bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of nimodipine, Bay K 8644 and pinacidil on α1‐ and α2‐adrenoceptor‐mediated vasoconstriction in human hand veins
Authors: ARNER M. , HÖGESTÄTT E. D. , ANDERSSON K.‐E.
Published: December 2008

The effects of nimodipine, Bay K 8644 and pinacidil, three drugs interfering with transmembrane Ca2+fluxes in different ways, were investigated in isolated human hand veins. Their ability to influence the concentration‐response relationship for noradrenaline (NA) was assessed in the absence and presence of prazosin or rauwolscine. The contractile response to NA was almost abolished in Ca2+‐free medium. Nimodipine and pinacidil depressed the NA concentration‐response curve both in the absence and presence of α‐adrenoceptor blockers. The NA response was only partially inhibited by nimodipine, indicating that NA may activate nimodipine‐insensitive influx pathways, presumably receptor‐operated calcium channels. Pinacidil inhibited the contractile response to 124 mM K+and reduced the NA‐induced contraction in the presence of nimodipine, suggesting that pinacidil has actions other than the opening of potassium channels and subsequent membrane hyperpolarization. Bay K 8644 increased the NA potency fourfold in the presence of rauwolscine, whereas it had no effect on the NA response in the presence of prazosin and in the absence of α‐adrenoceptor blockade. Such an action of Bay K 8644 can be reconciled with α‐adrenoceptor activation causing membrane depolarization and opening of potential‐operated calcium channels. It may be concluded that both α1‐ and α2‐adrenoceptor‐mediated contractions in human hand veins are highly dependent on Ca2+influx, although the mechanisms utilized to bring about this influx partly differ between the two receptor subtypes.
Permeability of renal capillaries. III. Theoretical analysis of hydraulic conductivity, pore structure and electric properties
Authors: ÖJTEG G. , WOLGAST M.
Published: December 2008

The functional characteristics of the capillary membranes of rat kidneys were analysed in a computer‐based model utilizing previous data on the hydraulic conductivity of the membranes and transport by diffusion, hydraulic flow and ion migration of: inulin, myoglobin (negative, neutral and positive), horseradish peroxidase (negative and neutral), lactate dehydrogenase (negative, neutral and positive) and albumin. The results showed that in the peritubular capillaries the main fluid reabsorption (26.8 times 10‐8ml nephron‐1100 g body wt‐1) occurs through a set of 20 Å pores with a total pore area over pore length of 30 cm x (nephron 100 g body wt)‐1, whereas the plasma proteins enter the renal interstitium through a few 140 Å large pores with a total pore area over pore length of 7.2 times 10‐4cm and a fluid reabsorption of 1.2 times 10‐10ml nephron‐1100 g body wt‐1. The intramembranous concentration of negative fixed charges in the large pore system was estimated at 20 mM (range 15–22 mM). Since this was accompanied by a potential difference of 0.3 mV, a net driving electro‐osmotic force, favouring reabsorption, of 4 mmHg developed. The charges and the electro‐osmotic force was found to be essential for protein transport, since if the membrane was uncharged, the transport and interstitial concentration of e.g. albumin was twice as high. The glomerular capillaries seem to have a more homogeneous structure, that is in essence a one‐pore system; the pore radius was 44 Å, the total pore area over pore length 2.8 cm and the concentration of negative fixed charges 40 mM (range 37–43 mM).
Effects of ureteral occlusion and ethacrynic acid infusion on renal prostaglandin degradation in the dog
Authors: BUGGE J. F. , STOKKE E. S. , DAHL E. , KIIL F.
Published: December 2008

The two major renal prostaglandins PGE2and PGI2are partly metabolized during a single passage of the kidney. To examine whether stopping glomerular filtration affected the renal degradation, PGE2and PGI2were infused into the suprarenal aorta of dogs during ureteral occlusion. Prostaglandin synthesis was blocked by indomethacin, 10 mg kg‐1b.w. i.v. About 20% of PGI2and 80–90% of PGE2were metabolized during one passage through the kidney. Prostaglandin degradation and arterial input were proportional (r> 0.95). Compared to control conditions at free urine flow, PGI2degradation was not changed, whereas the degradation of PGE2was slightly increased by ureteral occlusion. Ethacrynic acid might reduce degradation of PGE2by inhibiting two degradation enzymes. To examine the influence of ethacrynic acid, PGE2was infused in different doses into the suprarenal aorta of dogs before and after administration of ethacrynic acid 3 mg kg‐1b.w. i.v. At all dose levels of PGE2, 75–80% was degraded by one passage through the kidney, whether ethacrynic acid was administered or not. However, although ethacrynic acid did not alter the total renal output, the urinary fraction was reduced from 20–30% to 10–15%. We conclude that degradation of both PGE2and PGI2is mainly confined to the blood vessels, and that ethacrynic acid in conventional doses does not prevent degradation of PGE2, but redistributes PGE2output from urine to renal venous blood.
Further characterization of the contraction‐mediating prostanoid receptors in feline cerebral arteries. Effects of the thromboxane‐receptor antagonist AH 23848
Authors: USKI T. K.
Published: December 2008

