bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of hypotension induced by adenosine on brain surface oxygen pressure and cortical cerebral blood flow in the pig
Authors: EINTREI CHRISTINA , CARLSSON CHRISTER
Published: December 2008

Six pigs were anaesthetized with ketamine in combination with fentanyl and droperidol and paralysed with pancuronium. The pigs were tracheotomized and ventilated mechanically. Mean arterial blood pressure, MABP, was lowered from 97 ± 21 mmHg stepwise to 58 ± 2, 33±4 and 22±4 mmHg by intravenous infusion of adenosine (4‐8 mg kg‐1 min‐1). Regional cerebral blood flow (rCBF) was measured directly onto the cortex of the brain by local atraumatic application of I33xenon. Brain surface oxygen pressure (PtO2) was obtained using a multiwire oxygen surface electrode. At the level of 60 mmHg, rCBF showed a significant increase, while flow values were not changed from initial values with further hypotension. Ten minutes after adenosine was discontinued, rCBF showed a rebound effect with higher values than initially. During normotension mean cortical PtO2 varied between 2.1 KPa and 3.9 kPa. During adenosine infusion PtO2 was increased at MABP‐levels of 60 and 30 mmHg, while at 20 mmHg a decrease was seen in all animals. After discontinuation of the adenosine infusion, PtO2 values were higher than those measured at the initial normotension, a similar rebound phenomenon as seen with rCBF. During the experiments all hypotensive levels could be maintained at constant level without progressively increasing infusion rates, indicating no tachyphylaxis during these time periods. After discontinuation of the drug, blood pressure did not fully reach pre‐hypotensive level within 10 min. Thus, hypotension induced by adenosine down to a MABP of 30 mmHg in animal experiments does not cause deterioration in either cerebral blood flow or oxygen pressure.
Cardiac design and pressure‐volume characteristics of the left ventricle in normotensive (WKY) and hypertensive (SHR) rats after various dietary sodium treatments
Authors: FRIBERG P. , ELY D. L. , WÅAHLANDER H. , NILSSON H. , FOLKOW B.
Published: December 2008

Normotensive (WKY) and hypertensive rats (SHR) from 5 to 13–14 weeks of age were given ‘low’ (LNa; 0.5 mmol Na 100 g‐1 food), ‘control’ (CNa; 5 or 12 mmol), ‘high’ (HNa; 50 mmol) and in SHR also ‘medium low’ (mLNa; 2 mmol) and ‘very high’ (vHNa; 120 mmol) sodium diets, to explore how such 240‐fold variations in Na intake affect cardiac design. This was assessed in isolated perfused, temporarily‐arrested hearts by recordings of left ventricular (LV) diastolic pressure‐volume relationships (P/ V) LV and RV weights, and by calculations of the ratio between LV wall thickness and internal radius (w/ri), after in vivo recordings of awake mean arterial pressure (MAP) and heart rate (HR). In WKY, where MAP was the same in all diet groups, the IINa group showed an increased w/r1 due to a 20% reduction of LV diastolic volume, with signs of reduced wall compliance compared with CNa. The LNa WKY showed less marked changes in the same direction. In the SHR LNa group, where MAP was lowered about 20 mmHg, LV diastolic volume was reduced nearly 20% at a modest w/ri increase, while HNa and CNa SHR had equal MAP, LV weights, P/V and w/r1 relationships. However, in vHNa SHR, where MAP was elevated about 25 mmHg, the LV showed a mainly eccentric hypertrophy with 15% increase of diastolic volume at a slight increase of w/r1. These differentiated, and in WKY and SHR partially differing structural cardiac adaptations consequent to changes in Na intake, can hardly be ascribed only to the respective pre‐and afterload alterations, suggesting that also altered neuro‐hormonal profiles may have contributed with ‘trophic’ influences. The results thus show that even cardiac design can be considerably altered by low and high Na diets, with consequences also for cardiac performance.
Visualization of regenerating sciatic nerve fibres by neurofilament immunohistochemistry
Authors: NACHEMSON A. K. , HANSSON H. A. , DAHL D. , LUNDBORG G.
Published: December 2008

Regeneration of injured sciatic nerve in rats was studied with an immunohistochemical technique visualizing neurofilaments in nerve fibres as well as S‐100 protein in Schwann cells. Outgrowing axons with delicate sprouts could be demonstrated along pathways formed by Schwann cells. In contrast, axons which had stopped growing or were degenerating showed bulb‐like swellings in their terminal parts. The use of immunohistochemical techniques offers advantages over conventional neurohistochemical staining methods, enabling more detailed observations of nerve regeneration mechanisms in animals.
Effects of adenosine and two stable adenosine analogues on blood pressure, heart rate and colonic temperature in the rat
Authors: JONZON B. , BERGQUIST A. , LI Y.O. , FREDHOLM B. B.
Published: December 2008

