bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of verapamil on regional renal blood flow: a study using multichannel laser‐Doppler flowmetry
Authors: HANSELL P. , NYGREN A. , UEDA J.
Published: December 2008

In anaesthetized male Sprague Dawley rats the influence of the calcium entry blocker verapamil (2.4 mg h‐1kg‐1, i. v.) on renal superficial cortical (CO) and outer medullary (OM) blood flow was investigated with the aim of clucidating further the intrarenal heterogeneity in vasoreactivity. The blood flow of the two regions was monitored simultaneously with a laser‐Doppler flowmeter, using fibre probes with an outer diameter of 0.75 mm. One probe was directed towards the cortex and a second probe was inserted through the cortex and positioned in the outer medulla, measuring the flow within a hemisphere with a depth of 0.5‐1.0 mm. The OM probe position was verified by dissecting the kidneys after each experiment. Insertion of the OM probe did not affect whole‐kidney glomerular filtration rate, renal plasma flow or electrolyte excretion. Thirty minutes of verapamil infusion increased OM blood flow by 26%, but did not change CO blood flow (–1%). In spite of the increase in OM blood flow, the urine osmolality remained unaltered. Sodium excretion increased by 39%, while potassium excretion was unchanged. Mean arterial blood pressure decreased by 13%. In conclusion, this study has further supported the suggestion that the vasoreactivity is higher in the juxtamedullary than in the superficial cortical vasculature. The heterogeneity of the response is most probably due to the previously documented pressure drop along the interlobular arteries, which will create different haemodynamic conditions for the juxtamedullary and superficial afferent arterioles.
On the role of vasoactive intestinal polypeptide and tachykinins in the secretory reflex elicited by chemical peritonitis in the cat small intestine
Authors: BRUNSSON I. , FAHRENKRUG J. , JODAL M. , SJÖQVIST A. , THEODORSSON E. , LUNDGREN O.
Published: December 2008

Peritonitis induced by serosal application of 0.1 M hydrochloric acid causes net fluid secretion via the enteric nervous system. The aim of the present study was to investigate present study was to investigate the roles of vasoactive intestinal peptide (VIP) and tachykinins in this reflex(es). The release of tachykinins (substance P [SP], neurokinin A [NKA], neuropeptide K [NPK]) and VIP into the mesenteric circulation, net fluid transport, intestinal blood flow and sometimes motility were recorded simultaneously in extrinsically denervated jejunal segments of the catin vivo. The release of both VIP and NKA was increased upon application of HCI to the cat jejunal serosa. Tetrodotoxin, hexamethonium and methionine enkephalin inhibited both the induced VIP release and the secretory response. The increased release of NKA was unaffected by hexamethonium.

We propose that the intramural secretory reflex evoked by acid application of the serosa consists of an ‘afferent’ tachykinin neuron, a cholinergic interneuron and an ‘efferent’ VIPergic neuron innervating the secretory enterocytes.
Effects of noradrenaline and vasopressin analogues on resistance and capacitance vessels in the rat hindquarter preparation
Authors: GUSTAFSSON D. , ELG M. , MELIN P.
Published: December 2008

The isolated rat hindquarter preparation perfused at constant flow was used to determine resistance and capacitance responses from pressure and weight recordings. In response to noradrenaline at low concentrations, the capacitance effect was greater than the relative increase in total vascular resistance. 8‐L‐Arginine vasopressin showed capacitance responses only when the resistance vessel constriction was pronounced. Oxytocin and two synthetic analogues, 2‐phenylalanine‐8‐ornithine vasopressin (Phe‐Orn‐VP) and 2‐phenylalanine‐8‐ornithine oxytocin, showed varying potency for resistance vessel constriction but hardly any capacitance responses. However, when Phe‐Orn‐VP induced a small increase in total vascular resistance, a marked increase in post‐capillary resistance was observed. The results are discussed in relation to a study in which the effects of vasopressin analogues were studied with intravital microscopy (Altura 1973).
Relationship of recovery from intense exercise to the oxidative potential of skeletal muscle
Authors: JANSSON E. , DUDLEY G. A. , NORMAN B. , TESCH P. A.
Published: December 2008

This study examined if there was a relationship between the aerobic‐oxidative potential of skeletal muscle and the metabolic and force recovery after intense exercise. Eleven male subjects performed three bouts of unilateral knee extensions using an isokinetic device. Sixty seconds of rest separated bouts. Muscle biopsies were taken from the vastus lateralis prior to exercise, immediately after bout 2 and before bout 3. Samples were analysed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), inosine monophosphate (IMP), creatine phosphate (CP) and lactate contents and citrate synthase (CS) activity. Peak torque at the end of bout 2 was 45% of initial peak torque of bout 1 (IPT1). With recovery, initial peak torque of bout 3 (IPT3) was 81% of IPT1. Peak torque after recovery (IPT3/IPT1) was related to CS activity (r = 0.69). ATP, CP and ATP/ADP decreased with exercise. ADP, IMP and lactate increased. With recovery, ATP and CP remained depressed. IMP and lactate remained elevated. ATP/ADP and ADP returned towards ‘normal’, but only the latter attained resting levels. When analysing the individual responses the following correlations were found. After recovery, ATP/ADP (r = 0.57), ATP/ADP relative to rest (r = 0.71), lactate (r = ‐ 0.62), CP (r = 0.75) and CP relative to rest (r = 0.83) were related to CS activity. The changes in lactate (r = ‐ 0.76) and CP (r = 0.79) during recovery (bout 3 – bout 2) were also related to CS activity. The results suggest that the recovery of force and the ‘normalization’ of metabolite contents after short‐term, intense exercise are dependent on the aerobic‐oxidative potential of skeletal muscle. Thus, muscles with high CS activity showed marked decreases in lactate and increases in CP contents after recovery. A low CS activity, in contrast, was associated with no or only small recovery of these metabolites.
Mechanical work and efficiency in treadmill running at aerobic and anaerobic thresholds
Authors: LUHTANEN P. , RAHKILA P. , RUSKO H. , VIITASALO J. T.
Published: December 2008

