bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid simultaneous determination of regional blood flow and blood‐brain glucose transfer in brain of rat1
Authors: GJEDDE A. , HANSEN A. J. , SIEMKOWICZ E.
Published: December 2008

A new method was developed and used in rat to measure regional and whole‐brain blood flow and blood‐brain glucose transfer simultaneously and in 20 s. This simple method consisted of i. v. bolus injection of labeled butanol and tracer glucose, determination of the average arterial tracer concentration and subsequent assay of cerebral tissue activity 20 s after bolus injection. The whole‐brain blood flow rate averaged 129 ml (100 g)‐1 min‐1. The unidirectional blood‐brain glucose transfer was twice as high as previously estimated in similar studies on rat, or 144 μmol (100 g)‐1 min‐1 at 10 mM glucose in plasma. The magnitude is sufficient to explain the high cerebral glucose consumption rates recently determined by means of the autoradiographic 2‐deoxy‐D‐glucose method of Sokol off et al. (1977).
Rapid steady‐state analysis of blood‐brain glucose transfer in rat
Authors: GJEDDE ALBERT
Published: December 2008

A new kinetic analysis of blood‐brain glucose transport is described, based on a steady‐state model that takes account of cerebral blood flow, mean capillary glucose concentration, and cerebral metabolic rate. The maximal rate (Tmax) and half‐saturation constant (Km) of glucose transport from blood to brain were determined in rats by measuring the rate of blood‐to‐brain glucose transfer at different blood glucose concentrations. Each determination lasted 20 seconds. For whole‐brain, Tmaxand Kmaveraged 258±33 (S.E.) μmol (100 g)‐1min‐1and 5.9±1.6 (S.E.) mmol 1‐1, respectively. The regional variations were insignificant. The new approach permits kinetic parameters to be measured locally in brain in rapidly changing functional states.
Cholinergic vasoconstrictor effects in the rabbit eye: Vasomotor effects of pentobarbital anesthesia
Authors: BILL ANDERS , STJERNSCHANTZ JOHAN
Published: December 2008

Oculomotor nerve stimulation causes vasoconstriction in the anterior uvea, which is due partly to a muscarinic mechanism and partly to a non‐sympathetic aminergic mechanism. The labelled microsphere method was used to analyze the effect of pentobarbital anesthesia on the resting cholinergic vasomotor tone in the anterior uvea and to determine the relationship between stimulation frequency and vasomotor response. An attempt was made also to ascertain whether the aminergic part of the vasoconstriction is caused by release of 5‐hydroxytryptamine or norepinephrine. Induction of pentobarbital anesthesia caused a marked vasodilation in the iris and the ciliary processes and a subsequent muscarinic blockade had no effect on the blood flow. A similar result was obtained in the optic nerve. In the choroid plexus, heart muscle, pineal body and coecum, pentobarbital anesthesia caused vasodilation and a subsequent muscarinic blockade caused vasoconstriction. In the brain pentobarbital anesthesia caused a marked reduction in the blood flow of the grey matter and a moderate reduction in the white matter. After a muscarinic blockade there was some increase in the blood flow of the grey matter. Stimulation of the oculomotor nerve caused near maximum vasomotor responses at 10–20 Hz; maximum effect on the pupil size was obtained at 40–50 Hz. Depletion of 5‐hydroxytryptamine with fenfluramine did not prevent the aminergic part of the vasoconstriction and a marked vasoconstriction was also observed after pretreatment with reserpine. The results indicate that pentobarbital anesthesia abolishes most of the spontaneous cholinergic vasoconstrictor tone of the anterior uvea and that the aminergic part of the oculomotor nerve induced vasoconstriction is caused by the stimulation of phentolamine‐sensitive receptors by a mechanism probably not involving release of norepinephrine or 5‐hydroxytryptamine.
Depression of mechanical performance by active shortening during twitch and tetanus of vertebrate muscle fibres
Authors: EDMAN K. A. P.
Published: December 2008

Shortening during activity of frog single muscle fibres caused a graded depression of the contractile force that persisted for 800–900 ms during a partially fused or completely fused tetanus. The depression of force was not associated with a change of the shortening velocity at zero load. Passive shortening performed just before stimulation had no effect on the subsequent course of contraction. The decrease in isometric force produced by shortening was not significantly affected by a stretch applied immediately before or after the shortening phase. For a given amount of shortening the depressant effect during a fused tetanus was 8–28% of that produced during a twitch. The effect was substantially reduced, both during twitch and tetanus, in the presence of 0.5 mM caffeine. The length dependence of the movement effect was studied between 1.7 and 2.9 μm sarcomere spacing. Maximum depression of force (in per cent of the control at each length) was obtained at 2.1–2.2 μm sarcomere length, the effect being steadily reduced at shorter and more extended lengths. The Q10 of the depressant effect was 0.95±0.16 (S.D.). The features of the movement effect are consistent with a true deactivation of the contractile system as would occur if shortening reduced the binding of activator calcium to the regulatory proteins of the myofilaments.
Importance of spermatozoal zinc as temporary inhibitor of sperm nuclear chromatin decondensation ability in man
Authors: KVIST U.
Published: December 2008

