bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation of phosphatidylinositol hydrolysis and insulin secretion of cultured mouse pancreatic islets
Authors: HALLBERG A.
Published: December 2008

The correlation between hydrolysis of phosphatidylinositol (PI) and insulin secretion was investigated in cultured mouse pancreatic islets. After prelabelling with [3H] glycerol or [3H] inositol, islets were incubated in the presence of different insulin secretogogues. Carbamylcholine induced a rapid decrease of Pi‐bound radioactivity concurrent with stimulation of insulin secretion, and both these responses were blocked by atropine. After culture at a low (3.3 him), glucose concentration, carbamylcholine evoked PI hydrolysis, but no insulin secretory response was observed. Carbamylcholine induced PI hydrolysis also under Ca2+‐free conditions, which blocked insulin secretion. Stimulation of insulin secretion with high glucose (16.7 mM), K+(25 ijm), or arginine (10 mM), or addition of theophylline (5 mM) to high (16.7 mM) glucose, were associated with unchanged rates of PI hydrolysis. In labelling experiments, both carbamylcholine and glucose (16.7 mM) were found to stimulate the incorporation of [3H] inositol into islet PI. These results demonstrate that stimulation of muscarinic cholinergic receptors increases islet PI turnover. There was, however, no general correlation between islet PI turnover and insulin secretion.
Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity
Authors: KOFOD H. , LERNMARK Å. , HEDESKOV C. J.
Published: December 2008

Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L‐glutamine, l‐serine and the methyl ester of l‐phenylalanine, but neither l‐phenylalanine nor l‐serine methyl ester, stimulate insulin secretion. In the presence of l‐glutamine, however, the effect of L‐serine was additive, while the methyl esters of L‐serine and L‐phenylalanine as well as native L‐phenylalanine, potentiated the glucose‐stimulated release of insulin. Measurements of islet glutamate dehydrogenase activity showed that only the two methyl esters of l‐phenylalanine and L‐serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic β‐cell glutamate dehydrogenase activity.
Microelectrode recordings from the facial nerve in man
Authors: NORDIN M. , HAGBARTH K.‐E. , THOMANDER L. , WALLIN U.
Published: December 2008

Microneurographic recordings have for the first time been obtained from the human facial nerve trunk, close to its exit from the stylomastoid foramen. The aim was to search for evidence of an afferent or sympathetic component of the facial nerve at this level and to study the fascicular organization of motor fibres. Single unit discharges of motor axons were occasionally discerned, and all recordings showed multiunit motor impulses preceding the EMG activity of the appropriate facial muscles by about 5 ms during both blink reflexes and voluntary contractions. No evidence of low‐threshold mechanoreceptive afferents was found. Electron microscopic studies at the level of recording showed unmyelinated axons but attempts to record nociceptive and sympathetic activity failed. However, deep facial pain evoked by intraneural stimulation suggested the presence of nociceptive afferents of non‐cutaneous origin. Intrafascicular recording and stimulation showed that most fascicles were composed of motor axons innervating muscles within the whole ipsilateral half of the face.
A method for recording effects of anti‐epileptic drugs on interictal discharge in the cat's cerebral cortex. Factors determining the distribution of external carotid artery infusions
Authors: LANDGREN S. , SELSTAM G. , AASLY J. , DANIELSSON E.
Published: December 2008

The method utilizes infusion via the external carotid (ECA), the internal maxillary arteries and their anastomoses to the cerebral circulation. It takes into account the ipsilateral distribution of the carotid blood supply. A regular interictal epileptiform spiking from foci on both hemispheres was provided by local application to the cortical surface of small pieces of filter paper soaked in sodium benzylpenicillin, 100,000 IE ml‐1. The infused drug affects the ipsilateral foci, and the contralateral one functions as a simultaneous untreated control. The stability of the interictal frequency and the effect of non‐oxygen carrying solvents are described. The effect of changes in blood pressure, temperature andPCo2are considered as well as the coupling between activity in ipsi‐and contralateral foci. Experiments with infused radioactive microspheres were performed to determine the strictness of the ipsilateral distribution and the conditions under which it was upheld. With mean arterial blood pressures between 70 mm Hg and 170 mm H g and infusion speeds between 1.0 ml min‐1and 6.3 ml min the distribution to the contralateral cerebral hemisphere was 0.3% (SD 0.2, SEM 0.1). Infusions of [125I]albumin were used to determine the blood flow in ECA. The flow varied between 20 ml min‐1and 68 ml min‐1. The higher values were seen when the extracerebral shunting was high. Conditions influencing the dilution of the infusion and its distribution within the brain were investigated. Important factors were carotid and cerebral blood flow, arterial blood pressure, speed and duration of the infusion, recirculation and cerebral temperature. ArterialPCo2, pH andPo2should be carefully controlled. Computer‐supported treatment of interictal spike frequency and amplitude, as well as of circulatory and respiratory parameters, was utilized. The method was tested in experiments with infusions of 5α‐pregnanolone. It was shown that infusions, shorter than the estimated circulation time, reduced the interictal spike frequency and amplitude recorded from the ipsilateral foci without effects on the contralateral ones.
Endocrine effects of repeated sauna bathing
Authors: LEPPÄLUOTO J. , HUTTUNEN P. , HIRVONEN J. , VÄÄNÄNEN A. , TUOMINEN M. , VUORI J.
Published: December 2008

