bluuebunny/crossref_metadata_2025 huggingface dataset:
Release and vasoconstrictor effects of neuropeptide Y in relation to non‐adrenergic sympathetic control of renal blood flow in the pig
Authors: PERNOW J. , LUNDBERG J. M.
Published: December 2008

The possible involvement of neuropeptide Y (NPY) in sympathetic control of renal blood flow was investigated in the pigin vivo.Exogenous NPY caused renal vasoconstriction with a threshold effect at an arterial plasma concentration of 164 pmol 6‐1. Stimulation of the renal nerves (0.59, 2 and 10 Hz) in control animals evoked rapid and frequency‐dependent reduction in renal blood flow and overflow of NPY‐like immunoreactivity (NPY‐LI) and noradrenaline (NA) from the kidney, suggesting co‐release from sympathetic nerves. Following the administration of the α‐ and β‐adrenoceptor antagonists phenoxybenzamine and propranolol, the vasoconstrictor response to exogenous NA was reduced by 98%, whereas that of NPY was unaltered. The response to nerve stimulation with 0.59 Hz was abolished, whereas relatively slowly developing reductions in renal blood flow by 7 and 28%were obtained upon stimulation with 2 and 10 Hz respectively. The nerve stimulation‐evoked overflow of NA at 0.59 and 2 Hz, but not at 10 Hz and not that of NPY‐LI, was enhanced after adrenoceptor blockade. Twenty‐four hours after reserpine treatment (1 mg kg‐1i.v.) the contents of NPY‐LI and NA in the renal cortex were reduced by 80 and 98% respectively. Sectioning of the renal nerves largely prevented the reserpine‐induced depletion of NPY‐LI, but not that of NA. Nerve stimulation of the denervated kidney with 2 and 10 Hz 24 h after reserpine treatment evoked slowly developing and long‐lasting reductions in renal blood flow by 6 and 52% respectively. These responses were associated with overflow of NPY‐LI, which was similar to and threefold higher than that observed in controls at 2 and 10 Hz respectively, while no detectable overflow of NA occurred. Repeated stimulation with 10 Hz resulted in a progressive fatigue of the vasoconstrictor response and the associated overflow of NPY‐LI, giving a high correlation (r = 0.86, P < 0.001) between the two parameters. It is concluded that NPY is a potent constrictor of the renal vascular bed. Furthermore, although NA is the likely transmitter mediating most of the responses to low to moderate nerve activation under control conditions, the data suggest that NPY may mediate the non‐adrenergic reductions in renal blood flow evoked by high‐frequency sympathetic nerve stimulation after reserpine treatment.
Correlation of plasma erythropoiesis stimulating factor(s) and immunoreactive erythropoietin levels during rapid growth in the mouse
Authors: WIDNESS J. A. , SANENGEN T. , HÅGÅ P. , CLEMONS G. K. , MYHRE K. , HALVORSEN S.
Published: December 2008

During the early neonatal period of rapid growth in the mouse, increased plasma levels of erythropoiesis stimulating factor(s) (ESF) have been found when measured by an in‐vitro bioassay technique. It is unclear whether these increased ESF levels represent increased levels of circulating erythropoietin (Ep) alone or Ep in combination with other less‐defined erythropoietic stimulatory factors. To examine this issue, plasma from neonatal mice of varying post‐natal ages and from normoxic and hypoxic adult mice was studied. We found that plasma Ep levels measured by radioimmunoassay (RIA) correlated significantly with in‐vitro bioassayed ESF levels (r = 0.84, P < 0.0001, n = 21). Although an in‐vivo bioassay for plasma Ep proved too insensitive for rigorous correlation with data from the RIA and in‐vitro bioassay, the in‐vivo data were in qualitative agreement with the other two, more sensitive, assays. In all three assays the highest plasma levels were observed in the 20‐day‐old mice and in adult mice which had been subjected to hypobaric hypoxia for 8 h. Based on the strong agreement of the results obtained with the RIA and the in‐vitro bioassay in both neonatal and adult mouse plasma, we conclude that the high plasma ESF levels of 20‐day‐old mice measured with the in‐vitro bioassay are largely immunochemically identifiable Ep. However, the data also suggest the presence of non‐Ep factors in neonatal plasma which stimulate the in‐vitro bioassay.
Variability in muscle fibre areas in whole human quadriceps muscle. How much and why?
Authors: LEXELL J. , TAYLOR C. C.
Published: December 2008