Adenosine exerts effects via receptors of the A1‐ and A2‐subtype. L‐phenylisopropyl adenosine (L‐PIA) is more potent than N‐5′‐ethylcarboxamido adenosine (NECA) at the A1,‐subtype receptor whereas the potency order is reversed at the A2‐subtype receptor. Adenosine analogues have been shown to decrease blood pressure and heart rate and to induce a marked hypothermia. In the present series of experiments adenosine, L‐PIA and NECA were given i.p. or i.v. to rats, and blood pressure, ECG and colonic temperature were recorded. The NECA was the most potent of the compounds in reducing blood pressure (EC502 μkg‐1i.v.), followed by L‐PIA (EC50approximately 30 μ kg‐1i.v.) and adenosine (EC50approximately 300 μ kg‐1i.v.). In contrast, L‐PIA and NECA were equally active in reducing heart rate (EC50approximately 6 μ kg‐1i.v.) and considerably more potent than adenosine (EC50approximately 300 μ kg‐1i.v.). It is suggested that simultaneous measurement of blood pressure and heart rate could be a simplein vivomodel for comparison of A1‐ and A2‐receptor subtype mediated effects. Colonic temperature was markedly reduced after i.p. administration of the adenosine analogues. Thus, 100 μg NECA kg‐1reduced colonic temperature from 37.8 to 26 d̀C. A 5 d̀C temperature drop was obtained by 10 μg kg‐1NECA, by 200 μg kg‐1L‐PIA and by 200 mg kg‐1adenosine. The fall in colonic temperature was associated with a loss of muscular activity, as determined by needle electrodes or by palpation, indicating an inhibition of shivering. The fact that the agonist potency and the potency ratio were similar for the hypotensive and hypothermic effect could indicate that the fall in body temperature is dependent upon a peripheral vasodilatation. In addition there was an inhibition of shivering. The results are compatible with the opinion that adenosine analogues cause hypothermia largely because of peripheral effects, but a central inhibition of compensatory mechanisms, either at a spinal level or at the level of the hypothalamic temperature centre is probable.
Renal extraction of endogenous and radiolabelled catecholamines in the dog
Authors: BRADLEY T. , HJEMDAHL P.
Published: December 2008

Efferent renal nerve activity can be studied by measurements of the renal venous outflow of noradrenaline and dopamine. Accurate estimates of the intrarenal release to plasma of these catecholamines, however, require determinations of the net contribution of the catecholamines in arterial plasma to their renal venous outflow. We therefore studied the extractions of endogenous noradrenaline, dopamine and adrenaline, as well as 3H‐labelled tracer amounts of noradrenaline and dopamine in innervated and denervated canine kidneys. Approximately two‐thirds of noradrenaline and dopamine in arterial plasma were extracted in the kidney, while 80–90% of adrenaline in arterial plasma was extracted. The fractional extractions of the three catecholamines were not substantially altered when the sympathetic nervous system was moderately activated by bilateral carotid occlusion or when the renal nerve activity was abolished by acute denervation. It is concluded that biochemical assessment of renal sympathetic nerve activity by studies of the renal venous noradrenaline and dopamine outflow requires some estimate of the net arterial contribution to the renal venous outflow. Ideally, catecholamine extraction by the kidney should be evaluated by studies of the renal extraction of 3H‐labelled noradrenaline and dopamine, but the extraction of endogenous adrenaline may also be useful for this purpose.
Intravenous uridine treatment antagonizes hypoglycaemia‐induced reduction in brain somatostatin‐like immunoreactivity
Authors: AGNATI L. F. , FUXE K. , ENEROTH P. , ZINI I. , HÄRFSTRAND A. , GRIMALDI R. , ZOLI M.
Published: December 2008

By means of radioimmunoassay procedures, cholecystokinin‐(CCK) and somatostatin‐(SRIF) like immunoreactivity have been studied in the dorsal hippocampal formation and in the frontoparietal cortex of the male rat in insulin‐induced hypoglycaemia, leading to an isoelectric EEG pattern. It has been demonstrated that severe hypoglycaemia of 40‐min‐duration produces a disappearance of SRIF but not of CCK‐like immunore‐activity in both cortical regions. It was found that an i.v. injection of uridine but not of saline could significantly counteract the disappearance of SRIF‐like immunoreactivity induced by severe hypoglycaemia in both cortical areas. Uridine did not by itself change plasma glucose levels. It is suggested that uridine may prevent release and/or increase synthesis of cortical SRIF peptides in severe hypoglycaemia, possibly due to an action on the metabolism (e.g. by enhancing the resynthesis of phosphatidyl inositol) within the tissue of the cerebral cortex and/or on putative pyrimidine binding sites in the brain controlling SRIF synthesis and/or release. It is possible that uridine in this way may improve recovery of neuronal function within SRIF‐immunoreactive neurons of the cerebral cortex after severe hypoglycaemia (which also may be true in other states of reduced metabolic support). These findings suggest a possibility to use uridine in the treatment of Alzheimer's disease and Status epilepticus.
Altered cardiovascular responsiveness to adrenaline in endurance‐trained subjects
Authors: SVEDENHAG J. , MARTINSSON A. , EKBLOM B. , HJEMDAHL P.
Published: December 2008

The influence of physical training on responses to i.v. adrenaline infusions and to exercise were investigated in 10 endurance‐trained men (mean age: 35 y; Vo2max: 61.9 ml kg‐1min‐1) and 10 age‐matched and sedentary controls (36 y, 37.5 ml kg‐1min‐1). The untrained subjects were reinvestigated after a 4 month training period which increased their Vo2max by 18%. Resting heart rate and diastolic blood pressure were significantly lower in the trained state. The venous plasma adrenaline concentrations attained during infusions (4 dose levels, 8 min each) were lower in the well‐trained than in the untrained subjects(2.15vs.3.59 nmol 1‐1at the highest dose level,P< 0.01). The adrenaline‐induced increases in heart rate and in plasma cAMP and decreases in pre‐ejection period (PEP) and PEP/LVET ratio were not dependent on the training state. The adrenaline‐induced decrease in diastolic blood pressure was more pronounced (P< 0.05) in the well‐trained than in the untrained group and tended (0.05 <P< 0.1) to be enhanced by training in the latter group. The increases in systolic blood pressure were greater in the well‐trained subjects (P< 0.01) but training did not alter this response in the untrained subjects. The plasma noradrenaline response to maximal cycle ergometer exercise (Vo2maxtest) was significantly greater in the well‐trained than in the untrained subjects, while no difference was seen for adrenaline. The submaximal exercise systolic blood pressure was similar in all training conditions when related to the absolute rate of work. In summary, the present results indicate that both the vasodilator and systolic pressor responses to adrenaline are enhanced in endurance‐trained subjects. The cardiac chronotropic and inotropic effects of adrenaline seem, however, to be independent of the training state.
Lack of effect of amiloride, furosemide, bumetanide and triamterene on pancreatic NaHCO3 secretion in pigs
Authors: GROTMOL T. , BUANES T. , BRØRS O. , RÆDER M. G.
Published: December 2008

