIX J. S. , LUNDBERG J. M.
Published: December 2008

The airway vascular and bronchial responses were studied in pigs sensitized with Ascaris suum. Ascaris, histamine (H) and capsaicin aerosol all induced a clear‐cut increase in blood flow in the nasal, laryngeal and bronchial circulation with a decrease in vascular resistance of 20–40%. When delivered to the lung both ascaris and histamine, but not capsaicin, caused pulmonary airflow obstruction with increase in resistance and a fall in dynamic compliance of 40–70%. After pretreatment of pigs with a combination of the H1‐ and H2 ‐receptor antagonists terfenadine and cimetidine, the vascular and bronchial responses were strongly reduced to both histamine (by > 77%) and ascaris (by > 58%), but not to capsaicin aerosol. The bronchoconstriction to histamine was found to be mediated by H1‐receptors only, while both H1‐ and H2‐antagonists were necessary to block the vasodilatory response, with H2‐receptors being more important in the bronchial circulation and H1‐receptors being more important in the laryngeal and nasal circulation. Furthermore, when pigs were pretreated with capsaicin systemically 2 days before the experiment, the vasodilatation was decreased upon capsaicin (by 80%), ascaris (by > 40%) and histamine (by > 50%) aerosol challenge. When histamine was administered intravenously the desensitizing effect of capsaicin pretreatment was much less pronounced. The effect of capsaicin desensi‐tization on the pulmonary obstruction upon ascaris and histamine challenge was limited to a 60% reduction of the fall in dynamic compliance and a delayed peak in resistance upon ascaris challenge.

We conclude that histamine is one of the main vasodilatory mediators released upon allergen challenge at three different levels of the pig airways. A considerable part of the histamine effect is indirect and probably due to activation of capsaicin‐sensitive sensory nerves.
Stimulation of renin release by PGE2and PGI2infusion in the dog: enhancing effect of ureteral occlusion or administration of ethacrynic acid
Authors: BUGGE J. F. , STOKKE E. S. , VIKSE A. , KIIL F.
Published: December 2008

This study on 19 anaesthetized dogs had two objectives. The first was to compare the potencies of PGE2and PGI2as stimulators of renin release and demonstrate their dependency on activation of intrarenal mechanisms for renin release. The second objective was to demonstrate that ethacrynic acid (ECA) increases renin release not as a stimulator, but by activating intrarenal mechanisms. After inhibiting renal prostaglandin synthesis by indomethacin, PGE2and PGI2infused into the aorta proximal to the renal arteries exerted no significant effects on renin release, but increased renin release during ureteral occlusion. At equimolar infusion rates, PGI2increased renin release twice as much as PGE2, but this difference in potency may reflect differences in degradation since 86% of PGE2and 29% of PGI2(measured as 6‐keto‐PGFU) were degraded during one passage through the kidney. By infusing PGE2at 8 nmol min‐1and PGI2at 2 nmol min‐1renin release increased equally and the prostaglandin outputs increased to the same levels as during ureteral occlusion before indomethacin administration. ECA did not increase renin release after indomethacin administration. However, infusion of PGE2during continuous ECA administration increased renin release in a dose‐dependent manner similar to the experiments performed during ureteral occlusion. We conclude that PGI2and PGE2in the amounts synthesized in the kidney seem to be equally important stimulators of renin release but their relative potencies cannot be determined because the site of degradation is uncertain. Renin release is enhanced by intrarenal mechanisms activated by ECA infusion or ureteral occlusion, which both cause autoregulatory vasodilation and reduce NaCl reabsorption at the macula densa.
Transmitter characteristics of small mesenteric arteries from the rat
Authors: SJÖBLOM‐WIDFELDT N. , GUSTAFSSON H. , NILSSON H.
Published: December 2008

We have studied the neurogenic response of small mesenteric arteries from the rat to evaluate the involvement of possible co‐transmitters under various modes of stimulation.

Segments of small branches of the mesenteric artery were mounted in a myograph and the intramural nerves were activated with transmural electrical stimulation.

A single stimulation of the nerves caused a contraction that was reduced by only 20% in the presence of adrenergic blocking agents (prazosin or phenoxybenzamine), whereas the steady‐state response to continuous nerve stimulation of high frequency was reduced by 90–95 %. In contrast, all responses to applied noradrenaline in doses up to at least 1 mM were eliminated by phenoxybenzamine treatment. The stable ATP analogue, α,β‐methylene ATP, reduced the response to a single nerve stimulation by 70%, but reduced the contraction caused by continuous high‐frequency nerve stimulation by only 10%. None of these agents affected the response to applied neuropeptide Y (NPY). The response of relaxed vessels to nerve stimulation was totally blocked by the combination of an adrenoceptor‐blocking agent and α,β‐methylene ATP, although even in this situation a further neurogenic response could be revealed in vessels precontracted with vasopressin.

