bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Vasoactive Drugs on Circulation in Canine Subcutaneous Adipose Tissue
Authors: Fredholm B. B. , ÖBerg B. , Rosell S.
Published: December 2008

The circulatory effects of acetylcholine, bradykinin, isoprenaline, histamine, 5‐hydroxytrypt‐amine (5‐HT), noradrenaline and prostaglandin Ei (PGE1) were studied in the canine subcutaneous adipose tissue. PGE1produced clearcut vasodilatations at calculated blood concentrations as low as 10‐9M and was found to be the most potent of the drugs tested. PGE1was about 1000 times more potent than acetylcholine and about 10 times more potent than histamine. 5‐HT induced a moderate blood flow increase with no change or a decrease of tissue volume, indicating a constriction of the venous section. The vascular responses to noradrenaline infusions were essentially similar to those produced by sympathetic nerve activation,i.e. constriction of arterioles and veins and a markedly increased capillary filtration coefficient (CFC). Histamine and bradykinin induced increases of CFC of the same magnitude as did sympathetic nerve stimulation, whereas acetylcholine, isoprenaline, 5‐HT and PGE1induced smaller increases of CFC. Sympathetic nerve stimulation superimposed upon infusions of the latter drugs produced a further marked increase of CFC, while nerve stimulation applied during a period of histamine or bradykinin infusion produced no further rise or even a decrease of CFC. It is discussed that the pronounced CFC increase during sympathetic nerve stimulation is due to an increased permeability of the capillary membrane.
Variation in Total Body Water with Muscle Glycogen Changes in Man
Authors: Olsson Karl‐Erik , Saltin Bengt
Published: December 2008

19 subjects performed prolonged heavy arm and leg exercise after which they had a protein and fat diet for three days. Thereafter they switched to a carbohydrate enriched diet during a 4‐day period. The measurements were performed on the 3rd day and then repeated on the 7th day. The glycogen concentration in the thigh and the arm muscles was 4.5 and 2.6 g/kg wet muscle on the 3rd day and increased with the carbohydrate enriched diet to 19.9 and 16.9 g/kg wet muscle, respectively. Body weight increased 2.4 kg during this period of 4 days. The total body water increased 2.2 1 which is assumed to be caused by the glycogen storage in the muscles and the liver. The amount of glycogen stored was calculated to be at least 500 g, which means that 3—4 g of water is bound with each gram of glycogen.
Blood Flow and Oxygen Extraction in the Cat Uvea at Normal and High Intraocular Pressures
Authors: Alm Albert , Bill Anders
Published: December 2008

The rate of blood flow through the uvea and the arterio‐venous O2difference across the uveal tract were determined in cats. The normal rate of blood flow was 1.14 ± 0.23 ml/min and the normal a‐v O2difference was 1.02 ± 0.16 volume per cent. The O2extraction was 8.0 ± 0.6 μl NTP/min. The arterial O2saturation, Po2, Pco2, and pH were 95.6 ± 0.3 per cent, 93 ± 3 mm Hg, 25.8 ± 1.0 mm Hg, and 7.44 ± 0.01 units, respectively. An artificial rise in eye pressure reduced the rate of uveal blood flow and increased the a‐v O2difference. The O2extraction was relatively constant at blood flow rates above 0.3–0.5 ml/min. At lower flow rates the O2extraction decreased in spite of a high venous O2concentration. Blood collected from the choroidal veins had a slightly higher O2concentration than blood collected from the intrascleral venous plexus. A reduction in uveal blood flow, produced by a reduction in the mean arterial blood pressure, reduced the O2content both in blood collected from the choroid and in blood leaving the anterior uvea. The results suggest that at low perfusion pressures there is anoxia in some tissue supplied by the uveal vessels, in spite of a relatively well oxygenated venous blood.
Determination of Cortical Blood Flow in Rabbit Femur by Radioactive Microspheres
Authors: Lunde P. K. M. , Michelsen K.
Published: December 2008

The method for blood flow determination involving measurement of relative radioemission from radioactive microspheres retained in various tissues after intravascular injection has here been applied to minute tissue regions. 85Sr‐labelled plastic microspheres with a diameter of 15 ± 5 μ were injected in a retrograde manner into the aorta in 10 anesthetized adult rabbits. The tissues included in the present study were the m. quadriceps femoris tendon, the cortical bone and the corresponding bone marrow from the left femur diaphysis. The unknown blood flows through these tissue regions were calculated by relating the measured radioactivity from tissue samples to a known blood flow and a known blood radioactivity in cannulated branches from the left posterior tibial artery. The blood flow values estimated by this technique were (g/minxg tissue): Quadriceps femoris tendon ‐0.068 ± 0.044, bone marrow of femur diaphysis ‐0.250 ± 0.146, cortical bone of femur diaphysis ‐0.010 ± 0.007.
Time Relations of Degeneration Mydriasis and Degeneration Vasoconstriction in the Rabbit Ear after Sympathetic Denervation. Effect of Bretylium.
Authors: Bárány Ernst H. , Treister Giora
Published: December 2008