Mechanical work, mechanical power, energy consumption and mechanical efficiency were studied in constant‐speed treadmill running of 5 min at seven different exercises around aerobic (AerT) and anaerobic (AnT) thresholds. The true efficiency of concentric (positive) mechanical work and gross efficiency of the whole body in seven male subjects were calculated. The total mechanical work was calculated from film through the translational, potential and rotational energy states as the sum of the changes of all the mechanical energy states in all body segments allowing energy transfer between segments and from energy state to state. The total energy consumption was measured by combining aerobic and anaerobic energy production in resting and working conditions. When the speed of the treadmill was increased from the velocity of 10 km h‐1 (2.8 m s‐1) to 22 km h‐1 (6.1 m s‐1), the concentric mechanical work per one step increased from 129 ± 45 J to 228 ± 82 J (P < 0.01). Oxygen consumption increased from 2.22 ± 0.27 l min‐1 to 4.47 ± 0.24 l min‐1. The amount of blood lactate increased from 0.94 ± 0.53 mmol l‐1 at the lowest speed to 9.90 ± 2.89 mmol l‐1 at the highest speed (P < 0.001). The true efficiency of concentric work decreased from 74 ± 14% to 56 ± 8% (P < 0.05). At the speed of the AerT, the economy of running, the vertical rise of different body segments and mechanical efficiency of positive work were high. The highest gross efficiency was found at the running speed between the AerT and AnT.
Effects of amrinone on the electromechanical coupling in frog skeletal muscle fibres
Authors: MÖRNER S. E. J. N. , MÅNSSON A.
Published: December 2008

The contractile effects of I.I mM amrinone were studied on isolated skeletal muscle fibres of the frog (2–5 °C, slack length). Amrinone potentiated the twitch amplitude and the maximum tetanic tension and also enhanced the maximum contracture response elicited by 117.5 mM K+(mean increase 6.3 ± 1.8 %,n= 6,P< 0.02). The time to halfrelaxation of the potassium contracture was slightly increased (mean change 13.8 ± 3.5%,n= 7,P< 0.01). Amrinone furthermore shifted the S‐shaped curve relating contracture tension to log K+to the left, and thus reduced the threshold depolarization (the mechanical threshold needed) to elicit a contracture (mean reduction 11 ± 1 mV). The duration of the action potential at the –25 mV level was slightly increased by amrinone, whereas the resting membrane potential was unaffected.
The role of protein kinase C in histamine secretion from mast cells
Authors: CHAKRAVARTY N.
Published: December 2008

Receptor activation on the cell surface is coupled through a guanine nucleotide regulatory protein to polyphosphoinositide phosphodiesterase. The activation of this enzyme catalyses the hydrolysis of phosphatidylinositol biphosphate. One of the products of this hydrolysis is diacylglycerol, which activates protein kinase C. It can also be activated by tumour‐promoting phorbol esters. The synthetic diacylglycerol, 1‐oleoyl‐2‐acetyl‐rac‐glycerol (OAG) and the phorbal ester 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) have been used to stimulate protein kinase C in a pure population of rat peritoneal mast cells. Both of them caused histamine release, but the rate of release with TPA or OAG alone was slow. The release was inhibited by blocking the oxidative energy metabolism with antimycin A, and was associated with progressive exocytosis, showing that it is a secretory process. Studies on the interaction between the stimulation of protein kinase C by OAG/TPA and the secretagogues showed a dual effect, both potentiation and inhibition. Antigen (in sensitized cells) and compound 48/80 showed this pattern of response. With the calcium ionophore, A23187, potentiation was the dominant effect, although some inhibition could be shown with TPA. This is possibly related to the large calcium influx which causes translocation of protein kinase C to the membranes and enhances its activity. The potentiation suggests that protein kinase C is involved in the secretion process by the secretagogues, while the inhibition reflects a regulatory function, which is apparently exerted through an inhibition of phosphatidylinositol breakdown.

Calcium uptake was enhanced by both TPA and OAG. Protein kinase C may thus contribute to the replenishment of the intracellular calcium stores after the secretory response.
Vascular adrenergic responses in morphine‐dependent rats
Authors: GUSTAFSSON H. , DELLE M. , NILSSON H.
Published: December 2008

The circulatory effects of morphine abstinence have recently been found to involve decreased renal sympathetic nerve activity and increased mean arterial pressure, induced by vasoconstriction. A direct influence of morphine withdrawal on the peripheral vasculature could possibly contribute to the increased resistance. Therefore, contractile responses to transmural nerve stimulation and to applied noradrenaline of peripheral arteries from morphine‐dependent and untreated rats were examinedin vitrounder paired conditions.

