bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsaicin‐induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene‐related peptide rather than substance P or neurokinin A
Authors: FRANCO‐CERECEDA A. , RUDEHILL A.
Published: December 2008

In the present study the possible influence of capsaicin on human arterial coronary tone in vitro was studied in relation to the vasodilatory properties of calcitonin gene‐related peptide (CGRP), substance P (SP) or neurokinin A (NKA). In addition, the influence of vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) on the arteries was investigated.

CGRP application to potassium‐pre‐contracted human epicardial coronary arteries (0.4–0.6 mm in inner diameter) induced a concentration‐dependent, long‐lasting relaxation. SP also relaxed these pre‐contracted arteries, but the relaxation was transient and tachyphylaxis developed rapidly upon repeated administration. SP tachyphylaxis did not influence the relaxatory effects of CGRP. Furthermore, pre‐incubation with gossypol, an inhibitor of the formation and release of endothelium‐derived relaxing factors (EDRF), completely abolished the effects of SP without influencing the dilatory action of CGRP. NKA only induced a very minor relaxation of the pre‐contracted arteries. Both VIP and SOM concentration‐dependently relaxed the pre‐contracted arteries.

Capsaicin evoked a relaxation of the potassium‐pre‐contracted arteries. This effect was not influenced by SP tachyphylaxis or gossypol incubation. Thus, CGRP but not SP mimics the vasodilatory effects of capsaicin on human coronary arteries. This suggests that CGRP rather than SP is likely to mediate the relaxatory effects seen upon activation of cardiac sensory nerves.
Functional development of the visual system in normal and protein‐deprived rats. VII. Lamination of oxidative enzyme activity in the visual cortex during post‐natal development
Authors: CONRADI N. G. , SJÖUSTRÖUM A.
Published: December 2008

Lamination of activity of two mitochondrial enzymes ‐ succinate dehydrogenase (SDH) and menadione‐dependent a‐glycerophosphate dehydrogenase (M‐GPDH) ‐ was examined in the visual cortex of control (C) and protein‐deprived (PD) rats from 10 days old to adult. In C rats, lamination of enzyme activity was evident from 10 days by a band of higher activity in lamina IV. A band of higher SDH activity was seen in superficial lamina VI from 15 days. Lamination of M‐GPDH activity became less pronounced with increasing age, whereas distinct bands of high SDH activity in lamina IV and VI remained also in adult rats. PD rats showed a developmental delay of approximately 5 days with regard to the general increase in neuropile activity. A band of higher enzyme activity in lamina IV was present from 10 days, but it was markedly less distinct in the PD rats compared to the C rats between 15 and 25 days. A band of higher SDH activity in superficial lamina VI was not seen until 25 days in PD rats. No apparent differences were seen between adult C and PD rats. The observed developmental alterations are discussed in relation to other delays, distortions and deficits found in the visual system of PD rats.
Sympathetic and noradrenaline effects on C‐fibre transmission: single‐unit analysis
Authors: SHYU B. C. , OLAUSSON B. , ANDERSSON S. A.
Published: December 2008

Single afferent unmyelinated fibres were dissected from the otherwise intact sural nerve in anaesthetized rabbits. The sympathetic trunk could be stimulated via electrodes implanted through the abdomen. The response in single C fibres was elicited by electrical stimulation in the cutaneous innervation area of the fibre. Sympathetic stimulation (8 Hz, I ms pulses, 5 mA for 60 s) increased the latency in all tested C fibres (2.0%± 0.87%, mean ± SD, n= 17). In 48% of the units the amplitude of the action potential decreased (26.4% 12.3%) during sympathetic stimulation. Infusion of noradrenaline (5 μg min‐1) increased (7.7%±4.1%) the latency in all units and increased (36.9%± 29.8%) the amplitude of 25% of the units. The effects of sympathetic stimulation and noradrenaline infusion were blocked by pre‐treatment with phentolamine (3 mg kg‐1 i. v.). The results suggest that catecholamines change the membrane properties of unmyelinated fibres.
Effect of bumetanide on tubuloglomerular feedback in Necturus maculosus
Authors: PERSSON B.‐E. , SAKAI T. , EKBLOM† M. , MARSH D. J.
Published: December 2008

A non‐invasive technique was developed to measure single‐nephron glomerular blood flow (SNGBF) in Necturus maculosus. Erythrocytes labelled with rhodamine, a fluorescent dye, were injected systemically and the frequency at which labelled cells entered an arteriole was measured. Frequency was converted to flow by measuring the concentration of labelled erythrocytes in whole blood. Dependence of SNGBF on flow rate in early distal tubules was used to assess tubuloglomerular feedback (TGF). SNGBF decreased with increasing flow in the early distal tubule in a pattern typical of TGF; SNGBF decreased 25% at the highest flow rates. SNGBF increased when bumetanide was added to the perfusate, but the TGF response to flow rate persisted. IC50 (concentration that produces half‐maximal inhibition) was 2.4 × 10‐10, 9.8 × 10‐10 and 1.2 × 10‐9m bumetanide at distal perfusion rates of 5, 10 and 20 nl min‐1 respectively. These results are consistent with modulation of SNGBF according to the rate of luminal entry of NaCl into early distal tubule cells. This transport rate depends on the luminal concentration of NaCl, which is tubular flow rate‐dependent; NaCl and bumetanide compete.
Actions of the CI‐ channel blocker NPPB on absorptive and secretory transport processes of Na+ and CI‐ in rat descending colon
Authors: DIENER M. , RUMMEL W.
Published: December 2008

The effects of the Cl‐ channel blocker, NPPB (5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate), on the transport of Na+ and Cl‐ in the descending colon of the rat were studied in the Ussing chamber. In control tissue, NPPB administered at the mucosal side of the epithelium increased the short‐circuit current (Isc) and inhibited the unidirectional mucosa‐to‐serosa fluxes of Na+ and CI‐. In HCO‐3‐‐ or Cl‐‐free media or in the presence of SITS (4‐acetamido‐4′‐isothiocyanato‐stilbene‐2,2′‐disulphonic acid), this increase in Isc caused by mucosal NPPB was not observed. The serosal administration of NPPB was without effect.