Removal of the superior cervical ganglion in rabbits causes homolateral mydriasis starting about 14 hrs and ending about 32 hrs after the operation. In the external ear a vasoconstriction starts around 20 hrs and ends around 40 hrs after operation. A residual vasoconstriction sensitive to systemic ganglionblocking agents is often seen. Both phenomena are similarly delayed by bretylium. No time difference between the end of vasoconstriction at the base and at the tip of the ear (5–7 cm apart) was observed under conditions where a time difference of 2–3 hrs would have been detected. The conclusion is that the time between operation and transmitter release from the degenerating terminals is longer than is needed for the message of the interruption of the axon to reach the terminals. Time differences between degeneration release of transmitter in different organs may be partly due to intrinsic differences between the populations of terminals.
The Degeneration Contraction of a Sympathetically Innervated Smooth Muscle in the Rat after Reserpine, Inhibition of Monoamine Oxidase or Tyrosine Hydroxylase
Authors: Lundberg Dag
Published: December 2008

The degeneration contraction of the periorbital smooth muscle in conscious rats was measured after treatment with each of 3 different monoamine oxidase (MAO) — inhibitors, reserpine or the methylester of α‐methylthyrosine. Pheniprazine (10 mg/kg), nialamide (100 or 200 mg/kg) pargyline (100 or 200 mg/kg) given at the time of denervation and pargyline (100 or 200 mg/kg) given at 10 hrs after denervation significantly increased the size of the degeneration contraction. 200 mg/kg of pargyline tended to delay the onset of the contraction. However, pheniprazine, nialamide or pargyline at 100 mg/kg started it prematurely. An injection of reserpine (1 mg/kg) given at 2–3 hrs before the expected start of the degeneration transmitter release did not induce any excitatory effect and abolished the degeneration contraction. Inhibition of the synthesis of noradrenaline by the methylester of 1‐α‐methyltyrosine (H 22/07) given at the time of denervation or 10–12 hrs later did not influence the size or the time course of the degeneration contraction. It is concluded that: — The degeneration transmitter release is normally influenced by functional MAO. — Since the potent MAO‐inhibitors studied did not consistently delay the start of the degeneration contraction, it does not seem reasonable that bretylium, which earlier has been found both to possess MAO‐inhibiting and delaying effect, induces a delay only by inhibiting intraaxonal MAO. — There is no significant contribution of newly formed noradrenaline to the degeneration contraction.
Adrenergic Excitatory Influences on Initiation and Conduction of Electrical Activity in the Rat Portal Vein
Authors: Ljung Bengt , Stage Lars
Published: December 2008

The longitudinal smooth muscle of the rat portal vein shows synchronized spontaneous contractions. Both initiation and propagation of this activity are of myogenic nature. Under the influence of noradrenaline (NA), or postganglionic nerve stimulation, the contraction frequency is known to increase markedly. In order to analyse pacemaker function and synchronization of activity in the isolated portal vein, both during spontaneous activity and during NA induced excitation, a method was designed which allowed simultaneous recording of the mechanical contractions and of the electrical activity from three separate areas in the preparation.

Spontaneous, intermittent bursts of electrical spike activity spread over the preparation at a velocity of 5 to 30 mm/sec. Each propagated burst was associated with a mechanical response. Evidence is presented indicating that the individual spike potentials within a burst were propagated. Administration of exogenous NA markedly increased the frequency of burst discharge from an active pacemaker area, so that the preparation became synchronously driven at a higher rate, eventuelly leading to a maintained tetanus. In addition, propagated activity from “ectopic” pacemaker areas appeared, which caused irregular contractile responses. Qualitatively similar activity patterns were obtained by tyramine administration. The pronounced synchronization, and the increase in frequency of burst discharge elicited by such release of endogenous NA, suggest that myogenic propagation plays a most important role in the effectiveness of nervous control of this type of vascular smooth muscle.
Projections to the Cerebral Cortex from Afferents of the Interosseous Nerves of the Cat
Authors: Silfvenius H.
Published: December 2008

Evoked focal potentials from the contralateral fore‐ and hindlimb interosseous nerves Int.f. and Int.h. as well as from Pacinian afferents were recorded in sensorimotor cortex and in S II in cats anaesthetized with chloralose. Low threshold, short latency potentials from Int.f. were evoked in the lateral sigmoid gyrus, in the region of the post cruciate dimple, in the rostral bank of the lateral ansate sulcus, in the lower bank of the anterior suprasylvian sulcus and in S II. The shortest latencies varied between 5.0–6.0 msec. Mechanical stimulation of dissected clusters of Pacinian receptors in the interosseous region evoked cortical responses in the same areas with slightly longer latencies. Low threshold electrical stimulation of Int.h. afferents evoked in addition to the known projection to S II (McIntyre 1962) initially positive potentials in two loci of the postsigmoid gyrus, one on the dorsal, the other on the medial aspect of the hemisphere. The latencies in these loci were as short as those in S II. i.e. 9.5–10.0 msec. Zonal convergence between projections from interosseous and Group I muscle afferents was observed. The Int.f. path ascends in the dorsal column. A cortical potential was however, evoked in the postsigmoid gyrus by electrical stimulation of high threshold Int.h. afferents after transection of the dorsal columns at cervical level.
Quantitative Correlation between Degranulation and Histamine Release Following Exposure of Rat Mast Cells to Compound 48/80 in vitro
Authors: Nósal Radomír , Slorach Stuart A. , Uvnäs Börje
Published: December 2008