This study examines the effects of the Na entry blockers amiloride, furosemide, bumetanide and triamterene on pancreatic NaHCO3 secretion. The purpose of the study was to elucidate whether Na flux through a Na‐H‐antiport, a Na, K, Cl‐symport or a Na‐K(H)‐antiport respectively, may be rate limiting for pancreatic NaHCO3 secretion. The effect of each drug on secretion was tested in four groups of six anaesthetized pigs (20–25 kg body wt) during supramaximal, intravenous secretin infusion (3.0 CU kg‐1 body wt. h‐1), following laparotomy and cannulation of the pancreatic duct. Secretion was measured over a wide range of arterial pH values, both before and after drug administration in each animal. Pancreatic NaHCO3 secretion averaged 268 (219–308) μmol min‐1 at physiological arterial pH 7.40 in the control period. Neither amiloride (90 mg kg‐1 body wt), furosemide (10 mg kg‐1 body wt), bumetanide (0.6 mg kg‐1 body wt) nor triamterene (25 mg kg‐1 body wt) affected the rate of secretin‐dependent NaHCO3 secretion or the relation between NaHCO3 secretion and arterial pH. It is concluded that Na flux through neither a Na‐H‐antiport, a Na, K, Cl‐symport nor a Na‐K(H)‐antiport appears to be rate limiting for pancreatic secretion of NaHCO3.
In vitrointestinal transport of vasopressin and its analogues
Authors: VILHARDT H. , LUNDIN S.
Published: December 2008

The intestinal transport of vasopressin and oxytocin and their analogues 1‐deamino‐8‐D‐arginine vasopressin and 1‐deamino‐2‐tyrosine(o‐ethyl)‐oxytocin was studied in everted segments of rat jejunum. The transported peptides were identified by specific RIA methods and by quantitative high pressure liquid chromatography. Transport rates were highest for 1‐deamino‐8‐D‐arginine vasopressin and lowest for vasopressin. No transport maximum and no competitive inhibition could be demonstrated. The distribution volume of the peptides in the intestinal mucosa was found to be smaller than that of polyethylene glycol. It is concluded that peptides of this size are transferred across the intestinal mucosa by passive processes.
Identification of calmodulin‐binding proteins on membranes of secretory granules isolated from bovine neurohypophyses
Authors: CHENOUFI H.‐L. , ENGBERG E. , SLANINOVÁ J. , THORN N. A.
Published: December 2008

Membrane proteins from isolated, purified ox neurohypophyseal secretory granules were separated by sodium dodecylsulphate (SDS) polyacrylamide gel electrophoresis (PAGE). Using a gel overlay technique, after renaturation procedures, it was demonstrated that 125J calmodulin bound in a Ca2+‐dependent way to two protein bands with molecular weights (MW) of 58,000 and 52,000. Binding of small amounts of calmodulin to other protein bands was independent of calcium. No calmodulin binding to granule content proteins could be detected. Treatment of the granules with trypsin prior to separation of membrane proteins removed the Ca2+‐dependent binding proteins from the granule membrane. On incubation of granules with [y‐32P]ATP, protein bands with MW of 52,000 and 45,000 showed a marked phosphorylation activity. The 52,000 band had the same electrophoretic mobility as one of the calmodulin‐binding bands. However, no effect of calmodulin on phosphorylation of this band could be demonstrated.
Biosynthesis of a novel prostaglandin. Δ17 ‐PGE1, in the ram
Authors: OLIW E. H. , SPRECHER H. , HAMBERG M.
Published: December 2008

The prostaglandin, Δ17‐PGE1, was purified from extracts of ram seminal fluid by reversed phase high performance liquid chromatography (HPLC) and identified after conversion to Δ17‐PGB1, by UV‐analysis and by capillary column gas chromatography‐mass spectrometry (GC‐MS). It was also formed by incubation of a homogenate of ram vesicular glands. The amount of Δ17‐PGE1 in the seminal fluid and in the homogenate averaged 12% and 25% of the amount of PGE2, respectively. The results show that cis‐8,11,14,17‐eicosatetraenoic acid can be metabolized to prostaglandins in vivo in the ram.
Long‐lasting cardiovascular depression induced by acupuncture‐like stimulation of the sciatic nerve in unanaesthetized rats. Effects of arousal and type of hypertension
Authors: HOFFMANN P. , THORÉN P.
Published: December 2008

Prolonged low frequency stimulation of the sciatic nerve in conscious spontaneously hypertensive rats (SHR), is reported to induce a naloxone‐reversible long‐lasting depressor response (Yao et al. 1982a). In the present study this depressor response was compared during daytime and night‐time conditions to determine whether different degrees of arousal affect this response. In addition, the effect of sciatic nerve stimulation was examined in one‐clip, two‐kidney renal hypertensive rats (RHR); a type of secondary hypertension which lacks the central autonomic hyper‐reactivity which characterizes the SHR variant of primary hypertension. A maximal fall in blood pressure of 20 mm Hg was observed 1 h after sciatic nerve stimulation in SHR examined in daytime. We also found a significant bradycardia that lasted for 2.5 h. Neither poststimulatory depression nor bradycardia were observed in RHR examined at daytime. A short‐lasting, nonsignificant decrease in blood pressure and heart rate was found following sciatic stimulation in SHR examined at night.
Non‐muscarinic effects of scopolamine on N1E‐115 neuroblastoma cells
Authors: HEDLUND B. , ARHEM P. , LORENTZ M. , SYDBOM A.
Published: December 2008