The effects of the thromboxane‐receptor antagonist AH 23848 were investigated on isolated feline basilar arteries (BA). AH 23848 (10‐6 mol l‐1) had no effect on contractions induced by 5‐hydroxytryptamine or potassium, whereas the drug (10‐8‐10‐6 mol 1‐1) induced a parallel shift to the right in contractions induced by the thromboxane A2 mimic U46619. There was no depression of the maximum contraction, indicating competitive antagonism. The Schild plot revealed a slope index of unity with a pA2 value of 8.46. In contrast, 10‐6 mol l‐1 AH 23848 depressed the maximum PGF2α‐induced contraction significantly from 100% to 13%. U46619 was able to induce a contraction amounting to 98 % if the drug was added on top of the PGF2α‐induced contraction in the presence of 10‐6 mol l‐1 AH 23848. The results provide strong support for previous suggestions that prostanoid‐induced contractions in the feline BA are mediated by two receptor subtypes, one of which can be classified as a thromboxane‐sensitive (TP) receptor.
Importance of carbonic anhydrase for canalicular and ductular choleresis in the pig
Authors: BUANES T. , GROTMOL T. , VEEL T. , LANDSVERK T. , RIDDERSTRÅLE Y. , RvEDER M. G.
Published: December 2008

To assess the importance of carbonic anhydrase (CA) for canalicular and ductular choleresis, the effect of acetazolamide on bile secretion was measured in three experimental groups of anaesthetized pigs. CA activity in liver homogenate was 46 (43–54) U g‐1wet weight, 150 mg kg‐1b.w. acetazolamide completely abolished the CA activity. Acetazolamide reduced bile HCO‐3secretion in six secretin infused, bile‐acid depleted pigs by 67 (58–71)% at arterial pH 7.41 (7.38‐7.46). By contrast, acetazolamide did not affect HCO‐3secretion in six Na‐taurocholate (TCA) infused pigs in the absence of secretin stimulation. Acetazolamide reduced ursodeoxycholic‐acid‐ (UDCA) dependent HCO‐3secretion by 24 (11–38)% in six other pigs in the absence of secretin stimulation. Histochemical examination using modifications of Hansson's method showed strong reaction in bile ductules and weaker reaction in peripheral zones of liver lobules. Because acetazolamide impairs HCO3 secretion from cells sustaining high rates of H+/HCO‐3transport, it is suggested that high rates of H+/HCO‐3transport are confined to bile ductules under conditions of secretin‐ and UDCA‐induced choleresis.
Influence of the renin—angiotensin system on the autoregulation of renal blood flow and glomerular filtration rate in conscious dogs
Authors: PERSSON P. , EHMKE H. , KIRCHHEIM H.
Published: December 2008

Renal autoregulation of blood flow (RBF) and glomerular filtration rate (GFR) were examined in 10 conscious foxhounds under a normal sodium diet before and after a continuous intrarenal converting—enzyme inhibition (CEI) or during the application of the angiotensin II antagonist saralasinm®. In order to prevent α‐adrenergic interference, phenoxybenzamine was infused into the renal artery. In contrast to studies performed in salt depleted dogs there was no impairmentof RBPorGFRautoregulation after CEI or saralasin®. Renal blood flow was autoregulated at a level of 3.81 ± 0.18 ml min‐1g‐1in the control group, 3.98 ± 0.16 ml min‐1g‐1after CEI and 3.97 ± 0.41 ml min‐1g‐1after saralasin®. The lowest point of autoregulation was very much the same between the individual groups (control: 65.0 ± 1.4 mmHg; CEI: 66.5 ± 4.6 mmHg; saralasin®: 67.4 ± 3.2 mm Hg).GFRacted in a similar manner (autoregulation level control: 0.50 ± 0.03 ml min‐1g‐l; CEI: 0.52 ± 0.05 ml min‐1g‐1; saralasin®. 0.50 ± 0.04 ml min‐1g‐1). The lowest pressure ofGFRautoregulation differed slightly more (control: 81.5 ± z. z mmHg; CEI: 93.2 ± 4.2 mmHg; saralasin®: 85.9 ® 2.1 mmHg). The results suggest that the renal autoregulationof GFRandRBFis independent of the renin‐angiotensin system in conscious dogs during a normal sodium diet.
Renal response to parathyroid hormone in the weanling rat
Authors: KARLÉN J.
Published: December 2008

The renal response to parathyroid hormone and the activity of alkaline phosphatase in kidney cortex were studied in weanling and adult rats. Clearance studies for the determination of glomerular filtration rate and phosphate excretion were started z h after sham operation or thyroparathyroidectomy in 24– or 40‐day‐old rats. Urine was collected under basal conditions and following infusions with 0.5 and 1.0μmol phosphate per 100 g body wt min‐l. For enzyme studies, rats aged 14–40 days were used, and the activity of alkaline phosphatase in renal cortical slices was determined. Glomerular filtration rate was not influenced by thyroparathyroidectomy or phosphate infusions. Plasma phosphate increased during phosphate infusions and was significantly higher in thyroparathyroidectomized rats in all clearance periods. Both the net and the fractional excretions of phosphate were higher in intact than in thyroparathyroidectomized rats and the phosphate‐retaining effect of thyroparathyroidectomy was similar in weanling and adult rats. Alkaline phosphatase activity in renal cortical slices increased between days 14 and 24 (1400–3190 IU mg‐1 protein, P < 0.01). During later development, no significant change was seen. It is concluded that the immature kidney of the weanling rats shows a parathyroid hormone‐dependent adaptation to acute phosphate loading, and that changes in alkaline phosphatase activity are consistent with a maturation of this system only during early development.
Renal sympathetic nerve activation in relation to reserpine‐induced depletion of neuropeptide Y in the kidney of the rat
Authors: PERNOW J. , THORÉN P. , MILLBERG B.‐I. , LUNDBERG J. M.
Published: December 2008