The relationship between the release of histamine and 35S‐labelled heparin from mast cells exposed to compound 48/80 in vitro has been studied in order to elucidate the mechanism of histamine release induced. The cells were taken from rats injected 3, 6, 12 or 20 days earlier with Na235SO4. A good correlation was found between the two release curves. From studies of the 35S/protein ratio in the extruded granules and granules obtained by water lysis of the washed compound 48/80‐treated cells it appears that the 35S‐labelled heparin was first evenly distributed with respect to the granule protein 12 to 20 days after injection. Using cells taken after such an interval the ratio percentage histamine release/percentage 35S release was found to be 1.1–1.4. We conclude from these results and from the similarity between the time courses of histamine and 35S release that the mechanism of histamine release induced by compound 48/80 involves an initial extrusion of histamine‐cotnaining granules, followed by an exchange of histamine in the extruded granules and cations in the extracellular medium.
The Effect of Anesthetics upon Labile Phosphates and upon Extra‐ and Intracellular Lactate, Pyruvate and Bicarbonate Concentrations in the Rat Brain
Authors: Nilsson Lorentz , Siesjö Bo K.
Published: December 2008

The effects of volatile anesthetics (nitrous oxide, halothane, diethyl ether and cyclopropane), of Fentanyl, and of barbiturates (thiopentone, phenobarbital and amobarbital) on labile phosphates and on intra‐ and extracellular lactate, pyruvate and bicarbonate concentrations of brain tissue were investigated in rats, which were immobilized and artificially ventilated so as to give arterial CO2 tensions of 35–40 mm Hg. It was found that the type or the depth of anesthesia did not significantly influence the tissue concentrations of phosphocreatine, ATP, ADP or AMP. There were very small differences in the tissue lactate concentration in the nonbarbiturate groups, and thus no indication that the lactate concentration varied with the depth of anesthesia. However, in all barbiturate groups there was a lowering of the lactate concentration and an increase in the intracellular pH'. In contrast to the volatile anesthetics the barbiturates gave significant decreases also in the calculated cytoplasmatic NADH/NAD+ ratio. The experiments thus failed to indicate that anesthetics inhibit electron transport or energy transfer reactions in the brain, at least under the conditions studied. In addition, they suggest that barbiturates, including, amobarbital, shift the balance between energy‐yielding and energy‐requiring reactions in favour of an oxidated state.
Antagonism by Calcium of the Inhibitory Action of Prostaglandin E2on Sympathetic Neuro‐transmission in the Cat Spleen
Authors: Hedqvist P.
Published: December 2008

Experiments were carried out with the isolated, perfused cat spleen and bovine splenic nerve trunk to study the target for prostaglandin E2induced inhibition of noradrenaline release from sympathetic nervss. Increasing the calcium concentration in the medium perfusing the spleeen was found to increase the outflow of noradrenaline to nerve stimulation and to antagonize the inhibitory action of prostaglandin E2on this parameter. Prostaglandin E2did not affect the noradrenaline releasing effect of tyramine. Atropine did not alter the inhibitory effect of prostaglandin E2on noradrenaline release. Prostaglandin E2did not change the amplitude of action potentials in bovine splenic nerves. There is thus no support for a blocking action on nerve conduction. It is concluded that prostaglandin E2may prevent calcium from gaining access to those sites in sympathetic nerve terminals where it promotes secretion of noradrenaline.
Ontogenesis of Peripheral Adrenergic Neurons in the Rat: Pre‐ and Postnatal Observations
Authors: Champlain J. de , Malmfors T. , Olson L. , Sachs Ch.
Published: December 2008

The early development of the peripheral adrenergic neurons of the rat was followed with the Falck‐Hillarp fluorescence technique. In the 13 day embryo small fluorescent sympathicoblasts with short processes were found in segmentally arranged groups along the dorsal aspect of the embryo. The larger sympathetic ganglia and the strongly fluorescent adrenal medullary cells were easily identifiable at this stage. In the 18 day embryo, fluorescent axon bundles were found in most larger nerve trunks. The outgrowing fluorescent axons had a stronger fluorescence intensity than non‐terminal axons of adult animals until at least 2 weeks after birth. The postnatal development of the plexuse of adrenergic nerves was followed in the iris, auricles of the heart, salivary glands, vas deferens and small intestine. The adrenergic innervation of the gut seemed to develop earlier than that of the other organs. Thus, the duodenal muscle layer had a well developed adrenergic innervation of the plexus of Auerbach at birth while the other organs investigated demonstrated well developed networks of adrenergic nerves from about the fourth day on. It was concluded from some pharmacological experiments that, under optimal conditions, the fluorescence technique can reveal all or almost all adrenergic nerves also during early development.
The Effect of Glucose on Histamine Release from Isolated Rat Peritoneal Mast Cells Induced by Adenosine‐5‘‐Triphosphate
Authors: Diamant B. , Peterson C.
Published: December 2008

Histamine release from isolated rat peritoneal mast cells induced by ATP in an aerobic milieu increased in the presence of glucose. Irrespectively whether the cells were exposed to glucose prior to ATP or the two agents were added together to cells, optimal histamine release was noted with 0.3–0.5 mM of glucose and amounted to 1.5–2 times that observed in the absence of glucose. In contrast, under similar conditions compound 48/80‐induced histamine release was not affected by glucose. The velocity of ATP‐induced histamine release and the final amount of histamine released within 30 min of incubation increased in the presence of glucose. A lag period of about 1 min was noted before histamine release occurred when initiated by ATP (3.9 times 10‐5M). This lag period was not changed by glucose. Iodoacetate inhibited histamine release induced by ATP as well as by compound 48/80. The glucose‐activated part of ATP‐induced histamine release seemed especially sensitive to iodoacetate. The results suggest that glucose through its metabolism in the cells exerts an enhancing effect on ATP‐induced histamine release.
Synthesis of Noradrenaline from 3,4‐Dihydroxyphenylalanine (DOPA) and Dopamine in Adrenergic Nerves of Mouse Atrium — Effect of Reserpine, Monoamine Oxidase and Tyrosine Hydroxylase Inhibition
Authors: Jonsson Gösta , Sachs Charlotte
Published: December 2008

