bluuebunny/crossref_metadata_2025 huggingface dataset:
Actions of enprofylline in the rat hippocampus
Authors: FREDHOLM B. B. , BERGMAN B. , LINDSTRÖM K.
Published: December 2008

Enprofylline is a novel xanthine with a low adenosine antagonistic potency, but with a good bronchodilator activity. In order to further elucidate its central nervous actions we have studied its effects in the rat hippocampus, both electrophysiologically and biochemically. Adenosine was found to depress evoked field excitatory post‐synaptic potentials (EPSPs) in the rat hippocampus. The effect of adenosine was antagonized by theophylline but not by enprofylline. Both xanthines caused a slight increase per se of the field EPSP amplitude. Cyclic AMP accumulation in the rat hippocampus was stimulated by the adenosine analogue NECA, by isoprenaline and by noradrenaline in the presence of propranolol. The cyclic AMP accumulation induced by these agents was not significantly altered by omitting calcium. Enprofylline antagonized the effect of NECA and noradrenaline (after beta‐blockade) but not that of isoprenaline. The IC50 of enprofylline against NECA was about 20μmol I‐1. The inhibitory effect of enprofylline against NECA induced cyclic AMP accumulation was not affected by omitting calcium or by the calcium channel antagonist felodipine, but was decreased by the calmodulin inhibitor stelazine and the intracellular calcium chelator Quin‐2. The results show that enprofylline is much more potent as an inhibitor of adenosine A2‐receptor‐mediated cyclic AMP accumulation than against adenosine A1‐receptor‐mediated inhibition of field EPSP. The difference may depend on a role of a special pool of calcium in the former response.
Blood flow heterogeneity in the renal cortex during burn shock in dogs
Authors: KIRKEBØ A. , HAUGAN A. , TYSSEBOTN I.
Published: December 2008

Blood flow distribution and occurrence of intermittent, patchy ischaemia in the renal cortex were investigated in anaesthetized dogs before and during burn shock. Severe or moderate thermal injury was induced by scalding 30% of body surface by 900C or 70oC hot water. Local blood flow in outer and inner cortex was measured by microspheres and by electrodes recording hydrogen gas washout rates. The haematocrit rose much more in the moderately than in the severely scalded dogs, due to marked haemolysis in the latter group. Cortical blood flow was reduced more after severe than after moderate thermal injury. A significant redistribution of blood flow from outer to inner cortex was not demonstrated. Abrupt shifts in local washout rates were observed in most dogs during shock, but was consistently more frequent in the moderately scalded dogs. Such episodes of patchy intermittent ischaemia were not seen after inhibition of prostaglandin synthesis by indomethacin. Thus, prostaglandins may mediate focal vasoconstriction in the renal cortex during burn shock in dogs.
Skeletal muscle glycolysis during submaximal exercise following acute β‐adrenergic blockade in man
Authors: KAISER P. , TESCH P. A. , THORSSON A. , KARLSSON J. , KAIJSER L.
Published: December 2008

The present study describes the influence of β‐adrenergic blockade on glycogen utilization and lactate accumulation in skeletal muscle of exercising man. Twelve physically active men were examined during 25 min of continuous cycle exercise equivalent to 65% of their maximal oxygen uptake both with and without oral administration of 80 mg of propranolol (Inderal®). Heart rate, oxygen uptake, rate of perceived exertion (RPE) and blood lactate concentration were measured during exercise. Muscle biopsies were obtained from m. vastus lateralis after 5 and 25 min of exercise, β‐adrenergic blockade decreased steady state exercise heart rate by (mean + SD) 35 ± 10 beats min‐1 (P < 0.001) and oxygen uptake from 2.47 to 2.39 1‐min‐1 (P < 0.01). Muscle glycogen decreased from the 5th to the 25th min of exercise, and β‐blockade had no significant effect on this decrease. In contrast to without drug, β‐blockade resulted in a decrease (P < 0.05) in muscle lactate concentration from the 5th (6.9 mmolkg‐1 w./w.) to the 25th min (4.8 mmolkg‐1 w./w.). Similarly blood lactate levels were lower (P < 0.05) with than without β‐blockade in the last but not the first 10 min of exercise. The alteration in muscle lactate concentration pattern following β‐blockade, may imply that adrenergic effects per se contribute to the stimulation of glycolysis during submaximal exercise, except in its earliest phase. Nevertheless, the effect is not great enough to produce substantial differences in glycogen utilization.
Cerebral energy metabolism during bicuculline‐induced status epilepticus in spontaneously hypertensive rats
Authors: JOHANSSON B. B. , FREDRIKSSON K.
Published: December 2008

The cerebral blood flow is lower in spontaneously hypertensive rats than in normotensive anaesthetized and mechanically ventilated rats during bicuculline‐induced seizures, presumably due to the increase in vascular resistance in the hypertensive rats. This study investigates whether the hypertensive rats develop more severe derangement of the cerebral energy metabolites than normotensive rats because of the reduced cerebral blood flow. After 20 min of continuous seizure activity both normotensive and hypertensive rats had significantly decreased levels of phosphocreatine, ATP and glycogen as well as increased lactate and lactate/pyruvate ratio within the parietal cortex compared to controls. The metabolic disturbances were somewhat less pronounced in the hypertensive rats than in the normotensive rats. Thus, ADP was significantly increased in normotensive rats only and the lactate/pyruvate ratio was higher in the normotensive rats. We conclude that spontaneously hypertensive rats are not more prone than normotensive rats to derangement of cerebral energy metabolites during short term bicuculline‐induced seizures and that insufficient blood flow is not the primary cause of the metabolic alterations.
Physiological responses associated with feigned death in the American opossum
Authors: GABRIELSEN G. W. , SMITH E. N.
Published: December 2008