The effect of reserpine treatment on renal sympathetic nerve activity and tissue levels of neuropeptide Y (NPY)‐like immunoreactivity (LI) and noradrenaline (NA) were studied in rats. Injection of reserpine (I mg kg‐1i. v.) caused a clear‐cut (about 50%) increase in rectified activity of the post‐ganglionic sympathetic nerves to the kidney within 15 min in chloralose‐anaesthetized rats compared to a saline‐treated control group. This increase in nerve activity was still maintained 120 min after the reserpine injection. The renal nerve activation was accompanied by a progressive fall in mean arterial blood pressure and an initial tachycardia. In a separate group of conscious rats, the levels of NPY‐LI (1.3 ± 0.06 pmol g‐1) and NA (1.6 ± 0.07 nmol g‐1) in the kidney were significantly reduced (by 74 and 83 %, respectively) 24 h after reserpine treatment (I mg kg‐1i. v.). The reserpine‐induced depletion of NPY‐LI, but not that of NA, was inhibited by pretreatment with the ganglionic blocking agent chlorisondamine or the alpha2‐adrenoceptor agonist clonidine, both of which are known to decrease renal sympathetic nerve activity. The tissue content of NPY‐LI in the right atrium (16.3 ± 0.7 pmol g‐1) was not reduced by reserpine. Arterial plasma NPY‐LI in the rat was high (222 ± 5 pmol l‐1), and this value did not change after pretreatment with reserpine, chlorisondamine or clonidine, indicating that, in the rat, circulating NPY‐LI is not a good indicator of sympatho‐adrenal activity. In conclusion, reserpine treatment is associated with an increase in the renal sympathetic nerve activity, which might be a factor contributing to a depletion of NPY‐LI from sympathetic nerve endings, while the depletion of NA seems to be less dependent on the nerve activity. It is also likely that increased release of NPY‐LI per nerve impulse, due to lack of alpha‐adrenergic auto‐inhibition of release after depletion of NA, contributes to the renal depletion of NPY‐LI.
Co‐ordination of a simple voluntary multi‐joint movement with postural demands: Trunk extension in standing man
Authors: ODDSSON L.
Published: December 2008

The interaction between primary movements and associated postural adjustments was studied during trunk extension movements in standing man. Six healthy male subjects performed one series of six consecutive fast trunk extensions. Movements were recorded with an optoelectronic system (Selspot). Angular displacements, velocities and accelerations at the ankle, knee, hip and trunk were calculated. Trunk inclination was measured as the sum of pelvic tilt and spine flexion. The spatial and temporal coordination patterns chosen by the subjects to complete the task were compared. The self‐selected trunk movement amplitude ranged 14–30° for all subjects. The individual amplitude was maintained within 4–7° over the six consecutive trials. Peak velocity of the primary trunk movement was highly correlated with movement amplitude (r= 0.73, P < 0.01), whereas peak acceleration was not. Trunk extension, was the result of a simultaneous backward pelvic tilt and spine extension, together with hip extension and knee flexion. Knee flexion became increasingly important at larger movement amplitudes since hip extension as well as spine extension was limited. Associated postural adjustments occurred mainly as ankle flexion. In conclusion, individuals can accurately reproduce the multi‐joint co‐ordination pattern seen during a voluntary trunk extension movement. Movements at the ankle appear to be controlled to counteract the backward shift of the centre of gravity caused by the primary movement. Knee and ankle movements seem to be independently controlled in the preparatory phase, whereas they are closely linked later during the primary movement. It is suggested that the interaction between knee and ankle movements is necessary for optimal equilibrium control during trunk extension movements in standing.
Repeated measurements of cerebral blood flow in rats. Comparisons between the hydrogen clearance method and laser Doppler flowmetry
Authors: SKARPHEDINSSON J. O. , HÅRDING H. , THORÉN P.
Published: December 2008

Changes in cerebral blood flow (CBF), in chloralose‐anaesthetized spontaneously hypertensive rats, were measured simultaneously with the hydrogen clearance (HC) method and Laser Doppler flowmetry (LDFM) in order to examine the correlation between results obtained with the two techniques. To induce changes in CBF the rats were bled and CBF measured at different levels of mean arterial pressure. As would be expected, with the platinum electrode at the depth of about I mm in the somatosensory cortex, HC gave biexponential curves reflecting clearance in two distinct compartmenrs. During control situation the HC method gave the following values (mean ± SE, n= 20, mlmin‐' 100g‐1): fast (fCBF) 158.6 ± 11.5, slow (sCBF) 29.1 ± 1.6 with a weighted mean flow (mCBF) of 83.3 ± 7.4. These fCBF and sCBF values correspond well to those of others obtained with [14C]iodoantipyrine autoradiography in the cerebral cortex and corpus callosum, and better than the results of other studies using HC in rats. Our results, comparing data from HC and LDFM, show a linear relationship between relative values of blood flow changes, the coefficients being 0.658, 0.876 and 0.878 for the correlation between the LDFM data and relative changes in fCBF, sCBF and mCBF, respectively. All three regression lines were significantly different from the line of identity. Much of the discrepancy between the two methods may be related to limitations inherent in each of them, despite efforts to minimize their effects. Thus the depth sensitivity of LDFM in the brain may be greater than expected. In conclusion, the laser Doppler method seems, nevertheless, to be most useful for continuous estimations of changes in cerebral blood flow.
Metabolism of the black bear under simulated denning conditions
Authors: WATTS P. , CUYLER C.
Published: December 2008

Oxygen consumption of three black bears (Ursus americanus) under simulated denning conditions are reported. The results indicate that metabolic rate in large mammals can be significantly reduced during natural starvation. The paper summarizes data on the lowest and average metabolic rate of black bears during simulated denning.
The effect of β2‐adrenoceptor activation on ion‐shifts and fatigue in mouse soleus muscles stimulated in vitro
Authors: JUEL C.
Published: December 2008