Ten healthy male and seven female volunteers were exposed to dry heat (in a Finnish sauna 80 oC) 1 h twice a day for 7 days. The levels of ACTH in plasma, Cortisol, TSH, thyroid hormones, testosterone, gonadotropins, prolactin and GH in serum and urinary excretion of catecholamines were determined before the experiment, and on the first, third and seventh days. Females participated only in prolactin studies. During the experiments there were no statistically significant changes in serum thyroid hormones, TSH, testosterone, FSH and LH levels. Serum Cortisol and plasma ACTH decreased and urinary catecholamine increased slightly at the end of the experiment (P < 0.05). Serum GH and prolactin in males exhibited 16‐ and 2.3‐fold increases (P < 0.01), respectively. In females serum prolactin rose over four‐fold (P < 0.01). The GH rise in response to hyperthermia declined after the third day but prolactin remained elevated at the end of the experiments in males. The release of prolactin in females was also high and may be associated with the transitient amenorrhoea that occurred in five out of seven subjects after the experiment. The increased release of prolactin and perhaps that of GH may be associated to the heat‐exposure‐induced dehydration.
Exercise‐induced increase in dog adipose tissue blood flow before and after denervation
Authors: BÜLOW J. , MADSEN J.
Published: December 2008

Subcutaneous adipose tissue blood flow was examined during rest and exercise in the inguinal fat pads of four female dogs using the Xe wash‐out technique. The experiments were performed before and after denervation of one of the pads. No difference between the resting flows in the two pads could be demonstrated either before or after denervation. The flow increased about two‐fold on average from rest to exercise. This response was similar before and after denervation. It is concluded that direct sympathetic innervation is not involved in the regulation of adipose tissue blood flow during exercise.
Role of arginine‐vasopressin for the development of hypertension following aortic constriction
Authors: APERIA A. , SAHLGREN B. , EKLÖF A.‐C. , LUNDIN S. , MELIN P.
Published: December 2008

This study concerns the role of arginine‐vasopressin (AVP) for the development of hypertension after constriction of the abdominal aorta proximal to the renal arteries (PAC). The PAC was applied in AVP‐deficient Brattleboro (Bb) rats and the blood pressure was recorded 3 weeks later. In untreated rats, PAC did not cause hypertension. When the rats were given AVP 0.6 or 6 nmol day‐1 for 2 weeks using mini‐pumps, hypertension developed both proximal and distal to the constriction. The level of the hypertension was independent of the AVP dose. When the rats were given i‐deamino‐4‐valine‐8‐D‐arginine‐vasopressin (dVDAVP) a specific antidiuretic agonist without effect on the vascular AVP receptors, hypertension did not develop. Sham‐operated rats given AVP did not develop hypertension. The PAC rats treated with AVP but not with dVDAVP had an enhanced pressor response to an i.v. bolus dose of angiotensin II. It is concluded that AVP plays an important role in the development of hypertension following aortic constriction and that the action is mediated via the vascular AVP‐receptors. We suggest that the presence of AVP permits the expression of other hypertensive factors, such as angiotensin II.
Saliva and sweat secretion in man during a one‐hour calcium clamp
Authors: SAGULIN G.‐B. , TØRRING O. , HELLSING K. , ROOMANS G. M.
Published: December 2008

The effect of a 1‐h calcium infusion, directly regulated to obtain and maintain a predetermined blood calcium level (‘calcium clamp’), on the composition of parotid saliva, mixed saliva, and sweat was determined in healthy volunteers. An increase in amylase content of the parotid saliva under hypercalcaemic conditions was observed, but the ‘calcium clamp’ had no effect on flow rate, total and ionized calcium, sodium, potassium, and phosphate levels as well as pH in parotid and mixed saliva. The sweat calcium concentration was negatively correlated with sweat rate, in contrast to sodium and chloride concentrations. Increasing serum calcium levels did not affect ionic compositon of the sweat and sweat flow rate.
Somatosensory units in the cat's intercollicular region
Authors: DANIELSSON I. , NORRSELL U.
Published: December 2008

Sampling of unitary, neural activity was made with tungsten electrodes in the mesencephalon of cats anaesthetized with chloralose. Possible activation was studied with adequate somatosensory, visual and acoustic stimuli as well as electrical nerve stimulation via electrodes embedded in each forelimb and the contralateral hindlimb. Fifty units or about 10% of the total population were found in clusters of strictly somatosensory units which were activated by light tactile stimulation and with short latency from the contralateral body half. Some of these units had small receptive fields, but others showed convergence of information from large receptive fields which sometimes included parts of the ipsilateral body half. The different clusters appeared to constitute parts of a coherent structure which is located between 3–5 mm lateral to the midline at the anterior/posterior level of the trochlear nucleus, and with slanted dorso‐ventral distribution with the caudal parts above and the rostral parts below the Sylvian aqueduct. A somatotopical arrangement was found with the forelimb rostral to the hindlimb, and the suggested structure may be the somatosensory intercollicular nucleus which has been described by others.
Histamine storage and formation in canine gastric mucosa ‐ effect of pentagastrin stimulation
Authors: LUNDELL L. , FORSELL H. , LÖNROTH H. , ROSENGREN E. , WINGREN U.
Published: December 2008