No increase in contractile response was observed after chronic morphine treatment, either on nerve stimulation or on applied noradrenaline. Instead the smooth muscle sensitivity to adrenergic stimulation was reduced. Consequently, the present study does not support a peripheral adrenergic origin of the vasoconstriction during naloxone‐precipitated morphine abstinence.
Diet‐induced changes in subcutaneous adipose tissue blood flow in man: effect of β‐adrenoceptor inhibition
Authors: SIMONSEN L. , BÜLOW J. , ASTRUP A. , MADSEN J. , CHRISTENSEN N. J.
Published: December 2008

The effect of a carbohydrate‐rich meal on subcutaneous adipose tissue blood flow was studied with and without continuous i. v. infusion of propranolol in healthy volunteers.

The subcutaneous adipose tissue blood flow was measured with the133Xe washout method in three different locations: the forearm, the thigh and the abdomen. The subjects were given a meal consisting of white bread, jam, honey and apple juice (about 2300 kJ). The meal induced a twofold increase in blood flow in the examined tissues. Propranolol abolished the flow increase in the thigh and the abdomen and reduced it in the forearm. This indicates that the mechanism for the flow increase is elicited by a stimulation of vascular β‐adrenoceptors in the subcutaneous adipose tissue, since the β‐adrenoceptor inhibition did not affect the overall metabolic and hormonal responses to the meal.
Depressed metabolism and low protein catabolism in fasting grey seal pups
Authors: NORDØY E. S. , INGEBRETSEN O. C. , BLIX A. S.
Published: December 2008

Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid‐October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 ± 0.15 (SEM) W kg‐1 at day 2 of fasting to a stable level of 1.62 ± 0.06 (SEM) W kg‐1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 ± 8 (SEM) nmol 1‐1 throughout the fasting period. Daily urinary output decreased from 236 ± 20 (SEM) ml day‐1 at day 2 to a stable value of 87 ± 6 (SEM) ml day‐1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end‐product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770–1300 mosmol kg‐1). Total excreted urinary nitrogen decreased by 68% from 3.7±0.7 (SEM) g day‐1 to 1.2 ± 0.4(SEM) g day‐1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post‐weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.
Biochemical characterization and autoradiographic localization of [3H]PGE2binding sites in rat kidney
Authors: ERIKSSON L.‐O. , LARSSON B. , ANDERSSON K.‐E.
Published: December 2008

Specific binding sites for prostaglandin E2(PGE2) in membranes obtained from whole kidney and from different areas of rat renal tissue were identified and quantified byin‐vitroradioligand binding and localized by autoradiography. Analysis of the [3H]PGE2binding by Scatchard plots revealed a single class of high‐affinity binding sites in the whole kidney (KD= 5.1 ± 0.4 nM; 5max= 75 ± 9 fmol mg‐1protein), the cortex (KD= 6.1 ± 0.5 nM; Bmax= 58 ± 5 fmol mg‐1protein) and the outer medulla (KD= 3.3 ± 0.3 nM; Bmax= 376 ± 59 fmol mg‐1protein). No reproducible Scatchard plots could be obtained in the inner medulla. PGE1was equipotent with PGE2in inhibiting [3H]PGE2binding, whereas PGA2, PGB2, PGF2αand PGI2were 10‐ to 1000‐fold less potent. Autoradiographs revealed sparse or no binding in glomeruli, proximal tubules or blood vessels. The pattern of distribution of [3H]PGE2binding was consistent with the anatomical localization of the distal tubule and in particular the thick ascending limbs of Henle. Based on the distribution and cellular localization of the [3H]PGE2binding sites, our data support the hypothesis that the physiological role of PGE2receptors is coupled to the regulation of sodium transport across segments of the distal tubule.
Influence of reduced glycogen level on glycogenolysis during short‐term stimulation in man
Authors: REN J. M. , BROBERG S. , SAHLIN K. , HULTMAN E.
Published: December 2008

The relationship between muscle glycogen concentration and the rate of glycogen breakdown during short, intense contraction has been investigated in man. Prior to the experiment, muscle glycogen content was manipulated by a combination of exercise and diet, and varied from 155 ± 19 to 350 ± 25 mmol kg‐1 dry muscle (36–81 mmol kg‐1 wet wt). The quadriceps femoris muscle was stimulated electrically at a frequency of 20 Hz for 1 min. The blood flow to the leg was occluded during the experiment and muscle biopsies were taken before and after 10, 30 and 60 s stimulation. Force development and glycogenolytic rate were maintained constant during electrical stimulation and similar in all conditions, irrespective of the initial glycogen concentration. The phosphorylase a fraction was increased after 10 s stimulation, but returned to the initial values at the end of the stimulation. Muscle ATP was unaltered during the first 30 s stimulation, but decreased thereafter. The decrease in ATP was accompanied by a stoichiometric increase in inosine monophosphate. Phosphocreatine decreased during stimulation and was almost depleted at the end of stimulation. Muscle lactate and glucose 6‐phosphate (Glu 6‐P) increased during stimulation. None of these changes was significantly affected by the reduced glycogen contents. It is concluded that the rate of muscle glycogen breakdown is not affected by the initial glycogen level in the range of 155 ± 19 to 350 ± 25 mmol kg‐1 dry muscle.
Resumption of rat oocyte meiosis is paralleled by a decrease in guanosine 3‘,5’‐cyclic monophosphate (cGMP) and is inhibited by microinjection of cGMP
Authors: TÖRNELL J. , BILLIG H. , HILLENSJÖ T.
Published: December 2008

The aim of the present study was to measure the level of cyclic GMP (cGMP) compared with the level of cyclic AMP (cAMP) in rat oocytes during resumption of meiosis I (oocyte maturation) and to microinject these cyclic nucleotides into the oocyte to study their effects on oocyte maturation. Immature oocytes were obtamed from prepubertal rats primed with pregnant mare's serum gonadotropin. Oocytes were isolated and short‐term cultured under conditions enabling spontaneous maturation. The levels of cGMP and cAMP decreased in the oocyte during spontaneous maturation (from 0.41 to 0.25 and from 0.64 to 0.42 fmol per oocyte respectively). The decrease was observed during the first hour of culture, and no further decline was seen after 2 h. Microinjection of cGMP or cAMP into isolated immature oocytes delayed the spontaneous maturation, cGMP being slightly more effective than cAMP, whereas 2‐deoxy‐cAMP (which does not stimulate protein kinase A) did not.