Mhdcosal NPPB (10‐‐4 mol l‐1hd decreased the forskolin‐induced increase in Isc by only about 60%. However, the activation of the serosa‐to‐mucosa flux of Cl‐ caused by forskolin was inhibited completely. NPPB decreased the mucosa‐to‐serosa fluxes of Na+ and Cl‐ reduced additionally by forskolin. Serosal NPPB decreased Isc and JNasm, but had no effect on JNasm or JNasm. In HCO‐3‐free buffer the increase in Isc induced by forskolin was inhibited completely by NPPB.

The inhibition of Cl‐ secretion by NPPB fits well with the capacity of the drug to block Cl‐ channels. For the inhibition of neutral NaCl absorption two sites of action are discussed: an interaction with the Cl‐/HCO‐3 exchanger or an interference with the extrusion of Cl‐ through the basolateral membrane.,
Post‐occlusive reactive hyperaemia in the heart, skeletal muscle and skin of control and capsaicin‐pre‐treated pigs
Authors: FRANCO‐CERECED A. , LUNDBERG J. M.
Published: December 2008

In the present study we have tried to characterize and quantify the post‐occlusive hyperaemia in the pig heart, skeletal muscle and skin circulation. In addition, the possible involvement of caspaicin‐sensitive sensory nerves in the reactive hyperaemia was investigated. Reperfusion after total stop‐flow ischaemia for 1, 5 or 15 min elicited a marked hyperaemia in all vascular beds studied. The post‐occlusive hyperaemia after 5 min ischaemia was 512 ± 74 %, 328 ± 94 % and 444 ± 87 % in the heart, femoral artery and saphenous artery respectively. Also, in the skin the blood flow following 5 min ischaemia was increased fivefold. Furthermore, the duration of the hyperaemia after 5 min ischaemia was significantly (P < 0.01) longer in the heart (382 ± 32 s) than that in the femoral artery (192 ± 27 s), saphenous artery (182 ± 48 s) and skin (95 ± 14 s). Increasing the ischaemic time period prolonged the duration as well as elevated the peak increase of the hyperaemia. Capsaicin pre‐treatment significantly reduced (by about 70%) the tissue levels of calcitonin gene‐related peptide (CGRP)‐like immunoreactivity (‐LI), which is present in sensory nerves, but not neuropeptide Y‐LI, which is of sympathetic origin, in the left ventricle of the heart, quadriceps muscle and skin in the pig. However, there were no differences in the post‐occlusive hyperaemia in control and capsaicin‐pre‐treated pigs. Capsaicin administered intracutaneously caused a long‐lasting (about 20 min) increase in skin blood flow in the pig. This enhanced blood flow was completely abolished after systemic capsaicin pre‐treatment. It is concluded that ischaemia, especially in the heart but also in skeletal muscle and skin, is followed by a marked hyperaemia upon reperfusion of similar magnitude and duration in both control and capsaicin‐pre‐treated pigs. This argues against a primary involvement of peptides with vasodilatory activity released from sensory nerves in this reaction, although sensory nerve activation induced by capsaicin evoked an increase in local blood flow.,
Effect of papillary exposure on intrarenal distribution of glomerular filtration rate and of plasma flow
Authors: HANSELL P. , GÖRANSSON A. , SJÖQUIST M. , ULFENDAHL H. R.
Published: December 2008

Removal of the renal pelvis in order to expose the renal papilla has been shown to cause impairment of the renal concentrating ability by an unknown mechanism. To study this phenomenon, urine osmolality (Uosm), single‐nephron glomerular filtration rate (SNGFR) in outer and inner cortical nephrons and the inner and outer medullary plasma flow were determined. Measurements were performed on groups of rats before (control) and 15, 45 and 90 min after exposure of the left renal papilla. Rats with an intact ureter were studied in parallel to see whether the variables varied within the 90‐min period of the study. In all groups of animals with an exposed papilla, Uosm was lower than in non‐exposed animals. Outer cortical SNGFR in rats with exposed papillae, regardless of time, was not different from that in control rats. Inner cortical SNGFR after 45 and 90 min of exposure did not differ from that in controls, but after 15 min of exposure it was lower than in control animals. Outer and inner medullary plasma flow did not differ between rats with exposed papillae and controls, irrespective of exposure time.