The resting membrane potential (RMP), the intracellular free Na+ concentration ([Na+]1) and the intracellular free K+ concentration ([K+]1), were measured with double‐barrelled ion‐selective microelectrodes in mouse soleus muscles in vitro. In addition, the Na+ contents and K+ contents have been measured with the flame photometric technique. At rest the β2‐‐selective adrenoceptor agonist terbutaline (10‐5 m) increased the membrane potential and [K+]1, and decreased [Na+]1 when compared with control muscles. During a 5 min stimulation period the muscles, which were incubated with the β2‐adrenoceptor agonist, showed a smaller depolarization, a smaller decrease in [K+]1 and a smaller increase in [Na+]1 than stimulated control muscles. This difference was probably associated with an increased rate of Na‐K‐pumping in the β2‐adrenoceptor stimulated muscles. The P,‐agonist treated muscles were more resistant to fatigue than control muscles. This effect was significant with 10‐6 m terbutaline (25 °C). A depolarization obtained by increasing [K+]0 was shown to reduce the maximal tension. It is postulated, that the K+ shifts, which are responsible for the depolarization during muscle activity, are one of the mechanisms underlying muscle fatigue.
Fatigue during continuous 20 Hz stimulation of the rat phrenic nerve diaphragm preparation
Authors: RØED A.
Published: December 2008

The site and mechanism of action of fatigue was investigated in the isolated rat phrenic nerve diaphrigm preparation, with indirect and direct stimulation at 20 Hz and recording of tension and EMG. An equal decay of the subtetanic tension during indirect and direct stimulation, and a parallel decay of tension and EMG, suggested a mechanism of fatigue localized to structures that were ‘seen’ by the EMG electrodes. A comparison of the responses to sub‐ and supra‐maximum direct stimulation did not show increased fatigue at sub‐maximum stimulation. Therefore, the fatigue was probably not caused by an increased threshold of the excitability of the sarcolemma. However, prolongation of the stimulus pulse during direct stimulation from 0.5 ms to 5 ms in the Citigued preparation caused a two‐phasic recovery of tension. The initial phase, but not the slow phase, was inhibited by tetrodotoxin (TTX). Thus a recovery of sarcolemma action potentials could explain the initial phase. The slow phase was probably caused by a mechanism localized at more distal potential‐dependent sites, probably in the T tubules.
Haemodynamic regulation of renal prostaglandin and renin release
Authors: BUGGE J. F. , STOKKE E. S. , KIIL F.
Published: December 2008

To examine the relationship between renal release of the prostaglandins E2(PGE2) and I2(PGI2) and renin during autoregulatory vasodilation, experiments were performed in anaesthetized dogs with denervated kidneys. Autoregulatory vasodilation was induced by reducing renal arterial pressure (RAP) or by raising ureteral pressure in steps. During progressive renal arterial constriction, PGE2and PGI2release reached maximal values (10.6±1.7 for PGE2and 6.6±1.1 pmol min‐1for PGI2release) at RAP of 7–80 mmHg, associated with almost no increase in renin release. By further reduction of RAP, prostaglandin release was not significantly altered, whereas renin release reached maximal values (18.7 ± 2.4μg AI min‐1) when autoregulatory vasodilation was complete at RAP below 55–60 mmHg. During progressive elevation of ureteral pressure, the release of PGE2, PGI2and renin increased in concert in a curvilinear fashion, reaching maximal values at a ureteral pressure of 85 mmHg. There was no further increase during ureteral occlusion and the plateau values averaged 23.6 ± 3.7 pmol min‐1for PGE2, 8.0±1.6pmol min‐1for PGI2and 16.6 ± 3.4μg A1 min‐1for renin. We conclude that vascular dilation enhances both prostaglandin and renin release. During reduction of RAP, preglomerular arteries are dilated at higher RAP than are afferent arterioles. Release of prostaglandins synthetized in arteries consequently occurs at higher RAP than release of renin, which is not enhanced until afferent arterioles ultimately dilate at RAP approaching 60 mmHg. In contrast, elevation of ureteral pressure provides nearly uniform enhancement of prostaglandin and renin release, indicating a more uniform dilation of the whole preglomerular vascular tree.
Stimulation of D1dopamine receptors reveals direct effects of the preferential dopamine autoreceptor agonist B‐HT 920 on postsynaptic dopamine receptors
Authors: ANDÉN N.‐E. , GRABOWSKA‐ANDÉN M.
Published: December 2008

Possible postsynaptic effects of the preferential dopamine autoreceptor agonist B‐HT 920 were studied by means of the mouse motor activity. In reserpine‐treated mice, B‐HT 920 did not cause any motor activity by itself but it markedly potentiated the slight stimulating effect of the D1dopamine agonist SKF 38 393. The effect was blocked by either the D2‐receptor antagonist sulpiride or the D1‐receptor antagonist SCH 23 390, indicating that motor activity is dependent on simultaneous activation of both dopamine receptor types. The hyperactivity produced by 0.1 mg kg‐1B‐HT 920 in combination with SKF 38 393 in reserpine‐treated mice was at least as great as that following a maximal dose of apomorphine, indicating that B‐HT 920 is a full agonist at postsynaptic D, receptors. The effect of 0.1 mg kg‐1B‐HT 920 peaked earlier than those of I mg kg‐1and particularly, 10 mg kg‐1suggesting additional effects of the later two doses. B‐HT 920 stimulates dopamine autoreceptors almost maximally following 0.1 or I mg kg‐1but only the latter dose (with or without SKF 38393) caused hyperactivity of mice not treated with reserpine. This finding indicates that the postsynaptic D2receptors are less sensitive to B‐HT 920 than the D2dopamine autoreceptors.
In vivo measurement of intracellular pH in human brain during different tensions of carbon dioxide in arterial blood. A 31P‐NMR study
Authors: JENSEN K. E. , THOMSEN C. , HENRIKSEN O.
Published: December 2008