Histamine storage and formation in the dog gastric mucosa were studied during basal conditions and after pentagastrin stimulation. Histamine formation (histidine decarboxylase activity), histamine content as well as the density of mast cells of the oxyntic gland mucosa were evenly distributed. Histamine content of the mucosa was significantly correlated to the density of mucosal mast cells. In the basal secretory state, histamine formation and histamine content of the oxyntic gland mucosa were of the same magnitude as in the antral mucosa. Pentagastrin stimulation induced a small but significant decrease in histamine content of the oxyntic gland mucosa and a subsequent acceleration in the rate of amine formation. Neither histamine content nor histidine decarboxylase activity of the antral mucosa was affected by pentagastrin infusion.
Satellite cells express the trophic factor IGF‐I in regenerating skeletal muscle
Authors: JENNISCHE E. , SKOTTNER A. , HANSSON H.‐A.
Published: December 2008

The expression of insulin‐like growth factor I (IGF‐I, somatomedin C) was studied in regenerating skeletal muscle. Irreversible damage to skeletal muscle cells was induced in the extensor digitorum longus muscle (EDL) of adult rats by ischaemia, preceded by glycogen depletion, and the regeneration process was studied for periods up to 14 days after injury. The IGF‐I was demonstrated by indirect immunofluorescence. Immunoreactivity against ribonucleotide reductase (RR) was used as a marker for DNA synthesis, that is, cell proliferation. Increased IGF‐I immunoreactivity could be demonstrated within 24h after injury in satellite cells, intramuscular nerves and in blood vessels. The IGF‐I immunoreactivity remained virtually unchanged in the contralateral, undamaged EDL. An increasing number of satellite cells, expressing high IGF‐I immunoreactivity, could be demonstrated in the injured EDL, and within 72 h myoblasts, expressing high IGF‐I and RR immunoreactivity, were formed. Small immature muscle cells, displaying high IGF‐I immunoreactivity, were observed 4 days after injury. Increased IGF‐I immunoreactivity was still obvious in the regenerated muscle cells 14 days after injury while RR immunoreactivity was seen only in scattered satellite cells. It is concluded that IGF‐I may act as a trophic factor during regeneration of skeletal muscle after injury.
Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain
Authors: OLESEN S.‐P.
Published: December 2008

The effect of free oxygen radicals on the electrical resistance of brain venular endothelium was studied in anaesthetized frogs. The technique allowed continuous recording of the electrical resistance of the vascular wall reflecting its ionic permeability. The oxygen radicals were generated by an enzymatic reaction between xanthine oxidase and hypoxanthine supplied to the surface of the exposed brain. Electrical resistance of the venular endothelium decreased within 1–2 s after the reaction was initiated. Hypoxanthine (1 mM) and xanthine oxidase at a concentration of 10, 25, 50, 100, and 250 mU ml‐1 lowered resistance to 1.0, 0.9, 0.8, 0.5 and 0.2 × control value, respectively, within a 3 min period of administration. The effect induced by 25 and 50 mU ml‐1 of xanthine oxidase was readily reversible, whereas that induced by the two highest concentrations was irreversible within the observation time. The response was totally blocked by allopurinol as well as by superoxide dismutase plus catalase. Pretreatment with methylprednisolone or BW755C (an inhibitor of cyclo‐ and lipoxygenase) did not inhibit the response, nor did removal of calcium or magnesium from the extracellular medium. Free oxygen radicals are powerful agents that rapidly induce dynamic changes in the electrical resistance of brain vessels, supporting the notion that they may be important mediators of vascular endothelial damage in the brain.
The disappearance of adenosine from blood and platelet suspension in relation to the platelet cyclic AMP content
Authors: SÖDERBÄCK U. , SOLLEVI A. , FREDHOLM B.B.
Published: December 2008

Adenosine exerts anti‐aggregatory effects on human platelets in vitro, probably by increasing intraplatelet levels of cyclic AMP.In addition, adenosine prevents platelet loss in vivo. We have studied the relationship between the concentration of adenosine in the platelet media and the level of cAMP.In PRP, exogenous adenosine (2–16 μM) was eliminated with a half‐life close to 5 min. Approximately half of the added adenosine was deaminated (blocked by 1–2 μM EHNA), and half was eliminated by uptake into platelets (blocked by 2 μM dipyridamole).In whole blood the half‐life for adenosine was much shorter, about 155.Addition of adenosine deaminase (0.3 μg ml‐1) to PRP resulted in a measured half‐life for adenosine approximating that of whole blood. In PRP where adenosine was eliminated as quickly as in whole blood, the adenosine‐mediated stimulation of cAMP was 35% lower than in PRP, and the cAMP response lasted 2 min, versus 15 min in normal PRP.These results suggest that the magnitude and duration of adenosine's effect on platelets are markedly overestimated by studying platelet suspensions. In blood, the effect of adenosine is smaller in magnitude and very transient. The possibility is discussed that the action of adenosine in vivo on blood platelets can therefore be quite local.
CO2 sensitivity in humans breathing 1 or 2% CO2 in air
Authors: ELLINGSEN I. , SYDNES G. , HAUGE A. , ZWART J.‐A. , LIESTØL K. , NICOLAYSEN G.
Published: December 2008