In conclusion, papillary exposure results in a permanent decrease in urine osmolality. This impairment of the concentrating ability cannot be attributed to prolonged changes in renal haemodynamics.
Cytochrome c oxidase and cardiolipin alterations in response to skeletal muscle ischaemia and reperfusion
Authors: SOUSSI B. , IDSTRÖM J.‐P. , SCHERSTÉN T. , BYLUND‐FELLENIUS A.‐C
Published: December 2008

The effect of 2 and 4 h of tourniquet ischaemia followed by 1 h of reperfusion on the major mitochondrial phospholipids and on the cytochrome c oxidase kinetic parameters has been investigated in rat skeletal muscle. There was no change either in the mitochondrial phospholipid content or in the Vmax and the Km of the enzyme after 2 h of ischaemia with and without subsequent reperfusion. Four hours of ischaemia had no effect on the lecithin and the cephalin content, while the cardiolipin content decreased as well as the Vmax of the enzyme (P < 0.05). Tissue reperfusion caused a dramatic decrease in both cardiolipin (55% of the control, P < 0.001) and Vmax (38% of the control, P < 0.001). The corresponding reduction in lecithin and cephalin contents was 12% and 14% respectively (P < 0.05). The Km remained unchanged at all conditions. These findings suggest that mitochondrial dysfunction in response to ischaemia and reperfusion could be a consequence of the reperfusion itself following severe ischaemia. The results are discussed in terms of cardiolipin peroxidation and cytochrome oxidase as a functional parameter.
Effects of acute administration of omeprazole or ranitidine on basal and vagally stimulated gastric acid secretion and alkalinization of the duodenum in anaesthetized cats
Authors: FÄNDRIKS L. , JÖNSON C.
Published: December 2008

Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. In order to avoid sympathoadrenergic influences, the adrenal glands were ligated and the splanchnic nerves were cut bilaterally in all animals. The gastric lumen was perfused with saline and the H+ secretion was calculated from pH measurements in the perfusate. HCO3‐ secretion by the duodenal mucosa was titrated in situ. Omeprazole (4 mg kg‐1 i. v., dissolved in PEG400, 40% w/v) did not influence basal or vagally induced HCO3‐secretions, but inhibited by about 80% the H+ secretory response induced by electric vagal stimulation. Acute administration of ranitidine (5 mg kg‐1 i. v.) transiently lowered arterial pressure, an effect which was followed by a sustained compensatory tachycardia. Ranitidine raised basal duodenal HCO3‐ secretion by 50% and inhibited vagally induced gastric H+ secretion by about 70%, whereas vagally induced HCO3‐ secretion was not influenced. The results suggest that vagal nerve stimulation raises the duodenal bicarbonate secretion via a mechanism independent of the level of gastric H+ secretion.
Cholinergic‐induced oscillating transepithelial short‐circuit current in cultured human sweat duct cells
Authors: PEDERSEN P. S.
Published: December 2008

Human sweat duct cells in primary culture were investigated by voltage‐clamp technique. Stimulation with the muscarinic agonist, metacholine (MCh), produced an abrupt transient rise followed by sustained regular oscillations in the transepithelial short‐circuit current (Iscc), which in these cells is carried by a mucosal amiloride‐sensitive Na+ influx, secondary to a Ca2+‐activated, voltage‐dependent, large K+ shunt across the serosal membrane.

The time of latency, the initial transient phase, and the sustained oscillating phase of the MCh‐induced Iscc response were demonstrated to be differently affected by changes in temperature, agonist concentration and external Ca2+ supply. From these results a model is proposed for the MCh‐induced signal transduction in cultured sweat duct cells, involving a primary intracellular oscillatory Ca2+ mobilization, activated by IPP, sustained by a temperature‐regulated external Ca2+ supply, and counter‐regulated by cytosolic Ca2+.
Extracellular levels of quinolinic acid are moderately increased in rat neostriatum following severe insulin‐induced hypoglycaemia
Authors: WESTERBERG E. , MAGNUSSON K. , WIELOCH T. , UNGERSTEDT U. , SPECIALE C. , SCHWARCZ R.
Published: December 2008

Extracellular concentrations of the brain metabolite quinolinic acid, an endogenous excitotoxin, were monitored by microdialysis in rat neostriatum and hippocampus/cortex during and following a 30‐min period of insulin‐induced hypoglycaemia. During hypoglycaemia‐induced isoelectricity, extracellular levels of quinolinic acid in the striatum (basal value, 1.1±0.3pmol per 30‐μl fraction) were elevated 1.7 times as compared to the control period. Thirty to ninety minutes following hypoglycaemia a significant increase in extracellular quinolinic acid to 2.2 times basal level was noted. After 2 h recovery, the beginning of neuronal necrosis was observed in the dorsolateral striatum. Implantation of the dialysis probe did not influence the extent of neuronal damage. No changes in extracellular quinolinic acid levels were observed in the hippocampus/cortex.

The data indicate that following a severe hypoglycaemic insult vulnerable striatal cells are exposed to hyperphysiological extracellular quinolinic acid concentrations over an extended period of time. Considering the pronounced susceptibility of rat striatal neurons to the toxin, the small but prolonged elevation in the extracellular levels of quinolinic acid could be of significance for the development of delayed neuronal death in hypoglycaemia.
The effect of loop diuretics on the long‐term outcome of post‐ischaemic acute renal failure in the rat
Authors: BAYATI A. , NYGREN K. , KÄLLSKOG Ö. , WOLGAST M.
Published: December 2008