The effect of changes in carbon dioxide tension in arterial blood upon intracellular pH in brain tissue was studied in seven healthy volunteers, aged 22–45 years. The pH changes were monitored by use of 31P nuclear magnetic resonance spectroscopy, performed on a whole‐body 1.5 Tesla Siemens imaging system. The measurements were carried out during hyperventilation and with the subject breathing atmospheric air containing 5 vol. % and 7 vol. % carbon dioxide. Intracellular pH increased significantly during 15 min of hyper‐ventilation and decreased significantly during 18 min respiration of air containing 7 vol. %, carbon dioxide. The intracellular buffer capacity was estimated. These results suggest that the ventilation response to carbon dioxide is correlated to changes in intracellular fluid pH.
Elevated concentration of 5–hydroxytryptamine in ultrafiltrate of human liver vein plasma after infusion of amino acids
Authors: ZIMMERMAN L. , BERGSTRÖM J.
Published: December 2008

Intragastric infusion of amino acids causes the release from the liver of a factor with stimulatory effect on smooth muscle. The effect of liver vein plasma ultrafiltrate was tested on isolated preparations of rat fundus. The ultrafiltrates collected after amino acid infusion had a 3–5 times higher stimulatory effect on smooth muscle contraction than those collected from control plasma. The active principle was isolated, purified by different chromatographic procedures and identified as 5–hydroxytryptamine (serotonin). No other compound with contractile effect on smooth muscle was detected.
Apparent hyperalgesia in the mouse tail‐flick test due to increased tail skin temperature after lesioning of serotonergic pathways
Authors: EIDE P. K. , BERGE O.‐G. , TJøLSEN A. , HOLE K.
Published: December 2008

The relationship between tail skin temperature and responsiveness to noxious radiant heat in the tail‐flick test was investigated in mice. A significant negative correlation between tail skin temperature and tail‐flick latency was found when the tail skin temperature was increased by elevating the ambient temperature. After intra‐cerebroventricular injection of the serotonin neurotoxin5,7–dihydroxytryptamine (57–DHT, 80 μg) tail skin temperatures were increased and tail‐flick latencies reduced. In contrast, administration of the tryptophan hydroxylase inhibitor p‐chlorophenylalanine (PCPA, 400 mg kg‐1for 5 consecutive days) lead to a slight lowering of tail temperatures and a tendency towards elevation of tail‐flick latencies. The results show that factors which affect tail skin temperature also influence the tail‐flick test in mice. The divergent effects of5,7–DHT and PCPA on tail‐flick responsiveness may be due to the different effects of these compounds on the tail skin temperature. The results suggest that the reduced tail‐flick latency after partial destruction of serotonergic pathways by5,7–DHT is due primarily to the increased tail skin temperature. The dependence of tail‐flick latency on tail skin temperature limits the usefulness of the tail‐flick test unless changes in tail skin temperature are controlled for.
Regional differences in glucocorticoid receptor immunoreactivity among neuropeptide Y immunoreactive neurons of the rat brain
Authors: HÄRFSTRAND A. , CINTRA A. , FUXE K. , ARONSSON M. , WIKSTRÖM A.‐C. , OKRET S. , GUSTAFSSON J.‐Å. , AGNATI L. F.
Published: December 2008

By means of two‐colour immunocytochemistry using a mouse monoclonal antibody directed against the rat liver glucocorticoid receptor (GR) and a rabbit polyclonal neuropeptide Y (NPY) antiserum combined with the biotin‐avidin immunoperoxidase and a double immunofluorescence procedure, it has been possible to demonstrate nuclear GR immunoreactivity (IR) in neurons showing cytoplasmatic NPY IR in rat brain. The majority of NPY immunoreactive perikarya of the medial parvocellular part of the arcuate nucleus, locus coeruleus and the rostral and caudal part of the ventrolateral medulla oblongata contained strong nuclear GR IR. Many of the NPY immunoreactive neurons present in the subnuclei of the nucleus tractus solitarius also contained nuclear GR IR, while most of the NPY immunoreactive perikarya of the cerebral cortex and all of the neostriatum appeared to lack GR IR. These results indicate that NPY immunoreactive neurons in the upper and lower brain stem, but not in the cerebral cortex and in the neostriatum may be directly involved in mediating central effects of glucocorticoids.
Vagally mediated vasodilatation by motor and sensory nerves in the tracheal and bronchial circulation of the pig
Authors: MATRAN R. , ALVING K. , MARTLING C. R. , LACROIX J. S. , LUNDBERG J. M.
Published: December 2008

A newin vivomodel is described in which anaesthetized pigs were used to study vascular responses in the bronchial, upper tracheal and laryngeal circulation upon electrical stimulation of the vagal or superior laryngeal nerves. Vagal or superior laryngeal nerve stimulation increased blood flow in the bronchial artery and the superior laryngeal artery, respectively. After pre‐treatment with atropine the vasodilatory response in the bronchial artery upon stimulation was not modified while the increase in blood flow in the superior laryngeal artery was reduced. The ganglionic blocking agent chlorisondamine further reduced the nerve stimulation evoked decrease in vascular resistance in the superior laryngeal artery, but did not influence the response of the bronchial artery. Capsaicin induced a marked increase in blood flow both in the bronchial and superior laryngeal arteries after pre‐treatment with atropine, guanethidine and chlorisondamine. After capsaicin tachyphylaxis, the vasodilatation upon nerve stimulation in the bronchial artery and the smaller remaining decrease in vascular resistance in the superior laryngeal artery were strongly reduced. Thus, antidromic stimulation of afferent C fibres may increase blood flow via release of vasodilatory peptides such as tachykinins and calcitonin gene‐related peptide.