To determine the variability in fibre areas in the human vastus lateralis muscle, cross‐sections (15 μm) of whole autopsied muscles from eight young men have been prepared, and the cross‐sectional area (CSA) of 375 type 1 and 375 type 2 fibres has been measured in five different regions throughout each muscle. The CSA of both fibre types varied significantly within all muscle cross‐sections. Fibres in the deep parts of the muscle were larger than superficially. There was a significant correlation between the CSA of the two fibre types within each region: if a fibre of a given type was small, or large, the other fibre type was also small, or large. The CSA of type 2 fibres was larger than the CSA of type 1 fibres in 26 of the 40 regions: regions with type 1 fibres larger than type 2 fibres were mostly (71%) found deep in the muscle. The standard deviation of the CSA of type 1 fibres was significantly larger than for type 2 fibres in 35 of the 40 regions. In conclusion, the CSA of the different fibre types in the vastus lateralis of young men varies non‐randomly. The pattern of variation, both throughout the muscle and in small sample regions, supports the general opinion that the functional demands placed on the fibre population are an important factor in the development of the fibre properties.
Lactate transport in isolated mouse muscles studied with a tracer technique—kinetics, stereospecificity, pH dependency and maximal capacity
Authors: JUEL C. , WIBRAND F.
Published: December 2008

Lactate transport across the sarcolemma of isolated mouse muscles was studied with a 14C tracer technique. The cellular tracer uptake could be inhibited by unlabelled l‐lactate (and pyruvate) and to a lesser extent by d‐lactate. The stereospecific fraction had a Km of 3.5 mm, and made up 50% of the total transport. The tracer uptake was unaffected by 0.05 mM DIDS and 0.2 mM amiloride, but was inhibited by cinnamate (Ki= 8 mm) and PCMBS (Ki= 0.8 mm). With high concentrations of the latter inhibitor compounds or with high concentrations of unlabelled l‐lactate, the tracer uptake was inhibited 80%, which indicates that the main part of the transport involves facilitated diffusion. The remaining fraction (20%) was non‐saturable, reduced at high pH, and could not be inhibited; it is probably mediated by diffusion of undissociated lactic acid. Lactate transport was pH‐dependent, which is consistent with a lactate‐H+ symport. The maximal transport capacity, as calculated from the pH changes measured with pH‐sensitive micro‐electrodes while the lactate gradient was 30 mM, was 11.8 mmol kg‐1 min‐1 (pH 6.2).
Electrical and mechanical responses to inhibition of cell respiration in vascular smooth muscle of the rat portal vein
Authors: EKMEHAG B.L.
Published: December 2008

Metabolic regulation of contractility in vascular smooth muscle was studied in the spontaneously active rat portal vein using respiratory depression by cyanide (0.2–2.0 mm) as a model for tissue hypoxia. Intracellular recordings of electrical activity were done with concomitant registration of force development. Average membrane potential in the absence of cyanide was ‐ 61 ± 1 mV (n = 27). Addition of cyanide to normal Krebs solution resulted in a reduction of force amplitude and the number of action potentials per burst, with a relatively more pronounced effect on the mechanical activity. At moderate levels of inhibition of force amplitude the frequency of spontaneous bursts of action potentials transiently increased concomitant with a slight depolarization, but after prolonged (15–20 min) exposure to cyanide the membrane repolarized to the level prior to cyanide addition and the burst frequency decreased to be equal to or lower than that in the absence of cyanide. Higher concentrations of cyanide totally inhibited spontaneous mechanical and electrical activity. In contrast to the results with glucose, it was found that when p‐hydroxybutyrate was used as substrate the addition of 2 mm cyanide led to a marked hyperpolarization (13 ± 1 mV) after total inhibition of spontaneous activity. The hyperpolarization was not prevented by administration of 4‐aminopyridine (2.5 mm) or tetraethylammonium (44 mm) prior to the addition of cyanide. To investigate the effects of increased metabolic demand on the relation between force and membrane potential in cyanide‐treated muscle, high‐K+ (40 mm) contractures were studied. Contractures were associated with depolarization of 34 ± 3 mV (n = 5). I mm cyanide reduced the amplitude of the contractures to about 904 of control with a moderate reduction in the amount of depolarization (28 ± 1 mV, n= 5).