The effects of continuous treatment with loop‐acting diuretics on the long‐term functional and histopathological outcome in kidneys subjected to 45 min of warm ischaemia were studied. One month after the primary damage the inulin clearance in the untreated kidneys was 0.44 ± 0.05 ml min‐1, improving significantly to 0.69 ± 0.11 ml min‐1 in furosemide‐treated animals and to 0.75 ± 0.09 ml min‐1 in those treated with piretanide. Urine osmolality increased from 986 ± 89 mosmol kg‐1 in the untreated animals to 1479±195 mosmol kg‐1 in the furosemide‐treated ones. At the same time the total area of the outer medulla occupied by Tamm‐Horsfall protein cylinders decreased from 7.0 ± 1.2% in the untreated animals to 3.6 ± 0.52% in the treated ones. It is concluded that by decreasing the number of nephrons blocked by Tamm‐Horsfall cylinders an improvement in the function of ischaemically damaged kidneys can be achieved. This blockade, also called secondary damage, is of critical prognostic importance for the long‐term outcome of the ischaemic renal failure. Treatment of the animals with loop diuretics decreased the occurrence of these cylinders, leading to an improvement of kidney function 1 month after the primary damage, this despite the fact that the primary damage seen in the early recirculation period was not treated specifically.
Adrenal cortex contributes to the regulation of NaCl‐stimulated ANP release in the rat
Authors: ARJAMAA O. , VUOLTEENAHO O. , TASKINEN T. , TUOMINEN M. , LEPPÄLUOTO J.
Published: December 2008

The present study documents the effects of hypophysectomy and the effects of dexamethasone substitution on the NaCl‐stimulated release and on the basal secretion rates of ANP from the rat atria in vitro. We also measured the concentration of mRNA in the atria after hypophysectomy. Rats (n = 12) were subjected to hypophysectomy by a parapharyngeal approach. One group of rats (n = 6) received dexamethasone 0.2 mg s. c. daily for 4 weeks, while the other group was left unsubstituted. After 4 weeks, the atrial block (n = 10) was excised, placed in an organ bath (field stimulation 4 s‐1, 20 V, I ms; resting tension = 5 mN) and superfused (7 ml min‐1) either with a physiological buffer solution (295 mosmol kg‐1) or with a hyperosmotic NaCl solution (330 mosmol kg‐1). The atria from the hypophysectomized rats did not respond to the stimulus: the concentration of ANP in the I‐min samples of the perfusate was under 100 pg ml‐1. Dexamethasone treatment significantly (P < 0.05) increased the ANP concentration to a maximum of 165 ± 17 (mean ± SEM) pg ml‐1 during the superfusion while the control concentration was 110±19 pg ml‐1. The ANP mRNA/18 S RNA ratios did not differ between the atria of hypophysectomized and control rats.

In conclusion, glucocorticoids are required in the stimulus‐induced release of ANP and the impaired release of ANP after hypophysectomy does not depend on an impaired synthesis of ANP.
Protective effects of pretreatment with superoxide dismutase, catalase and oxypurinol on tubular damage caused by transient ischaemia
Authors: BRATELL S. , HARALDSSON G. , HERLITZ H. , JONSSON O. , PETTERSSON S. , SCHERSTEN T. , WALDENSTRÖM J.
Published: December 2008

The effect of 60 min of ischaemia on glomerular and tubular functions (osmolar clearance, fractional Na+ excretion, K+ clearance, concentrating ability) after different periods of time was studied in New Zealand White rabbits. Pronounced changes in both glomerular and tubular functions were observed immediately on reperfusion and after 48 h. One week after ischaemia the functions appeared to be normalized. Mannitol is routinely used in clinical kidney transplantation due to its hyperosmolar effects and its ability to scavenge the hydroxyl radical. In the present study the possible additive protective effect against ischaemia‐reperfusion damage of a combined pretreatment with mannitol and oxygen free radical scavengers or mannitol and a xanthine oxidase inhibitor was examined. Oxypurinol was chosen as the xanthine oxidase inhibitor due to its direct inhibitory effect. Concerning glomerular function, no protective effect of the combined pretreatment compared with mannitol alone was observed. However, concerning the tubular function tests combined pretreatment with either mannitol‐superoxide dismutase‐catalase or mannitol‐oxypurinol turned out to be superior compared with that of mannitol alone.
Multiunit neural responses to strong finger pulp vibration. I. Relationship to age
Authors: SCHMIDT R. F. , WAHREN L. K. , HAGBARTH K.‐E.
Published: December 2008

The effect of age on mechanoreceptive function in the distal part of the fingers was studied in 12 healthy subjects aged 18–64 years.

A recording microelectrode was inserted into a sensory fascicle of the median nerve at the wrist. Multiunit mechanoreceptor activity was recorded from the fascicular field, which is typically restricted to the ulnar or radial half of one finger, corresponding to the innervation zone of one digital nerve. Strong standardized vibration (40 Hz) was applied to the finger pulp, with the amplitude of the vibration pulses high enough to induce maximal neural impulse volleys. With the same microelectrode recording position, maximal neural impulse volleys were also induced by electrical pulses applied to the ventral digital nerve supplying the finger pulp. In each subject, the areas of the mechanically and the electrically induced responses were measured (after integration and averaging) and the ratio of mechanically to electrically induced responses (MR/ER) was determined.

The MR/ER ratio decreased with increasing age of the subject. This finding was considered to indicate that it is the peripheral parts of the sensory units, involved in the mechanoelectrical transfer functions, that exhibit the most pronounced degenerative changes during the ageing process. This is in line with previous histological findings of pronounced age‐related degeneration of Meissner corpuscles and other mechanoreceptive end organs in the finger pulps.
Lack of fusimotor modulation in a motor adaptation task in man
Authors: AL‐FALAHE N. A. , NAGAOKA M. , VALLBO Å. B.
Published: December 2008

Single‐unit activity was recorded from the radial nerve of human subjects along with surface electromyogram, joint angle, velocity, and torque at a metacarpophalangeal joint. Nine afferents from muscle spindles in the extensor digitorum muscles were studied in a motor adaptation task which involved modulations of the long‐latency stretch reflex. While subjects slowly moved one finger, a perturbation which rapidly stretched the parent muscle was applied. The subjects' task was to return their finger as fast as possible. In a series of identical control experiments, electromyographic activity and performance alone were recorded, but not spindle afferents.