These results demonstrate for the first time that the level of cGMP decreases in the oocyte parallel to spontaneous meiosis, as already shown for cAMP. This suggests that cGMP, as well as cAMP, may be of importance for regulating this process. This assumption is further supported by data demonstrating a delay in the maturation of oocytes injected with cGMP.
Resistance responses in proximal arterial vessels, arterioles and veins during reactive hyperaemia in skeletal muscle and their underlying regulatory mechanisms
Authors: BJÖRNBERG J. , ALBERT U. , MELLANDER S.
Published: December 2008

The reactive hyperaemia response cat skeletal muscle to 2–120 s arterial occlusions was analysed with regard to amplitude, duration, ‘excess blood flow’ and site of dilator action along the vascular bed. The last‐mentioned was assessed with a new whole‐organ technique permitting continuous segmental resistance recordings in arterial vessels > 25 μm, arterioles < 25 μm and veins. Peak amplitude, duration and excess flow all increased with increasing occlusion length, of which excess flow was linearly related to occlusion length. The site of active dilatation was preferentially confined to arterioles < 25 μm in which complete relaxation was observed after only 20 s occlusion, although the duration of the response continued to increase with more prolonged occlusions. A graded, but less pronounced, dilatation occurred in the arterial vessels > 25 μm and in the veins, the former exhibiting a 63% inhibition of tone as a maximum response at 120 s occlusion. The recovery phase was characterized by a vivid active constrictor component apparently protecting the capillaries from excessive pressure load upon arterial occlusion release, but this constriction became attenuated at long occlusions, thereby prolonging the hyperaemia response. The role of myogenic regulatory mechanisms in the responses was assessed from observed segmental resistance reactions to selectively applied transmural pressure stimuli similar to those elicited by arterial occlusion/release. It was concluded that myogenic mechanisms alone could explain the amplitude of the reactive hyperaemia response at short (up to 30 s) occlusions. Metabolic mechanisms seemed to be responsible for further relaxation of the proximal arterial vessels at longer occlusions, and also for the increased duration of the hyperaemia response at occlusions exceeding 10 s. Blockade of nitric oxide formation (endothelium‐derived relaxing factor) did not seem to affect the reactive hyperaemia response.
Inotropic mechanisms of amrinone in papillary muscles from guinea‐pig hearts
Authors: MÖRNER S. E. J. N. , WOHLFART B.
Published: December 2008

Isometric force and action potentials were recorded in papillary muscles from guinea‐pigs (temperature 33 d̀C, stimulation frequency 0.5 Hz). Amrinone (1 mM) increased peak twitch force (to 220% of control,n= 12) and rate of rise of force (to 221% of control,n= 12), while time from peak to half‐relaxation was markedly reduced (to 70% of control). The time to peak force was not significantly changed. Action potential at 50% repolarization was shortened (93.3% of control,n= 8), whereas plateau voltage became more positive. Peak twitch force in response to a test stimulus after a varied interval, i.e. mechanical restitution, was increased at all intervals by the drug. However, the time to full mechanical restitution (1.5 s) was not affected. Forces in response to the test interval preceding the previous contraction (post‐extrasystolic potentiation) were analysed. Maximum potentiation was 16.0 mN mm‐2(2.7 ± 0.4%) before and 22.6 mN mm‐2(1.7 ± 0.1%) after addition of the drug, i.e., the relative potentiation was diminished in the presence of the drug. The test interval for optimum potentiation was shortened from 370 to 320 ms (P < 0.05,n= 12) in 1 mM amrinone. During decay of post‐extrasystolic potentiation peak force of the post‐potentiated contraction was linearly related to force of the potentiated contraction. The slope of this line (which is believed to monitor recirculation of activator calcium) was increased by amrinone from 0.37 to 0.50 (P < 0.01,n= 12). The results support the view that the positive inotropic action of amrinone is due to (1) an enhanced calcium inflow during excitation and (2) a more rapid and (3) a more effective calcium uptake by the sarcoplasmic reticulum.
Galanin of the homologous species inhibits insulin secretion in the rat and in the pig
Authors: LINDSKOG S. , DUNNING B. E. , MÅRTENSSON H. , AR'RAJAB A. , TABORSKY G. J. , AHREN B.
Published: December 2008

It is known that pig galanin inhibits insulin secretion in dogs, rats and mice. The present study examined whether species‐specific, homologous, galanin inhibits insulin secretion. Thus, the effects of rat galanin were examined in the rat, and the effects of pig galanin were examined in the pig, both in vivo and in vitro. In conscious rats, synthetic rat galanin (2 nmol kg‐1) abolished the glucose‐ (0.56 mmol kg‐1) induced increase in plasma insulin levels. In vitro, rat galanin (10‐9 to 10‐6 mol l‐1) inhibited glucose‐ (8.3 mmol l‐1) stimulated insulin release from isolated rat islets. In anaesthetized pigs, 15 min infusion of synthetic pig galanin (207 pmol min‐1) into the pancreatic artery decreased the insulin output with a subsequent recovery. In vitro, pig galanin (10‐6 mol l‐1) inhibited glucose‐ (8.3 mmol l‐1) stimulated insulin release from isolated pig islets. We conclude that homologous galanin inhibits insulin secretion in both the rat and the pig.
Force production following transient potential changes in voltage‐clamped myocardium
Authors: ARLOCK P. , WOHLFART B.
Published: December 2008