Heart rate, respiratory rate and body temperature of four free‐ranging American opossums, Didelphis marsupialis of both sexes (2.47 ± 0.27 kg; ± +± SE), were monitored during mild provocation and during death feigning (‘play possum’). Mild provocations, caused by the approach of either man or dog, elicited a freezing response. The behavioural response was accompanied by a 12% decrease in heart rate (218 ± 11 to 192 ± 10 beats‐min‐1; ± SE) and a 31% reduction in respiratory rate (26.7 ± 1.7 to 18.4 ± 1.4 breaths‐min‐1) from pre‐stimulation values. Death feigning was induced by vigorous tactile stimulation by either investigator or dog. The response was marked by immobility, prone position and stiffness of the body. Mouth was open and the animal showed no response to touch or pinching. Death feigning was always accompanied by salivation, urination, defaecation and erection of the penis (in males). Heart rate decreased 46% (222 ± 10.6 to 120 ± 17 beats‐min‐1) and respiratory rate was reduced 30% (27.4 ± 1.5 to 19.2 ± 2.3 breaths‐min‐1) from pre‐stimulation values. Body temperature dropped from 34.8 ± 0.2 to 34.2 ± o.3oC. During death feigning the animal was fully conscious as was evident by heart rate reduction during the re‐approach of the dog. Atropine treatment had no obvious effect on behaviour but abolished the bradycardia when compared to pre‐stimulus condition.
The origin and fall of plasma motilin during Escherichia coli endotoxin shock in pigs
Authors: JENSSEN TROND G. , REVHAUG ARTHUR , BURHOL PER G. , GIERCKSKY KARL‐ERIK , LYGREN IDAR
Published: December 2008

Plasma motilin decreased significantly during a 120 min intravenous Escherichia coli endotoxin infusion which induced deep shock in six anaesthetized pigs. Plasma motilin was significantly higher in the portal vein and significantly lower in the internal jugular vein than in the aorta and the superior caval vein. Following gastrointestinal resection with blood sampling from the portal vein, the aorta and the superior caval vein in another six pigs, motilin almost disappeared in non‐portal plasma, while it decreased significantly in portal plasma in which it also fell further during E. coli endotoxin infusion. The results support the opinion that the gastrointestinal tract is the main source of plasma motilin.
Determinations of catecholamine half‐lives and turnover rates in discrete catecholamine nerve terminal systems of the hypothalamus, the preoptic region and the forebrain by quantitative histofluorimetry
Authors: ANDERSSON KURT , FUXE KJELL , AGNATI LUIGI F.
Published: December 2008

To determine whether amine pool sizes, half‐lives and turnover rates could be measured in discrete hypothalamic, preoptic and forebrain catecholamine (CA) nerve terminal networks by quantitative histofluorimetry, the CA fluorescence disappearance was studied at different time intervals after tyrosine hydroxylase inhibition. For comparison, the depletion of DA and NA following tyrosine hydroxylase inhibition in discrete brain regions was determined by high pressure liquid chromatography (HPLC). Following tyrosine hydroxylase inhibition using a‐methyl‐DL‐p‐tyrosine methyl ester, an apparently monophasic decline of the CA stores was demonstrated in all brain regions analysed both histochemically and by HPLC. A multiphasic DA disappearance was measured by HPLC in the peri‐ and paraventricular hypothalamic area. The DA nerve terminal networks generally had shorter half‐lives than the NA nerve terminal networks. The shortest half‐life (99 min) of the regions demonstrating a monophasic decline of CA stores was found in the CA nerve terminal system in the medial palisade zone of the_ median eminence. By the use of CA standards in the histochemically prepared sections, it was possible to convert the measured CA fluorescence into absolute amounts of catecholamines expressed in nmol. g˜ of tissue wet weight. It was shown that the CA stores and the turnover rates measured by quantitative histofluorimetry were 20–30 times greater than those measured using HPLC. The difference has been related to amine dilution with amine‐poor areas in the specimens analysed by HPLC. By studying the accumulation of catecholamines after monoamine oxidase inhibition, it could be demonstrated that no concentration‐dependent quenching of CA fluorescence occurred.
Serum factors other than albumin are needed for the maintenance of normal capillary permselectivity in rat hindlimb muscle
Authors: HARALDSSON BORJE , RIPPE BENGT
Published: December 2008

To investigate the effects of different perfusates on capillary permeability, we determined the capillary filtration coefficient (CFC), the capillary diffusion capacity (PS) for Cr‐EDTA and clearance of albumin during isogravimetric conditions and maximal vasodilatation in the isolated, perfused rat hindquarter preparation. Experiments were conducted in 30 rats with different perfusates. We were able to confirm the classical ‘protein effect’. Absence of proteins, using pure dextran solution as perfusate, induced a 45% increase in CFC and a three‐fold increase in albumin clearance. However, we also found evidence for a ‘serum effect’. Hence, the clearance of albumin was normal when the serum content exceeded 5% (v/v) in perfusates otherwise composed of albumin in Tyrode, but increased three‐fold from 0.0305 to 0.0912 ml (min‐100 g)‐1 when the rats were perfused with albumin in Tyrode with no serum present, without any change in CFC, PS for Cr‐EDTA or vascular resistance to flow. Thus, certain non‐dialysable serum factors, other than albumin, seem to be needed for the maintenance of normal capillary permselectivity in rat hindquarters. These factors are probably needed for the capillary membrane to maintain its character of a negatively charged barrier.
Influence of extracellular calcium and nifedipine on α1‐and α2‐adrenoceptor‐mediated contractile responses in isolated rat and cat cerebral and mesenteric arteries
Authors: SKÄRBY TOR , HÖGESTÄTT EDWARD D. , ANDERSSON KARL‐ERIK
Published: December 2008