Nuclear chromatin decondensation (NCD) of ejaculated human spermatozoa was studied in vitro. Spermatozoa subjected to membrane disintegration induced by the detergent sodium dodecyl sulphate (SDS) were found to undergo NCD if previously or afterwards treated with substances known to deplete the spermatozoa of zinc (albumin and EDTA). Zn2+, but not other, “prostatic” cations (Ca2+, Mg2+), inhibited the experimentally induced NCD and the NCD of spermatozoa from men with impaired prostatic function. It is suggested that the human spermatozoon has an intrinsic mechanism for NCD, that is preserved by temporary zinc inhibition and might be reactivated by zinc removal within the female genital tract.
Inhibition of fast anterograde axoplasmic transport by a pressure barrier. The effect of pressure gradient and maximal pressure
Authors: HAHNENBERGER RUDOLPH W.
Published: December 2008

Fast anterograde axoplasmic transport was studied in the motor fibres of the vagus nerve of rabbits in vitro at 22°C with a pressure barrier applied to a small section of the nerve. The barrier was characterized by the maximal pressure and the gradients on each side of the maximum. The range tested was 16 to 45 mmHg maximal pressure and 30 to 140 mmHg/mm length of nerve for the pressure gradients. It was found that in the ranges tested the maximal pressure was of major importance for the inhibition of transport, the pressure gradient being of little significance. The results indicate that at least one part of fast anterograde axoplasmic transport occurs within collapsible canalicular structures.
Local cerebral glucose consumption in the artificially ventilated rat: influence of nitrous oxide analgesia and of phenobarbital anesthesia
Authors: INGVAR M. , ABDUL‐RAHMAN A. , SIESJÖ B. K.
Published: December 2008

The objectives of the present study, which concerns local glucose consumption (1‐CMRg1) in the rat brain as measured with the 14C‐deoxyglucose technique of Sokoloff et al. (1977), were (1) to provide data for l‐CMRg1 in nitrous oxide analgesia and in phenobarbital anesthesia, allowing a comparison with previous results on oxygen consumption, and (2) to test a recent proposal that 70% N2O markedly reduces 1‐CMRg1 in (mainly) cortical structures. Under 70% N2O, 1‐CMRg1 in frontal and parietal cortex was close to 0.7 μmol·g‐1·min‐1. This value is in excellent agreement with previous values for “cortical” oxygen consumption. In phenobarbital anesthesia, 1‐CMRg1 was lower than that expected from oxygen consumption, probably reflecting the fact that barbiturate anesthesia is accompanied by consumption of endogenous substrates. Experiments on adrenalectomized animals that were given local anesthesia and protected from external stimuli failed to demonstrate that 70% N2O depresses 1‐CMRg1. In fact, N2O was found to increase 1‐CMRg1 in many structures. It is concluded that if I‐CMRg1 is lower in ventilated animals than in spontaneously breathing, conscious controls, the depression is more likely to be due to the neuromuscular blockade.
Blood flow in arteries determined transcutaneously by an ultrasonic doppler velocitymeter as compared to electromagnetic measurements on the exposed vessels
Authors: GULDVOG IVAR , KJÆRNES MORTEN , THORESEN MARIANNE , WALLØE LARS
Published: December 2008

We have compared the instantaneous mean blood velocity measured transcutaneously from total cross‐sections of arteries in dogs by the use of a new pulsed heterodyne ultrasound doppler equipment, with instantaneous blood flow as measured simultaneously by an electromagnetic flowmeter applied on the exposed vessels. The experiments were performed on the common carotid and the femoral arteries in a variety of flow situations, always with a close fit between the two curves. The results show that the output from the ultrasound equipment is proportional to flow.
Effects of glucagon and pentagastrin on glibenclamide‐induced insulin release
Authors: AHRÉN BO , LUNDQUIST INGMAR
Published: December 2008

It was recently reported that administration of sulphonylureas may lead to a stimulation of the release of glucagon and a gastrin‐like peptide. These peptides may then eventually influence the insulin releasing action of the sulphonylureas. Therefore, the effects of glucagon and pentagastrin on basal and glibenclamide‐induced insulin secretion were studied. It was found that at a dose of 4.25 nmol/kg the two peptides induced a significant stimulation of basal insulin secretion. However, pentagastrin at the dose of 4.25 nmol/kg did not influence the insulin release induced by glibenclamide, whereas an equimolar dose of glucagon potentiated the insulin secretory response to this sulphonylurea drug by about 40%. Glucagon in contrast to pentagastrin thus positively modulates the insulin secretory pathway stimulated by the sulphonylurea drug glibenclamide.
Local cerebral blood flow in the rat during severe hypoglycemia, and in the recovery period following glucose injection
Authors: ABDUL‐RAHMAN A. , AGARDH C.‐D. , SIESJÖ B. K.
Published: December 2008