Responses to either single stimuli or brief burst stimulations were potentiated after high‐frequency stimulation. Both the adrenergic and non‐adrenergic components were enhanced to roughly the same extent. Also the potentiated response was eliminated by the combined application of prazosin and α,β‐methylene ATP.

The non‐adrenergic transmitter in the sympathetic nerves of small arteries thus appears to be the dominant transmitter during low‐frequency nerve stimulation, causing rapid but phasic activation. Noradrenaline is the most important transmitter for higher frequencies, exerting slower but sustained contractions. The post‐stimulatory potentiation affects both the adrenergic and the non‐adrenergic part of the neurogenic response.
Cooling enhances alpha2‐adrenoceptor‐mediated vasoconstriction in human hand veins
Authors: BODELSSON M. , ARNEKLO‐NOBIN B. , NOBIN A. , OWMAN CH. , SOLLERMAN C. , TÖRNEBRANDT K.
Published: December 2008

The contribution of different receptor subtypes in the contractile response during cooling in human hand vessels is of considerable interest in the understanding of cold‐induced peripheral vasospasm as it appears in Raynaud's phenomenon. Subcutaneous vein segments from 50 patients undergoing hand operations not related to vascular disorders were examined in vitro. The temperature in the organ bath was initially 37 °C and was either continuously lowered to 10 °C or kept constant at 37 °C, 29 °C or 20 °C. The characteristics of the α‐adrenoceptor‐mediated motor response were elucidated with the use of the α1‐antagonist, prazosin, and the α2‐antagonist, yohimbine. A great variability between individuals in the proportions of α1‐ and α2‐adrenoceptors was found. In the majority of the vessels continuous cooling to 25 °C augmented a noradrenaline‐induced contraction. This augmentation was unaltered in the presence of prazosin but abolished by yohimbine, suggesting that it was mediated via the α2‐adrenoceptor. In the remaining vessels with a predominating α1‐adrenoceptor‐mediated response a cold‐induced relaxation was registered. This could be the result of a reduced α1‐adrenoceptor‐mediated contraction at this low temperature. These varying reactions to cooling were unaffected by the β‐antagonist, propranolol, and by endothelial denudation. The results obtained in corresponding experiments with the α1‐agonist methoxamine and α2‐agonist, oxymetazoline, were conflicting, probably due to the poor selectivity of these agonists in human tissues. The results suggest that in patients with peripheral cold‐induced vasospasm administration of an α2‐adrenoceptor antagonist might be of therapeutic interest in order to relieve vasospasm in the hand vessels.
Evidence for an influence of CSF sodium concentration upon ACTH‐mediated Cortisol response to intravenous and intracerebroventricular angiotensin II
Authors: JUNKERGÅRD J. , AUGUSTINSSON O.
Published: December 2008

The influence of cerebrospinal fluid (CSF) NaCl concentration upon the Cortisol release induced by intracerebroventricular (i. c.v.) and intravenous (i. v.) infusions of angiotensin II (All) was studied in conscious goats. A first series of experiments involved i. c.v. infusion (20 min; 20 μl min‐1) of simply hypertonic (0.5 M) NaCl, or of All (2 pmol kg‐1min‐1) dissolved in 0.5 M or isotonic (0.15 M) NaCl or in isotonic glucose. The most pronounced rise in plasma Cortisol concentration (PC) was elicited by All in 0.5 M NaCl, but responses of nearly the same size were obtained by merely 0.5 M NaCl and by All in isotonic NaCl, whereas All in glucose induced a smaller PC rise. An urge to drink developed during all infusions, except during the All/glucose infusion. Here, however, thirst became apparent 2–6 min post‐infusion. When, in a second series, the hypertonicity of the NaCl was reduced to 0.3 M, and the dose of All to 0.5 pmol kg‐1min‐1, only the infusion of All in 0.3 M NaCl elicited any appreciable rise in PC. The response was approximately the same size as that earlier obtained as the effect of the larger dose of All dissolved in isotonic saline. In a third series of experiments, a 30‐min i. c.v. infusion of isotonic glucose, preceding and out‐lasting a 10‐min i. v. infusion of AN (40 pmol kg‐1min‐1), was found to extinguish the rise in PC obtained as the effect of a separate i. v. infusion of AIL The results suggest that the potency of i. c.v. as well as of systemic angiotensin in stimulating the pituitary‐adrenocortical axis is positively correlated to the Na concentration of the CSF.
Effect on cortical blood flow of electrical stimulation of trigeminal cerebrovascular nerve fibres in the rat
Authors: SUZUKI N. , HARDEBO J. E. , KÅHRSTRÖM J. , OWMAN CH.
Published: December 2008