The influence of extracellular Ca2+and nifedipine on contractile responses to 10 μM noradrenaline (NA) was investigated in isolated rat and cat middle cerebral (RCA, CCA) and mesenteric (RMA, CMA) arteries. In the CCA (containing predominantly α2‐adrenoceptors), the NA‐induced contractions developed considerably more slowly than in the RCA, RMA (containing mainly α1‐adrenoceptors) and CMA (sensitive to both at,‐ and α2‐adrenoceptor selective antagonists). The tonic component of the NA‐induced contraction in the four types of artery was substantially suppressed after only short periods in Ca2+‐free solution. In each type of artery, excluding the CCA, the contractile response to 124 mM K+was more sensitive to Ca2+deprivation than that to NA. This suggests that NA, besides mobilizing extracellular Ca2+, can also release Ca2+from an intracellular pool in the RCA, RMA and CMA, but not in the CCA. Thus, α1‐adrenoceptor‐mediated contractions in the RCA and RMA seem to depend on both Ca2+influx and intracellular Ca2+release, whereas α2‐adrenoceptor‐mediated contractile responses in the CCA appear to rely almost entirely on Ca2+influx. Both the maximum response and the tonic component of the NA‐induced contraction were significantly more sensitive to nifedipine in the CCA than in the RCA. In comparison with the NA‐induced contractions in these arteries, those in the RMA and CMA were relatively resistant to nifedipine. In the CCA exposed to NA in Ca2+‐free medium, nifedipine almost abolished the contraction induced by re‐addition of Ca2+, whereas in the other types of artery, Ca2+re‐application evoked a significant contraction also in the presence of the drug. The differential effects of nifedipine presumably reflect differences between the arteries, not only in the relative contribution of Ca2+influx and intracellular Ca2+release to the contractile activation, but also in the nifedipine sensitivity of the Ca2+entry pathways utilized by NA. It is concluded that the mechanisms through which NA induces contraction seem to be related both to the subtype of α‐adrenoceptor stimulated by NA and to the type of vessel studied.
Effects of a three‐hour calcium clamp on calcium, phosphate, magnesium and zinc concentrations of human parotid saliva
Authors: SAGULIN G‐B. , TØRRING O. , SJÖBERG H. E. , ARVER S. , APPELGREN B.
Published: December 2008

Ionized (saliva‐Ca2+) and total calcium (saliva‐CaT), inorganic phosphate (saliva‐P), magnesium (saliva‐Mg), and zinc (saliva‐Zn) levels in parotid saliva were studied in eight healthy volunteers during a 3‐h calcium infusion, directly regulated to obtain a pre‐settled standardized blood calcium level. Frequent determinations of whole blood ionized calcium (B‐Ca2+) were used for continuous adjustments of the calcium infusion rate (‘calcium clamp’). Basal B‐Ca2+ (1.26 ± 0.04 mmol.l‐1, mean ± SD) was thus elevated to and maintained at 1.51 ± 0.05 mmol.l‐1 from + 30 to + 180 min. Saliva samples were taken prior to the infusion and at regular intervals during the infusion period. Saliva‐Ca2+ decreased from 0.38 ± 0.06 to 0.33 ± 0.05 mmol.l‐1 (P < 0.01) and saliva‐Ca2+ as a percentage of saliva CaT from 63 ± 7% to 53 ± 10% (P < 0.001) during the infusion. No changes could be observed in saliva‐CaT, saliva‐P, saliva‐Mg, saliva‐Zn, saliva‐Na and saliva‐K. Possible mechanisms behind these findings might be decreased parathyroid hormone and increased calcitonin concentrations in serum.
Atropine and naloxone block the colonic contraction elicited by cholecystokinin and pentagastrin
Authors: HELLSTRÖM PER M.
Published: December 2008

The effects of cholecystokinin (CCK) and gastrin on proximal and distal colonic motility were investigated because of the possible role of these peptides in feeding‐induced colonic motility. Experiments were performed using 22 chloralose‐urethane anaesthetized cats in which the colon was acutely denervated. The volume changes of the proximal and distal colon were recorded with water‐filled flaccid balloons. The venous effluxes from the proximal and distal colon were recorded separately using drop recorder units. CCK‐8, 1–200 pmol. min‐1close i.a., and pentagastrin, 1–200 pmol. min‐1close i.a., evoked dose‐dependent contractions of the colon without altering systemic arterial blood pressure and colonic blood flow. The CCK peptides ‐8, ‐33 and ‐39 produced contractions of similar magnitude in the proximal and distal colon. The stimulatory effect of CCK‐8 and pentagastrin on colonic motility was blocked by tetrodotoxin (1 μg. kg‐1i.a.) and hexamethonium (10 mg. kg‐1i.v.). Atropine (0.5 mg. kg‐1i.v.) completely blocked the responses to CCK‐8 and pentagastrin in the distal colon but only partially in the proximal colon. Additional administration of naloxone (1 mg. kg‐1i.a.) abolished the remaining contractile response to the peptides in the proximal colon. The present results support the idea that CCK and pentagastrin have a stimulatory effect on distal colonic motility mediated via preganglionic and postganglionic cholinergic pathways. The possible role of opioid peptides and cholinergic mechanisms in the proximal colon is discussed.
The effect of non‐esterified long‐chain fatty acids on blood flow and thermogenesis in brown adipose tissue in the young dog
Authors: ASTRUP A. , BÜLOW J. , CHRISTENSEN N. J.
Published: December 2008