In order to assess the influence of severe hypoglycemia on local cerebral blood flow (1‐CBF) artificially ventilated rats, maintained on 70% N2O, were injected with insulin to provide either an EEG pattern of slow‐wave poly spikes, or cessation of spontaneous EEG activity for 5, 15, or 30 min (“coma”). In other animals, glucose was injected at the end of a 30 min period of “coma” and 1‐CBF was measured after recovery periods of 5, 30, 90, or 180 min. Local CBF was measured autoradiographically with 14C‐iodoantipyrine as the diffusible tracer. In the slow‐wave poly spike period 1‐CBF was increased in most of the structures studied, and reached values that were 1.4 to 3.2 times greater than control. In many structures, cessation of EEG activity was accompanied by a further increase in 1‐CBF, with some structures (thalamus, hypothalamus, pontine gray, and cerebellar cortex) showing flow rates of 400–500% of control. The increase in 1‐CBF was unrelated to arterial hypertension, hypercapnia, or hypoxia. 5 min after glucose injection the hyperemia persisted in only some of the structures studied; in others, the 1‐CBF were close to, or below, control values. During the subsequent recovery period 1‐CBF was markedly reduced with some structures (cerebral cortical areas, hippocampus, and caudate‐putamen) showing flow rates of only 20–35% of control. In others, notably pontine gray and cerebellar cortex, secondary hypoperfusion was never observed. The hypoperfusion was unrelated to arterial hypotension, hypocapnia, or increase in intracranial pressure. It is concluded that, like hypoxia and ischemia, substrate deficiency due to hypoglycemia is accompanied by vasodilatation in the brain. Furthermore, like long‐lasting ischemia, severe hypoglycemia is followed by a delayed hypoperfusion syndrome that, by restricting oxygen supply, may well contribute to the final cell damage incurred.
Amylase secretion in response to activation of different autonomic receptors in the rabbit parotid gland
Authors: ASKING BENGT , GJÖRSTRUP PER
Published: December 2008

The contribution by different autonomic receptors to the amylase secretion from the parotid gland of the anaesthetized rabbit was studied as the response to various parasympathomimetic and sympathomimetic drugs. Amylase secretion by infusions of pilocarpine or parasympathetic nerve stimulation was low, but regularly higher in response to pilocarpine than to parasympathetic nerve stimulation. These effects were reduced to the same level by β‐adrenoceptor block indicating the presence and for pilocarpine also the release of catecholamines, probably from the adrenals, Isoprenaline injections produced a high amylase secretion, that was blocked by atenolol, indicating that predominantly β1‐adrenoceptors were activated. Phenylephrine was without amylase secretory effects. By accepting isoprenaline maximum as maximum for sympathetically produced amylase secretion, a theoretical frequency‐response relationship for amylase secretion by sympathetic nerve stimulation could be calculated; ED50was 0.9 Hz. The results indicate that under experimental conditions in vivo there are certain differences between the rat and the rabbit parotid glands in the autonomic control not only of fluid, but particularly of amylase secretion.
6‐Hydroxydopamine and the blood‐brain barrier in adult conscious rats
Authors: JOHANSSON BARBRO B. , HENNING MATTS
Published: December 2008

6‐hydroxydopamine (6‐OHDA), 15 or 50 mg kg‐lgiven as bolus i.v. injection to adult conscious rats with aortic catheter, rapidly increased mean arterial pressure by 70–78 mmHg. The pressure returned to normal within 4060 min. The cerebrovascular permeability in rats given 6‐OHDA and sacrificed 10 or 60 min later was enhanced as indicated by extravasation of Evans blue albumin and significant increase of125I human serum albumin content in brain tissue compared to control rats. When the increase in blood pressure was diminished by i.v. phentolamine, 6‐OHDA treated rats did not differ from controls. It is concluded that the blood pressure elevation induced by i.v. 6‐OHDA facilitates the entry of the drug into the brain parenchyma.
Plasma water and 51Cr EDTA equilibration volumes of different tissues in the rat
Authors: LARSSON M. , JOHNSON L. , NYLANDER G. , ÖHMAN U.
Published: December 2008

The EDTA space and the plasma water volume of the whole animal and selected tissues were investigated with constant EDTA infusions of different duration in the rat. The calculated EDTA space increased with the duration of the infusion both in the whole animal and the tissues sampled. The plasma water volume remained constant. and therefore the calculated increase of the EDTA space suggests a slow intracellular accumulation of the tracer. As intracellular accumulation of EDTA increases with experimental time, it is necessary to use as short an experimental interval as possible to reduce this error when determining extracellular fluid volumes.
Local cerebral glucose consumption during insulin‐induced hypoglycemia, and in the recovery period following glucose administration
Authors: ABDUL‐RAHMAN A. , SIESJÖ B. K.
Published: December 2008

Using the 14C‐deoxyglucose technique, we estimated local glucose consumption in the rat brain (1–CMRgl) in hypoglycemia of sufficient severity to cause cessation of spontaneous EEG activity, and in the recovery period following a 30 min period of such hypoglycemia. After 5 and 30 min of hypoglycemia, 1–CMRgl was markedly reduced in many cerebral structures (cerebral cortices, caudateputamen, thalamus, and hippocampus) but unchanged or only moderately reduced in other structures (cerebellar cortex, hypo thalamus, and pontine grey). The results indicate that differences in 1–CMRgl were caused by regional differences in the true or apparent kinetic constants for glucose transport, or that the consequences of a hypoglycemic derangement of cellular metabolism interfered with glucose transport in some regions. Local CMRgl was markedly heterogenous in the recovery period, induced by glucose administration in animals with a prior (30 min) period of hypoglycemia. In general, a reduced posthypoglycemic glucose consumption was correlated to low 1–CMRgl values during hypoglycemia. However, the hippocampus provided an exception since its CMRgl returned to control values. A correlation with previous measurement of local cerebral blood flow (1–CBF) demonstrates that regions having a pronounced reduction in 1–CMRgl during hypoglycemia developed a mismatch between blood flow and metabolic rate in the recovery period, the flow showing a disproportional reduction.
Output of bile and pancreatic enzymes after test meals with different fat content. Influence of body weight on pancreatic enzyme composition
Authors: EKELUND K. , JOHANSSON C.
Published: December 2008