Subjects improved their performance by a varying degree when the test was repeated. Optimal performance was usually associated with increased electromyographic activity at a latency of about 60 ms, which was interpreted as a long‐latency stretch reflex.

The response of the individual spindle afferents to perturbation was uniform in repeated tests regardless of the size of the reflex, e.g. whether it was large or lacking altogether.

It was concluded that modulations of the size of the long‐latency stretch reflex in the present motor adaptation task were accounted for by mechanisms other than adjustments of the fusimotor activity, because spindle response to an invariant perturbation remained invariant when the size of the reflex varied substantially.
Changes in size and shape during histochemical preparation for light and electron microscopy of neurons intracellularly labelled with horseradish peroxidase
Authors: ÖRNUNG G. , ULFHAKE B.
Published: December 2008

In this study we show that neurons labelled intracellularly with horseradish peroxidase react differently from surrounding unlabelled neurons in vibratome sections during histological preparations for light and electron microscopy. The diameters and cross‐sectional area of the cell bodies of intracellularly horseradish peroxidase‐labelled neurons increased by about 6 and 11 % respectively, while the surrounding unlabelled neurons decreased by the same amount. Also, the caliber of the proximal dendrites of horseradish peroxidase‐labelled neurons increased during the histological preparation while dendritic path lengths remained unchanged. Since the surrounding tissue shrunk, the dendritic path shapes became more tortuous during histological processing. The demonstrated reaction of horseradish peroxidase‐labelled neurons is suggested to be caused by the horseradish peroxidase reaction product.
Decreased nerve conduction velocity in optic nerve following early post‐natal low‐dose lead exposure
Authors: CONRADI N. G. , SJÖSTRÖM A. , GUSTAFSSON B. , WIGSTRÖM H.
Published: December 2008

A study was made on nerve conduction velocity of the optic nerve in rats subjected to lead exposure during the first 2 weeks of post‐natal life. The rats were given intraperitoneal injections with a calculated daily exposure of 7.6 μg (low‐dose) or 15.8 μg (high‐dose) lead g‐1 body weight. Growth retardation at 30 days was seen only with the higher dose. Littermates of low‐dose exposed rat were injected with vehicle only and served as controls. Lead concentrations in blood and brain were measured in rats of 20 days of age in order to ascertain that exposure was adequate in the present litters. Nerve conduction velocity of the optic nerve was examined in 14 rats of 30 days of age taken from 10 different litters. The optic nerve(s) was prepared in anaesthetized rats and placed in a flow‐through incubation chamber. One stimulating and two recording tungsten electrodes were used. In all rats, three positivenegative waves, regarded as representing three functional groups of optic nerve axons, could be recorded. The last one often had a long duration and a small amplitude without distinct peaks and hence was omitted from further analysis. The mean conduction velocities for the two faster axonal groups were 16.8 and 5.4 m s‐1 in control rats, 10.3 and 5.8 m s‐1 in low‐dose rats and 9.4 and 5.2 m s‐l in high‐dose rats. The difference in conduction velocity for the fastest axons was significant for controls versus low‐dose and high‐dose but not for low‐dose versus high‐dose. The results indicate lead‐induced changes in central myelinated axons resulting from either alterations during development or direct actions of lead on the nodal membrane.
Effects of depolarization and QX‐314 injection on slow prepotentials in rat hipocampal pyramidal neurones in vitro
Authors: HU G.‐Y.
Published: December 2008

A slow prepotential preceding the action potential elicited by 40–80 ms depolarizing current pulses injected in CA1 pyramidal cells in rat hippocampal slices was isolated and characterized using a subtraction procedure. The exponentially rising slow prepotential showed enhanced amplitude at depolarized membrane potential levels. In sufficient doses, intracellular injection of the lidocaine derivative QX‐314 selectively blocked the slow prepotential, leaving the action potential largely unchanged. These results suggest that the slow prepotential might be mediated by a persistent sodium conductance or threshold channels recently found in various nerve cells, and could trigger action potentials in situations with a long‐lasting depolarization.
Ion (H+, Ca2+, Co2+) and temperature effects on a hyperpolarization‐activated membrane current in the lobster stretch rceptor neurone
Authors: EDMAN Å. , GRAMPP W.
Published: December 2008

Teh effct of some ions (H+, Ca2+, Co2+) and temperature on the Q‐channel (a channel which conducts a hyperpolarization‐activated membrane current, IQ) was investigated in the slowly adapting lobster stretch receptor neurone. It was found: (1) that increases in pH cause an increase in the maximum channel conductance; (2) that Co2+ (1mM) and increase in extracellular Ca2+ produce a positive shift of the relationship between the membrane voltage and the steady‐state channel activation along the voltage scale; (3) that Co2+ and decreases in extracellular pH cause a decrease in rate of the voltage‐depedent step of the channel's gating reaction; (4) that none of the ions has an effect on the rate of the voltage‐independent step of the gating reaction; and (5) that Co2+ and K+ do not interfere with each other's actions on the channel's gating reaction and maximum ion conductivity. Increase in temperature from 13 to 23 d̀C were found: (1) to cause an increase in the maximum Q‐channel conductance by a factor of 1.7; (2) to have no effect on the voltage dependence of the channel's gating reactionl; but (3) to lead to an increase in rate of the gating reaction by a factor of about five for the voltae‐dependent, and by a factor of about thrree for the voltage‐independent gating step. The temperature sensitivity of the IQ mechanism proved to be mathematically reproducible by a previously developed, and slightly modified Q‐channel model (Edman et al. 1987, Edman & Grampp 1989), and to be of no significant in the control of membrane exicitability in a thermally unstabel environment.
Effects of endothelin on renal haemodynamics and segmental sodium handling in conscious rats
Authors: CLARIA J. , JIMENEZ W. , LA VILLA G. , ASBERT M. , CASTRO A. , LLIBRE J. , ARROYO V. , RIVERA F.
Published: December 2008