The present findings show that local blood flow in the larynx and upper trachea is regulated by cholinergic and non‐cholinergic parasympathetic mechanisms and a small capsaicin sensitive, sensory component. On the other hand, the vagal control of the bronchial circulation seems to exclusively involve capsaicin sensitive sensory nerves.
The influence of the pelvic nerves on. anorectal motility in the cat
Authors: CARLSTEDT A. , NORDGREN S. , FASTH S. , HULTEN L.
Published: December 2008

The influence of the parasympathetic pelvic nerves on anorectal motility was studied in anaesthetized cats. Anal pressure and rectal motility were recorded by a manometric and a volumetric method, respectively. Severing of the pelvic nerves did not cause any pressure change in the anus, indicating that these nerves are not significantly tonically active. Efferent low intensity (0.05–0.5 ms, 8 V at 5 Hz) electrical stimulation of the pelvic nerves (PNS) elicited a contraction of the internal anal sphincter (IAS), while high intensity stimulation (> 1 ms, 8 V at 5 Hz) caused a sphincter relaxation. A rectal contraction was noted on both low and high intensity stimulation. After sectioning of the sympathetic nerves, PNS elicited a contraction in both the anus and the rectum irrespective of stimulation intensity. PNS inhibited the anal contraction elicited by simultaneous stimulation of the sympathetic nerves or noradrenaline infusion. The inhibitory anal responses to PNS were unaffected or augmented by atropine, unaffected by propranolol and abolished by hexamethonium. The excitatory anal effects of PNS were reduced or abolished by atropine and abolished by phentolamine. The rectal contraction induced by low intensity PNS was abolished by atropine or converted to a relaxation. In half of the experiments an atropine resistant rectal contraction was observed in response to high intensity PNS.

The results are consistent with a pelvic nerve influence on IAS pressure through several mechanisms, including modulation of the activity in the sympathetic nerves and activation of inhibitory non‐adrenergic, non‐cholinergic neurons. The pelvic nerves convey both cholinergic and non‐cholinergic excitatory, as well as non‐adrenergic, noncholinergic inhibitory fibres to the rectum.
Effects of calcitonin, katacalcin, and calcitonin gene‐related peptide on basal and TSH‐stimulated thyroid hormone secretion in the mouse
Authors: AHRÉN B.
Published: December 2008

It is known that transcripts of the calcitonin gene in the thyroid C cells are processed to mRNAs generating precursors for the three peptides, calcitonin, katacalcin, and calcitonin gene‐related peptide (CGRP), and that these peptides are produced and secreted from the C cells. The present study investigated the effects of these three peptides on basal and TSH‐stimulated thyroid hormone secretion in the mouse, according to the McKenzie technique. Mice were pre‐treated with 125I and thyroxine. Calcitonin (3 nmol animal‐1) reduced the basal blood radioiodine levels to 72 ± 5% compared to 95 ± 6% in controls (P< 0.01). This effect is likely to be renal, since calcitonin significantly increased the renal excretion of a concomitantly injected 125I load. In contrast, katacalcin and CGRP were without effect on basal blood radioiodine levels. All three peptides (1 or 3 nmol animal‐1) were without effect on TSH (70 μU animal‐1)‐induced increase in blood radioiodine levels. However, when the peptides were given together (either two and two concomitantly, or all three together), the TSH‐induced increase in blood radioiodine levels was inhibited. This inhibition of TSH‐induced thyroid hormone secretion might represent an intrathyroidal regulatory mechanism of the follicular cell activity.
The role of tail skin temperature in the facilitation of the tail‐flick reflex after spinal transection or interference with descending serotonergic neurotransmission
Authors: EIDE P. K. , ROSLAND J. H.
Published: December 2008

We examined in mice whether tail skin temperatures and tail‐flick reflexes were changed after spinal transection or intrathecal (i.th.) injection of the serotonin (5‐HT) neurotoxin 5,6‐dihydroxytryptamine (5,6‐DHT) or the 5‐HT receptor antagonist metergoline. Transection of the spinal cord reduced tail‐flick latency (the time needed to evoke the tail‐flick reflex by radiant heat) and increased tail skin temperature 15–21 days after surgery. Analysis of covariance showed that the effect of tail skin temperature on tail‐flick latency was far more pronounced than the effect of spinal transection. Intrathecal injection of 5,6‐DHT (5 or 10μg mouse‐1), which extensively reduced the spinal levels of 5‐HT, reduced tail‐flick latency and increased tail skin temperature 1–5 days after treatment. Similarly, tail‐flick latency was shortened and tail skin temperature elevated 15 min after i.th. injection of metergoline (0.5μg mouse‐1). Analysis of covariance showed no significant effect of i.th. 5,6‐DHT or i.th. metergoline on tail‐flick latency. Tail skin temperature, on the other hand, had a highly significant effect on tail‐flick latency. The results show that the facilitation of the tail‐flick reflex in spinally transected mice and mice injected i.th. with 5,6‐DHT or metergoline is mainly caused by increased tail skin temperature. The data do not indicate that descending 5‐HT pathways tonically inhibit the tail‐flick reflex.
Neurotensin modulates the binding characteristics of dopamine D2receptors in rat striatal membranes also following treatment with toluene
Authors: VON EULER G. , FUXE K. , BENFENATI F. , HANSSON T. , AGNATI L. F. , GUSTAFSSON J.‐Å.
Published: December 2008