Thein vitrosynthesis of noradrenaline (NA) from 3,4‐dihydroxyphenylalanine (DOPA) and dopamine (DA) in the mouse atrium has been investigated, using isotope, subcellular distribution and histochemical techniques. Incubation of atrial tissue in 5 times 10‐6M14C‐DOPA resulted in a formation of14C‐NA and14C‐DA at a rate of about 0.13 μg/g/hr, and 0.14 μg/g/hr respectively, whereas the same medium concentration of3H‐DA gave a formation of3H‐NA of about 0.25 μg/g/hr. The synthesis of NA and DA was found to be almost exclusively associated with the presence of adrenergic nerves, since it was considerably reduced after pretreatment with 6‐OH‐DA. Pretreatment with reserpine decreased formation of radioactive NA and DA which could be counteracted by nialamide. The effect of reserpine may be explained by inhibition of DA uptake in the amine storage granules. The antagonistic effect of nialamide is certainly due to inhibition of DA catabolism. Tyrosine hydroxylase inhibition produced by H44/68, which depleted the endogenous NA store to about 40% of normal, increased the formation of radioactive NA both from3H‐DA and14C‐DOPA. This may in part be explained by decreased competition of the endogenous precursor DA for DA‐β‐hydroxylase but also in part by increased storage sites available for newly formed NA.
Cytoplasmic Distribution of Endogenous and Exogenous 5‐Hydroxytryptamine in Rat Peritoneal Mast Cells
Authors: Jansson Sten‐Erik
Published: December 2008

The distribution of endogenous and exogenous 5‐hydroxytryptamine (5‐HT) in rat peritoneal mast cells was investigated by in vitro experiments using chemically 5‐HT measurements in granules and supernatants after degranulation of the cells in a ion‐free medium, and histochemically by the formaldehyde‐induced fluorescence in semi‐thin Epon sections. About 20–30% of the total amounts of 5‐HT was found in the supernatant upon degranulation of a practically pure mast cell suspension. It is probably a solubilization artefact, because the formaldehyde‐induced fluorescence was always observed exclusively in the granules, while the intergranular cytoplasm was non‐fluorescent. Even after incubation in exogenous 5‐HT when the 5‐HT content per cell was about 3 times that of normal cells, no intergranular fluorescence was observed. Imipramine, reserpine and, to a lesser extent, ouabain at a concentration of 10‐5 M inhibited the uptake but did not alter the normal granular distribution. This observation implies a reserpine‐resistant uptake of 5‐HT by mast cell granules.
Fate of3H‐Noradrenaline in Canine Subcutaneous Adipose Tissue1
Authors: Fredholm Bertil B. , Rosell Sune
Published: December 2008

Canine subcutaneous adipose tissue was isolated and perfused with defibrinated blood at a constant rate. Infused3H‐noradrenaline was taken up by the tissue and released spontaneously into blood. Following a washout period of 40 min or more, plasma samples were withdrawn. Radioactive compounds in venous plasma were separated by chromatography on alumina and Dowex. About 30 per cent of the venous radioactivity was identified as unchanged noradrenaline, about 7 per cent as normetanephrine and 14 per cent as deaminated catechols: deaminated O‐methylated metabolites accounted for about 45 per cent. This indicates the presence in adipose tissue of both monoamineoxidase and catechol‐O‐methyl‐transferase. Upon stimulation of sympathetic nerves to adipose tissue peripheral resistance increased, the3H‐presence in adipose tissue of both monoamine oxidase and catechol‐O‐methyl‐transferase. Upon cessation of the stimulation the peripheral resistance decreased and the outflow of noradrenaline metabolites increased above control values. After dihydroergotamine, nerve stimulation induced a decreased peripheral resistance, an increase of3H‐noradrenaline outflow and no change or an increase in the outflow of noradrenaline metabolites. Totally more radioactivity was released upon nerve stimulation after dihydroergotamine. The changes seen are interpreted to be associated with vascular reactions in adipose tissue.
Metabolism of Subcutaneously Injected14C‐Histamine in Myxine Glutinosa
Authors: Holstein Björn
Published: December 2008

The recovery of total radioactivity,14C‐histamine and14C‐methylhistamine in extracts of wholeMyxine glutinosawas determined after s.c. injection of14C‐histamine. 24 hrs after injection the same parameters were determined in single organs. Total radioactivity declined very slowly, 10 days after administration 71% was recovered. At that time14C‐histamine and14C‐methylhistamine amounted to 44% and 1% respectively of the given dose. The liver was the most efficient organ in extracting radioactivity.
Inhibitory Control of the Abdominal Stretch Receptors of the Crayfish
Authors: Jansen J. K. S. , Njå A. , Walløe L.
Published: December 2008