In vitro experiments have demonstrated that increasing the molar ratio of extracellular non‐esterified fatty acids (NEFA) to albumin stimulates thermogenesis in brown adipocytes. To test these results, in vivo blood flow and local temperature were measured in perirenal brown adipose tissue (BAT) in puppies during thermogenesis induced by increasing the plasma NEFA: albumin ratio by injection of intralipid and heparin. Plasma NEFA concentration increased to 1.5 mmol.l‐1 and plasma NEFA: albumin ratio to 4. Concomitantly, the whole body oxygen consumption rose on average about 100% above baseline level. Plasma noradrenaline concentration increased about three‐fold and plasma adrenaline concentration about six‐fold. The BAT temperature increased by an average of 0.9 °C. However, since BAT blood flow was simultaneously reduced by about 50%, it can be calculated that the local heat production was also reduced. Consequently, the increase in whole body oxygen consumption was not due to stimulation of BAT thermogenesis. It is concluded that in vivo assessment of BAT thermogenesis requires concomitant measurements of both local BAT temperature and blood flow.
Haemodynamic conditions for renal PGE2and renin release during α‐ and β‐adrenergic stimulation in dogs
Authors: VIKSE ARILD , HOLDAAS HALLVARD , SEJERSTED OLE M. , KIIL FREDRIK
Published: December 2008

Constriction of the renal artery and infusion of an α‐adrenergic agonist induce autoregulated vasodilation and increase prostaglandin E2(PGE2) and renin release. The enhancement of renin release during autoregulated vasodilation might be mediated by prostaglandins. To examine this hypothesis, experiments were performed in three groups of anaesthetized dogs. In six dogs constriction of the renal artery to a perfusion pressure below the range of autoregulation raised renin release from 2 ± 1 to 27 ± 6 μg AI.min‐1and PGE2release from 1 ± 1 to 10 ± 2 pmol. min‐1. After administration of indomethacin (10 mg. kg‐1b. wt), PGE2release was effectively blocked and constriction of the renal artery raised renin release only from 0.1 ± 0.1 to 6 ± 1 μg AI.min‐1. During subsequent continuous infusion of a β‐adrenergic agonist, isoproterenol (0.2 μg. kg‐1.min‐1), constriction of the renal artery raised renin release from 0.1 ± 0.1 to 52 ± 11 μg AI.min‐1, although there was no rise in PGE2release. In six dogs, intrarenal infusion of phenylephrine, an α adrenergic agonist, increased PGE2and renin release before, but not after, indomethacin administration. In six other dogs, phenylephrine infused during isoproterenol infusion increased renin release equally before and after indomethacin administration. Thus the enhancing effect of constricting the renal artery or infusing an α‐adrenergic agonist is not dependent upon prostaglandins. We propose that autoregulated dilation enhances renin release whether the stimulatory agent is a prostaglandin or a β‐adrenergic agonist.
Absence of capillary recruitment during increased coronary blood flow in the working dog heart
Authors: ELIASEN P. , AMTORP O.
Published: December 2008

Myocardial plasma flow (MPF) and capillary permeability‐surface area product (PS) were determined simultaneously on a regional basis in subendocardial and subepicardial layers of the left ventricular free wall in the working dog heart at control flow rate and during coronary vasodilation. The value for MPF was determined by the radioactive microsphere method and PS was assessed by an integral tissue‐uptake method using [51Cr]‐EDTA as test molecule. During coronary vasodilation achieved by intracoronary infusion of adenosine, MPF increased markedly from 101.5 ± 14.2 to 778.1 ± 135.2 ml. min‐1. 100 g‐1 in subendocardial layers and from 77.7 ± 10.3 to 635.3 ± 85.9 ml. min‐1. 100 g‐1 in subepicardial layers of the left ventricular wall. Raising MPF by 800% was accompanied by a modest but statistically significant increase in PS[51Cr]‐EDTA. In subendocardial layers PS increased from 49.3 ± 5.0 to 60.0 ± 3.3 ml. min‐1. 100 g‐1 and in subepicardial layers from 43.8 ± 4.1 to 52.1 ± 2.4 ml. min‐1. 100 g‐1, respectively. Taking into account back‐diffusion of the tracer from the tissue to capillary blood which was higher at low flows than at high flows, PS[51Cr]‐EDTA showed no increase with an eight‐fold increment in flow. This observation rebuts the concept of additional perfusion of capillaries which are devoid of plasma flow under resting conditions during coronary vasodilation.
Zinc preserves an inherent capacity for human sperm chromatin decondensation
Authors: KVIST ULRIK , BJÖRNDAHL LARS
Published: December 2008