It has recently been demonstrated in the rat that the majority of cerebrovascular pain fibres containing immunoreactive substance P and calcitonin gene‐related peptide reach the vessels via the nasociliary nerve, a branch of the ophthalmic trigeminal division. In order to elucidate the effect of these nerves on blood flow in vivo, the relative changes in cortical microvascular flow were continuously monitored by a laser‐Doppler flowmeter system during electrical nerve stimulation, with the central nerve connection cut and after removal of neighbouring dilatory parasympathetic nerves. The nasociliary nerve on one side was stimulated proximal to the ethmoidal foramen by a bipolar platinum electrode. Activation at different frequencies, continuously or as bursts with a constant voltage, impulse duration and total stimulus length, revealed that a maximum increase in blood flow amounting to 16.7% after 36 s was obtained with continuous stimulation at 10 Hz. Flow markedly declined during the following i‐min stimulation period. No changes in contralateral cortical blood flow, mean arterial blood pressure or blood gases were observed during or after stimulation. The present study demonstrates for the first time that direct and selective electrical activation of trigeminal cerebrovascular nerves induces an increase, albeit small and transient, in blood flow within the brain.
Enhanced vasoconstrictor effect of endothelin in cerebral arteries from rats with subarachnoid haemorrhage
Authors: ALAFACI C. , JANSEN I. , ARBAB M. A.‐R. , SHIOKAWA Y. , SVENDGAARD N.‐AA. , EDVINSSON L.
Published: December 2008

The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline‐injected controls. Endothelin elicited concentration‐dependent contractions of rat basilar artery segments. The endothelin‐induced contractions were much stronger in the SAH compared to control animals, which suggests a role in the pathophysiology of cerebral vasospasm.
Alpha‐adrenergic regulation of splanchnic volume and cardiac output in the dog
Authors: BELL L. , HENNECKEN J. , ZARET B. L. , RUTLEN D. L.
Published: December 2008

The present study examined whether α‐adrenergic stimulation causes a change in splanchnic intravascular volume in the anaesthetized animal with an intact circulation, which region(s) mediate the volume change, and whether the splanchnic volume change influences cardiac output. In order to ascertain that a radionuclide imaging technique could be used to assess total splanchnic volume changes, drugs known to increase or decrease splanchnic volume were infused on 21 occasions in eight dogs studied under conditions of selective perfusion and drainage of the splanchnic vasculature with erythrocytes labelled with99Tcmand a gamma camera placed over the abdomen. For these 21 infusions, volume and radionuclide count changes were related:r≥ 0.90 (n= 20),r= 0.76 (n= 1). After ascertaining tissue attenuation and blood radioactivity in four of the animals, the standard error for a single estimate of the absolute volume change using the radionuclide technique was determined to be 75 ml. In six animals with intact circulations, phenylephrine (40–80 μg min‐1) for 20 min was associated with an increase in cardiac output of 12 ± 2% (P< 0.001) and a decrease in total splanchnic volume estimated to be 431 ± 95 ml (P< 0.001). The splanchnic volume decrease was due entirely to decreases in splenic and intestinal volume. In eight eviscerated animals, cardiac output decreased by 30 ± 2% (P< 0.001) during phenylephrine. With 40–160 μg phenylephrine boluses in the splenic artery in three dogs, splenic volume decreased by 11 ± 2% (P< 0.001)and cardiac output increased by 18 ± 4% (P< 0.01), but neither parameter changed with left atrial boluses. Thus, a‐adrenergic stimulation is associated with a decrease in splanchnic volume in the animal with an intact circulation, and this decrease acts to increase cardiac output.
Influence of renal sympathectomy, sodium depletion and prostaglandin synthetase inhibition on prostaglandin production and [3H]PGE2binding characteristics in rat kidney
Authors: ERIKSSON L.‐O. , LARSSON B. , KULLENDORFF C.‐M. , ANDERSSON K.‐E.
Published: December 2008

The effects of renal sympathectomy (unilateral, renal microsurgical denervation), sodium depletion (hypovolemia) and prostaglandin synthetase inhibition on the rate of prostaglandin synthesis and [3H]PGE2binding characteristics were studied in the rat kidney. The intrarenal rate of prostaglandin synthesis was measured by monitoring the urinary excretion of 6‐keto‐PGFlα, the stable hydration product of prostacyclin. Dietary sodium restriction was associated with a 99% decrease in urinary sodium excretion (P< 0.001) and a 17% decrease of urine volume (n. s.). Renal denervation or sodium deprivation changed neither the rate of excretion of 6‐keto‐PGF1αnor the density or affinity of [3H]PGE2binding sites as compared to control. However, in sodium‐depleted rats, prostaglandin synthesis inhibition, induced by naproxen, decreased the urinary excretion of 6‐keto‐PGF1αby 40% (P= 0.011) and increased the number of [3H]PGE2binding sites by almost 30% (P=0.031) with no change in binding affinities as compared with sodium‐depleted controls. In contrast, sulindac was not able to suppress the renal synthesis and excretion of 6‐keto‐PGFla, and did not modulate the [3H]PGE2binding characteristics. The lack of effect on the excretion of 6‐keto‐PGF1aand on the [3H]PGE2binding characteristics supports the view that sulindac spares renal prostaglandin synthesis.
Colchicine inhibits the effects of secretin on pancreatic duct cell tubulovesicles and HC03 secretion in the pig
Authors: VEEL T. , BUANES T. , ENGELAND E. , RAEDER M. G.
Published: December 2008