Inter‐relationships between force, membrane voltage and currents were studied in ferret and guinea‐pig papillary muscles using the single sucrose gap technique (37 “C). The preparations were held at — 90 or — 40 mV and depolarized (excited) to 0 mV for 180 ms at 1.0 Hz. At regular intervals the shape of a single clamp pulse (called ‘ 1’) was varied and its effects were investigated during the same test cycle and in two subsequent test cycles (‘2’ and ‘3’). Peak force of contraction 1 (Fl) increased with the duration of the test clamp up to 90 ms and was constant thereafter. F1 increased with clamp amplitude (Vl) between —30 and 10 mV and decreased at greater amplitudes. This relation was similar to the relation between peak second inward current (11) and V1. The peak force of contractions 2 and 3 rose with the clamp duration and clamp amplitudes of cycle 1. The relation between F3 and F2 was linear (slope 0.40), except at the lowest and highest F2 values where there was a small deviation. There was an inverse relation between I2 and F2. The results support the idea that increased duration or amplitude of the voltage clamp pulse leads to a greater calcium entry which is manifested in the following potentiated contraction. The relation between F3 and F2 implies that about 40% of calcium recirculates between the contractions. The inverse relationship between F2 and I2 indicates that the second inward current is regulated by release from the sarcoplasmic reticulum via negative feedback.
Histamine receptors in brain vessels of guinea‐pig:in‐vitropharmacology and ligand binding
Authors: OTTOSSON A. , HILL S. J. , EDVINSSON L.
Published: December 2008

The subtype of histamine receptors in brain vessels of guinea‐pig has been characterized by ligand binding andin‐vitropharmacology using selective antagonists. In the basilar artery histamine caused a concentration‐related contraction with an EC50of 1.6 ± 0.3, μ m. H1‐receptor blockade with mepyramine and chlorpheniramine caused a displacement to the right of the histamine concentration‐response curve with an apparentKDof 0.4 and 4.6 nM respectively, whereas H2‐receptor blockade with cimetidine was without effect. Histamine did not induce any dilatatory responses of vessels procontracted by 60 mM potassium‐containing buffer in the presence or absence of histamine antagonists. Ligand‐binding studies with [3H]mepyramine yielded aKDvalue of 5.5 nM in pial vessel membranes and 1.7 nM in the choroid plexus, confirming the presence of H1‐receptors. Nimodipine caused a concentration‐related blockade of histamine‐induced contractions. Omission of Ca2+from the extracellular medium for 30 min reduced the contractile responses to histamine in the basilar artery by 96%. Subsequent addition of Ca2+caused concentration‐related contractions which were inhibited by nimodipine. Thus, the histamine H1‐receptor activation in guinea‐pig basilar artery is coupled to dihydropyridine‐sensitive Ca2+channels.
Lactate and potassium fluxes from human skeletal muscle during and after intense, dynamic, knee extensor exercise
Authors: JUEL C. , BANGSBO J. , GRAHAM T. , SALTIN B.
Published: December 2008

This study examines lactate and K+ fluxes from muscle to blood during and after intense exercise. Ten men performed exhaustive dynamic exercise (mean load 65 W, mean duration 3.18 min) with the knee extensors of one leg. The mean lactate efflux was 15.5 (range 8.9–24.0) mmol min‐1 at exhaustion, and it was linearly related to the lactate gradient. A linear relationship was also obtained if the H+ gradient was taken into account. Muscle pH decreased from 7.14 at rest to 6.71 (range 6.50–6.87) at exhaustion. At rest and during late recovery blood lactate was distributed across the erythrocyte membrane according to the membrane potential (intra‐/extracellular ratio of 0.5), but during rapid lactate release this ratio decreased to 0.2. In‐vitro experiments demonstrated a time constant of 1.2 min for lactate efflux from the erythrocytes.

Approximately 70% of the K+ ions released from the muscle to the blood accumulated in the plasma; the rest were taken up by other tissues. However, erythrocytes were not involved as a dilution space. The small change in erythrocyte K+ concentration was due to cellular volume changes. During recovery the kinetics of K+ reuptake by the muscle were described by a very fast (< 1 min) and a slow component (> 1 min): the magnitude of the former was equivalent to what had accumulated in the plasma. Individuals displayed a wide range of intramuscular lactate concentrations and pH values at exhaustion. Further, the pH changes were not as extreme as previously reported, suggesting that pH may not be the only factor involved in the fatigue process. A possible role for the potassium shifts as a limiting factor for muscle function is discussed.
The effect of a meal on cardiac output in man at rest and during moderate exercise
Authors: WAALER B. A. , ERIKSEN M. , JANBU T.
Published: December 2008

Cardiac output at rest increased by 11–63 % in a group of healthy individuals after the consumption of a medium‐sized, mixed meal. The maximum post‐prandial levels of cardiac output were reached from 10 to 30 min after termination of the meal. Cardiac output values at rest fluctuate around a mean level, and this fluctuation was considerably more marked after a meal, when changes in cardiac output from one 15–s period to another could be of the order of 1–1.5 1 min‐l.