The effect of zinc on the nuclear chromatin decondensation ability of human, ejaculated spermatozoa was studied by exposing washed spermatozoa to the detergent sodium dodecyl sulphate (SDS) before and after sperm storage. Treatment with EDTA increased the proportion of decondensing spermatozoa before storage. Zinc supplementation before storage reversibly inhibited spontaneous decondensation as well as EDTA‐enhanced decondensation. Treatment with EDTA before storage decreased the proportion of spermatozoa decondensing after storage. Zinc supplementation during storage reduced the decrease in the proportion of spermatozoa decondensing after storage. Two effects of zinc were observed: one immediate effect (reversible inhibition of the decondensation) and one long‐term effect (protection of the intrinsic capacity for decondensation during storage). Both effects may be explained by a zinc‐thiol interaction in the chromatin. Spermatozoal zinc is suggested to protect an inherent capacity for decondensation, thereby helping to extend the functional life‐span of the ejaculated spermatozoon.
Characteristics of repeated isokinetic plantar flexions in middle‐aged and elderly subjects with special regard to muscular work
Authors: FUGL‐MEYER AXEL R. , GERDLE BJÖRN , LÅNGSTRÖM MATS
Published: December 2008

Contractional work (CW), mean power (CP) and peak torque (PT) were recorded for each of up to 200 full range‐of‐motion (RoM) repetitive isokinetic (60°.s‐1) maximum effort plantar flexions. Subjects were 88 unselected clinically healthy males and females aged 40–44, 50–54 and 60–64 years with similar distributions of age and sex. Simultaneous recordings of integrated electromyograms (iEMGs) were obtained from the three heads of the m. triceps surae. Within approximately 50 contractions CW had decreased 36‐21% for the different groups (by age and sex). The corresponding decreases for PT and CP were 28‐14% and 25‐13%, respectively. During the remaining part of the experiment only minor changes occurred. For CW but not for PT and CP reductions were negatively related to age while no sex differences were evident. Decreases in CW were significantly smaller in subjects physically active during leisure time than in those relatively inactive. Decreases in active range‐of‐motion provide an explanation for greater reductions in CW than in PT and CP. The iEMGs of the mm. gastrocnemii decreased significantly more than that of the m. soleus. Close associations between CW and iEMG were evident. Hence the chosen expression of output/input balance: CW/iEMG was nearly constant throughout the experiments. Results indicate that measurements of contractional work throughout the range‐of‐motion may provide more differentiated information on mechanical output during supposedly fatiguing dynamic manoeuvres than can recordings of maximum strength.
Locally applied133Xenon for the measurement of regional cerebral blood flow (rCBF): an experimental study in the pig
Authors: EINTREI CHRISTINA , LESZNIEWSKI WACLAW , ÖDMAN SVANTE , LEWIS DAVID H.
Published: December 2008

A method for measuring regional cerebral blood flow has been developed. On pig brain cortex a 1 cm2size polyester film was placed, under which 0.6‐1.3 mCi of133Xenon in 2–4 μl of saline was applied atraumatically. The wash‐out process was registered with an external detector, and can be described as a sum of monoexponential functions. The first component of the curve, obtained by curve resolution, indicates blood flow in grey matter and the second slow component indicates blood flow in white matter. When total ischaemia was induced, there was no wash‐out of the isotope. Freezing the brain after isotope application at different stages during the wash‐out showed isotope in both grey and white matter. The isotope did not diffuse into the polyester film. This technique was also used in studies on the spinal medulla where white matter is outermost and grey innermost. The wash‐out curve obtained consisted of only one monoexponential function; blood flow from grey matter was not present in the wash‐out curve. For calculation of cerebral blood flow a modified two‐compartment model was used. It is concluded that this method measures local cerebral blood flow in both grey and white matter. The method can be used clinically to measure the local cerebral blood flow during neurosurgical operations.
Effects of acute intermittent exposure to cigarette smoke on catecholamine levels and turnover in various types of hypothalamic DA and NA nerve terminal systems as well as on the secretion of adenohypophyseal hormones and corticosterone
Authors: ANDERSSON KURT , FUXE KJELL , ENEROTH PETER , MASCAGNI FRANCO , AGNATI LUIGI F.
Published: December 2008

Male rats were exposed to cigarette smoke (Walton Horizontal Smoking Machine) from one to four cigarettes (Kentucky reference IR‐1 type). Catecholamines in the diencephalon were measured by quantitative histofluorimetry in discrete dopamine (DA) and noradrenaline (NA) nerve terminal systems. Blood TSH, prolactin, LH, FSH, ACTH, vasopressin and corticosterone levels were determined by radioimmunoassay procedures. Exposure to unfiltered, but not to filtered (Cambridge glass fibre filters) cigarette smoke resulted in dose‐dependent reductions of NA levels in the various hypothalamic NA nerve terminal systems. Evidence was obtained that exposure to unfiltered but not to filtered cigarette smoke resulted in dose‐dependent increases of amine turnover (αMT‐induced CA disappearance experiments) in the various DA and NA nerve terminal systems in the hypothalamus. The lowering of TSH, LH and prolactin secretion induced by unfiltered smoke were probably induced by nicotine and were independent of tyrosine hydroxylase inhibition. Furthermore, unfiltered cigarette smoke produced a dose‐related increase in corticosterone secretion. The inhibitory effects of TSH, LH and prolactin secretion were probably in part related to the ability of unfiltered smoke via its nicotine component to activate the lateral and medial tubero‐infundibular DA neurons. The increases in corticosterone secretion may at least in part be related to a smoke induced increase in the facilitatory influence of paraventricular NA nerve terminals on CRF activity.
Electromyographic activity related to aerobic and anaerobic threshold in ergometer bicycling
Authors: VIITASALO JUKKA T. , LUHTANEN PEKKA , RAHKILA PAAVO , RUSKO HEIKKI
Published: December 2008