The effects of endothelin (100 and 600 pmol/kg) on renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (UNa V) and segmental sodium handling were investigated in conscious rats. Low‐dose endothelin decreased renal plasma flow by 26% without affecting glomerular filtration rate and sodium excretion. High‐dose endothelin reduced renal plasma flow, glomerular filtration rate, sodium excretion and lithium clearance by 57, 45, 38 and 52%, respectively. The fall in sodium excretion was not due to a direct effect of endothelin on tubular sodium transport since sodium excretion corrected by glomerular filtration rate and fractional proximal and distal sodium reabsorption did not change throughout the study. These results indicate that the impairment in renal perfusion is responsible for the antinatriuretic effect of endothelin in conscious rats.
Effect of longstanding venous stasis and hypoproteinaemia on lymph flow in the rat tail
Authors: AARLI V. , REED R. K. , AUKLAND K.
Published: December 2008

This study was performed to provide information on the determinants of lymph flow by comparing the effect of venous stasis and hypoproteinaemia in the rat tail. This low‐compliant tissue was chosen in an attempt to induce preferential changes in interstitial pressure or volume. The removal rate (kAIb) of 1251‐labelled human serum albumin (I‐HSA) injected subcutaneously was monitored with external gamma‐counting equipment and used as a measure of lymph flow. Interstitial fluid hydrostatic pressure (Pi) was measured with wick‐in‐needle technique, and interstitial fluid was collected post mortem by dry wicks. Colloid osmotic pressure of plasma (COPp) and wick fluid (COPi) was measured with a colloid osmometer. In a separate group of experiments, 51Cr‐EDTA and [125I]HSA were used to measure the interstitial fluid volume. Venous stasis, induced by bilateral ligation of the external tail veins, increased interstitial fluid hydrostatic pressure from 1.7 to 16 mmHg and A/b from 0.030 to 0.063 h‐1, whereas tail circumference was nearly constant. Interstitial volume averaged 1.17 ml/g dry weight in control animals and 1.27 ml/g during increased venous pressure. Daily injections of aminonucleoside in salt‐loaded rats (0.3yo NaCl as drinking water) reduced colloid osmotic pressure of plasma from 19.1 to 8.5 mmHg and of wick fluid from 11.2 to 2.9 mmHg, while interstitial fluid hydrostatic pressure increased to 5.2 mmHg. The removal rate of 125 I‐labelled human serum albumin increased to 0.113 h‐1, compared to 0.051 h‐1 in salt‐loaded controls. The interstitial volume showed a marked increase in salt‐loaded hypoproteinaemic rats, 1.75 ml/g dry weight, compared to 1.30 ml/g in salt‐loaded controls. The results indicate that absolute interstitial fluid pressure is not the main determinant of lymph flow and rather support the hypothesis that an increase of interstitial volume promotes lymph formation by pulling open the initial lymphatics through their anchoring filaments.
Pulmonary flow‐resistive work during hydrostatic loading
Authors: TAYLOR N. A. S. , MORRISON J. B.
Published: December 2008

This paper focuses upon flow‐resistive pulmonary work during upright immersion, and during changes in the air delivery pressure. Nine male non‐smokers (aged 26.2 ± 3.5 years), with normal lung function history, performed spontaneous respiration while seated in air (control) and during total immersion. During the immersed state subjects were supplied with air at four hydrostatic pressures: mouth pressure (PM; simulating a mouth‐held demand regulator), lung centroid pressure (PLc; + 1.33 kPa relative to the sternal notch), and 0.98 kPa (10 cmH2O) above and below the lung centroid pressure. Inspiratory, expiratory and total flow‐resistive pulmonary work were computed from the integration of transpulmonary pressure (difference between oesophageal and mouth pressure) with respect to lung volume change. When breathing air delivered at mouth pressure, immersion significantly elevated all total flow‐resistive pulmonary work components (P < 0.05). Each increment in breathing pressure resulted in a progressive reduction in expiratory and total flow‐resistive pulmonary work, so that when air was provided at lung centroid pressure and lung centroid pressure + 0.98 kPa both components were similar to control values (P > 0.05). Inspiratory was always less than expiratory pulmonary work. During immersion inspiratory pulmonary work was significantly reduced when air supply pressure was increased above mouth pressure (P < 0.05). Subsequent pressure increments failed to produce further changes in inspiratory pulmonary work. The difference in response between the inspiratory and expiratory components of total flow resistive pulmonary work was attributed primarily to the volume‐dependence of the expiratory component.
Antisecretory effect of splanchnic nerve stimulation on choleratoxin‐induced secretion in the cat, an effect mediated at the crypts
Authors: SJÖQVIST A. , III R. BEEUWKES
Published: December 2008