Recording of flow in the superior mesenteric artery before and also after a meal was successful in two subjects in whom anatomical conditions were favourable. Flow in the artery was approximately doubled from the fasting to the post‐prandial situation, an augmentation that accounted for about 50% of the concomitant increase in cardiac output.

The increases in cardiac output caused by 2–min bouts of standardized, moderate and rhythmic exercise were consistently larger in the post‐prandial than in the fasting situation. It thus appears that any tendency for redistribution of blood flow, for example from the gastrointestinal tract to the working muscles, during moderately intense exercise is less marked after a meal than before.
Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders
Authors: KLITGAARD H. , ZHOU M. , RICHTER E. A.
Published: December 2008

The myosin heavy chain (MHC) composition of single fibres from m. biceps brachii of young sedentary men (28 ± 0.4 years, mean ± SE, n= 4) and male body builders (25 ± 2.0 years, n= 4) was analysed with a sensitive one‐dimensional electrophoretic technique. Compared with sedentary men, the body builders had a higher proportion of fibres containing only MHC type IIa (36 ± 4 us 12 ±2%; P < 0.05), but a lower proportion of fibres with a coexistence of MHC types IIa and IIb (16 ± 3 us 34 ± 2%; P < 0.05) and nearly no fibres containing only MHC type IIb(1 ±1vs12 ±1%;P< 0.05). Myofibrillar ATPase histochemistry only demonstrated a trend towards a higher proportion of type IIa fibres (31 ± 6 us 25 ± 6%)and a lower proportion of type IIb fibres (18 ± 5 us 26 ± 6%) within the body builders. These results, therefore, suggest an altered expression of MHC isoforms within histochemical type II fibres of human skeletal muscle with body building. Furthermore, in human skeletal muscle differences in expression of MHC isoforms may not always be reflected in the traditional histochemical classification of types I, IIa, IIb and IIc fibres.
Effect of 12‐O‐tetradecanoyl phorbol 13‐acetate on solute transport and production of cAMP in isolated frog skin
Authors: ANDERSEN H. , BJERREGAARD H. , NIELSEN R.
Published: December 2008

In the present study we have examined the action of the phorbol diester tetradecanoyl phorbol acetate, an activator of protein kinase C, on the transepithelial transport of sodium, chloride and water and the production of cAMP in the isolated frog skin epithelium (Rana esculenta).

Addition of tetradecanoyl phorbol acetate to the mucosal solution resulted initially in an increase in the short‐circuit current, which was followed by a progressive decrease. If the short‐circuit current was first activated by addition of the antidiuretic hormone, arginine vasotocin, then the addition of tetradecanoyl phorbol acetate resulted only in a pronounced inhibition. The changes in the short‐circuit current were the result of changes in the active influx of Na+.

The effect of tetradecanoyl phorbol acetate on the intracellular potential measured under short‐circuited conditions (Vscc) was time‐dependent. Just after addition of tetradecanoyl phorbol acetate to the mucosal solution. Vscc depolarized; this was followed by a slight hyperpolarization, after which Vscc continued to decline.

The inhibition of the Na+ transport by tetradecanoyl phorbol acetate was associated with a decline in the response to the antidiuretic hormone (arginine vasotocin), but the ability of arginine vasotocin to increase the cellular level of cAMP and to stimulate the osmotic water flow was not affected by the presence of tetradecanoyl phorbol acetate.

In skin halves in which the short‐circuit current was stimulated with arginine vasotocin, addition of tetradecanoyl phorbol acetate resulted in a dose‐dependent inhibition of the short‐circuit current, but only minor changes in Vscc were observed.

The results presented suggest that the addition of tetradecanoyl phorbol acetate to the isolated frog skin first increases and then decreases the arginine vasotocin‐sensitive sodium permeability of the apical membrane. This might be due to a stimulating effect of tetradecanoyl phorbol acetate on both the activation and deactivation (turnover) of the sodium channels.
Effects of isozyme‐selective phosphodiesterase inhibitors on rat aorta and human platelets: smooth muscle tone, platelet aggregation and cAMP levels
Authors: LINDGREN S. H. S. , ANDERSSON T. L. G. , VINGE E. , ANDERSSON K.‐E.
Published: December 2008

The inhibitors of the cGMP‐inhibited, low‐KmcAMP phosphodiesterase—milrinone and OPC 3911‐and an inhibitor of a non‐cGMP‐inhibited low‐KmcAMP phosphodiesterase—rolipram—were used to evaluate the functional importance of the two cAMP phosphodiesterase activities in vascular smooth muscle and in platelets. Vinpocetine, an inhibitor of a calcium‐calmodulin‐dependent phosphodiesterase was also studied. OPC 3911 and milrinone relaxed the contracted rat aorta, inhibited ADP‐induced platelet aggregation and also enhanced isoprenaline‐induced relaxation as well as the antiaggregatory effects of adenosine. In platelets, OPC 3911 and milrinone increased cAMP levels, but in the rat aorta the increase was significant only for milrinone (OPC 3911P= 0.062). In both tissues OPC 3911 and milrinone enhanced the increase in cAMP caused by activators of adenylate cyclase (isoprenaline/adenosine). Rolipram had no effects on aggregation or cAMP levels in platelets and no overadditive effects in combination with adenosine. Rolipram had little effect on relaxation and cAMP levels, did not alter isoprenaline‐induced relaxation of guanfacin‐contracted rat aorta, but showed synergistic effects with isoprenaline in raising cAMP levels. In PGF2α‐contracted aorta rolipram enhanced relaxation caused by isoprenaline. Vinpocetine had a relaxant effect without affecting cAMP levels, but had no effect on platelets. These results support the concept that the cGMP‐inhibited phosphodiesterase is an important modulator of vascular smooth muscle tone and platelet function. The role of the non‐cGMP‐inhibited phosphodiesterase in these tissues is less obvious.
Forces involved in transcapillary fluid movement in exercising cat skeletal muscle
Authors: BJÖRNBERG J.
Published: December 2008