Electromyographic activity (EMG) of the knee extensor musculature (m. vastus lateralis, m. vastus medialis, m. rectus femoris), triceps surae (m. gastrocnemius, m. soleus) and m. tibialis anterior was studied in ergometer bicycling at five different power outputs around aerobic (AerT) and anaerobic (AnT) thresholds. EMGs were sampled with surface electrodes for ten revolutions at the beginning, in the middle and at the end of each work load and integrated (IEMG) separately for each of the muscles and for the descending (work) and ascending (rest) phase of the revolution. The mean power frequency (MPF) of the power spectral density function for the descending periods was also calculated. The first work load was 50% of the maximal load, the second at the level of AerT, the third at the AnT, the fourth between the AnT and the maximal load and the fifth load was maximal. The AerT and AnT were determined using blood lactate, ventilation volume and oxygen consumption. Five males from 21 to 38 years of age volunteered as subjects. When the IEMGs of the knee extensor and triceps surae musculature were related to the work load a nonlinearity was found at the aerobic threshold while no further change in the linearity was found at the AnT. The non‐linear increase of the IEMG at the AerT was found both for the working (descending) and resting (ascending) phases of the cycling. In the MPF no difference below and above the AnT was found. It was thought that the integral of EMG activity could serve as an indicator of the aerobic threshold of an individual muscle.
Effects of graded focal cold block in the solitary and para‐ambigual regions of the medulla in the cat
Authors: BUDZIŃSKA KRYSTYNA , von EULER CURT , KAO FREDERICK F. , PANTALEO TITO , YAMAMOTO YUJI
Published: December 2008

Unilateral focal cold blocks in the region of the nucleus tractus solitarius and the dorsal respiratory group of neurons, DRG, of anaesthetized cats consistently caused apneustic‐type breathing. There was no concomitant change in the initial rate of rise of inspiratory activity. The apneustic prolongation of inspiratory duration, T1, was most pronounced in, but was not confined to, the DRG. The apneustic effects were more marked after vagotomy. In cats with intact vagus nerves being given artificial ventilation, focal cooling at certain sites of the DRG region could produce ‘unlocking’ of the respiratory rhythm from that of the respiratory pump. At other sites in this region, focal cooling could selectively block the effects of the inspiration‐facilitating reflex induced by deflation without blocking the inspiration‐inhibiting Hering‐Breuer reflex. Unilateral focal cold blocks in the region of the intermediate part of the ventral respiratory group of neurons, VRG, generally caused depression of the rate of rise of inspiratory activity, but almost never apneustic effects. All effects of unilateral focal cooling both in the DRG and VRG were bilaterally symmetrical. No systematic differences between the effects on phrenic and external intercostal inspiratory activity were found in response to focal cooling either of the DRG or VRG suggesting that differential control of phrenic and external intercostal motoneurons is not exerted mainly at the level of these medullary structures. The results suggest that the DRG and VRG areas exert somewhat different effects on the respiratory pattern: DRG appears to be more concerned with integration of vagal and other inputs contributing to the inspiratory off‐switch mechanisms which, however, are not confined only to the DRG. The VRG inspiratory mechanisms, on the other hand, appear to be more involved in the gain control of the inspiratory output intensity.
Release of expiratory muscle activity by graded focal cold block in the medulla
Authors: BUDZIŃSKA KRYSTYNA , von EULER CURT , KAO FREDERICK F. , PANTALEO TITO , YAMAMOTO YUJI
Published: December 2008

Disinhibition or ‘release’ of expiratory muscle activity in response to focal cooling of various medullary structures was of two kinds: (1) release of rhythmic expiratory activity even when no such activity was recruited in the control situation and (2) release of tonic activity in the ‘expiratory’ muscles. Release of rhythmic expiratory activity was mainly elicited by focal cooling of structures in the intermediate part of the medulla and release of tonic activity was preferentially induced by cooling rostroventral structures, although a considerable overlap did occur. Release of rhythmic expiratory activity was not related to any changes in expiratory time (TE) or to any associated variations in the pattern of inspiratory activity. It showed a marked increase with increasing levels of PCO2. The release of tonic activity was not CO2‐dependent. Both types of effects could be mimicked by focal microinjections of lignocaine and were reflected by corresponding changes in activity of a majority of the expiration‐related neurons. These results suggest that complex and widespread neural substrates subserve the control of the intensity of rhythmic expiratory activity and of the tonic activity of the abdominal and intercostal muscles. These neural mechanisms can apparently operate independently from those controlling the inspiratory activity. The release of the tonic activity observed in the ‘expiratory’ muscles might reflect a disinhibition of mechanisms involved in non‐respiratory functions of expiratory muscles.
Effects of α‐ and β‐adrenoceptor stimulation on45Ca2+efflux and insulin secretion from perfused rat islets
Authors: AHRÉN BO , LUNDQUIST INGMAR
Published: December 2008