Membrane effects of scopolamine on N1E‐115 neurobalstoma cells were studied using intracellular recording techniques. Scopolamine in concentrations of 50 nM‐1 μM induced a depolarization together with a decreased cell input resistance. This response had a reversal potential at + 10 to + 20 mV in a medium with normal sodium concentration (146.5 mM), and a reversal potential around –10 mV when the sodium concentration in the medium was lowered to 80 mM. The scopolamine‐induced depolarization could not be blocked by carbachol (100 μM), and had a reversal potential at +10 to + 20 mV. The simplest explanation of the results obtained is that scopolamine increases the membrane permeability for sodium and potassium, in a manner which is not related to muscarinic cholinergic receptors.
Oxygen consumption by the mouse blastocyst at activation for implantation
Authors: MAGNUSSON C. , EINARSSON B. , NILSSON B. O.
Published: December 2008

When activated from delayed implantation by an oestrogen injection, mouse blastocysts rapidly increase their oxygen consumption and degree of cytochrome oxidase staining. In the present study, oxygen consumption was augmented to a similar extent also in vitro using a culture system known to permit trophoblast outgrowth. To see whether the increase of oxidative phosphorylation needs the synthesis of new protein or just activation of enzyme precursors, different anti‐metabolites were added to the cultures. Inhibitors of transcription (cytosine arabinoside and a‐amanitin) and RNA translation in the mitochondria (chloramphenicol) were all without effect, whereas blocking cytoplasmic translation by cycloheximide inhibited the increase in oxygen consumption after blastocyst culture. The results suggest that the trophoblast control of oxidative phosphorylation lies post‐transcriptionally, and that activation of oxygen consumption involves translation of preformed RNA templates in the cytoplasm.,
On the functional relationship between 45Ca2+ release and prolactin secretion in cultured rat pituitary tumour (GH3) cells
Authors: IVERSEN J.‐G. , SLETHOLT K. , HAUG E. , GAUTVIK K. M.
Published: December 2008

We have evaluated the role of cellular Ca2+ transport associated with stimulus‐secretion coupling in prolactin (PRL) producing rat pituitary adenoma cells (GH3 cells). The action of different substances, known to modify PRL secretion, on release of 45Ca2+ from preloaded cells were examined. Surface‐bound 45Ca2+ was removed by pretreatment with trypsin in EDTA buffer. During the first 6 min, basal efflux of 45Ca2+ occurred at a constant rate (0.24 min‐1) at 37 °C. Addition of TRH (5 times 10‐7 M) resulted in an immediate enhancement of 45Ca2+ release representing about 20% of the remaining cellular 45Ca2+. In the same experiments PRL secretion increased by 45%. The EDTA in the external medium reduced the basal rate of 45Ca2+ release by 60%, but did not apparently affect the TRH‐stimulated release. Somatostatin (10‐6 M) and verapamil (5 times 10‐5 M) inhibited both basal and TRH‐stimulated PRL secretion, whereas high extracellular concentration of K+ (5 times 10‐2 M) had a stimulatory effect. However, neither of these treatments changed cellular 45Ca2+ release. Interference with energy‐dependent Ca2+ transport by using metabolic inhibitors (iodoacetate, 6 times 10‐3 M; and antimycin, 2 times 10‐6 M) or by replacing Na+ in the medium by choline or by lowering the incubation temperature from 37 to 25 °C, had no effect on TRH‐stimulated 45Ca2+ release although basal and TRH‐stimulated PRL secretion were reduced. Thus, TRH apparently releases 45Ca2+ from calcium binding sites in the cell membrane.,
Catecholamines of endoneurial laryngeal paraganglia in the rat
Authors: DAHLQVIST Å. , PEQUIGNOT J.‐M. , HELLSTRÖM S. , CARLSÖÖ B. , PEYRIN L.
Published: December 2008

The catecholamines in the recurrent and superior laryngeal nerves of the rat were assayed by high performance liquid chromatography. The nerves were shown to contain high levels of dopamine (1.9 ± 0.6 and 2.3 ± 0.4 pmol, respectively) and noradrenaline (1.3 ± 0.3 and 0.9 ± 0.2 pmol, respectively). No adrenaline could be detected in any of the nerves. Reserpine markedly depleted the stores of these amines in both nerves. A significant increase in dopamine level was seen in the superior laryngeal nerve after treatment with a monoaminoxidase inhibitor, but not in the recurrent laryngeal nerve. The high levels of dopamine detected are presumably derived from endoneurial paraganglia which were demonstrated by glyoxylic acid‐induced fluorescence. The source of noradrenaline is less evident, but noradrenaline is probably stored in both endoneurial paraganglia and in sympathetic nerve endings.,
Atriopeptins and renal cortical and papillary blood flow
Authors: HANSELL P. , ULFENDAHL H. R.
Published: December 2008