Ihd is concluded that the decrease of mechanical activithd during respiratory inhibition may partly reflect a reduction in the number of spikes per burst but that other mechanisms, independent of membrane activity, also contribute to the inhibition. The increase of glycolysis during respiratory inhibition seems to prevent more pronounced changes in membrane potential.
Effect of the neuropeptides β‐MSH, neurotensin, NPY, PHI, somatostatin and substance P on proliferation of lymphocytes in vitro
Authors: JOHANSSON O. , SANDBERG G.
Published: December 2008

Various neuropeptides were tested in a wide dose range for an effect on lymphocyte proliferation. The response of spleen cells to the mitogen phytohaemagglutinin (PHA) was stimulated by somatostatin in doses ranging from 10‐‐6 to 10‐18 m. The effect of somatostatin was only seen when the peptide was added at the start of incubation, indicating an effect on the inductive phase of mitogen stimulation. Weak stimulative effects were also seen of somatostatin (10‐6 m) on spontaneous proliferation of thymocytes and of β‐MSH on PHA‐treated thymocytes and PHA‐treated spleen cells when the peptide was added after 24 h of culture.
Analysis of reabsorbate concentrations in the proximal tubules of dog kidneys during osmotic diuresis
Authors: ØSTENSEN J.
Published: December 2008

To examine to what extent the reabsorbate concentrations, calculated as the flux ratios between solutes and water, represent the fluid composition in the lateral intercellular space (LIS) in the proximal tubules, reabsorption was stimulated by elevating Pco2 from 5 to 13 kPa before and during infusion of mannitol to a plasma concentration of 70 mM in volume‐expanded dogs receiving ethacrynic acid. The reabsorbate concentration of NaHCO3 increased by 50 Mm during mannitol infusion. The real concentration of NaHCO3 in LIS could not, however, be elevated by this amount, since the driving forces for fluid reabsorption then would have increased during osmotic diuresis due to diffusion of mannitol into LIS from plasma. A model analysis of diffusion in LIS showed that transcellular transport can only lead to trivial increases of LIS concentrations compared to plasma, whereas diffusion across tight junctions can increase LIS concentrations by several mM. NaCl diffusion and coupled transcellular water transport map therefore represent a significant contribution to total bicarbonate‐dependent NaCl and water reabsorption in the proximal tubules.
Difference between hypertonic NaCl and NaHCO3 as osmotic diuretics in dog kidneys
Authors: ØSTENSEN J. , STOKKE E. S. , BUGGE J. F. , LANGBERG H. , KIIL F.
Published: December 2008

To compare the osmotic inhibitory effects of NaCl and NaHCO3 on proximal tubular fluid reabsorption, plasma osmolality was raised by 40 mosmol kg‐1 H2O by infusing hypertonic NaCl and NaHCO3 in volume‐expanded dogs receiving ethacrynic acid. In five dogs studied at constant plasma pH 7.5, both NaCl and NaHCO3 reduced water reahsorption by 29 ± 2%. However, NaCl infusion reduced hicarbonate rcabsorption by 31 ± 2%, whereas bicarbonate reabsorption remained unchanged during NaHCO3 infusion. In six dogs, bicarbonate reabsorption was kept constant during NaCl and NaHCO3 infusion by adjustments of plasma pH. At similar glomerular filtration rates (42.4 ± 2.9 ml min‐1), water reabsorption was 28.7 ± 1.7 ml min‐1 in the control period, 29.4 ± ‐2.5 ml min‐1 during hypertonic NaCl infusion and 20.6 ± 1.2 ml min‐1 during hypertonic NaHCO3 infusion. Therefore, NaCl did not reduce proximal tubular water reabsorption by a direct osmotic effect. By calculating the regression coefficient for the relationship between measured chloride reabsorption and maximal convective chloride flux, the effective reflection coefficient for NaCl averaged 0.11 ± 0.01. The combination of a low reflection coefficient and high permeability may explain why hypertonic NaCl is not an osmotic diuretic.
Evidence for a countercurrent exchanger in the intestinal villi of suckling swine
Authors: BUSTAMANTE S. A. , JODAL M. , NILSSON N. J. , LUNDGREN O. , Köhlin Thorvald
Published: December 2008

The possible existence of a countercurrent exchanger (multiplier) in the intestinal villi of suckling swine was investigated with three different methods:

Comparing venous appearance of oxygen and red cells ihd the mesenteric vein after close i. a. injection of a blood sample equilibrated with pure oxygen and containing methaemoglobinaemic red cells.