Exposure to the β2‐adrenoceptor agonist terbutaline resulted in a transient stimulation of45Ca2+efflux from45Ca2+preloaded rat islets perfused in 2 mm Ca2+and 8.3 mm glucose. Concomitantly, an increase in insulin secretion occurred. Under the same experimental conditions, the α‐adrenoceptor agonist noradrenaline promptly inhibited insulin release without any apparent influence on45Ca2+efflux. In contrast, in a medium containing 2 mm Ca2+and a low glucose concentration (2.8 mm), terbutaline stimulated insulin secretion without any apparent effects on45Ca2+efflux. Noradrenaline had no effect on insulin secretion or45Ca2+efflux in this medium. When islets were perfused with 8.3 mm glucose in a Ca2+deficient medium, with or without addition of the chelating agent EGTA, terbutaline induced a marginal stimulation of insulin secretion and a negligible stimulation of45Ca2+efflux. On the contrary, noradrenaline stimulated to an immediate and notable45Ca2+efflux in these Ca2+deficient media. Noradrenaline also clearly inhibited insulin secretion, though less markedly and with a slower onset than in islets perfused in 2 mm Ca2+. When the islets were perfused in a Ca2+deficient medium with 2.8 mm glucose, terbutaline had a slight insulin releasing effect, but stimulated45Ca2+efflux potently. Noradrenaline had no influence on insulin secretion but a weak stimulatory effect on45Ca2+efflux. The data suggest that the β2‐adrenoceptor agonist terbutaline has the ability to stimulate insulin secretion in perfused rat islets, requiring extracellular Ca2+for the full expression of its effects. These effects may be exerted through a Ca2+‐Ca2+exchange over the cell membrane and/or through cAMP and intracellular Ca2+perturbations. Moreover, terbutaline directly stimulates45Ca2+efflux, an effect inhibited by glucose. Further, the α‐adrenoceptor agonist noradrenaline can inhibit insulin secretion in the absence of extracellular Ca2+, but the full expression of its inhibitory action is dependent on extracellular Ca2+and glucose. In addition, noradrenaline stimulates45Ca2+efflux in a Ca2+deficient medium, an effect which appears independent of the glucose concentration.
Effects of some peptides on isolated human penile erectile tissue and cavernous artery
Authors: HEDLUND H. , ANDERSSON K.‐E.
Published: December 2008

Contractant and relaxant effects of four peptides known to occur in nerves innervating human penile vessels and erectile tissue, namely substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and somatostatin, were studied in isolated preparations from the corpus cavernosum (CC), corpus spongiosum (CS) and cavernous artery (Acc). In addition, the actions of another peptide, arginine vasopressin (AVP), were investigated. In erectile tissue proper, SP induced concentration‐dependent contractions. No effect of this peptide was observed in Acc segments. CC and CS preparations contracted by noradrenaline (NA) were relaxed by 30–40%; the effect in NA‐contracted Acc preparations was inconsistent. AVP had a potent contractant effect in preparations from all the tissues studied, the effect being most conspicuous in CS strips. VIP was without contractant actions in any of the preparations. NA‐contracted preparations were relaxed by VIP, and electrically induced contractions inhibited. The inhibitory effect was particularly marked in electrically stimulated CC and CS preparations. NPY had no effects; somatostatin contracted Acc segments, and in high concentrations CC and CS strips. It is concluded that among the peptides studied only VIP has effects compatible with a role as a neurotransmitter in penile erection.
The variation in action of excitatory amino acids in relation to distance of iontophoretic application to spinal motoneurones
Authors: FLATMAN J. A. , LAMBERT J. D. C. , ENGBERG I.
Published: December 2008

Intracellular recordings were made from lumbosacral motoneurones of barbiturate‐anaesthetized cats. dl‐Homocysteate (DLH) and l‐glutamate were iontophoresed extracellularly over a range of distances from the impaled motoneurone. Movement of the iontophoretic electrode unit was controlled by a micromanipulator which was advanced independently of that moving the intracellular electrode. Depolarizations to DLH were first detected at a greater distance from the impaled motoneurones (mean, 383 μm) than depolarizations to l‐glutamate (mean, 165 μm). As the point of application approached the soma of the motoneurone, depolarizations developed more rapidly, were larger and the latent period of the l‐glutamate depolarization became shorter. Dendritic ‘hot‐spots’ of the depolarizing action of l‐glutamate were not detected.
Effects of portacaval shunt on the rat stomach
Authors: EKELUND M. , HÅKANSON R. , HOLMIN T. , OSCARSON J. , REHFELD J. F. , SUNDLER F. , WESTRIN P.
Published: December 2008

In portacava‐shunted rats, basal but not pentagastrin‐stimulated acid secretion was higher than in sham‐operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell‐associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine‐containing ECL cells) proliferated greatly and the pentagastrin‐ and cholecystokinin octapeptide‐induced activation of the histamine‐forming enzyme, histidine decarb‐oxylase, in these cells was much greater than in control rats. Analysis of the dose‐response curves for the enzyme‐activating effect of pentagastrin and cholecystokinin‐octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.
The use of isolated fish opercular epithelium as a model tissue for studying intrinsic activities of loop diuretics
Authors: ERIKSSON ORJAN , MAYER‐GOSTAN NICOLE , WISTRAND PER J.
Published: December 2008