Studies were made of the effect of two pure synthetic atrial natriuretic factors (ANF) on renal cortical and papillary blood flow and on the excretion of sodium, potassium and water in young Munich Wistar rats by means of laser‐Doppler flowmetry. The effects of Atriopeptin I (AP I), which selectively relaxes intestinal smooth muscle, were compared with those of Atriopeptin II (AP II), which relaxes both vascular and intestinal smooth muscle. Both peptides were administered by continuous intravenous infusion at 10 μg h‐1 kg‐1 body wt after a control period. A time control group was studied in parallel to see whether the variables investigated varied with time. In rats receiving vehicle alone (time control) and in those receiving AP I, there was no significant change either in the cortical or papillary blood flow, or in blood pressure (BP). The AP II infusion resulted in an increase in blood flow which was only transient despite the continous infusion. Cortical blood flow increased by 22% (peak value) and papillary blood flow increased by 95% (peak value). The blood pressure (BP) decreased by 12% to a steady state level (103 ± 2 vs. 91 ± 2 mm Hg). The AP I caused a steady two‐fold increase in sodium excretion (UNaV), a 35 % increase in potassium excretion (UKV) and an 85% unsient increase in urine flow rate (V). Infusion of AP II resulted in a more than 60‐fold increase in UNaV during the period of increased blood flow, and then reached a steady state level 10 times higher than the control value. The UKV increased four‐fold and then reached a steady state level 60% above the control value. The urine flow rate showed a 10‐fold increase and then reached a steady state level 85% above the control value. In conclusion, AP I and AP II appear to increase solute excretion predominantly by affecting tubular transport mechanisms. The AP II, through its vascular effects, will transiently increase renal blood flow, preferentially in the inner medulla, and presumably the glomerular filtration rate (GFR), which in turn will contribute to the natriuretic response.,
Restricted diffusion of CrEDTA and cyanocobalamine across the exchange vessels in rat hindquarters
Authors: HARALDSSON B. , RIPPE B.
Published: December 2008

The degree of diffusional restriction of skeletal muscle capillary walls to small solutes was estimated from the permeability surface area products (PS) of CrEDTA (MW = 341) and cyanocobalamine (MW = 1355), using computerized ‘on‐line’ recordings of venous single injection indicator dilution curves. Experiments were performed on isolated perfused maximally vasodilated rat hindquarters during largely isogravimetric conditions and the arrangements allowed for measurements of capillary filtration coefficients (CFC). Extraction of tracer varied markedly as a function of transit time and, furthermore, PS increased with increasing flows, both these phenomena indicating tissue and flow heterogeneity. At maximal flows the disturbing influence of heterogeneity will be minimal and hence the diffusion capacities obtained by extrapolating PSarea to infinite flows, so called PStot values, were considered to give the best estimation of the ‘true’ capillary diffusion capacities. The value of PStot was 12.9 ± 0.5 for CrEDTA and 5.1 ± 0.3 ml min‐1 per 100 g for vitamin B12. The calculated PStot ratio of 2.59 ± 0.11 indicates restricted diffusion through equivalent pores of radius 53 Å, whereas the ratio of the free diffusion coefficients for these solutes is 1.79. Using PSpeak for the calculations (totally neglecting heterogeneity) the pore radius was, however, markedly overestimated. Thus, for a PS‐ratio of 1.89 ± 0.04 for CrEDTA vs. B12 an equivalent pore radius of 300 Å was calculated. Also, using PSarea (only partly correcting for heterogeneity) overestimated the pore radius (70 Å) from a mean PS‐ratio of 2.33 ± 0.05. It was concluded that the equivalent pore radius in rat hindquarter microvascular walls is 53 A or even smaller in essential agreement with data from osmotic transient experiments in the same preparation (r ‐ 40 Å).
Effects of N‐ethylmaleimide and forskolin on glutamate release from rat hippocampal slices. Evidence that prejunctional adenosine receptors are linked toN‐proteins, but not to adenylate cyclase
Authors: FREDHOLM B. B. , FASTBOM J. , LINDGREN E.
Published: December 2008

In the present experiments we have examined the effect ofN‐ethylmaleimide (NEM) on the release of [3H] glutamate from rat hippocampal slices. Pretreatment of slices with NEM in a concentration between 50 μM and 200 μM, can inhibit the GTP‐binding protein (N) that transmitts receptor signals into inhibitions of adenylate cyclase, without affecting theNs‐protein, that transmits signals into stimulation of the cyclase, or the cyclase. The adenosine receptor agonist R‐phenylisopropyladenosine (R‐PIA, I μM) caused an approximately 50% inhibition of the evoked [3H] glutamate release. This effect was completely prevented by NEM treatment, which did not affect basal or stimulated release of the amino acid. By contrast, the effect of R‐PIA was unaffected by adding an adenylate cyclase stimulator (forskolin 1 μM) and a phosphodiesterase inhibitor (rolipram, ZK 62.711, 30 μM) which raised the cyclic AMP content of the slices approximately 1 o‐fold. In conclusion, these results suggest that the adenosine receptor that mediates prejunctional inhibition of glutamate release is coupled to a protein similar to theN1‐protein, but that another effector than adenylate cylase is involved.,
Effect ofα,β‐methylene ATP on distal colonic and rectal motility‐a possible involvement of P2‐purinoceptors in pelvic nerve mediated non‐adrenergic, non‐cholinergic contraction
Authors: HEDLUND H. , FANDRIKS L. , DELBRO D. , FASTH S.
Published: December 2008