Determining sodium (μg) over protein (mg) ratios along villi.

Estimating tissue osmolality in the villus tissue frohd measurements of freezing‐point depression.

It was observed that oxygen appeared earlier than red cells in the mesenteric vein after i. a. injection. Furthermore, both the chemical measurements of sodium/protein ratios in the villi and the estimations of tissue osmolality indicate that there exists a gradient of osmolalities along the villus length, the villus tip being hyperosmolar as compared to the villus base. We conclude that a countercurrent exchanger (multiplier) exists in the villi of suckling swine. Its possible pathophysiological significance is discussed.,
Opposite effects of centrally administered neuropeptide Y (NPY) on locomotor activity of spontaneously hypertensive (SH) and normal rats
Authors: HEILIG M. , VECSEI L. , WIDERLÖV E.
Published: December 2008

Centrally administered neuropeptide Y has been shown to produce sedation manifested by a suppression of locomotor activity and a synchronizing effect on the EEG pattern in normal rats. It has been suggested that this sedative effect of NPY is largely due to a facilitation of the α2‐adrenergic transmission line. In the spontaneously hypertensive (SH) rat, the NPY‐induced up‐regulation of α2‐adrenoceptors observed in normal rats is absent, and NPY produces a desynchronization of the EEG. In the present study, we have therefore examined the effects of NPY on locomotor activity of SH rats and of inbred controls of the Wistar‐Kyoto (WKy) strain, in both morning and evening sessions. In morning sessions, NPY (0.2–5.0 nmol intracerebroventricularly, i. c.v.) increased locomotor activity of SH rats in a dosc‐related manner. WKy rats were largelj inactive per se, and no effects of NPY could be detected. In evening sessions, when spontaneous activity is high, NPY (1.0 nmol i. c.v.) still increased the activity of the SH rats. In WKy rats, an activity suppression similar to that previously reported for normal Sprague‐Dawley rats was seen. The present results indicate that the sedative action of NPY in different rats strains correlates with the ability of the peptide to up‐regulate α2‐adrenergic receptors.,
Fluid balance and arterial blood pressure during intracarotid infusions of atrial natriuretic peptide (ANP) in water‐deprived goats
Authors: OLSSON K. , DAHLBORN K. , NYGREN K. , KARLBERG R. E. , ANDÉN N.‐E. , ERIKSSON L.
Published: December 2008

The aim of this study was to investigate if atrial natriuretic peptide (ANP) plays a role in the control of water balance in goats and whether ANP affects the increase in mean arterial blood pressure (MAP) which accompanies drinking in water‐deprived animals. Bilateral intracarotid infusions werc made in female adult goats deprived of water for 48 h. ANP (1.5 μg min‐1, n = 5, or 4.75 μg min‐1, n = 5) was infused for 40 min. In control experiments isotonic saline (n= 7) was infused. The goats got access to water 35 min after the start of the infusions. During saline infusions they drank 2.9 ± 0.4 litres, during the low dose of ANP 1.9 ± 0.6 litres (ns. vs saline), and during the high dose of ANP 0.6 ± 0.2 litres (P < 0.01 vs saline). Plasma vasopressin conccntration did not change during saline infusions until after drinking, when it decreased. The vasopressin concentration increased in one goat after infusion of the low dose of ANP and in two goats after the high dose of ANP. The low dose of ANP caused no change in hlAP in four goats, but MAP dropped in the one in which vasopressin concentration increased. MAP fell in all goats infused with the high dose (P < 0.01), with the largest changes occurring in animals showing increased vasopressin concentration.