Ventilation increases when the concentration of CO2 in the inspired gas is increased, thereby limiting the increase in alveolar and arterial PCO2 The extent of this compensation at low levels of inspired CO2 has been debated. In five healthy humans, we have measured arterial PCO2, arterial pH and ventilation during exposure to 1 and 2% CO2 in the inspired gas. Each exposure lasted at least 7 min and arterial blood was sampled over at least 30 s during the last minute of each period. The ventilation was measured in the sixth and seventh min. The protocol included the sequences: control test‐control and test‐control‐test with ‘test’ representing CO2 loading and ‘control’ 0% CO2, respectively. We found that arterial PCO2 increased and pH decreased at both levels of inspired CO2.The mean increase in arterial PCO2 was 0.09 and 0.25 kPa, at CO2 1 and 2%, respectively. Three subjects were exposed to 1 % CO2 in the inspired gas for 28 min flanked by similar control periods. In each period arterial blood samples were taken at 2‐or 3‐min intervals. Arterial PCO2.remained elevated for at least 20 min during the CO2 loading. The sensitivity to CO2 (ratio of increase in ventilation to increase in arterial PCO2) was within the range described by others at higher levels of inspired CO2.Arterial PCO2 increased by about 10% of the imposed load. We conclude that the increase in ventilation provides only incomplete compensation for exposure to CO2: arterial CO2 is increased and arterial pH decreased also at very low levels of inspired CO2.
Mechanisms of neurotensin‐induced fluid secretion in the cat ileumin vivo
Authors: EKLUND S. , FAHRENKRUG J. , JODAL M. , LUNDGREN O. , SJÖQVIST A.
Published: December 2008

Neurotensin (NT) is released from N cells in the small intestinal epithelium. Among other effects NT is known to elicit fluid secretion in the small intestine. This study was carried out in order to elucidate the mechanism by which NT elicits this secretion. Neurotensin infusions at two rates (4.5 and 45 pmol min‐1kg‐1body wt) to isolated segments of cat ileumin vivo, caused a steady rate of net fluid secretion and a release of vasoactive intestinal polypeptide into the mesenteric vein. The secretion was totally inhibited by tetrodotoxin. Hexamethonium, a nicotinic receptor antagonist, inhibited the secretion elicited by the lower but not by the higher dose of NT.Met‐enkephalin also inhibited the induced secretion while pyrilamine, a histamine‐1 receptor antagonist had no effect. No significant change in enteric blood flow was caused by the NT infusion. These results indicate that NT elicits a nervous reflex in the enteric nervous system which, accordingly, turns the transport of the enterocytes into net fluid secretion.
Postnatal loss of synaptic terminals in the partially denervated mouse soleus muscle
Authors: FLADBY T. , JANSEN J.K.S.
Published: December 2008

The present work aims to distinguish between processes that lead to neonatal synapse elimination. We have partially denervated the mouse soleus muscle just after birth by cutting one (L5) of the two (L4 and L5) spinal nerves which supply its innervation. After 4–6 weeks' survival times, we determined the number of remaining motor units (MUs) and the number of innervated fibres in the muscle by conventional physiological and histological techniques. There was no significant overlap between the remaining MUs. Their average size was reduced from about 230 muscle fibres at birth to about 80 after 4–6 weeks, compared to only 30 in normal animals of the same age. We conclude that two processes are required to explain synapse elimination in the muscle: (1) a non‐competitive process, inherent to the immature motor neurons and leading to a substantial reduction in their field of innervation; (2) a competitive process between axon terminals innervating the same muscle fibre.
Prostaglandin E2 20‐hydroxylase in ampulla of vas deferens of sheep
Authors: OLIW E.H.
Published: December 2008

Microsomes were prepared from the ampullary muscosa of ram ductus deferens. The microsomal fraction was supplemented with 1 mM NADPH and was found to metabolize PGE2 to 20‐hydroxy‐PGE2.The product was identified by gas chromatography‐mass spectrometry (GC‐MS).The biosynthesis of 20‐hydroxy‐PGE2 was assessed by re versed‐phase high performance liquid chromatograpy (HPLC) using 19‐hydroxy‐PGE1 as an internal standard and 0.2 mM PGE2 was found to be metabolized to 20‐hydroxy‐PGE2 at a rate of 7.1 pmol min‐1 mg‐1 of protein. Like a prostaglandin 20‐hydroxylase of sheep vesicular glands, the 20‐hydroxylase of the ampulla was only partly inhibited by metyrapone.20‐Hydroxy E prostaglandins, which occur in ram semen, are likely to be formed by the vesicular glands and the ampulla of vas deferens in the sheep.
Action potential fatigue in single skeletal muscle fibres of Xenopus
Authors: LÄNNERGREN J. , WESTERBLAD H.
Published: December 2008

Action potential fatigue has been studied in single short toe muscle fibres of Xenopus under three different conditions: (1) in rested fibres which produced maximum tension, (2) in fibres during post‐contractile depression (PCD), a state of depressed tension generation but seemingly normal membrane properties, and (3) in fibres de‐tubulated by glycerol treatment. The fibres were stimulated continuously at 70 Hz (22.5 ±C) and membrane potential was measured throughout the stimulation period with an intracellular microelectrode. Rested and PCD fibres exhibited similarities in the development of action potential fatigue during a 30 s stimulation period; the amplitude was reduced by 86 and 70 mV, respectively, and the duration, measured at a level of one‐third of the peak amplitude, was increased from 1.1 to 4.2 and 1.3 to 3.7 ms, respectively. De‐tubulated fibres were more resistant to action potential fatigue; the amplitude decreased by only 20 and 35 mV during 30 and 60 s of stimulation, respectively, and the duration was increased from 1.1 to 2.7 ms. It is concluded that action potential fatigue in skeletal muscle fibres is primarily caused by failing regenerative activity in the t‐tubules, which is reflected in an altered shape of conventionally recorded action potentials.
Method for continuous recording of hydrostatic exchange vessel pressure in cat skeletal muscle
Authors: MELLANDER S. , BJÖRNBERG J. , MASPERS M. , MYRHAGE R.
Published: December 2008