The possible involvement of purinoceptors in the parasympathetic nervous control of large intestinal motility was investigated in cats anaesthetized with chloralose and treated with adrenolytics. Distal colonic and rectal motor responses to efferent pelvic nerve stimulation (PNS) and drugs injected close i. a., were recorded by a volumetric method. Single dose i. a. injections of α, β‐methylene ATP (mATP) induced colonic and rectal contractions which were resistant to atropine, hexamethonium and indomethacin, as well as to the nerve blocking agent tetrodotoxin. Repeated injections of mATP were followed by attenuated motor responses and eventually complete tachyphylaxis to the compound developed. In the presence of atropine, or a combination of hexamethonium and atropine, contractions elicited by PNS were inhibited during mATP tachyphylaxis. In contrast, prior to such anticholinergic drugs, or in the presence of hexamethonium alone, pelvic nerve mediated contractions persisted despite mATP tachyphylaxis, which did not affect the colonic and rectal contractions evoked by acetylcholine or histamine. The results suggest that P2‐purinoceptors are involved in non‐adrenergic, non‐cholinergic large intestinal excitatory motor responses to PNS.
The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCI in the sheep is mediated mainly by the Na ion
Authors: RUNDGREN M. , DENTON D. A. , McKINLEY M. J. , WEISINGER R. S.
Published: December 2008

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCI, the water intake in response to 30‐min ICV infusons of hypertonic solutions of different Na salts (0.25 M NaCI, Nal, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/o.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCI in the sheep is mainly caused by the increased Na rather than the CI ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.
Studies of the renal component of the hypertension in rats with aortic constriction. Role of angiotensin II
Authors: SAHLGREN B. , EKLÖF A.‐C. , APERIA A.
Published: December 2008

The object of this study was to investigate the renal component of hypertension in aortic constriction. In 40‐day‐old Sprague‐Dawley rats the aorta were constricted either proximal (PAC) or distal (DAC) to the renal arteries. The rats were examined 3 weeks later together with control rats. The arterial pressure proximal to the constriction was elevated in the PAC group but not in the DAC group. In PAC rats the arterial pressure was also elevated distal to the constriction. There was a significant pressure gradient across the constriction in both PAC and DAC rats. The PAC rats had a significant decrease of renal blood flow, a significant increase in renal vascular resistance and a numerical but not significant decrease of glomerural filtration rate. Serum levels of angiotensin II were not significantly different in PAC and control rats. The pressor effect of a bolus dose of angiotensin II was significantly increased in PAC rats. Captopril, a converting ezyme inhibitor, decreased the arterial pressures and renal vascular resistance in PAC rats. The pressure elevating effects of angiotensin II and pressure lowering effect of captopril were more pronounced distal than proximal to the constriction. We conclude that the kidneys play a major role in the development of hypertension in PAC, and that the local effect of angiotensin II on the renal vascular bed is an important contributor to the renal component of the hypertension.
Increased β1‐adrenoceptor density after 6‐hydroxydopamine pretreatment in rat colon and lung
Authors: EK B. , LUNDGREN B.
Published: December 2008

Estimation of β‐adrenoceptor‐binding sites with125I‐(‐)‐pindolol in rat colon show a proportion of 30%β1,‐adrenoceptors and 70%β2‐adrenoceptors. Studies on the isolated colon strip have revealed a neuronal β‐adrenoceptor involved in the inhibitory response of colon motility to β‐adrenoceptor stimulation. In order to further characterize the β‐adrenoceptors in the colon, acute and chronic treatments with 6‐hydroxydopamine were made. Both acute pretreatment of rats with 6‐hydroxydopamine for 8 and 24 h (one intravenous injection) and chronic treatment for 3 days (implanted osmotic mini‐pumps), reduced the noradrenaline tissue content by 90%, and successively increased the β‐adrenoceptor‐binding sites from 14.3 to 21.7 fmol mg_1P_1in colon and from 158 to 240 fmol mg‐1P_1in lung membranes. Displacement of the radiolabelled ligand by the selective β‐adrenoceptor antagonists, pafenolol and ICI 118.551 showed that the density of β1,‐adrenoceptor binding sites was more than doubled, whereas the density of β2‐adrenoceptor‐binding sites was only marginally increased by chronic treatment with 6‐hydroxydopamine. Thus sympathetic denervation by 6‐hydroxydopamine treatment produced a selective increase in β1‐adrenoceptors in the rat colon. These results may indicate that stimulation of β1‐adrenoceptors in both colon and lung have a neuronal linkage.
Intracellular free Mg2+ in Balanus photoreceptor measured with Eriochrome Blue
Authors: RYDQVIST B. , BROWN H. M.
Published: December 2008

Intracellular free Mg2+ (Mgf) in darkness and during illumination was measured in the Balanus photoreceptor using the Mg2+ sensitive dye Eriochrome Blue SE (EB). The EB was pressure injected in the cell and Mgt determined from measurements of absorption changes at 570 nm and 600 nm. Mgf is 1.7 mM in the dark‐adapted photoreceptor. There was no indication of a change in Mg, when the cell was illuminated with bright light, indicating that Mgf is not elevated during the phototransduction. Changes less than 5 times 10‐5 M could have occurred and remained undetected. The spectrophotometric properties of the indicator were studied at 10‐4 and 10‐3 M, at ionic conditions relevant to the intracellular measurements. Both the differential molar absorption coefficient for the EB‐Mg complex at 600 nm (Δ600MEBMg) and the apparent dissociation constant (KD) for the complex formation were different at 10‐4 M and 10‐3 M EB.
Lung mechanics of the guinea‐pig isolated perfused lung
Authors: KRÖLL F. , KARLSSON J.‐A. , NILSSON E. , PERSSON C. G. A. , RYRFELDT Å.
Published: December 2008