Dhdring the act of drinking a temporary increase of MAP wahd observed when saline or the low dose of ANP was infused, hut this response was attenuated during infusions of the high dose. Plasma adrenaline concentration did nut change during the infusions until the animals drank, when it tended to increase. In connection with drinking, plasma noradrenaline concentration increased during both doses of ANP, hut not during saline. Mean plasma protein concentration increased by 16.5% and 12.5% during low and high doses of ANP respectively. The renal Na excretion increased by about three times during the low dose of ANP, and by about 10 times during the high dose of ANP. The K excretion increased for both doses of ANP.

In conclusion, our results indicate that pharmacological doses of ANP are needed to attenuate water intake in dehydrated goats and that even such high doses do not decrease the plasma vasopressin Concentration. Instead, no change or a large increase in the vasopressin concentration was observed, the latter probably secondary to a fall in MAP. We have confirmed in goats that drinking in water‐deprived animals is accompanied by a transient increase in MAP, and hake shown that this increase is diminished when infusions of ANP cause reduced water consumption.,
Effects of intravenous calcitonin gene‐related peptide (CGRP) on local blood flow in the cat
Authors: ANDERSSON S. E.
Published: December 2008

The effects of i. v. calcitonin gene‐related peptide (CGRP) on regional blood flow, vascular resistance, heart rate and cardiac output in cats were studied using the microsphere method. Three series of experiments were performed. In the first there was no pre‐treatment of the animals. In the second the animals were pre‐treated with indomethacin (5 mg kg‐1) in order to prevent the formation of prostaglandins. In the third series the ganglionic blocking agent hexamethonium bromide (80 mg kg‐1) was given in order to prevent autonomic reflexes. CGRP was given as an i. v. infusion. Two doses were tested in each series. Animals with no pre‐treatment and those pre‐treated with indomethacin received first 60 pmol kg‐1infused over a 5‐min period and then 180 pmol kg‐1infused over a 3‐min period. Animals under ganglionic blockade received the same dose as the total infusions in the other series (240 pmol kg‐1) infused over 4 min and a second infusion of 1.2 nmol kg‐1over 5 min.

Vhdsodilatory effects were observed in most of thhd tissues tested, but there were marked differences in sensitivity. The most sensitive tissues seemed to be the lacrimal, submandibular and parotid glands, the nictitating membrane, the tongue and the gallbladder. The patterns of sensitivity were similar in all the series, indicating that neither prostaglandins nor autonomic reflexes were involved in the effects.

In experiments with animals under ganglionic blockade, an increase in blood pressure, concomitant with an increase in heart rate, was seen 5 min after the infusions ended. Thus, it is likely that the peptide exerts a direct positive chronotropic effect on the feline heart.,
Beta‐adrenoceptor agonists and hypoxia in sheep fetuses
Authors: DAGBJARTSSON A. , HERBERTSSON G. , STEFANSSON T. S. , KJELD M. , LAGERCRANTZ H. , ROSEN K. G.
Published: December 2008

Sheep fetuses, near term, were studied to test the influence of a tocolytic β agonist, terbutaline, on fetal responses to hypoxia. After fetal exteriorization the drug was administered intravenously to the mother in three different doses: The max group comprised 11 ewes receiving 67–134 μg min‐1. Seven ewes were given 30 μg min‐1 and eight ewes were infused with 10 μg min‐1. Seventeen fetuses served as controls. Hypoxia was induced by intermittent complete occlusions of the maternal abdominal aorta. Maternal terhutaline levels were high (range 50–748 nmol I‐1) in the max group and the 30–μg group, whereas those in the 10–μg group were in the clinical range (range 11–58 nmol I‐1).

Fhdtuses in the max and 30–μg groups reacted thd moderate hypoxia with excessive responses of heart rate, blood pressure myocardial contractility and ST waveform changes and a 50%) mortality rate during severe hypoxia as compared with 12% in the control animals. Ten pg min‐1 did not decrease the survival but caused an increase in myocardial workload and a negative energy balance during severe hypoxia.,
VIP antisera inhibit the relaxatory motor responses of the feline sphincter of Oddi and gall‐bladder induced by VIP or vagal nerve stimulation
Authors: DAHLSTRAND C. , THEODORSSON E. , DAHLSTRÖM A. , AHLMAN H.
Published: December 2008