Average capillary pressure (Pe) close to the venous end (fluid equilibrium point) of the exchange vessels (denoted Pev) arterial (PA) and venous pressure, and the rate of net transcapillary fluid flux were continuously recorded in sympathectomized muscle during 30 min of graded exercise and for 30 min in the post‐exercise period. Regional changes in colloid osmotic pressure (±p1) and total osmolality in plasma, the latter reflecting work‐induced interstitial hyperosmolality, were measured at intervals. In the control state at rest with a Starling fluid equilibrium, Pcv, averaged 17.6±40.8 mmHg. Exercise caused a rapid transcapillary plasma fluid loss, the net driving pressure for which in the initial phase of heavy work was 58 mmHg (transcapillary fluid flux divided by the capillary filtration coefficient). This comprised an increase in Pcv of 16 mmHg, a nonprotein osmotic force (Posm) related to exercise‐induced tissue hyperosmolality corresponding to 46 mmHg and an opposing force established by a raised ±p1 of 4 mmHg. A theoretical analysis indicated that the main fraction of the osmotic fluid loss passed through transcellular ultrapores and only a minor part through conventional small pores. In spite of the fact that Pc remained high throughout the exercise period, the outward fluid flux gradually declined and a Starling equilibrium was re‐established 23 min after the commencement of heavy exercise. This was explained by a gradual decline of Posm and apparently also by a secondary increase in tissue pressure (Pu) and/or a decrease in interstitial colloid osmotic pressure (±if). Net fluid absorption occurred in the post‐exercise period as a result of a gradual decrease in Pe, reversed transcapillary Posm and also maintained high Pif and/or low ±if. Exercise (even light) abolished normal Pc autoregulation, implying that the filtration component of net transcapillary fluid flux becomes distinctly modulated if PA is altered.
Adenosine A1‐receptor‐mediated inhibition of evoked acetylcholine release in the rat hippocampus does not depend on protein kinase C
Authors: FREDHOLM B. B.
Published: December 2008

The possible involvement of protein kinase C and/or a lipoxygenase product in the mechanism by which adenosine inhibits release of [3H]acetylcholine evoked by electrical pulses from [3H]choline‐labelled hippocampal slices was examined. For comparison, the muscarinic autoreceptors were examined using carbachol. The order of potency of adenosine analogues (CHA = R‐PIA > NECA± CGS 21680, CV 1808) indicates that the adenosine receptor responsible is of the A1subtype. Adenosine (10 μM) and R‐PIA (0.1 μm) were virtually equiactive as inhibitors and were antagonized to an equal extent by 8–CPT with a potency (IC50approximately 25 nm) which is also compatible with A1‐receptor mediation. The effects of carbachol and of R‐PIA were not antagonized by the lipoxygenase inhibitor NDGA (10 or 50 μm). Stimulation of protein kinase C by the phorbol ester 4β‐phorbol 12, 13–dibutyrate caused a concentration‐dependent increase in stimulation‐evoked3H overflow, but did not antagonize the presynaptic inhibitory effect of R‐PIA or carbachol (0.01–1 μm). Staurosporine (0.1 μm), which inhibited the stimulating effect of phorbol dibutyrate, did not alter the effects of carbachol or R‐PIA. The presynaptic effects of phorbol dibutyrate, R‐PIA and adenosine were reduced by pretreatment withN‐ethylmaleimide (100, μ M for 10 min), which inactivates G‐proteins. The evoked transmitter release was unaffected by nifedipine (1 μ M) in the presence and in the absence of phorbol dibutyrate.

These results indicate that adenosine, by acting at presynaptic A,‐receptors, reduces transmitter release by a mechanism that involves neither an NDGA‐sensitive lipoxygenase nor protein kinase C. The results also indicate that the enhancement of transmitter release by phorbol esters is due to protein kinase C activation and that a G‐protein may be involved in the effect but a dihydropyridine‐sensitive L‐type Ca2+channel probably is not.
Adrenergic influence on bile secretion—an experimental study in the cat
Authors: FRIMAN S. , RADBERG G. , SVANVIK J.
Published: December 2008

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h‐1kg‐1body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an α‐adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly α‐adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a β‐adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the α‐adrenergic receptors reduces the bile acid‐independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.
The effects of μ, δ‐ and ±‐opioid receptor antagonists on the pain threshold increase following muscle stimulation in the rat
Authors: HOFFMANN P. , CARLSSON S. , THORÉN P.
Published: December 2008

In a previous study, prolonged low‐frequency muscle stimulation, inducing dynamic contractions in the hind leg of unanaesthetized rats, was shown to give rise to a hypoalgesia. The increase in pain threshold, measured as squeak threshold to noxious electric pulses, lasted 3 h.

In the present study, the involvement of the endogenous opioid system in the post‐stimulatory analgesia was investigated using selective opioid receptor antagonists. The post‐stimulatory analgesia was completely reversed back to prestimulatory control levels by naloxone, 1 mg kg‐1. ICI 154, 129 and MR 2266 BS, selective δ‐ and ±‐receptor antagonists respectively, did not significantly influence the post‐stimulatory analgesia, although ICI 154, 129 had a minor pain threshold‐lowering effect. Rats pretreated with β‐funaltrexamine, a μ‐preceptor antagonist, did not exhibit any post‐stimulatory analgesia.