A venous microcannulation technique applied to the cat gastrocnemius muscle was developed which, based on morphological and functional demonstrations of anastomotic connections between two supplying segmental vascular circuits at the level of capillaries and/or post‐capillary venules, seems to permit continuous recordings of hydrostatic pressure (denoted Pcvenule) transmitted from such anastomoses, that is, from a site close to the main fluid exchange vessels. For validity tests, such Pcvenule recordings were compared with simultaneous estimates of capillary pressure (Pc) with the isogravimetric technique (Pclso) and, further, with data for experimentally evoked changes of PC derived from volumetric recordings of net transvascular fluid flux divided by the capillary filtration coefficient (ΔPcvol). Simultaneously obtained data for Pcvenule and Pciso showed close agreement, and the Pcvenule and Pcvol data showed a highly significant linear correlation over a wide range of PC changes. These results indicate that reliable estimates of PC can be obtained with the Pcvenule method. It allows for continuous PC recordings without interfering with normal vascular reactivity and can be applied to non‐isogravimetric conditions and combined with simultaneous observations of whole‐organ transvascular fluid exchange. At normal arterial and venous pressures and vascular tone, Pcvenule averaged 16.2 ± 0.2 mm Hg, at which a Starling fluid equilibrium prevailed, and increased with decreasing vascular tone, resulting in net transvascular fluid filtration.
Autoregulation of capillary pressure and filtration in cat skeletal muscle in states of normal and reduced vascular tone
Authors: MELLANDER S. , MASPERS M. , BJÖRNBERG J. , ANDERSSON L.‐O.
Published: December 2008

The controversial hypothesis that capillary pressure (Pc) is autoregulated in response to arterial pressure (PA) alterations was tested in sympathectomized cat skeletal muscle by studying the relation betweenPCandPAunder conditions of well preserved vascular tone and reactivity, during papaverine‐induced maximal vasodilatation (passive vascular bed), and during impaired vascular reactivity caused by preparatory surgery, or by low dose isoproterenol administration. The latter states resembled such under whichPCautoregulation unintentionally seems to have been studied previously. Capillary pressure was assessed with thePcvenulemethod for continuous direct pressure recordings from capillaries/postcapillary venules (Mellanderet al.1987) and simultaneously derived from observed net transvascular fluid flux divided by CFC. Resistances in the whole vascular bed and in its pre‐and postcapillary segments (RaandRv) were determined from recordings of blood flow,PA,PA, andPv. During preserved vascular reactivity,PCwas found to be virtually constant, that is, almost perfectly autoregulated, over thePArange from 50 to 180 mmHg, whereas in the passive vascular bed there was a direct linear relation betweenPCandPA(y= 0.137x+ 11.69;r= 0.97). The ΔPc/ΔPAratio was about 1/70 in the normal reactive, and 1/7 in the passive, vascular bed, implying an increase inPCby 1 mmHg for every 70 mmHg and every 7 mmHg increase inPA, respectively. Capillary pressure autoregulation was explained by precise adjustments ofRa/Rvin relation toPAelicited by myogenic and metabolic regulatory mechanisms. This protective reaction against plasma loss during increasedPAwas abolished during maximal vasodilatation, and was much impaired by surgical trauma, partly via a β‐adrenergic inhibitory effect, and by isoproterenol, in turn causing gross transcapillary fluid fluxes. The latter findings might explain failingPAautoregulation in some previous studies undertaken under seemingly similar conditions.
The dopamine‐γ aminobutyric acid interaction in the striatum of the rat is differently regulated by dopamine D‐1 and D‐2 types of receptor: evidence obtained with rotational behavioural experiments
Authors: HERRERA‐MARSCHITZ M. , UNGERSTEDT U.
Published: December 2008

The effects of GABA antagonists on apomorphine‐and pergolide‐induced rotational behaviour were studied with models combining intracerebral and systemic pharmacological treatments. Whether given systemically or intrastriatally to 6‐hydroxydopaminelesioned rats, the GABA antagonist picrotoxin inhibited the rotational responses produced by s. c. administration of the dopamine (DA) D‐1/D‐2 agonist apomorphine while it enhanced the rotational behaviour produced by the DA D‐2 agonist pergolide. Following unilateral injection of picrotoxin or bicuculline into the striatum of naive rats, apomorphine produced ispsilateral rotation, while pergolide produced contralateral rotation. These contrasting effects are compared to the behavioural responses produced by intracerebral administration of GABAergic drugs alone. Intrapallidal injection of picrotoxin produced contralateral rotational behaviour which was independent of pallido‐nigral pathways. Contralateral rotation was also produced by GABA agonists, but only following intranigral injections. The results are discussed in terms of differences in the localization of DA D‐1 and DA D‐2 receptors on striatal GABAergic neurons. The DA D‐2 receptor agonist pergolide may induce inhibition of striato‐pallidal GABAergic neurons, as well as of a local GABAergic circuit exerting inhibition on a striato‐pallidal enkephalinergic pathway. However, the DA D‐1/D‐2 receptor agonist apomorphine may inhibit striatal interneurons exerting inhibition on a striato‐nigral GABAergic projection. Such a neuronal arrangement may explain that striatal DA stimulation increases GABA release from the striato‐nigral terminals.
Erythropoietic factors in plasma from neonatal mice. In vivo studies by the exhypoxic polycythaemic mice assay for erythropoietin
Authors: SANENGEN T. , MYHRE K. , HALVORSEN S.
Published: December 2008