The effects of neurotensinin vitro(1–100 nm) on the binding characteristics of [3H]N‐propylnorapomorphine ([3H]NPA) were analysed in striatal membrane preparations of the adult male rat. Subsequently, it was investigated whether the modulatory effects of To nmt neurotensin on [3H]NPA binding were altered by treatment with toluenein vivo(80 p.p.m., 3 days, 6 h day‐1) andin vitro(19μmol ml‐1). Displacement of [3H]NPA binding by raclopride (IC50about 15 nm) and SCH 23390 (without effect) indicated that [3H]NPA labelled only D2dopamine receptors in the present study. Neurotensin was found to reduce the affinity of D2receptors with a maximum response at to ma. At this concentration the KD value was increased by 30–40% without any consistent changes in the number of binding sites. The modulatory effect of neurotensin remained intact also following toluene treatmentin vivoandin vitro, although at a higherKDrange, since toluene alone increased the KD value of [3H]NPA binding by 40–50%. Thus, the mechanisms mediating the effects of neurotensin and toluene on the D2receptor are likely to be different. When neurotensin and toluene treatments were combined, theKDvalues of [3H]NPA binding were about twice as high as in non‐treated controls. These additive effects may lead to a severely decreased efficiency of dopamine D2mediated neurotransmissionin vivo.
In‐vivoquantification of myocardial Na‐K pump rate during β‐adrenergic stimulation of intact pig hearts
Authors: ELLINGSEN Ø. , SEJERSTED O. M. , VENGEN O. A. , ILEBEKK A.
Published: December 2008

Maintenance of adequate electrical activity of the heart depends critically on the ability of the Na‐K pump to compensate for normal passive sodium and potassium fluxes. Using sudden injections of [3H]ouabain into the left coronary artery in anaesthetized open‐chest pigs, we monitored transient changes in myocardial potassium balance by PVC‐valinomycin mini‐electrodes. When related to the number of pumps blocked and fractional inhibition, these data provided estimates of total Na‐K pump capacity as well as actual pump rate and perturbations of the Na‐K balance. Experiments were performed in hearts with and without intracoronary isoprenaline infusion (2.5 nmol min‐1). After injection of 120 nmol [3H]ouabain into the left coronary artery, myocardial [3H]ouabain concentrations were 118 (74–178) and 103 (76–145) pmol g‐1and total concentrations of [3H]oubain binding sites were 893 (752–1076) and 785 (691–877) pmol g‐1(median, 95% confidence interval) in isoprenaline‐treated and control hearts respectively (differences not significant). The [3H]ouabain injection caused a net potassium release of 81 (56–132) and 43 (23–75) μcool 100 g‐1(median, 95% confidence interval) in isoprenaline‐treated and control hearts respectively (n= 6–8; significance of difference,P= 0.03). Na–K pump rate estimated from mono‐exponential release curves was 6363 (3942–10,858) K+ions min‐1site‐1during β‐adrenoceptor stimulation and 2514 (1380–4322) in control (significance of difference,P= 0.03). This corresponds to 40 and 16%, respectively, of the maximum possible pump rate determined from ATP hydrolysis. Comparison of accumulated potassium release and relative Na‐K pump rate indicates that catecholamines enhance the sensitivity of the Na‐K pump for intracellular sodium.
Much larger transcapillary hydrodynamic conductivity in skeletal muscle and skin of man than previously believed
Authors: LUNDVALL J. , LÄNNE T.
Published: December 2008

The capillary filtration coefficient (CFC) in the human forearm, determined with the ‘venous occlusion’ method, was found to be about 0.005 ml rnin‐1 100 mh‐1 soft tissue mmHg‐1 when capillary pressure (Pc) was raised by about 30 mmHg, a finding in accordance with previous literature. With gradually smaller increments of Pc, however, the calculated CFC became gradually larger to reach maximal values of about 0.05 ml min‐1 100 ml‐1 mmHg‐1 at increases in venous pressure that raised Pc by only 1.5–2 mmHg. It is suggested that these high CFC values, obtained at increases of intravascular pressure so low as to ensure minimal interference with the normal circulation, reflect the true prevailing transcapillary hydrodynamic conductivity in the tissue. The low CFC values during high increases in capillary (microvascular) pressure, on the other hand, seem to represent serious underestimations of the true CFC as a result of experimentally induced undesired active smooth muscle constrictor responses and/or passive deterioration of capillary exchange function. The conclusion is therefore reached that CFC in skeletal muscle and skin in man might be about 10 times higher than previously believed.
Effects of amrinone on twitch, tetanus and shortening kinetics in mammalian skeletal muscle
Authors: MÅNSSON A. , MÖRNER J. , EDMAN K. A. P.
Published: December 2008

The contractile effects of amrinone were studied on twitch and tetanus responses of mouse lumbrical muscles. Amrinone (1.1 mM) increased the maximum force level during the tetanus, reduced the rate of rise of force during the onset of tetanus and prolonged the time from the last stimulus to half‐relaxation. The rate of redevelopment of force after a release during the tetanus plateau was likewise reduced. Amrinone (I.I 0.5 mM) increased the time to peak twitch force and the time to half‐relaxation during the twitch. The peak twitch force was not significantly changed. The force‐velocity relation was markedly affected by amrinone: there was a decrease in maximum velocity of shortening, an increase in maximum isometric force and a decrease in curvature of the force–velocity relation. The results suggest that amrinone modulates the kinetic properties of the myosin cross‐bridges by exerting a specific effect upon the myofilament system. The latter effects are mainly responsible for the contractile changes produced by amrinone in mouse skeletal muscle. Amrinone appears to have little effect on the metabolism of activator calcium in this particular preparation.
Cerebrovascular serotonergic receptors mediating vasoconstriction: further evidence for the existence of 5‐HT2receptors in rat and 5‐HTVIike receptors in guinea‐pig basilar arteries
Authors: CHANG J.‐Y. , OWMAN CH.
Published: December 2008