These results suggest that opioid systems are involved in the increase in pain threshold after muscle stimulation and that the analgesic response is both elicited and maintained by the μ‐preceptor.
Functional responses of different muscle types of the female rat urethra in vitro
Authors: ANDERSSON P. O. , MALMGREN A. , UVELIUS B.
Published: December 2008

The influence of muscle type on functional responses of the female rat urethra was investigated using morphological and functional in‐vitro techniques. The urethral submucosa was found to contain longitudinally or obliquely oriented smooth muscle cells. The muscularis layer is composed of circularly oriented muscle cells. Near the bladder orifice smooth muscle fibres dominate, but in the mid‐urethra the vast majority is circularly oriented striated muscle cells.

Circular preparations responded to electrical field stimulation in vitro with a rapid contraction. Stimulation with single impulses resulted in a twitch response; frequencies exceeding 5–10 Hz induced a summation and tetanus. The response was unaffected by phenoxybenzamine, propranolol and scopolamine and had a low sensitivity to calcium‐free solution but was sensitive to suxamethonium and tetrodotoxin. Using longer impulse trains stimulation evoked also a slow contraction, sensitive to calcium‐free solution.

In longitudinal preparations stimulation induced a relaxation followed by a contraction, responses much smaller than those seen in the circular preparations.

Both preparations relaxed on addition of calcitonin gene‐related peptide or capsaicin. The relaxation to calcitonin gene‐related peptide was larger than that to capsaicin in longitudinal preparations but equally large in the circular ones. Substance P and 5‐hydroxytryptamine contracted both preparations. The longitudinal urethra showed a larger contraction to 5‐hydroxytryptamine than to substance P, whereas both substances induced similar responses in the circular preparations.

The study shows a similar muscle arrangement in the female rat urethra as described in humans and further points to a functional differentiation between the different types of muscle.
The role of Ca2+in the time‐dependent pepsinogen secretion of frog oesophageal peptic glands stimulated by bombesin
Authors: HIRSCHOWITZ B. I. , UEMURA N. , MATSUMOTO H. , E.J. DICKINSON K.
Published: December 2008

Time‐ and dose‐related stimulation of pepsinogen secretion by bombesin was studied in perifused dispersed peptic glands from the oesophagus of the American bullfrogRana catesbeiana. The dose response to bombesin was monophasic between 10‐10and 10‐7M, with an EC50of 10‐9M. Time‐dependent secretion was closely monitored at 1–2 min intervals. Though there was overlap, we could discriminate an early response at ˜ 2 min (phase I) and a delayed or sustained response at ± 2 min (phase II) on the basis of responses in the presence and absence of external Ca2+. Phase I was relatively independent of external [Ca2+] and coincided with45Ca efflux following a dose‐dependent increase in cytosolic [Ca2+], measured by Fura‐2AM. Phase II was sustained at ˜ 80% of control at an external [Ca2+] of 1–5,μM, but was eliminated by adding 0.5–1 MmEGTA. Bombesin caused a sustained Ca2+influx and, when this was prevented by EGTA, the response to successive stimulations by bombesin and by acetylcholine was greatly attenuated. The phorbol ester, 12–O‐tetradecanoyl phorbol 13–acetate, which stimulates secretion at high concentrations, was used as background at a thresehold concentration of 10‐7M, which did not by itself stimulate secretion. At this concentration, 12–O‐tetradecanoyl phorbol 13–acetate potentiated the responses to bombesin and to acetylcholine. These results define the different Ca2+dependencies of the immediate and sustained secretory responses to bombesin, but indicate a complex relationship of stimulation responses to Ca2+homeostasis in various agonist‐sensitive Ca2+pools.
Isoprenaline augments total myocardial K+influx of thein‐situbeating porcine heart
Authors: ANDERSEN F. R. , SEJERSTED O. M. , ILEBEKK A.
Published: December 2008

To determine the total rate of K+flux into myocardial cells of thein‐situbeating heart and how this influx is affected by β‐adrenoceptor stimulation, we measured42K+content in myocardial biopsies taken at intervals after an intra‐atrial infusion of42K+before and during an i.v. isoprenaline infusion (20 μgmin‐l) in six anaesthetized, open‐chest pigs. Determination of the total K+influx during β‐adrenoceptor stimulation was initiated 10 min after the start of isoprenaline infusion, when the transient net myocardial K+uptake had subsided. Total K+influx increased from a control value of 414 ± 42 to 1086 ± 246pmol 100 g‐1min‐1during isoprenaline infusion. A quantitatively smaller increase in K+influx carried by the Na+‐K+pump has previously been demonstrated during isoprenaline infusion. Left ventriculardP/dtrose from 1350 ± 146 to 4833 ± 150 mmHg s‐l, stroke volume remained unchanged, but heart rate and peak left ventricular systolic pressure rose as expected, by 52 ± 4 and 32 ± 4% respectively during isoprenaline stimulation. All haemodynamic parameters, total plasma K+concentration and plasma42K+activity remained stable throughout each experimental period. The number of ouabain binding sites was 65.5 ± 1.0 before and 66.9 ± 1.6 nmol 100 g‐lduring isoprenaline infusion (difference n.s.). The present data indicate that not only the K+influx carried by the ouabain‐sensitive Na+‐K+pump but also the influx through ouabain‐insensitive pathways is increased during β‐adrenoceptor stimulation of thein‐situbeating pig heart.