The output of bile and pancreatic enzymes after two mixed meals with different fat content was studied in 16 healthy volunteers of normal body‐weight. A quantitative multiple indicator dilution method was used. The delivery of more fat per time to the duodenum after the fat rich compared to the low fat meal was followed by the emptying of more bile but did not significantly increase the pancreatic response. The ratio between amylase and lipase was constant throughout the course of a single experiment but differed between the subjects. The ratio decreased with an increasing body weight, indicating a relative dominance of amylase over lipase in the lighter and the reverse in the heavy subjects. The same correlation was found when results from a previously reported series with a glucose containing mixed meal were reexamined. It is proposed that long time dietary differences might influence the enzyme composition of the postprandial pancreatic secretion.
Thermoregulatory responses to tyramine in the pigeon
Authors: HISSA R. , GEORGE J. C. , STEVENS E. D. , SAARELA S.
Published: December 2008

Intravenous injections of different doses of tyramine induced hypothermia in the pigeon in the cold and a moderate hyperthermia in the warm environment. The hypothermia was correlated with a dose‐dependent decline in shivering. Hyperthermia was attributed to the chrono‐ and inotropic effects of tyramine. The indirect stimulatory effects of noradrenaline (NA) at the tissue level were studied. Pretreatment with α‐methyl‐para‐tyrosine (α‐MpT) and blocking α‐adrenoceptors with phentolarnine, diminished the hypothermia induced by tyramine in the cold. The results obtained indicate that the release of endogenous NA stimulated by tyramine might result either in hypothermia or hyperthemia, thus resembling similar effects obtained with exogenous NA in birds.
Kinins in relation to kallikrein activity, kininogen, electrolytes, aldosterone and catecholamines in urine from normal individuals
Authors: HULTHÉN U. L. , DYMLING J.‐F. , HÖKFELT B.
Published: December 2008

The object of the present study was to test the hypothesis that urinary kinin excretion is an indicator of intrarenal kinin formation and to investigate urinary excretion of kinins in relation to natriuresis, kaliuresis, diuresis and urinary aldosterone and catecholamines in normal individuals on a free salt and water intake. In freshly voided urine collected from 24 normal individuals kinin concentration was directly related to kallikrein activity. Kininogen concentration was very low and neither related to kallikrein activity nor to kinin concentration. The excretion rates of kinins and kininogen were unrelated to the time interval between micturitions. In 24 hour urine collections from 50 normal individuals the excretion of kinins was positively correlated to natriuresis, kaliuresis and diuresis and also to dopamine but not to aldosterone, noradrenaline and adrenaline. Kinin excretion was inversely related to age and was lower in women than in men. On the basis of these results it is concluded that urinary kinin excretion reflects intrarenal kinin formation in normal ambulatory individuals and that urinary kinins are formed mainly in the interstitial and vascular space of the kidney. Furthermore, kinins and dopamine seem to play a physiological role in the renal handling of electrolytes and water.
Cerebrovascular sympathetic denervation and blood‐brain barrier function in conscious rats
Authors: HARDEBO JAN ERIK , EDVINSSON LARS , JOHANSSON BARBRO B.
Published: December 2008

Electrical stimulation of the sympathetic nerves to the cerebrovascular bed enables the resistance vessels to better withstand a high blood pressure in terms of blood‐brain barrier integrity. Sympathetic denervation could hence be expected to lead to a decrease in cerebrovascular tone and increased vulnerability of the blood‐brain barrier. In the present study acute hypertension was induced in conscious unrestrained rats by administration of angiotensin or bicuculline. The albumin leakage into the brain, as studied by Evans blue‐albumin and125I labelled human serum albumin. was not enhanced in acutely or chronically sympathectomized rats compared to controls.
Pre‐ and postjunctional effects of prostaglandin E2, prostaglandin synthetase inhibitors and atropine on cholinergic neurotransmission in guinea pig ileum and bovine iris
Authors: GUSTAFSSON LARS , HEDQVIST PER , LUNDGREN CÖSTA
Published: December 2008

The effects of prostaglandin E2, arachidonic acid, prostaglandin synthetase inhibitors and atropine on cholinergic neuromuscular transmission were examined in isolated guinea pig ileum longitudinal muscle and bovine iris sphincter muscle. Prostaglandin E2and arachidonic acid markedly enhanced contraction responses induced by nerve stimulation. In addition, prostaglandin E2enhanced contraction responses to acetylcholine and direct muscle stimulation, approximately to the same extent as those to nerve stimulation. Prostaglandin synthetase inhibitors (indomethacin, meclofenamic acid and eicosatetraynoic acid) very effectively reduced contraction responses to nerve stimulation or acetylcholine, and they annulled the stimulant effect of arachidonic acid. Basal and nerve‐induced efflux of acetylcholine from the eserinized tissues, as measured by mass fragmentography, was unaltered by prostaglandin E2, but diminished slowly during indomethacin. Subsequent prostaglandin administration caused a slight increase of nerve‐induced release of acetylcholine. Atropine markedly increased overflow of acetylcholine form stimulated preparations of both types. This indicates that muscarinic receptors, causing diminished acetylcholine release in eserinized tissue, may be present also at postganglionic terminals. During atropine, an effect of prostaglandin E2on acetylcholine release could still not be seen. Thus, using physicochemical determination of acetylcholine, we could not verify earlier reports, employing bioassay, claiming enhanced release of transmitter during prostaglandin E2treatment. However, it seems likely that prostaglandin Eltakes part in the regulation of contractility and tone of the smooth muscle cells.
Distensibility of left atrium in normotensive and spontaneously hypertensive rats
Authors: RICKSTEN S.‐E. , YAO T. , LJUNG B. , THOREN P.
Published: December 2008