The erythropoiesis stimulating factor(s) (ESF) in plasma from 20‐day‐old WLO‐mice have previously been studied by a cell culture assay, and also by means of gel filtration chromatography and affinity chromatography. It was concluded that the high levels of ESF found in the neonatal mouse plasma probably consisted of erythropoietin (Ep) alone. The objective of the present investigation was to obtain further information of whether this high ESF found in vitro is Ep alone, or Ep in combination with other factors. To accomplish this plasma from 20‐day‐old WLO mice and a standard Ep were studied in vivo by the exhypoxic polycythaemic mice assay for Ep, with and without preincubation with rabbit anti‐Ep serum (AS). Aliquots of some samples were also studied in vitro by the exhypoxic polycythaemic mice assay for Ep, with and without pre‐in both assays (P < 0.01). However, incubation with AS significantly reduced (P < 0.001) but did not totally block either the in vivo or the in vitro activity of the plasma (P < 0.005). This also was the case regarding the in vivo activity of the standard Ep (P < 0.001), while the in vitro activity of this Ep preparation was totally blocked by incubation with AS (P > 0.3). These results indicate that a considerable part of the high erythropoietic stimulatory activity found in plasma from 20‐day‐old mice, with both assays, is Ep. This supports the previous in vitro studies. However, the present results also support the conclusion that part of the activity is due to non‐Ep stimulatory factors.
Oestradiol increases baseline growth hormone levels in the male rat: possible direct action on the pituitary*
Authors: CARLSSON L. , ERIKSSON E. , SEEMAN H. , JANSSON J.‐O.
Published: December 2008

The effect of oestradiol treatment on the secretion of growth hormone (GH) was investigated in normal unrestrained male rats with chronic i. v. cannulae and in hypophysectomized male rats with autotransplanted pituitaries. The effect of gonadectomy of normal rats on the plasma GH secretory pattern was also evaluated. Baseline plasma GH levels were elevated following estradiol treatment of normal male rats (1.5 mg kg‐1 per 15 days). Gonadectomy of male rats also resulted in increased baseline GH levels, although the effect was less apparent than after oestradiol administration. The pulse height was not influenced by gonadectomy or oestradiol administration. In male rats with the pituitary autotransplanted to the kidney capsule, oestradiol caused a dose‐dependent increase in plasma GH levels, while there was no such effect of testosterone. These results suggest that the stimulatory influence of oestradiol on baseline GH levels is, at least partly, due to a direct effect on the pituitary. Plasma prolactin levels were elevated in rats with pituitary transplants receiving oestradiol. It is concluded that oestrogen administration to normal male rats increases baseline plasma GH levels, possibly by an effect exerted directly at the pituitary level.
Modulation of oxotremorine‐induced tremor by central β‐adrenoceptors
Authors: HALLBERG H. , ALMGREN O.
Published: December 2008

The muscarinic agonist oxotremorine was used to induce tremor in rats pretreated with methylatropine. An objective assessment of tremor intensity was accomplished by means of an accelerometer‐based recording system. The non‐selective, lipophilic β‐adrenoceptor antagonist propranolol dose‐dependently suppressed tremor intensity, whereas ther‐isomer of propranolol was without effect, verifying β‐adrenoceptor involvement. Since the hydrophilic, non‐selective β‐antagonist nadolol was ineffective, the effect appears to be located inside the blood‐brain barrier. The β2‐selective antagonist ICI 118, 551 dose‐dependently reduced tremor intensity, whereas selective blockade of β1‐adrenoceptors with metoprolol had no effect, indicating the participation of a β2‐adrenoceptor. On the other hand, the lipophilic β2‐agonist clenbuterol dose‐dependently enhanced tremor induced by oxotremorine. Determination of circulating plasma catecholamine concentrations revealed that the effect of β‐antagonists on tremor was not secondary to an effect on the oxotremorine‐induced rise in catecholamine levels. Thus, the results suggest that β2‐adrenocpetors located inside the blood‐brain barrier are able to modulate oxotremorine‐induced tremor in rats.
Capsaicin‐induced excitation of locus coeruleus neurons
Authors: HAJÓS M. , JANCSÓ G. , ENGBERG G.
Published: December 2008

The noradrenergic pontine nucleus locus coeruleus (LC) seems to be involved in sensory processing. In the present study, the effect of capsaicin, a drug which specifically interferes with chemosensitive primary afferents, on LC firing rate was analysed, utilizing electrophysiological techniques. In control rats, low doses of capsaicin (1–8 μg kg1–1 i. v.) caused a marked excitation of LC units. The effect was instantaneous in onset but short‐lasting and no signs of tachyphylaxis were observed. The excitation was maintained in adult rats treated as neonates with high doses of capsaicin (50 mg kg‐1 s. c.) but almost totally prevented by pretreatment of adult rats with high doses of capsaicin (300 mg kg‐1 s. c.). According to our histological data, using selective silver impregnation techniques, the LC seems not to receive innervation by sensory primary afferents. It is proposed that the capsaicin‐induced excitation of LC neurons is a centrally mediated effect and might, in part, be involved in the analgetic effect induced by the drug.
Intravenous administration of atriopeptin III affects arterial blood pressure differentially in young and old male rats
Authors: GRIMALDI R. , ZINI I. , AGNATI L.F. , FUXE K. , HÄRFSTRAND A.
Published: December 2008