The experiments were performed on cats anaesthetized with α‐chloralose. Segments of the small intestine were perfused with sodium‐free hypotonic choline‐mannitol solution and intestinal net fluid transport was recorded with a volumetric technique. The content of sodium and chloride in the lamina propria of the small intestinal villus was measured with an electron microprobe in freeze‐dried paraffin embedded tissue. In absorbing control intestine, there was an even distribution of electrolytes along the villi. Sympathetic nerve stimulation (5 Hz, 5 ms, 5 V) did not significantly affect electrolyte distribution and net fluid transport. Intestinal secretion was elicited by pretreatment of the intestine with cholera toxin. The concentration of sodium and chloride was elevated in the apical third of the villi in intestines during the secretion since secreted sodium from the crypts was reabsorbed into the villi. Sympathetic nerve stimulation decreased the cholera secretion significantly in intestines pretreated with cholera‐toxin. Furthermore, the apical gradients of sodium and chloride in the villi, caused by the reabsorbed sodium and chloride, disappeared during sympathetic nerve stimulation. It is concluded that, in the used experimental model, the antisecretory effect of sympathetic nerve stimulation was caused by inhibition of crypt secretion and not by augmented villus absorption.
Effects of angiotensin ll on blood flow in rat submandibular gland
Authors: FAZEKAS A. , OLGART L. , GAZELIUS B. , KEREZOUDIS N. , EDWALL L.
Published: December 2008

The effect of angiotensin II (Ang II) was studied on blood flow in the submandibular gland and tongue in male rats. Blood flow changes were determined with laser Doppler flowmetry and Ang II was infused into the common carotid artery before and after i.v. doses (18 nmol kg‐l) of the angiotensin II antagonist saralasin. Angiotensin II (10–60 pmol min‐l) dose‐dependently increased blood pressure and tongue blood flow, whereas glandular blood flow decreased at all of the doses used. After saralasin administration the angiotensin II effects on blood pressure, tongue and glandular blood flow were significantly diminished (glandular blood flow reduction was diminished from 29%‐3%, P < 0.005, n = 9). However, the responsiveness of these 3 parameters to local infusions with noradrenaline (0.75–3.0 pmol min‐1) was unaffected by saralasin. The dose of saralasin used in the present study did not affect any of the parameters on it's own. Our results show that vascular receptors sensitive to angiotensin II operate in the submandibular gland but not in the tongue.
Stimulus–response properties of the slowly adapting stretch receptor neuron of the crayfish
Authors: RYDQVIST B. , SWERUP C.
Published: December 2008

The receptor potential and receptor current in response to ramp‐and‐hold extensions were measured in the slowly adapting stretch receptor of the crayfish, using potential clamp technique. The stimulus‐response relationship for the peak amplitude of the receptor current showed a linear behaviour for extensions less than 2% and a nonlinear behaviour for extensions larger than 5%. Using the Stevens power law, R=k(S—So)“, where R is response, S is stimulus, So is threshold stimulus and n the power coefficient, n was found to be 3 for extensions between 5 and 15%. The receptor current saturated at extensions above 20–25% of the zero length of the muscle, resulting in a lower n value. However, the n value is difficult to define in this region due to the saturation.

The stimulus‐response relation for the receptor current can be explained by the properties of the stretch‐activated channels for which the open probability is exponentially dependent on the square of the membrane tension, as suggested by recent findings.

The receptor potential, using tetrodotoxin, in response to identical ramp‐and‐hold extensions as those used to record current responses showed a more complex time‐course, indicating involvement of potential‐dependent channels, potassium channels being the most probable candidate. This was supported by a mathematical model which takes into account the viscoelastic properties of the receptor muscle, the properties of the stretch‐activated channels and a potential dependent K+ current.
Block of receptor response in the stretch receptor neuron of the crayfish by gadolinium
Authors: SWERUP C. , PURALI N. , RYDQVIST B.
Published: December 2008

The trivalent lanthanide gadolinium was found to block the mechanotransducer response in the stretch receptor neuron of the crayfish. At normal calcium concentration (13.5 mm) a 50 per cent block of the receptor current was found at 395 ± 59 (mean ± SD), μM gadolinium. At a calcium concentration of 1.35 mm a 50 per cent block of the receptor current was obtained at 103 ± 14 (mean ± SD) μM gadolinium. The potential activated potassium current was also affected by gadolinium. At 200 μM the amplitude of the peak outward current as a result of a 90 mV positive potential step was decreased by about 40 per cent. The fast inward sodium current was decreased less than 10 per cent by gadolinium. It is concluded that in the crayfish stretch receptor gadolinium blocks the receptor current, reflecting block of stretch‐activated channels, but at higher concentrations than have been described for other stretch‐activated channels. In addition the outward rectifier potassium current is also blocked reflecting a block of potassium channels.
Difference in the actions of calcitonin gene‐related peptide on pig detrusor and vesical arterial smooth muscle
Authors: PERSSON K. , GARCIA‐PASCUAL A. , ANDERSSON K.‐E.
Published: December 2008

Calcitonin gene‐related peptide has been demonstrated in urinary bladder nerves, and suggested to play a role in local control of bladder motility. In isolated strips of pig detrusor muscle, calcitonin gene‐related peptide did not affect spontaneous contractile activity, or contractions induced by high K+, carbachol, substance P, and electrical field stimulation. In contrast, calcitonin gene‐related peptide elicited a concentration‐dependent and pronounced (78–99%) relaxation of vesical arteries precontracted with endothelin‐1, noradrenaline or prostaglandin F2x. As a vasodilator, CGRP was approximately 50 times more potent than acetylcholine. Removal of the endothelium abolished acetylcholine‐induced relaxation, but did not affect the relaxation produced by calcitonin gene‐related peptide. Pretreatment with methylene blue, glibenclamide or indomethacin had no influence on CGRP's ability to relax the vessels. The inhibitor of NO‐synthesis, NG‐nitro‐L‐arginine, had no effect on the maximum vascular relaxation induced by calcitonin gene‐relate peptide.