In spontaneously hypertensive rats (SHR) left atrial mechanoreceptors are reset. Thus, left atrial pressure must be almost twice as high in SHR as in normotensive rats to produce comparable degrees of receptor activation and reflex sympathetic inhibition. The present study was performed to investigate whether this resetting is due to a decreased atrial distensibility in SHR. Static load‐length relationships were therefore investigated on isolated left atrial strips from 11 pairs of male SHR and Wistar Kyoto rats (WKR). After each experiment the strips were fixed at a passive tension of 4 mN and the average wall thickness was determined histologically. Furthermore, pressure‐volume relationships were studied on non‐beating, isolated left atria from SHR and WKR. Distensibility was here defined as % volume increase when LAP was increased from 2.5 to 12.5 mmHg either rapidly (0.5–1 s, “dynamic” distension) or slowly (3 min, “static” distension). Atrial wall thickness did not differ significantly in SHR and WKR. but the passive force (mN) per crossectional area exerted during elongation above 80% was greater (P<0.05) in SHR. Also the “dynamic”, but not the “static” volume distensibility was significantly lower in SHR (P<0.01). The decreased dynamic distensibility of SHR left atrial walls can at least partly explain the resetting of the atrial receptors activated during the rapid filling phase.
Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man
Authors: WALLIN B. GUNNAR , SUNDLÖF GÖRAN , ERIKSSON BRITT‐MARIE , DOMINIAK PETER , GROBECKER HORST , LINDBLAD LARS ERIK
Published: December 2008

Recordings of multiunit sympathetic activity were made in muscle branches of the peroneal nerve in 22 healthy subjects at rest in recumbent position. Nerve activity was quantitated in terms of burst incidence (number of pulse synchronous sympathetic bursts per 100 heart beats or per min). In a separate session, 4–45 months later, blood was drawn from an antecubital vein for noradrenaline analysis. Both sympathetic activity and plasma concentrations of noradrenaline varied widely between subjects and both parameters increased with age. There was a significant positive correlation between a subject's level of sympathetic activity and his plasma concentration of noradrenaline. It is suggested that overflow of transmitter from sympathetic terminals in muscles contributes significantly to plasma levels of noradrenaline at rest.
Effects of fatigue on isometric force‐ and relaxation‐time characteristics in human muscle
Authors: VIITASALO JUKKA T. , KOMI PAAVO V.
Published: December 2008

Effects of intermittent one leg isometric fatigue on maximal isometric force, force production, relaxation and blood lactate were studied using 29 male students as subjects. The relative changes of variables during fatigue and recovery were intercorrelated together with muscle structure variables, which were determined using needle biopsy technique. Maximal force decreased, force production and relaxation became slower and muscle lactate increased during fatigue. Change of maximal force, force production and lactate during fatigue as well as recovery of maximal force and lactate after fatigue were correlated significantly to muscle fiber distribution. Fatiguability of the force‐time characteristics was therefore influenced by the differences in the metabolic profiles of the individual muscle fibers. However, ability to relax the muscle quickly was not observed to be dependent on muscle structure. This suggests that different fatigue mechanisms might be present in relaxation than in force production.
Autoradiographic localization of 35‐S‐furosemide at different stages of its renal excretion1
Authors: ODLIND BO , DENCKER LENNART
Published: December 2008

The renal localization of 35‐S‐activity was studied by autoradiography at different times (1/2 min intervals) following the rapid injection of a bolus of 70μg 35‐S‐furosemide into the renal portal system of hens. After removal, both kidneys were freeze‐sectioned, freeze‐dried and subjected either to apposition autoradiography according to Ullberg or to microautoradiography. There was extensive labelling over cortical areas of the ipsilateral kidney, in the periphery of lobuli, the site of proximal tubular cells. This labelling was maximal at 1 and insignificant already at 4 min post injection. At this time, however, there was a distinct patchy labelling corresponding to collecting ducts. At 7 min post‐injection no specific labelling was found. The findings suggest that furosemide in the peritubular blood is accumulated in proximal tubules, rapidly transferred (tubular secretion) to their lumina and carried distally by the tubular fluid, subsequently resulting in high concentrations of the diuretic in the lumina of collecting ducts. Thus the findings are in keeping with the view that active tubular secretion of furosemide in the hen contributes significantly to a high luminal concentration of the drug in more distal parts of the tubules, the likely site of diuretic action.
Secretory effects of gastric inhibitory polypeptide on the isolated perfused porcine pancreas
Authors: JENSEN S. LINDKÆR , HOLST J. J. , NIELSEN O. VAGN. , LAURITSEN K. B.
Published: December 2008