The efferent activities in the thick and thin “accessory” axons in the dorsal nerve of the crayfish abdomen have been studied during reflex activation from the same and neighbouring segments. The reflex input was either adequate stimulation of the slowly or the rapidly adapting stretch receptor or electrical stimulation of the afferent fibres from the receptors. The results support Eckert's finding (1961a) that the thick accessory nerve is reflexly activated from both the slowly and the rapidly adapting receptors. The thick accessory nerve is most effectively activated ipsilaterally while the thin accessory nerve predominantly participates in crossed reflexes.
Effects of Prostaglandin E1in Canine Subcutaneous Adipose Tissue in Situ1
Authors: Fredholm Bertil B. , Rosell Sune
Published: December 2008

The effect of PGE1on the uptake of glucose and the release of FFA and glycerol before and after sympathetic nerve stimulation (4 cps) was investigated in perfused canine subcutaneous adipose tissuein situ. Glucose uptake was significantly increased by PGE1at all concentrations used (5 times 10‐10to 7 times 10‐7M in blood). The effect of PGE1on the release of FFA and glycerol in unstimulated adipose tissue was inconsistent. Increases as well as decreases were observed. Lipolysis, as measured by glycerol release, induced by nerve stimulation was inhibited dose‐dependently. A 50 per cent inhibition was produced by approximately 1.2 times 10‐7M PGE1. Stimulated FFA release was also inhibited but there was no clear dose‐response relationship. It is concluded that PGE1has similar effects in canine subcutaneous adipose tissue with an intact blood supply as are known to be producedin vitro.
Potentiating Action of Desmethylimipramine on the Cardiovascular Effects of Noradrenaline and Some Other Pressor Agents
Authors: ÅStröm A.
Published: December 2008

The influence of desmethylimipramine (DMI) on the cardiovascular responses to i.v. injected noradrenaline (NA), adrenaline, metaraminol and isoprenaline, as well as to some chemically unrelated pressor agents (angiotensin, vasopressin, and the vasopressin analogue felypressin), was studied in anesthetized dogs and cats. The cardiovascular effects of NA were potentiated very markedly by moderate doses of DMI (0.1–1.0 mg/kg). The responses to adrenaline and metaraminol were only slightly potentiated. In the case of adrenaline, DMI was slightly more effective in enhancing the pressor action of this amine after partial β‐blockade (propranolol). In analogy with the carotid occlusion response, the effect on the peripheral vascular resistance elicited by electrical stimulation of the lumbar sympathetic nerves was not significantly potentiated by DMI.

A method of “delayed autoperfusion” was developed to record reflex vasomotor counter‐regulation. DMI was found to reduce the activity of this counter‐regulation suggesting that this may be one way in which this drug potentiates the cardiovascular effects of the non‐catecholamine pressor agents.
The influence of high salt intake and/or chronic blood volume expansion on renin‐angiotensin system in Brattleboro rats
Authors: POHLOVÉ I. , ZICHA J.
Published: December 2008

The influence of chronic saline drinking and/or DOCA‐salt treatment on plasma renin activity and renal renin concentration was studied in vasopressin‐deficient homozygous (DI) Brattleboro rats and their vasopressin‐secreting heterozygous (non‐DI) littermates. The activity of renin‐angiotensin system (RAS) can be suppressed even in the absence of vasopressin under the conditions of a sufficiently high salt intake that is achieved in DI rats by consumption of 0.6% saline instead of water. An almost complete RAS suppression in both plasma and kidney was observed in young animals in which high salt intake induced not only blood volume expansion but also blood pressure elevation, i.e. in mildly hypertensive unilaterally nephrectomized saline drinking DI rats as well as in moderately hypertensive DOCA‐salt treated DI rats and in non‐DI rats with a severe DOCA‐salt hypertension. Our results indicate that intravascular expansion and blood pressure changes are important factors for the modulation of plasma and renal renin activity even in the absence of vasopressin.
Splanchnic and renal vasoconstrictor and metabolic responses to neuropeptide Y in resting and exercising man
Authors: AHLBORG G. , WEITZBERG E. , SOLLEVI A. , LUNDBERG J. M.
Published: December 2008

The local clearance of neuropeptide Y (NPY) and whether NPY influences splanchnic and renal metabolism in man have not been investigated previously. The influence of NPY on splanchnic and renal blood flows at physiologically elevated levels has also not been investigated. The effects of a 40‐min constant NPY infusion (3 pmol kg‐1 min‐1) at rest and during 130 min of exercise (50% of Vo2max) were studied in six healthy subjects and compared with resting and exercising subjects receiving no NPY. Blood samples were drawn from arterial, hepatic and renal vein catheters for the determination of blood flows (indicators: cardiogreen and paraaminohippuric acid [PAH]), NPY, catecholamines, glucose, lactate and glycerol. NPY infusion was accompanied by: (1) significant fractional extraction of NPY‐like immunoreactivity (NPY‐Li) by splanchnic tissues at rest (58±5%) and during exercise (53±6%), while no arterial–venous differences could be detected across the kidney; (2) a reduction in splanchnic and renal blood flows of up to 18 and 13% respectively (P < 0.01–0.001) at rest without any additional changes during exercise; and (3) metabolic changes as reflected in: (a) a more marked fall in arterial glucose during exercise compared to the reference group (P < 0.05); (b) a 35% lower splanchnic glucose release (P < 0.01) during exercise due to diminished glycogenolysis (P < 0.01); and (c) a lower arterial lactate level (18%P < 0.05) together with unchanged splanchnic lactate uptake during exercise, suggesting reduced lactate production by extrahepatic tissues. The disappearance of plasma NPY‐Li after the infusions was biphasic with two similar half‐lives at rest (4 and 39 min) and during exercise (3 and 43 min).
Pro‐oxidant effects of normobaric hyperoxia in rat tissues
Authors: AHOTUPA M. , MÄNTYLÄ E. , PELTOLA V. , PUNTALA A. , TOIVONEN H.
Published: December 2008