It is concluded that in the pig, calcitonin gene‐related peptide has no functionally important mechanical effects on isolated detrusor muscle strips, but is a potent dilator of vesical arteries. The vascular effects of the peptide are endothelium‐independent, and seem to be exerted directly on the vascular smooth muscle.
A multinephron model of renal blood flow autoregulation by tubuloglomerular feedback and myogenic response
Authors: ØIEN A. H. , AUKLAND K.
Published: December 2008

Tubuloglomerular feedback implies that a primary increase in arterial pressure, renal blood flow, glomerular filtration and increased flow rate in the distal tubule increase preglomerular resistance and thereby counteract the primary rise in glomerular filtration rate and renal blood flow. Tubuloglomerular feedback has therefore been assumed to play a role in renal autoregulation, i. e., the constancy of renal blood flow and glomerular filtration at varying arterial pressure. In evaluating this hypothesis, the numerous tubular and vascular mechanisms involved have called for mathematical models. Based on a single nephron model we have previously concluded that tubuloglomerular feedback can account for only a small part of blood flow autoregulation. We now present a more realistic multinephron model, consisting of one interlobular artery with an arbitrary number of evenly spaced afferent arterioles. Feedback from the distal tubule was simulated by letting glomerular blood flow exert a positive feedback on preglomerular resistance, in each case requiring compatibility with experimental open‐loop responses in the most superficial nephron. The coupling together of 10 nephrons per se impairs autoregulation of renal blood flow compared to that of a single nephron model, but this effect is more than outweighed by greater control resistance in deep arterioles. Some further improvement was obtained by letting the contractile response spread from each afferent arteriole to the nearest interlobular artery segment. Even better autoregulation was provided by spreading of full strength contraction also to the nearest upstream or downstream afferent arteriole, and spread to both caused a renal blood flow autoregulation approaching experimental observations. However, when the spread effect was reduced to 25% of that in each stimulated afferent arteriole, more compatible with recent experimental observations, the autoregulation was greatly impaired. Some additional mechanism seems necessary, and we found that combined myogenic response in interlobular artery and tubuloglomerular feedback regulation of afferent arterioles can mimic experimental pressure‐flow curves.
The interaction between cAMP‐dependent and cAMP‐independent mechanisms in mediating the somatostatin inhibition of insulin secretion in isolated rat pancreatic islets
Authors: MALM D. , VONEN B. , BURHOL P. G. , FLORHOLMEN J.
Published: December 2008

To characterize the intracellular mechanisms by which somatostatin modulates the insulin secretion, studies were performed with isolated rat pancreatic islets at 12 mmol 1‐1 glucose. Somatostatin (0.1–1000 nmol 1‐1) inhibited the glucose‐induced insulin secretion concentration‐dependently. Increasing intracellular cAMP concentration either with dibutyryl‐cAMP (1 mmol 1‐1) or by the adenylate cyclase activator forskolin (20 μmol 1‐1) partly reversed the inhibition by somatostatin (100 nmol l‐1). Neither somatostatin (100 nmol 1‐1) nor dibutyryl‐cAMP (1 mmol 1‐1 were able to affect the low insulin secretion observed in the absence of extracellular Ca2+. To study cAMP‐independent mechanisms of somatostatin, the experiments were performed with and without dibutyryl‐cAMP (1 mmol 1‐1) present. Both somatostatin (100 nmol 1‐1) and the Ca21‐channel blocker verapamil (25 μmol 1‐1) inhibited the insulin secretion both with and without dibutyryl‐cAMP present. An additional inhibition of the insulin secretion was observed when somatostatin was combined with verapamil in the absence, but not in the presence of dibutyryl‐cAMP.

We conclude that somatostatin inhibits the glucose‐induced insulin secretion both by cAMP‐dependent mechanism which requires extracellular Cat2+, and by cAMP‐independent/verapamil‐sensitive Ca+2‐channel‐dependent mechanism.
Regional distributions of blood flow and tissue uptake rates of vitamin B12 and albumin within single rabbit skeletal muscles
Authors: IVERSEN P. O. , NICOLAYSEN G.
Published: December 2008

The mechanism underlying the marked regional variations in blood flow within single skeletal muscles has not been identified. The present investigation was prompted by previous data pointing to a regional distribution of the number of perfused vessels as one possible determinant for the heterogeneous perfusion pattern. We examined this possibility by assessing the regional tissue uptake rates of vitamin B12 and albumin assuming that these are related to the number of perfused vessels. This is the first study that has included simultaneous measurements of regional blood flow and of regional tissue uptake rates of vitamin B12 and albumin within single skeletal muscles in the intact animal.

The microsphere method was adopted to measure regional blood flow in 0.25 g muscle regions in awake and in anaesthetized rabbits. Various tracers were used to assess the regional distributions of tissue uptake rates and of vascular and interstitial volumes.

Albeit displaying a marked regional heterogeneity, neither the tissue uptake rate of vitamin B12 nor that of albumin were correlated to regional blood flow (P < 0.05) at rest (awake or anaesthetized rabbits) or during exercise hyperaemia (anaesthetized). At rest, but not during exercise, the distributions of regional tissue uptake rates of the two tracers showed a striking bimodal pattern. Vascular and interstitial volumes showed minimal interregional variations.

The lack of correlation between regional blood flow and tissue uptake rates and the minute interregional variation in vascular volume, argue against variations in the number of perfused vessels as the explanation for the regional heterogeneity in blood flow.