In the isolated perfused guinea‐pig lung, lung resistance (RL) and dynamic compliance (CDYN) as well as flow, pH, PO2 and PCO2 of the perfusate were recorded. The baseline values were stable up to 2.5 h. Mean values (± SEM) for RL and CDYN were 0.36 cm HzO mL1 s_I± 0.04 and 0.27 ml cm‐1 H2O ± 0.02, respectively, which agree with in vivo values reported for unanaesthetized guinea‐pigs. The pH was always slightly raised and the Pco2 always lowered in the effluent compared to the inflowing medium (P < 0.001), indicating that the lung had an operative ventilation. Intravascularly administered acetylcholine, histamine and adenosine caused reproducible dose‐dependent broncho‐constrictions recorded as increased RL and decreased CDYN. It is noteworthy that adenosine in this model and in vivo consistently produced bronchoconstriction which is in contrast to findings in other in vitro airway preparations. We conclude that this isolated perfused guinea‐pig lung preparation has stable in vivo‐likc characteristics offering interesting possibilities for combining studies of respiratory effects with, for example, metabolism, pharmacokinetic and vascular reactivity studies.
The net fluid secretion caused by cyclic 3'5‘‐guanosine monophosphate in the rat jejunum in vivo is mediated by a local nervous reflex
Authors: EKLUND S. , JODAL M. , LUNDGREN O.
Published: December 2008

The tissue concentration of cyclic 3'5′‐guanosine monophosphate (cGMP) has been shown to increase in the small intestine when net fluid secretion is evoked by the heat‐stable enterotoxine of Escherichia coli. Lipophilic cGMP analogues are also known to elicit intestinal fluid secretion. It is therefore believed that an increase in intracellular cGMP concentration in enterocytes mediates this secretion. The present study reports that the fluid secretion, elicited by placing two different cGMP analogues, di‐butyryl‐cGMP and 8‐Br‐cGMP, in the intestinal lumen of anaesthetized rats in vivo, is significantly inhibited by atropine, hexamethonium and lidocaine. It is proposed that cGMP activates a reflex in the enteric nervous system which, in part, explains the observed fluid secretion.
Short and long latency reflex responses elicited by electrical and mechanical stimulation in human hand muscle
Authors: TARKKA I. M. , LARSEN T. A.
Published: December 2008

The relationship between electrically and mechanically induced reflex responses in the rectified, averaged surface electromyogram of the first interosseus dorsalis muscle was examined in 18 healthy human subjects. Both methods evoked identifiable short and long latency reflex responses. The onset latencies for short latency reflexes with electrical and mechanical stimulations were 30.6 ms (± 2.2 ms) and 28.9 ms (± 2.2 ms) and for long latency reflexes 50.0 ms(± 2.8 ms) and 51.2 ms (± 5.2 ms), respectively. The correlation of the onset latencies of the reflexes revealed significant correspondence between the electrical and mechanical methods implying at least partly mutual mechanisms.
Studies on the mucosal hyperaemia of the feline small intestine observed at endoluminal perfusion with substance P
Authors: GRÖNSTAD K. O. , DAHLSTRÖM A. , JAFFE B. M. , ZINNER M. J. , AHLMAN H.
Published: December 2008

Substance P‐like immunoreactivity (SPLI) was found in the luminal contents of the feline small intestine. A physiological role for endoluminal substance P (SP) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of SP. A jejunal segment was initially perfused with saline, followed by SP in saline, and finally perfused with saline alone. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with SP caused a selective mucosal/submucosal hyperaemia of the experimental jejunum, which was normalized upon subsequent saline perfusion. Since neither acute vagotomy, local neural blockade (TTX, lidocaine), adrenergic blockade (phenoxybenzamine, propranolol), cholinergic blockade (hexa‐methonium, atropine), histamine ‐ nor prostaglandin blockade ‐ could antagonize the hyperaemic effects of luminally administered SP, it is suggested that this effect is directly paracrine in nature. Substance P may be released from SP nerves on physiological stimulation, that is, augmented vagal tone by a meal, and act at the effector cell, that is, vascular smooth muscle.
The effect of fatigue on store and re‐use of elastic energy in slow and fast types of human skeletal muscle
Authors: BOSCO C. , TIHANYI J‐ , ATTERI F. L. , FEKETE G. , APOR P. , RUSKO H.
Published: December 2008

Stretch‐shortening exercises are characterized by enhancement of performance when compared to the work output performed in shortening conditions. There is evidence that fast subjects are unable to re‐use great amounts of elastic energy during stretch‐shortening cycles performed with slow stretching speed and large stretching length. In the present study, 14 subjects possessing different fibre types in m. vastus lateralis performed vertical jumps with and without preliminary countermovement and with large angular displacement and slow stretching speed The jumping tests were executed before and immediately after fatigue induced by short intense exercises (60 s of continuous rebound jumping). The results indicated that the percentage of re‐use of elastic energy was more pronounced in slow subjects compared to fast ones during the test performed before fatigue (28.3%vs. 22.8%). In contrast fast subjects demonstrated a greater percentage re‐use of elastic energy than slow ones after fatigue (32%vs. 22.5%). Similarly, the negative relationship observed before fatigue, between the percentage of re‐use of elastic energy and percentage of fast twitch fibres (r= 0.50, n= 14, P < 0.05), was reversed after fatigue (r= 0.55, n= 14, P < 0.05). The results can be interpreted through differences in sarcomere cross‐bridges life‐times between fast and slow twitch muscle fibres. The slow twitch‐type muscle fibre may be able to retain the cross‐bridge attachment for a longer period of time during no fatigued conditions, and therefore it may utilize elastic energy better in slow type ballistic motion. On the other hand, fast twitch type muscle fibres are more affected by fatigue, which might have induced a remarkable decrease of the cross‐bridge attachment detachment cycle. Decrease of the cross‐bridge rate cycle might allow fast twitch‐type muscle fibres to retain longer the elastic energy stored during the stretching phase and then re‐use it during positive phase. In conclusion, the present work suggests that the effect of fatigue allows fast twitch‐type muscle fibres to re‐use greater amounts of stored elastic energy than slow twitch ones during stretch‐shortening cycle exercises performed with slow stretching speed and large stretching length.
Axonal transport of synapsin I‐ and cholinergic synaptic vesicle‐like material; further immunohistochemical evidence for transport of axonal cholinergic transmitter vesicles in motor neurons
Authors: BÖÖJ S. , LARSSON A. , DAHLLÖF A.‐G. , DAHLSTRÖM A.
Published: December 2008