Rats were exposed to 100% O2 atmosphere for 12, 36 or 48 h, and their lungs, brain, liver and kidneys were studied for signs of oxidative damage. Oxidative damage at molecular level was estimated by: (1) the appearance of conjugated diene double bonds and (2) the amount of fluorescent chromolipids in lipids extracted from tissues. As important intracellular regulators of oxidative stress, the response of enzymes detoxifying reactive oxygen species was also studied. Macroscopically, the brain and the lungs were most susceptible to oxygen‐induced effects. As an indication of oxidative tissue damage, hyperoxia caused accumulation of fluorescent chromolipids in brain and lung tissues, whereas diene conjugation did not reveal any signs of lipid peroxidation. Accumulation of fluorescent chromolipids was most prominent in the brain, where 99 and 138% increases over the control were detected after 36 and 48 h hyperoxia, respectively. Fluorescent chromolipids appeared in urine already before their concentrations were elevated in tissues. The activity of superoxide dismutase in the brain was initially decreased, followed then by a slight induction of activity at the later time‐points. Pulmonary and hepatic catalase activities were markedly decreased after prolonged (36 and 48 h) hyperoxia.

In conclusion, fluorescent chromolipid formation seems to be a sensitive indicator of hyperoxia‐induced oxidative damage in rat tissues. The lipid peroxidation‐derived fluorescent chromolipids are eliminated from the body via urinary excretion. Moreover, impaired detoxication of reactive oxygen may be implicated in tissue damage due to hyperoxia.
Comparison of the effect of a mitochondrial uncoupler, 2,4‐dinitrophenol and adrenaline on oxygen radical production in the isolated perfused rat liver
Authors: OKUDA M. , LEE H.‐C. , KUMAR C. , CHANCE B.
Published: December 2008

Using the isolated perfused rat liver, we examined the effect of stimulation of mitochondrial respiration by 2,4‐dinitrophenol (2,4‐DNP) and adrenaline on reactive oxygen species (ROS) production, liver damage and lipid peroxidation. ROS production was monitored by luminol‐ and lucigenin‐enhanced chemiluminescence and oxygen uptake was measured simultaneously. Liver damage and lipid peroxidation were evaluated by measuring hepatic lactate dehydrogenase (LDH) and thiobarbituric acid reacting substances (TBARS) release. Tissue ROS level decreased and oxygen uptake increased soon after 2,4‐DNP infusion. On termination of 2,4‐DNP infusion, there was a sharp increase in lucigenin‐enhanced chemiluminescence, which declined slowly, but luminol‐enhanced chemiluminescence did not change prominently. Hepatic LDH and TBARS release increased gradually during 2,4‐DNP infusion and were manifested by termination of the infusion. Allopurinol did not affect ROS production and TBARS release, but delayed increases in LDH release after termination of 2,4‐DNP infusion. Adrenaline, which stimulates mitochondrial respiration without uncoupling caused similar but smaller ROS changes observed in 2,4‐DNP. LDH and TBARS release were not affected significantly by adrenaline infusion. These results indicate that uncoupling of oxidative phosphorylation decreases ROS production and restoration of oxidative phosphorylation enhances ROS production and liver damage. Xanthine oxidase is unlikely to contribute to enhanced ROS production after termination of 2,4‐DNP but has some protective effect during uncoupling.
Increased resistance to haemorrhage induced by intracerebroventricular infusion of hypertonic NaCl in conscious sheep
Authors: HJELMQVIST H. , ULLMAN J. , GUNNARSSON U. , HAMBERGER B. , RUNDGREN M.
Published: December 2008

The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg‐1 min‐1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to < 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg‐1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min‐1) of 0.5 m NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 ± 1.2 ml vs 16.9 ± 0.9 ml kg‐1). In one animal, subjected to 0.5 m NaCl infusion, the blood pressure was still maintained at 25 ml kg‐1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance.

The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotension II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment.

We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration.
2‐Amino‐3‐phosphonopropionate fails to block postsynaptic effects of metabotropic glutamate receptors in rat hippocampal neurones
Authors: HU G.‐Y. , STORM J. F.
Published: December 2008

Metabotropic glutamate receptors (mGluRs) operate via the phosphoinositide second messenger cascade and have various modulatory effects on central neurones. 2‐Amino‐3‐phosphonopropionate (AP3) has been proposed as a selective antagonist of mGluR and used to explore the physiological functions of mGluR. We have compared the effects of mGluR agonists in the presence and absence of AP3 using intracellular recording from CAl pyramidal neurones in rat hippocampal slices. Two mMd, l‐AP3 or 1 mMl‐AP3 did not cause any detectable change in the effects of mGluR agoniststrans‐1‐amino‐cyclopentyl‐1,3‐dicarboxylate (t‐ACPD) or quisqualate. These agonists still induced depolarization, inhibition of the slow after‐hyperpolarization and slowing of the spike repolarization. The results argue against AP3 being an antagonist of postsynaptic mGluRs.
Evidence for an electrically silent, neurogenic fluid secretion in the rat jejunum in vivo
Authors: HEMLIN M. , MELLANDER A.
Published: December 2008

The aim of this study was to evaluate the mechanism behind neurogenic fluid secretion in the rat jejunum. In vitro, short‐circuit current (SCC) and potential difference (PD) were measured with the conventional Ussing technique. In vivo, electric parameters and net fluid transport (NFT) were simultaneously recorded with two different techniques. In separate in vivo experiments alkaline secretion (As) was estimated.