Pharmacological experiments were carried out on isolated basilar arteries (BA) from the brain vasculature of guinea‐pig and rat in order to characterize post‐junctional serotonergic receptors mediating contraction by the use of selective agonists and antagonists. The sensitivity to 5‐HT was higher, but the intrinsic activity lower, in guinea‐pig compared to rat vessels. The contractile potency of the 5‐HT1agonist, 5‐carboxamidotryptamine (5‐CT), was three times higher than 5‐HT in guinea‐pig but 16 times lower in rat BA. In arteries from both species the 5‐HT1Aagonist, 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin (8‐OH‐DPAT), only caused weak contraction. In rat BA, where the serotonergic contractile receptors are ketanserin‐sensitive, mesulergine inhibited the contraction in doses high enough to block 5‐HT2receptors, and also propranolol slightly inhibited the contraction, probably due to its binding to these receptors. Methiothepin, a potent antagonist of the 5‐HT1‐like receptors, affected the contraction in a non‐competitive manner. The antagonist profile was different in guinea‐pig BA: propranolol was ineffective, mesulergine caused a slight, non‐surmountable inhibition, whereas methiothepin acted as a true, competitive antagonist. The data support previous suggestions that the serotonergic contraction in rat BA is mediated by 5‐HT2receptors, whereas the present data show that 5‐HT1‐like receptors predominate in guinea‐pig BA.
Role of the coronary endothelium in the regulation of sympathetic transmitter release in isolated rabbit hearts
Authors: WENNMALM Å. , KARWATOWSKA‐PROKOPCZUK E. , WENNMALM M.
Published: December 2008

The roles of endothelium‐derived relaxing factor (EDRF) and endothelin in the regulation of vascular tone are intensely studied at present. Since factors which directly affect vascular tone also frequently modulate sympathetic transmitter release, we found it of interest to study whether EDRF or endothelin displays such modulatory activity as well. Isolated rabbit hearts were perfused according to Langendorff, and the release of transmitter induced by sympathetic nerve stimulation was estimated by analysis of the effluent content of noradrenaline (NA) with liquid chromatography. The activity of EDRF spontaneously formed in the heart was counteracted by addition of haemoglobin (Hb, 2.4–15 g l‐1) or facilitated by addition of superoxide dismutase (SOD, 14–140 U ml‐1), to the perfusion solution. In other experiments authentic endothelin (0.1–10 nM) was given to the heart. Nerve stimulation (5 Hz for 30 s) elicited a release of NA into the cardiac effluent amounting to 319 ± 28 pmol (n= 53). Hb lowered the coronary flow to 68± 9% (P0.01) and impaired the outflow of NA to 62 ± 9% of control (P0.01). SOD facilitated coronary flow by 11 ± 4% (P0.005), and augmented the outflow of NA by 15±6% (P0.05). Endothelin dose‐dependently inhibited the coronary flow, with an IC50of about 1 nM, and in parallel decreased the efflux of NA. Mechanical obstruction of the coronary flow induced an attenuation of the efflux of NA that was quantitatively similar to the flow reduction. The data indicate that the efflux of NA from this rabbit heart preparation is closely dependent on the coronary flow rate. EDRF and endothelin seem to affect the efflux of NA by changing coronary flow, but not by direct interference with the process of sympathetic transmitter release.
Changes in transport functions of isolated rabbit choroid plexus under the influence of oestrogen and progesterone
Authors: LINDVALL‐AXELSSON M. , OWMAN CH.
Published: December 2008

Isolated choroid plexuses from rabbits were used to determine uptake and accumulation of 10‐5M radiolabelled choline (expressed as tissue/medium ratio) and the activities of various types of ATPases (based on ouabain inhibition and bicarbonate stimulation) following pre‐treatment of the animals with 0.5 mg kg‐117‐β‐oestradiol, alone or in combination with 2 mg kg‐1progesterone. The combined treatment reduced the choline uptake by 35% and also lowered the activity of Na+, K+‐ATPase by 31%, without influencing tissue wet weight. The reduction in HCO3‐ATPase was smaller and not statistically significant. There was a tendency also for oestrogen alone to lower these activities, but only by less than 20%. The Ca2+, Mg2+‐ATPase activity was not significantly affected by any of the hormones.
Acute and chronic effects of strenuous exercise on glucose metabolism in isolated, incubated soleus muscle of exercise‐trained rats
Authors: LEIGHTON B. , BLOMSTRAND E. , CHALLISS R. A. J. , LOZEMAN F. J. , PARRY‐BILLINGS M. , DIMITRIADIS G. D. , NEWSHOLME E. A.
Published: December 2008

Male and female Wistar rats were exercise‐trained for 6 or 11 weeks respectively, to examine the effects of acute exercise or exercise training per se on insulin‐stimulated glucose utilization in soleus muscles. isolated and incubated in vitro. The maximal activities of hexokinase and 2‐oxoglutarate dehydrogenase were significantly elevated (by > 50%) in gastrocnemius muscle of exercise‐trained male and female rats, indicating an adaptation to the training regime. No significant differences in any of the variables studied were observed between appropriately matched male and female rats. There were no significant differences in the sensitivity or responsiveness of the rates of lactate formation or glycogen synthesis in soleus muscles isolated from exercise‐trained and sedentary animals at rest (exercise‐trained animals were studied 40 h after the last exercise bout). On the other hand, acute exercise caused significant changes in soleus muscle glucose metabolism. Basal and insulin‐stimulated rates of glycogen synthesis were significantly elevated in soleus muscles incubated from both sedentary and exercise‐trained rats immediately after an exercise bout. In addition, the responsiveness of glucose utilization to insulin in soleus muscles from exercise‐trained rats was significantly increased after acute exercise. The results indicate that significant changes in the control of glucose metabolism by insulin in soleus muscle occur as a result of an acute exercise bout, while no adaptive changes in insulin sensitivity occur in soleus muscle after exercise training.