The axonal transport of organelles in motor axons in the sympathectomized rat sciatic has been studied using two antisera which recognize specific components of synaptic vesicles. Anti‐synapsin I recognizes synapsin I (SYN I) which is affiliated with the external membrane of synaptic vesicles, while rabbit‐anti‐synaptic vesicle antiserum (RASVA) recognizes integral membrane glycoproteins in cholinergic synaptic vesicles. Immunofluorescence studies, including cytofluorimetric scanning, show that immuno‐reactive (IR) material recognized by both antisera: (1) rapidly accumulate proximal to a crush; (2) the material has a granular appearance in the microscope; (3) is redistributed in an isolated segment, and (4) that the transport of the material is sensitive to vinblastine. Thus the proximodistal transport has the characteristics of fast axonal transport. Furthermore, recycling organelles, accumulating on the distal side of a crush are recognized by RASVA, but carry only very little SYN I‐IR. The results give further support to the hypothesis that motor cholinergic axons transport axonal cholinergic vesicles towards the motor endplates.
Enkephalin and capsaicin‐resistant substance P‐like immunoreactivities in intra‐ocular grafts of different fetal spinal cord areas
Authors: HENSCHEN A. , KESSLER J. , SEIGER A. , OLSON L.
Published: December 2008

Fetal spinal cord tissue was grafted to the anterior chamber of the eye of adult rats in order to evaluate survival and distribution of substance P‐ and enkephalin‐immunoreactive neurons. Capsaicin treatment was used to evaluate any possible contribution of host iris‐derived substance P fibres to the innervation of the grafts and to check for capsaicin sensitivity of graft substance P‐positive systems. Substance P‐ and enkephalin‐immunoreactive nerve fibres were present in grafts of half‐transverse segments of the spinal cord and were clearly co‐distributed throughout the grafts. Areas with a high density of substance P‐ and enkephalin‐positive fibres resembling substantia gelatinosa were seen. Grafts of the dorsal horn alone had a moderate to high density of substance P‐ and enkephalin‐positive fibres, while ventral horn grafts contained a low amount of such fibres. Capsaicin eliminated the substance P innervation of the host iris and the dorsal root ganglion‐derived substance P innervation of the host spinal cord, while sparing the intrinsic substance P innervation of both host spinal cord and spinal cord grafts. These experiments show that intra‐ocular grafts of defined spinal cord areas express relatively organotypic amounts of substance P‐ and enkephalin‐positive nerve fibres, and thus emphasize the importance of intrinsic genetic determinants for spinal cord development.
Effect of MPTP and its pyridinium metabolites on monoamine uptake and on central catecholamine neurons in mice
Authors: JONSSON G. , NWANZE E. , LUTHMAN J. , SUNDSTROM E.
Published: December 2008

The effect of MPTP and its pyridinium metabolites MPDP+ and MPP+ on the in vitro [3H]monoamine uptake in synaptosomal preparations from mouse striatum and cerebral cortex was investigated. All compounds inhibited [3H]monoamine uptake in a dose‐dependent manner in both regions analysed. MPP+ had the highest affinity to dopamine and noradrenaline uptake sites, while MPTP had the highest affinity to serotonin uptake sites. The results indicate that the affinity of MPP+ to different monoamine uptake sites appears to be better correlated to MPTP neurotoxicity as expressed in vivo than MPTP and MPDP+. Intracerebral injection of MPP+ into substantia nigra produced an almost complete disappearance of dopamine in striatum and noradrenaline in cerebral cortex, while injection of MPTP or MPDP+ had no or only moderate catecholamine‐depleting effects. The MPP+‐induced catecholamine depletion could be partially reversed by pretreatment with the catecholamine uptake blocker nomifensine. Histological analysis disclosed that MPP+ was a potent generally cytotoxic agent, while MPDP+ less and MPTP least so. The present results are compatible with the view that an interaction with the catecholamine uptake mechanism, probably through an uptake and accumulation of extraneuronally formed MPP+, is most likely the explanation for neuron‐specific neurotoxic action on catecholamine neurons following MPTP administration.
Alpha‐adrenoceptors in the vessels of human finger skin
Authors: LINDBLAD L. E. , EKENVALL L.
Published: December 2008

To characterize alpha‐adrenoceptors in the blood vessels of finger skin the effects of selective alpha‐i and alpha‐2 adrenoceptor agonists and antagonists on skin blood flow were studied in vivo. The vasoactive substances were administered into the skin by iontophoresis and the effects on blood flow were evaluated with a laser‐doppler. After blockade of alpha‐i adrenoceptors with doxazosine, the blood flow reduction induced by the alpha‐i selective agonist, phenylephrine, was diminished but not that caused by the alpha‐2 selective agonist, B‐HT 933. In contrast, after alpha‐2 selective blockade by rauwolscine, phenylephrine but not B‐HT 933 caused a marked decrease in blood flow. The results are compatible with the concept that postjunctional alpha‐adrenoceptors in human finger skin vessels are of both alpha‐i and alpha‐2 subtypes.