Isolated opercular epithelia of killifish (Fundulus heteroclitus). were mounted in an Ussing chamber. The epithelia displayed a transepithelial electrical potential difference (PD) of 10.6 ± 0.3 mV (sea‐water side negative) and a short‐circuit current (SCC) of 72.1 ±2.1 μA cm‐2. The electrical resistance was 160 ± 3 Ω cm2(mean ± SE, n 269). The unidirectional flux of36C1 from blood side to sea‐water side compared well with the SCC. No net flux of22Na or24Na across the epithelium was observed. Raising of cyclic AMP levels by theophylline, 3‐isobutyl‐1‐methyl‐xanthine, isoprenaline and forskolin, increased SCC and PD. Prostaglandins PGE2and to some extent PGF2αinhibited SCC and PD. Inhibition of Na+‐K+‐ATPase by ouabain and orthovanadate reduced SCC and PD. Pretreatment of the epithelium with the stilbene disulphonic acid (DIDS) did not prevent the action of orthovanadate. Different types of diuretics were tested, but only the loop diuretics bumetanide, piretanide, and furosemide, rapidly and strongly inhibited PD and SCC and unidirectional36C1 serosal to mucosal flux. Dose‐response curves for these agents were parallel and EC50values for effects on SCC were 40, 52, and 295 μM, respectively. The same relative activities of these diuretics have been seen in the renal thick ascending limb of Henle's loop (TALH). It is concluded that the killifish opercular skin responds to hormonal stimuli and various pharmacological agents in a manner similar to that of mammalian renal TALH. It should therefore be a useful model for studies of the modes of action and the structure‐activity relationships of diuretics which act by inhibition of chloride transport or Na+‐K+‐ATPase activity.
Structural adaptation of the rat left ventricle in response to changes in pressure and volume loads
Authors: FRIBERG P. , FOLKOW B. , NORDLANDER M.
Published: December 2008

Female Wistar‐Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used to explore the structural changes of cardiac dimensions in connection with a sustained hyperkinetic circulation, as induced by pregnancy or thyroxine administration. Cardiac design was assessed by recordings of the diastolic left ventricular pressure‐volume relationships in isolated arrested hearts. Left ventricular weight:body weight and end‐diastolic volume (EDV) for given end‐diastolic pressures (EDP), were both increased about 50% in control SHR, with a marginal reduction of the wall: lumen ratio (wri) compared with control WKY. During the hyperkinetic circulatory states of pregnancy and hyperthyroidism, EDV was in WKY increased about 30% and 50%, respectively, with concomitant w: ri. reductions. In SHR pregnancy did not significantly alter left ventricular dimensions, whereas EDV was increased by about 20% in hyperthyroid SHR. Thus, the rat left ventricle can, within 3 weeks, markedly alter not only the wall mass but also, and independently, the luminal design in response to different haemodynamic interventions. Early established SHR hypertension is characterized mainly by eccentric left ventricular hypertrophy, despite the elevated arterial pressure. Volume overloads in WKY due to pregnancy or hyperthyroidism can induce marked structural widening of the left ventricle. In SHR these structural luminal changes were only minor, perhaps because considerable eccentric hypertrophy is already present. Such a structural cardiac enlargement may allow delivery of an increased stroke volume for a given myocardial fibre shortening.
The relation between in vitro. efflux of noradrenaline from platelets and vas deferens in man
Authors: MATTIASSON INGRID , NYSTRÖM IRENE , ABRAHAMSSON PER‐ANDERS , HOOD BERTIL
Published: December 2008

The efflux of isotope‐labelled noradrenaline from platelets and vas deferens was compared in 29 healthy males. Platelets and a preparation of tissue from vas deferens were incubated with isotope‐labelled noradrenaline until equilibrium in the uptake was obtained. The spontaneous efflux of noradrenaline in buffer was measured for 20 min. There was a significant positive correlation between the efflux of noradrenaline from platelets and vas deferens (r 0.56, P < 0.001).
Influence of temperature on stimulus‐secretion coupling in the sympathetic nerves and on neuromuscular transmission, in guinea‐pig vas deferens
Authors: Stjärne L. , ALBERTS P.
Published: December 2008

In guinea‐pig isolated vas deferens moderate cooling (within the range 16–41 °C) improved, while further cooling depressed, sympathetic neuromuscular transmission. Moderate cooling: (a) enhanced the contractile responses both to electrical nerve stimulation and (although less strongly) to exogenous noradrenaline or to the adenosine 5′‐triphosphate (ATP) analogue, α, β‐methylene ATP; (b) enhanced the overflow of [3H]noradrenaline evoked by electrical nerve stimulation at 1–8 Hz, but not that caused by direct depolarization of varicosities with 80 mM potassium; (c) reduced the depressing effect of exogenous noradrenaline, as well as the enhancing effect of the a‐adrenoceptor blocking agent phentolamine, on the secretory responses to electrical nerve stimulation; (d) while not altering the maximal secretion of tracer noradrenaline at infinitely high frequency or external calcium, lowered the frequency or calcium concentration required for half‐maximal secretion, both in the absence and in the presence of phentolamine. In conclusion: moderate cooling improves sympathetic neuromuscular transmission in guinea‐pig vas deferens, both prejunctionally, by enhancing transmitter secretion, and post‐junctionally, by increasing the responsiveness of the smooth muscle to transmitter.
Changes in oviductal VIP content induced by sex steroids and inhibitory effect of VIP on spontaneous oviductal contractility
Authors: HELM G. , EKMAN R. , RYDHSTÖM H. , SJÖBERG N.‐O. , WALLES B.
Published: December 2008

The content of vasoactive intestinal polypeptide (VIP) in rabbit oviducts was determined using a radioimmunoassay technique. Treatment with oestrogen (polyestradiolphosphate) alone for 5 days caused a significant increase in oviductal VIP content, whereas addition of progesterone during the last 3 days of an 8 day polyestradiol‐phosphate treatment resulted in a return of VIP content to control levels. The effect of VIP on oviductal smooth muscle contractility was investigated using an in vitro system. It was found that VIP caused a reduction of spontaneous contractile activity in doses as low as io‐10 M and this reduction in motor activity was strictly dose dependent with an ED50 value similar to that reported for the VIP activity on rabbit myometrial smooth musculature.