The effects of intravenous administration of various doses of atriopeptin III (0.4–36 nmol kg‐1) on arterial blood pressure, urinary flow and Na+ and K+ excretion were analysed in awake animals. A dose‐related reduction of arterial blood pressure was obtained in 4‐and 24‐month‐old unrestrained, freely moving male rats. A dose‐related increase in the diuresis and in sodium and potassium excretion was present in both young and old rats. The hypotensive action was significantly prolonged in the aged animals, indicating possible alterations in the control of the cardiovascular system by the endocrine activity of the heart in the old animal.
The effects of anabolic steroids and endurance training on systolic time intervals in the dog
Authors: RÄMÖ P. , KETTUNEN R. , HIRVONEN L.
Published: December 2008

The effects of administration of anabolic steroids (SG, n= 6), endurance training (EG, n= 7) and a combination of steroid administration (Methandienone R) and training (ESG, n= 7) on systolic time intervals (STI) in the dog heart were compared with control dogs (CG, n= 7) by a catheterization technique. Isoproterenol infusion was used as a positive inotropic load. Physical performance was checked with submaximal exercise test, a 30 beats min‐1 decrease in heart rate response was considered a sufficient training effect. During isoproterenol infusion, exercise was found to enhance the pump performance of left ventricle and increased stroke volume was related to shortened pre‐injection period (PEP) (P < 0.05), whereas steroid administration failed to induce any significant differences in PEP or PEP/LVET (LVET = left ventricular ejection time) when compared with CG. However, when steroid administration was combined with endurance training, both PEP and PEP/LVET were lengthened significantly in comparison with EG (P < 0.05 and P < 0.01, respectively). In conclusion, it seems that the anabolic steroids affected the STIs only, when their administration was combined with endurance training.
Cardiac end‐diastolic dilation during acute blood pressure elevation is inotropy dependent
Authors: VENGEN Ø.A. , ILEBEKK A.
Published: December 2008

To examine if the degree of left ventricular (LV) end‐diastolic dilation during an acute blood pressure elevation is inotropy dependent, the descending thoracic aorta was occluded before and during a continuous isoproterenol infusion into the left coronary artery in 10 open‐chest pigs. The increase in peak LV systolic pressure and in LV tension‐time‐index induced by aortic occlusion, were equal before and during the isoproterenol infusion. Left and right ventricular (RV) segment lengths were continuously recorded in the free walls of both ventricles, by an ultrasonic technique. A slight fall in LV end‐diastolic segment length by the intracoronary isoproterenol infusion was corrected by an i. v.saline infusion. Left ventricular end‐diastolic volume was therefore equal at both levels of inotropy when the aorta was occluded, and the heart rate was kept constant by right atrial pacing. At control inotropy, aortic occlusion induced a rise in LV end‐diastolic segment length; 6.0 (4.0–8.2)% (median and 95% confidence interval), compared with the smaller (P < 0.05) increase of 3.8 (2.6–5.5)% during isoproterenol infusion. The end‐systolic segment length increased more (P < 0.01) at control inotropy than during intracoronary isoproterenol infusion: 10.9 (6.9–14.4)% and 4.1 (1.5–7.4)%, respectively. In the RV, both end‐diastolic and end‐systolic segment length increased slightly during aortic occlusion but only at control inotropy. Thus during an acute blood pressure elevation, the end‐diastolic and end‐systolic ventricular volumes are better maintained at high than at control inotropy.
Transient neocortical, hippocampal and qmygdaloid EEG silence induced by one minute inhalation of high concentration CO2 in swine
Authors: FORSLID A.
Published: December 2008

The study is part of a series of investigations performed with the ultimate goal of obtaining an objective evaluation of the ethical aspects and the narcotic efficiency of CO2 inhalation used as pre‐slaughter anaesthesia for swine. Six Yorkshire swine were exposed twice to 80% CO2 for I min during simultaneous recording of the EEGs from the frontal neocortex, the dorsal hippocampus, and the amygdaloid region via permanently implanted electrodes. In five of the animals myoclonic jerks started at 28 ± 1 s of CO2 exposure and lasted for 6 ± 2 s. Neocortical slow wave (delta) activity and increased amplitude of the hippocampal theta (5–7 Hz) waves (i.e. EEG changes seen during the second stage of barbiturate anaesthesia) had developed before the brief period of myoclonic jerks. After this period the EEG activity gradually declined, resulting in neocortical EEG silence at the end of the exposure. This apparent isoelectricity lasted for on average 1 min. The return of the neocortical EEG activity exhibited a pattern reverse to its disappearance, but was much prolonged in comparison to the EEG extinction. Pre‐exposure newortical EEG pattern was not regained until 3–5 min postexposure. In eight out of 11 experiments the CO2 inhalation also induced hippocampal EEG silence lasting for on average 30 s. EEG flattening was further obtained when recording from the amygdaloid nuclear complex and the adjacent pyriform cortex. The observed changes in the neocortical and hippocampal EEGs suggest that the present swine were unconscious already when they exhibited motor reactions. This does not exclude the possibility that CO2‐independent stress/arousal factors present in a slaughterhouse environment may facilitate the development of motor phenomena similar to seizures, with the result that such reactions become manifest before the neocortical EEG exhibits an anaesthesia pattern. The duration of the observed EEG silence implies that, from the ethical point of view, exsanguination might safely be performed within 1 min after the moment when the animal is removed from the high concentration CO2. However, the slow return to a pre‐exposure neocortical EEG pattern suggests that the swine remains unconscious for at least another minute.
Changes in sympathetic nerve activity during morphine abstinence in the rat
Authors: DELLE M. , THORÉN P.
Published: December 2008