The effect of gastric inhibitory polypeptide (GIP) in physiological concentrations (250, 500, 1000 and 2000 pg/ml) upon endocrine and exocrine secretion from the isolated perfused porcine pancreas was studied at various glucose concentrations in the perfusate. GIP increased insulin release in a dose‐dependent manner. The sensitivity of the beta‐cells to GIP was glucose dependent. No effect was observed on glucagon or exocrine secretion regardless of the glucose concentration in the perfusate. We conclude that GIP is powerful insulin‐stimulator even in low physiological concentrations in the presence of glucose concentrations comparable to those seen during an oral glucose load, which makes GIP to one of the strongest incretin candidates known, i. e. the factor(s) contributing to the augmented insulin response after ingestion of glucose.
Anaphylactic shock in monkeys passively sensitized with human reaginic serum
Authors: REVENÄS B. , SMEDEGÅRD G. , SALDEEN T. , FREDHOLM B. B. , STRANDBERG K.
Published: December 2008

Seven monkeys were passively sensitized intravenously (i. v.) with human serum containing IgE antibodies specific to dog albumin. I.v. administration of the antigen resulted in an immediate increase in pulmonary resistance (Rpulm) with a concomitant decrease in pulmonary dynamic compliance (Cdyn). Initially these changes in the respiratory system resulted in pronounced effects on venous admixture, arterial oxygen saturation (SaO2) and arterial pH. After 30 min, as Rpulm and Cdyn returned towards control levels, the blood gas changes were mainly due to low cardiac output. There was a transient increase in hematocrit, a decrease in plasma fibrinogen and a transient reduction in the number of circulating leukocytes. The anaphylactic reaction resulted in a 10‐ to 30‐fold increase in plasma adrenaline with time and in a substantial but less marked increase in plasma noradrenaline and dopamine. Probably as a consequence of the increase in plasma catecholamines, there was a rise in plasma cyclic AMP, glucose and glycerol. No increase in plasma histamine levels was found. In two animals sensitized with purified IgE a reaction which was less severe but had the same general pattern was observed. The findings show that IgE‐mediated anaphylaxis in the monkey results in a bronchoconstriction leading to a profound respiratory disturbance characterized by decreased SaO2 due to increased venous admixture. After 30 min these variables were normalized and the shock state was dominated by poor tissue perfusion due to a low cardiac output.
Theophylline interferes with the modulatory role of endogenous adenosine on cholinergic neurotransmission in guinea pig ileum
Authors: GUSTAFSSON LARS , FREDHOLM BERTIL B. , HEDQVIST PER
Published: December 2008

The ability of theophylline and other phosphodiesterase inhibitors to alter contractile responses to cholinergic nerve stimulation was investigated in isolated longitudinal muscle of the guinea pig ileum. Theophylline in low concentrations (10–100 μM), having no or little effect on measured phosphodiesterase activity, antagonized inhibitory effects of exogenous adenosine. In higher concentrations (0.1–10 mM), shown to be effective in inhibiting phosphodiesterase, theophylline as well as a “pure” cAMP phosphodiesterase inhibitor, ZK 62, 711, inhibited contractile responses. Dipyridamole and dilazep, inhibitors of adenosine inactivation, and also selective inhibitors of cAMP and cGMP phosphodiesterase, respectively, were found to enhance effects of exogenous adenosine and to cause a marked leftward shift of adenosine threshold dose. When dipyridamole and dilazep by themselves had inhibitory effects these could be antagonized by theophylline, suggesting an action through increased levels of endogenous adenosine. As a further indication of endogenous adenosine modulating neurotransmission low concentrations of theophylline enhanced responses to transmural stimulation. Endogenous purine concentrations in tissues and bath media were measured by HPLC. Because of tissue and microbial adenosine inactivation direct estimates of extracellular adenosine concentration could not be obtained. However, adenosine levels increased during transmural stimulation, and during inhibition of adenosine inactivation were sufficient, even in the bath medium, to interfere with the cholinergic neurotransmission.
Duration of increase in vascular volume during venous stasis
Authors: SEJRSEN PER , HENRIKSEN OLE , PAASKE WILLIAM P. , NIELSEN STEEN LEVIN
Published: December 2008

Duration of increase in vascular volume in the crus following application of venous stasis was studied in 3 healthy subjects placed in a supine position. Changes in calf volume during venous stasis was measured by plethysmography. In one series of experiments changes in vascular volume were studied by measurements of accumulation of133Xenon proximal to a depot located in the anterior tibial muscle. In another series of experiments changes in activity of99mTc‐labelled erythrocytes were used as indicator for changes in vascular volume. Following application of venous stasis in the horizontal position the rate of increase in calf volume declined to a steady level after about 5 min. Both the studies with133Xenon and with99mTc‐erythrocytes indicate that vascular volume continued to increase for 3, 3.5 and 5 min following venous stasis of 20, 30 and 40 mmHg, respectively. When the crus was lowered 50 cm below heart level the duration of increase in vascular volume following an additional increase in venous pressure induced by venous stasis was shorter than in the horizontal position. When the calf is placed at heart level the results indicate that for up to 5 min after application of venous stasis of 40 mmHg both increase in vascular volume and transcapillary fluid filtration contribute to the observed increase in calf volume. Using the rate of increase in calf volume within 5 min after induction of venous stasis thus leads to overestimation of CFC. After 5 min vascular volume appears to remain constant and the observed increase in calf volume seems to be solely due to a net increase in interstitial fluid volume.
Effect of extracellular potassium on the loss of potassium from human red blood cells treated with propranolol
Authors: MANNINEN V. , SKULSKII I. A.
Published: December 2008