Secretin stimulation clears the cytoplasm of intralobular pancreatic duct cells in pigs of tubulovesicles and causes these cells to secrete HCO3‐ into the pancreatic juice. To determine whether the clearance of cytoplasmic tubulovesicles involves the microtubule system and is important for initiation of HCO3‐ secretion, the effect of the microtubule poison colchicine on duct cell morphology and pancreatic HCO3‐ secretion was measured in anaesthetized pigs. Before colchicine, secretin reduced the density of tubulovesicles in the cytoplasm of pancreatic duct cells from 92 ± 8 U to 8 ± 2 U and initiated pancreatic secretion of 176 ± 21 μmol min‐1 HCO3‐. After colchicine, secretin failed to lower duct cell tubulovesicle density and caused the secretion of only 77 ± 14μmol min‐1 HCO3‐. By contrast, lumicolchicine, an isomer of colchicine that does not affect microtubules, did not inhibit pancreatic HCO3 secretion. Colchicine did not reduce carbonic anhydrase or Na,K‐ATPase activities in in‐vitro assays. The clearance of tubulovesicles from the cytoplasm of pancreatic duct cells therefore seems to be microtubule‐dependent and important for the pancreatic HCO3‐ secretion.
Angiotensin II stimulates airway ciliary motility in rabbit cultured tracheal epithelium
Authors: KOBAYASHI K. , TAMAOKI J. , SAKAI N. , KANEMURA T. , HORII S. , TAKIZAWA T.
Published: December 2008

We studied the effect of angiotensin II on ciliary activity in cultured rabbit tracheal epitheliumin vitro.Administration of angiotensin II (10‐6M) elicited an increase in ciliary beat frequency (CBF), as assessed by a photoelectric method, from the baseline value of 906 ± 21 to 1260 ± 33 beats min1(mean ± SE,P< 0.001). This ciliostimulatory effect was dose‐dependent, with the maximal increase and EC50value being 35.6 ± 5.2% (P< 0.001) and 5 ± 10‐12M respectively. Nifedipine, Ca2+‐free medium, indomethacin and the phospholipase A2inhibitor mepacrine, but not nordihydro‐guaiaretic acid, reduced the change in CBF. The ciliostimulation induced by angiotensin II was abolished by pretreatment of tissues with [Sar1‐Ile8]angiotensin II, an angiotensin II receptor antagonist. Angiotensin II did not increase cyclic AMP levels in epithelial cells. These results suggest that angiotensin II interacts with its specific receptors and stimulates airway ciliary activity through a Ca2+‐dependent prostaglandin release, without affecting intracellular cyclic AMP levels. Thus, angiotensin II may modulate mucociliary transport function in the respiratory tract.
Sympathetic transmission in small mesenteric arteries from the rat: influence of impulse pattern
Authors: SJÖBLOM‐WIDFELDT N. , NILSSON H.
Published: December 2008

We have previously studied the transmitters involved in, and the calcium dependency of, the neurogenic response to continuous, regular nerve stimulation in small mesenteric arteries from the rat. We have now studied responses to irregular nerve stimulation in these respects.

Small mesenteric arteries from rat were mounted into a myograph and the intramural sympathetic nerves were activated by field stimulation. Irregular nerve stimulation was patterned after recorded activity in human cutaneous nerves.

The response to irregular stimulation was reduced by only approximately 50% in the presence of the α1‐adrenoceptor antagonist prazosin. In particular, responses to low‐frequency stimulation were resistant to prazosin.

When the extracellular calcium concentration was reduced from 2.5 to 1.0 mM, approximately 50% of the response to irregular nerve stimulation remained. Responses to low‐frequency stimulation were particularly reduced.

Thus in these arteries the neurogenic response is caused by noradrenaline and a, perhaps purinergic, co‐transmitter. The co‐transmitter is important for the response to low‐frequency stimulation and for the initial part of the contraction caused by high‐frequency stimulation. Reducing the calcium concentration affects more strongly the response to low‐frequency nerve stimulation.