The aim of the study was to examine sympathetic nerve activity, heart rate and blood pressure during naloxone‐precipitated withdrawal reactions in morphinedependent rats. In two groups of rats, one group conscious and the other anaesthetized with chloralose, renal sympathetic nerve activity (rSNA), heart rate (HR) and mean arterial blood pressure (MAP) were recorded before and during naloxone‐precipitated abstinence. The conscious rats showed a biphasic pattern in the withdrawal responses. Initially, after small doses of naloxone, rSNA and HR increased and increased somatomotor activity including ‘wet‐dog’ shakes were observed. However, upon further administration of naloxone, rSNA and HR promptly decreased while MAP increased. As rSNA was lowered, the withdrawal behaviour of the rats was markedly diminished and the animals rested calmly in the cages. In contrast, the anaesthetized group reacted with an immediate decrease in rSNA after the lowest dose of naloxone, followed by an increase in MAP and HR after higher doses of naloxone, although rSNA was still decreased. In both groups, rSNA remained below pre‐naloxone control levels when the increased MAP was lowered to the pre‐naloxone level with sodium nitroprusside, indicating a central origin of the sympathetic inhibition. It is concluded that naloxone elicits a biphasic rSNA response in the conscious, morphinedependent rat. This includes an initial increase upon low naloxone doses followed by a pronounced inhibition of rSNA after higher doses. In chloralose‐anaesthetized rats, rSNA declined already after low doses of naloxone. It is suggested that there might be a tonic, excitatory input on rSNA, mediated by the activation of opiate receptors by high levels of circulating morphine in the addicted animal. Naloxone will therefore decrease the tonic sympathetic nerve activity in these rats.
Respiratory stimulant effects by TRH into the mesencephalic region in the rat
Authors: HEDNER J. , McCOWN T. J. , MUELLER R. A. , HEDNER T. , JONASON J. , BREESE G. R.
Published: December 2008

Thyrotropin‐releasing hormone (TRH) has previously been found to have a potent respiratory stimulant effect following intracerebroventricular administration. One part of the respiratory response, the shortening of inspiratory time, seems to be elicited from the raphe obscurus in the medulla. The prominent tachypnoea however is not elicited after local injections in the medullary region. In the present paper a micro‐injection technique was employed to study respiratory actions of TRH in lightly anaesthetized rats kept in a whole body plethysmograph. Thyrotropin‐releasing hormone in a dose of 100 ng per 0.5 μl was found to induce an immediate tachypnoea after injections into the region of the interpeduncular nucleus of the midbrain. No effects on systemic circulation were seen. More rostral or dorsal sites of injection were without effect. The localization of the sites responsible for respiratory stimulation corresponds to the reticular activating system where electrical stimulation induces hyperventilation in cats. The tachypnoea might be closely related to the well known arousal effects of TRH.
Ischaemia‐induced release of noradrenaline and creatine kinase in the isolated, working rat heart
Authors: CARLSSON L. , ABRAHAMSSON T. , ALMGREN O. , SVENSSON L.
Published: December 2008

In order to examine an early ischaemia‐induced local release of myocardial noradrenaline (NA), the left coronary artery of the isolated working rat heart was ligated for periods varying between 7.5 min and 30 min, followed by reperfusion for 5 min. As perfusion substrate, glucose, lactate or both were used. In part of the experiments, hearts were pre‐labelled with [3H]NA. Already after 7.5 min of ischaemia, an increased efflux of endogenous NA was observed in the perfusate at reperfusion, concomitant with a decrease in tissue NA content. This effect was most pronounced with lactate as substrate. Qyalitatively similar effects were seen on [3HINA efflux from labelled hearts. The combination of glucose and lactate as substrate markedly reduced (compared with lactate alone) the efflux of NA, whereas no such reduction was observed on the efflux of creatine kinase (CK). It is concluded that ischaemia is associated with an early local release of NA. Furthermore, ischaemia may induce different effects on the metabolic processes of the myocyte as compared with the adrenergic nerve ending.
Section of fibular nerve affects activity pattern and contractile properties of soleus motor units in adult rats
Authors: HENNIG R.
Published: December 2008

Transection of the common fibular (FIB) nerve caused an immediate reduction in the total amount of soleus (SOL) motor unit activity, which declined further during the following 10 days and then remained stable at less than half of normal values. In addition, there was an immediate reduction in median impulse rate from about 20.0 to 14.9 Hz followed by a return to normal values during the first 10 days. Short interval (3–4 ms) double discharges, occurring either in isolation or at the same regular intervals as single impulses, were observed 2–5 days after FIB nerve section in a few motor units. Brief, high frequency impulse bursts with interspike intervals of 12–16 ms were observed in a few units from the third day and until the end of the experiment (up to 31 days). It was not established whether the high frequency discharge pattern occurred only in a fixed population of the SOL motor units, or whether the units could switch between high and low frequency activity. Two months after FIB nerve section, the SOL muscle in the same leg contracted faster than normal (mean isometric twitch contraction time 29.6 ms, n = 4; vs. 38.7 ms, n = 8), contained a larger than normal percentage of type II fibres (13–36 vs. 0–0.2%) and weighed less than the contralateral SOL muscles (180 vs. 206 mg). SOL muscles (n= 4) in the opposite leg were comparable to normal SOL muscles except for a small reduction in mean isometric twitch contraction time (35.5 ms).