The Ca++‐dependent propranolol‐induced increase of K+permeability of human red blood cells, well documented in previous studies, was found to depend on extracellular K+. This was shown by studying the passive transport of86Rb and the loss of bulk cellular K+in both K+‐free and K+‐containing media. The maximal effect of propranolol was achieved with 5–10 mM K+in incubation media. The external K+could be substituted with TI+, but not with Na+. When added after propranolol, extracellular K+failed to initiate the effect of propranolol on membrane permeability. The cell/medium distribution of permeant204TI showed that the propranolol‐induced increase of K+permeability did not result in considerable hyperpolarization of the red blood cell membrane. The data obtained seem to be more consistent with a counter‐transport model for explaining the propranolol effect than with a mechanism based on free diffusion of K+through the membrane.
Reversal of α1‐receptor mediated relaxation in intestinal smooth muscle
Authors: WIKBERG JARL E. S.
Published: December 2008

The α1‐receptor agonist phenylephrine relaxed longitudinal rabbit jejunal muscle contracted in vitro by low concentrations of barium ions (1 mM). When the Ba2+concentration was increased to 10–15 mM the response to phenylephrine was a contraction, and at Ba2+concentrations in between the high and low range this response was biphasic—a relaxation followed by a contractile phase. The α2‐receptor agonist clonidine did not affect the tone of the Ba2+contracted preparation. When the muscle preparation was contracted by Sr2+(1–20 mM) in the presence of Ca2+(2.5 mM), phenylephrine relaxed it, and no contractile response to phenylephrine was observed. In the absence of extracellular Ca2+, 5 mM Ba2+caused a contraction. Under these conditions phenylephrine had no effect on the tissue tone. When Ca2+was added in a low concentration (0.2‐2 mM), phenylephrine elicited a gradually increasing contractile response. At 5 mM Ca2+the contractile response was replaced by the normal relaxation. The contractile response to phenylephrine in the presence of 5 mM Ba2+and 2.5 mM Ca2+was partially blocked by low concentrations of verapamil. In higher concentrations verapamil abolished the tissue tonus completely. The contractile response to phenylephrine in the presence of 5 mM Ba2+and 2.5 mM Ca2+could be reverted to the normal relaxation by the addition of 20 mM Mg2+. Increasing the K+concentration from the normal 5.9 to 62.9 mM blocked the phenylephrine‐induced relaxation. No contractile response to phenylephrine occurred. It is concluded that Ba2+could reverse the response of α1receptor stimulation in rabbit jejunum from a relaxation to a contraction and that this contractile response was dependent on the presence of Ca2+.
Angiotensin I converting enzyme activity in portal vein studied in normotensive rats and in models of primary and secondary hypertension
Authors: LJUNG B. , JANDHYALA B. , KJELLSTEDT A.
Published: December 2008

The effects of angiotensin I (AT I), angiotensin II (AT II) and the activity of AT I converting enzyme (ACE) were investigated in isolated portal veins of normotensive rats (WKR and NCR) and of rats with primary (SHR) and secondary (one clip 2 kidney renal; RHR) hypertension. Based on ED50values, the tissue sensitivity to AT II was slightly less in the portal veins of RHR than SHR, while the sensitivity of smooth muscle in NCR and WKR was similar to that of SHR. Angiotensin I induced contractions were inhibited by saralasin and by captopril, indicating presence of functionally active converting enzyme in this vascular tissue. The local concentration of AT II formed from AT I, was evaluated based on AT II dose response curves and AT I response magnitude. The AT II formation was essentially similar in SHR, WKR and NCR and slightly enhanced in RHR. Inhibition of AT II formation with captopril and/or blockade of AT II receptors with saralasin failed to alter the spontaneous myogenic activity of the portal vein. Captopril reduced smooth muscle activity only in concentration several orders of magnitude greater than that needed to inhibit ACE. The concentration of captopril needed to inhibit AT I responses was similar in all strains of rats. It is concluded that AT II is rapidly formed in the portal vein due to local conversion of AT I. In the RHR portal vein the extent of AT I conversion is increased and the tissue sensitivity to AT II is decreased possibly due to mechanisms involved in the development of renovascular hypertension.
Axonal transport and subcellular distribution of dopamines‐β‐hydroxylase in the cod,Gadus morhua
Authors: JÖNSSON ANN‐CATHRINE , NILSSON STEFAN
Published: December 2008

The axonal transport of dopamine‐β‐hydroxylase (DBH; E.C. 1.14.17.1) was studied in the splanchnic nerve of the cod in vivo, and the subcellular localization of the same enzyme was studied in the chromaffin tissue from the cod head kidney. The mean rate of axonal transport for cod DBH was 18.6 mm/24 h at 10°C. The mobile fraction was estimated to 22 %, giving an absolute rate of transport of 85 mm/24 h at 10°C. Evidence for a retrograde transport of DBH was also obtained, with an accumulation distal to a ligature of 12% of the accumulation proximal to the ligature at 3 days. DBH from the chromaffin tissue appeared to be strongly bound to the adrenergic granules, with only a small amount (ca 4%) recovered in the soluble phase.
Cerebrovascular response during and following severe insulin‐induced hypoglycemia: CO2‐sensitivity, autoregulation, and influence of prostaglandin synthesis inhibition
Authors: NILSSON B. , AGARDH C.‐D. , INGVAR M. , SIESJÖ B. K.
Published: December 2008