In vitro, the chloride channel blocking substance 5‐nitro‐2(‐3‐phenylpropyl‐amino)benzoic acid (NPPB) and the loop diuretic substance furosemide (F) inhibited SCC, whereas the carbonic anhydrase inhibitor acetazolamide (Ace) lacked effect. Noradrenaline inhibited SCC and this effect was antagonized by NPPB and F.

In vivo, cholera toxin induced a parallel increase in PD/SCC and fluid secretion. Conversely, mesenteric nerve stimulation (MNS) or administration of the nicotinic antagonist hexamethonium (Hx), concomitantly inhibited PD/SCC and fluid secretion. However, there was a poor correlation between the magnitudes of these effects. F inhibited SCC in vivo and also the SCC‐effect of MNS. However, F had no effect on fluid secretion in vivo, nor on the NFT‐effect of MNS. Jejunal As was stimulated by cholera toxin and MNS significantly inhibited As. The present results challenge the current view on the role of electrogenic chloride secretion in intestinal secretion. Alternative mechanisms are tentatively discussed.
Contractions induced by angiotensin I, angiotensin II and bradykinin in isolated smooth muscle from the human detrusor
Authors: ANDERSSON K.‐E. , HEDLUND H. , STAHL M.
Published: December 2008

In isolated human detrusor preparations angiotensin (At)II 10‐9‐10‐5mcaused concentration‐dependent contractions. The contractile effect was immediate, and had an amplitude which at the highest concentration used, 10‐5m, reached 103 ± 16% of the mean contraction produced by K+124 mm(27.6 ± 1.4 mN). The AtII effect was completely blocked by saralasin 10‐6m, but was not affected by pre‐treatment of the preparations with captopril or enalaprilate. There was a marked tachyphylaxis to the actions of the peptide. AtI (10‐8–10‐5m) also caused contractions which were rapidly developing, and subject to a marked tachyphylaxis. At a concentration of 10‐5m, the mean amplitude was 66 ± 9% of the K+‐induced contraction. The contractions were blocked by saralasin 10‐6m, but not by captopril or enalaprilate 10‐5m. In contrast, contractions produced by AtI in rabbit mesenteric arteries were practically abolished by the angiotensin converting enzyme (ACE) inhibitors. The contractions induced by both Ad and AtII were practically abolished after pre‐treatment in a nominally calcium‐free Krebs solution. However, blockade ofl‐type calcium channels by nifedipine 10‐6mreduced the responses to both AtI 10‐6M (by 38 ± 4%) and AtII 10‐6m(by 39 ± 7%), but never abolished the contractions. Bradykinin (Bk; 3 times 10‐8–10‐5m) had a contractile effect in detrusor preparations which varied widely between strips. At a concentration of 3 times 10‐6m, a maximum was reached amounting to 30 ± 10% of the K+‐induced contraction. Bk‐induced contractions were practically abolished (0–3% of K+‐induced contraction) by a 30 min exposure of the preparations to calcium‐free medium. In the presence of nifedipine 10‐6m, the mean response to Bk 10‐5M did not differ significantly from the control value. Thirty min pretreatment with captopril or enalaprilate 10‐5msignificantly increased the Bk 10‐5minduced contractions. These contractions were significantly reduced by pretreatment for 30 min with indomethacin.

The results suggest that Ad, AtII, and Bk all have marked contractile effects on isolated human detrusor smooth muscle. The conversion of AtI to AtII seems to occur through an enzyme which cannot be inhibited by ACE‐inhibitors. ACE‐inhibition can, however, enhance the effects of Bk.
Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs
Authors: ANDERSEN S. E. , ENGSTROM T. , BIE P.
Published: December 2008

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water‐diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo‐controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg‐1min‐1(arginine vasopressin) or 1 ng kg‐1min‐1(oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 ± 0.2 (arginine vasopressin alone) and 1.8 ± 0.3 pg kg‐1(arginine vasopressin plus oxytocin and plasma oxytocin to 72 ± 5 (oxytocin alone) and 77 ± 8 pg ml‐1(oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 ± 2 to 15 ± 6 μmol min‐1and from 7 ± 4 to 25 ± 13 μmol min‐1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 ± 4 to 101 ± 27 μmol min‐1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ratio by a factor of 3.7.