The objective of the present experiments was to study mechanisms governing cerebrovascular responses during severe hypoglycemia, and in the posthypoglycemic recovery period. To that end, lightly anesthetized (70% N2O) and artificially ventilated rats were injected with insulin so as to abolish spontaneous EEG activity for 15 or 30 min (“coma”). In separate animals, recovery was induced by glucose administration. Previous experiments have shown that in normo‐ or moderately hypertensive animals hypoglycemic coma is accompanied by a relatively marked increase in cerebral blood flow (CBF), and that a delayed hypoperfusion develops in the recovery period. The present results demonstrate that oxygen supply is in excess of the demands during coma, and falls below control during recovery. During hypoglycemic coma, the CO2 response of the circulation was retained but autoregulation was lost. In the recovery period, both CO2 response and autoregulation were lost. Pretreatment with indomethacin was introduced in order to evaluate the possible influence of fatty acid cyclo‐oxygenase products on the pattern of CBF changes. Measurements of local cerebral blood flow (1‐CBF) showed that, in the majority of structures analysed, indomethacin failed to modulate the changes in CBF. It is concluded that alterations in cerebrovascular tone and loss of autoregulation induce flow changes that may influence substrate and oxygen availability during hypoglycemia. The pronounced decrease in CBF and the loss of autoregulation and CO2‐response in the posthypoglycemic period may influence functional, metabolic and morphological recovery. The 1‐CBF findings indicate that neither the increase in CBF during hypoglycemia nor the reduction in flow in the posthypoglycemic period are mediated by mechanisms related to prostaglandin metabolism.
The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions
Authors: DAHLGREN NILS , NILSSON BENGT , SAKABE TAKEFUMI , SIESJÖ BO K.
Published: December 2008

The effect of the fatty acid cyclo‐oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO2) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg·kg‐1i. v.) reduced CBF to 50% of control without a measurable effect on CMRO2. During hypercapnia (PaCO270–80 mmHg) the increase in CBF was reduced by about 80% but CMRO2remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg·kg‐1and maximal effects were obtained with 3–5 mg·kg‐1. Following i. v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1–2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO2tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.
Albumin concentration and colloid osmotic pressure of interstitial fluid collected by wick technique from rat skeletal muscle. Evaluation of the method
Authors: REED ROLF K.
Published: December 2008

Interstitial fluid from rat skeletal muscle has been collected by multifilamentous nylon wicks. The wicks consisted of 5–600 single filaments and had an overall diameter of 1–2 mm. The wicks were implanted in the muscle by means of a mending needle. The wicks were removed at various times after implantation, and colloid osmotic pressure (COP) or albumin concentration in wick fluid was measured. The fluid contained in the wick had a COP of 8–10 mmHg and an albumin concentration about 1/3 that of plasma. COP in wicks preloaded with serum or serum/saline dilution was higher after 1/2 and 1 h of implantation, but was nearly identical to that of saline soaked wicks after 2 h implantation. Intravenous injection of labelled albumin showed that wick implantation caused a marked leakage of proteins from plasma to the wick. However, 1/2 to 1 h after implantation the leakage was markedly reduced. The initial leakage of albumin could be diminished with protease inhibitor (aprotinin), but not with prostaglandin‐, serotonin‐or histamin antagonists. The experiments show that wick fluid colloid osmotic pressure reflects interstitial fluid colloid osmotic pressure, while the protein composition of wick fluid may not be identical to that of undisturbed interstitial fluid.
Noradrenaline release and uptake in isolated small dense cored vesicles from rat seminal ducts
Authors: FRIED GABRIEL
Published: December 2008

Noradrenaline (NA) release and uptake was investigated in an improved preparation of isolated small dense cored vesicles from rat seminal ducts. The vesicle preparation exhibited an Mg2+‐ATP‐dependent uptake of NA. Half maximal uptake after 20 min was seen at 22 μM. Exchangeability of NA between medium and vesicles was 100%. The kinetics of exchange suggested that mos NA is stored in a single pool. The t1/2 for release of NA was 43 min in the presence of Mg2+‐ATP, as compared to 15 min in the absence of Mg2+‐ATP. Addition of reserpine (20 μM) did not significantly alter the NA release. The kinetic properties of this preparation was compared to those of earlier reported noradrenergic vesicle preparations from different tissues.
On the localization and mediation of the centrally induced hyperactive urinary bladder response to L‐dopa in the rat
Authors: SILLÉN U. , RUBENSON A. , HJÄLMÅS K.
Published: December 2008

The hyperactive bladder response observed after central adrenergic stimulation with L‐dopa, following enzymatic blockade of its peripheral metabolism, was studied in the rat. The bladder response was recorded by a cystometric procedure. The hyperactive bladder action thus produced was noted after transection of the CNS at the level of the superior colliculi but not when the transection was made caudal to the inferior colliculi. No effect was seen after transection of the cauda equina at L6, i. e. parasympathetic decentralisation of the bladder. It is concluded that the hyperactive bladder reaction seen after central adrenergic stimulation is produced in the mesencephalic‐pontine region and mediated to the bladder via a central coupling to parasympathetic pathways.