It is concluded, that oxytocin at plasma concentrations of 70–80 pg ml‐1has modest antidiuretic and natriuretic effects and that the combined action of arginine vasopressin oxytocin may elicit supra‐additive natriuretic effects.
Increased release of tissue plasminogen activator and its inhibitor in human parotid saliva upon stimulation
Authors: KJAELDGAARD M. , LAGERLOF F. , JOHANSSON I. , GAFFNEY P. J. , KJAELDGAARD A.
Published: December 2008

Parotid saliva from 12 healthy volunteers was collected prior to and after 5 and 25 min of stimulation at a constant flow rate of 0.25 or 1.0 ml min‐1. In the salivary samples the concentrations of tPA (tissue‐type plasminogen activator), PAI‐1 (plasminogen activator inhibitor type‐1), albumin and total protein were determined and the activity of amylase, tPA and PAI assessed. Presence of both tPA and PAI‐1 antigen was demonstrated in all samples, and in unstimulated saliva the ratio between the activator and its inhibitor was 1:7. Upon stimulation we found a significantly increased concentration of PAI‐1, a less pronounced increase in tPA concentration, unchanged amylase and total protein levels and significantly decreased albumin concentration. tPA activity was significantly reduced after prolonged stimulation which had no effect on PAI activity. In stimulated saliva a significant positive correlation between concentration of tPA and PAI‐1 was demonstrated. Stimulation with citric acid had no effect on output of albumin which is passively filtered from blood, whereas the increase in flow rate corresponded to the significantly increased secretion rate of total protein and amylase which is secreted by gland cells. The secretion pattern of tPA and PAI‐1 differed significantly from that of albumin in showing markedly increased output rate during the stimulation period, and the relative increase in output of PAI‐1 was significantly higher than that of amylase and total protein. Thus, the results from this study suggest an active release of both tPA and its main inhibitor PAI‐1 into saliva.
Force‐frequency relationship, contraction duration and recirculating fraction of calcium in postnatally developing rat heart ventricles: correlation with heart rate
Authors: VORNANEN M.
Published: December 2008

Heart rates (HR) of awake unrestrained animals, isometric contraction duration and force‐frequency relationship of ventricular tissue were determined in adult and postnatally developing rats. Resting HR was lowest in newborns (256 beats min‐1), reached maximum at the age of 2.5 weeks (506 beats min‐1) and then declined to the level of adult rats (381 beats min‐1). Duration of isometric contraction correlated negatively with HR. Time to peak tension (TPT) was 185 ms in newborns but fell rapidly during the first days of post‐natal life. Minimum was attained at the age of 2.5 weeks (TPT = 98 ms), followed by a slight prolongation towards adulthood. Recirculating fraction of activator Ca2+increased parallel with HR, being 6% in newborns, 33% in 11‐day‐old pre‐weanlings, and 87% in adult rats. Similar developmental pattern of the parameters suggests that a post‐natal increase in HR and a shortening of contraction duration are closely associated with a shift from extracellular to intracellular source of activator Ca2+. Force–frequency curves were similar at different developmental stages and consisted of three phases; a negative staircase between 0.05 and 1.0 Hz, a positive staircase between 1.0 and 4.0 Hz, and a secondary decline above 4.0 Hz. In adult rats the positive force staircase was weak or absent. Furthermore, our results show that negative staircase is not only a property of adult rat heart but is present, and even more pronounced, in preweanling and weanling rat heart. Therefore negative staircase is not solely explained by quantitative changes in the contribution of sarcoplasmic reticulum (SR) to contractile activation, but rather by the mechanisms which regulate loading and/or release of sarcoplasmic reticular Ca2+.
Influence of angiotensin II, α‐ and β‐adrenoceptors on peripheral noradrenergic neurotransmission in canine gracilis musclein vivo
Authors: SCHWIELER J. H. , KAHAN T. , NUSSBERGE J. , JOHANSSON M.‐C. , HJEMDAHL P.
Published: December 2008

Interactions between angiotensin II and adrenoceptor‐mediated effects on peripheral sympathetic neurotransmission were investigated in constant flow blood‐perfused canine gracilis musclein situ, without and with pretreatment by non‐competitive α‐ adrenoceptor blockade.

Angiotensin converting enzyme (ACE)‐inhibition by benazeprilat increased nerve stimulation (2 Hz, 4 min)‐evoked noradrenaline (NA) overflow (+21 ± 5 yo) with α‐ adrenoceptors intact, but reduced NA overflow (– 18 ± 6%) when α‐adrenoceptors were blocked. Vasoconstrictor responses were slightly reduced by benazeprilat. Subsequent infusion of angiotensin II (Ang 11, 20 and 500 ng kg‐1min‐1i.v., raising arterial concentrations from 0.6 ± 0.2 PM to 1390 ± 240 and 25 110 ± 3980 PM, respectively) failed to increase NA overflow or to enhance stimulation‐evoked vasoconstriction. Adrenaline (0.4 nmol kg‐1min‐1i.v.) did not change evoked NA overflow before or after benazeprilat, either with or without α‐adrenoceptor blockade, despite high concentrations (± 10 nM) in arterial plasma. Following benazeprilat, propranolol reduced NA overflow (–24 ± 3 yo) only if the α‐adrenoceptors were blocked.

In conclusion, benazeprilat reduced evoked NA overflow in the presence of α‐ adrenoceptor blockade to a similar degree as previously shown in the presence of neuronal uptake inhibition in this model. However, contrasting to our previous findings, benazeprilat enhanced NA overflow and reduced the post‐junctional response to nerve stimulation in the absence of α‐adrenoceptor blockade. This could be related to bradykinin accumulation during ACE‐inhibition, in addition to the reduction of Ang II generation. Our data are not compatible with facilitation of NA release by circulating Ang II even at pharmacological dose levels. Although activation of prejunctional β‐adrenoceptors may facilitate evoked NA overflow in this model, circulating adrenaline is ineffective under physiological conditions even after α‐adrenoceptor blockade. Also, β‐adrenoceptor‐mediated prejunctional effects do not seem to involve Ang II in canine skeletal musclein vivo.