Regional administration of VIP elicited a dose‐dependent relaxation of the feline sphincter of Oddi and gall‐bladder. Relaxatory motor responses of these regions at efferent electrical stimulation of the vagal nerves were unmasked after atropine (resistant to propranolol but sensitive to hexamethonium). These findings in combination with the presence of a rich VIP‐ergic innervation, including intrinsic VIP neurons, have made VIP a tentative post‐ganglionic non‐adrenergic, non‐cholinergic neurotransmitter to these regions. The relaxatory motor responses elicited by VIP or vagal activation were selectively antagonized using regional administration of specific VIP antisera in support of this hypothesis.
Presence of a fast‐acting specific inhibitor of plasminogen activator in human parotid saliva
Authors: KJAELDGAARD A. , KJAELDGAARD M. , GAFFNEY P.
Published: December 2008

The plasminogen activator in parotid saliva has recently been characterized as a tissue‐type plasmhogen activator (t‐PA). In this study stimulated parotid saliva from 21 healthy volunteers was analysed for (a) t‐PA activitl‐ using the fibrin plate assay or a bioimmunoassay coupled to the plasmin‐specific chromogenic substrate S‐2251, (b) t‐PA antigen using an enzyme‐linked immunospecific assay and (c) activity of the specific fast‐acting plasminogen activator inhibitor (t‐PA inhibitor) assayed by its inhibitory effect on one‐chain t‐PA added to the samples. In parotid saliva the median t‐PA activity was 0.2 IU ml‐1 (normal range 0.05–0.35 IU ml‐1), but activity of free t‐PA could not be demonstrated by bioimmunoassay in any sample. The mean antigen concentration of t‐PA was 2.2 IU ml‐1 in the 10 samples with levels above the detection limit (0.5 IU ml‐1). High activity of t‐PA inhibitor was demonstrated in all parotid salivas, and the mean inhibitory effect on t‐PA was 13.2 IU t‐PA quenched per millilitre. This study thus demonstrates a fibrinolytic system in parotid saliva characterized by high t‐PA inhibitor activity and relatively low concentration of inactive, probably complex‐bound, t‐PA which is activated in the presence of tibrin.
Suppression of small intestinal motility and morphine withdrawal diarrhoea by clonidine: peripheral site of action
Authors: THOLLANDER M. , HELLSTRÖM P. M. , SVENSSON T. H.
Published: December 2008

The effects of systemic administration of morphine (4.0 mg kg‐1) and clonidine (‐2.5–10.0 μg kg‐1), as well as the peripherally active α2‐adrenoceptor agonist oxymetazoline (2.8–11.2 μg kg‐1), were studied on the migrating myo‐electric complexes (MMCs) of the small intestine in conscious, naive rats. Furthermore, the effects of naloxone (1.0 mgkg‐l) and the peripherally acting opioid antagonist, methylbromide naloxone (1.0–2.0 mg kg‐1) were studied on the MMCs in morphine‐dependent animals. Similar doses of clonidine or oxymetazoline inhibited the MMCs of the small intestine, which suggests a peripheral site of action of clonidine. Since naloxone (1.0 mg kg‐1) did not antagonize the effect of clonidine, and yohimbine (1.0 mg kg‐1) failed to antagonize the effect of morphine on the MMC, the inhibitory effects on intestinal motility of clonidine and morphine are mediated through different receptors. Morphine‐dependent rats showed a prolonged interval between activity fronts and decreased propagation velocity of the activity fronts. Both naloxone (1.0 mg kg‐1) and methylbromide naloxone (1.0–2.0 mg kg‐1) induced intense spiking activity and profuse diarrhoea. Clonidine (5.0–10.0 μg kg‐1) as well as oxymetazoline (5.6–11.0 μg kg‐1) given prior to naloxone prevented the intense spiking as well as the concomitant diarrhoea. We conclude that the potent inhibition of small intestinal myoelectric activity by α2‐adrenoceptor agonists is mainly executed via peripheral mechanisms. This effect may contribute to their beneficial action in morphine withdrawal diarrhoea, and partly underlie a general antidiarrhoeal action. Thus, peripherally acting α2‐adrenoceptor agonists, lacking side effects of clonidine such as sedation and hypotension, may prove interesting tools in the treatment of diarrhoea.
Potential‐dependent potassium currents in the slowly adapting stretch receptor neuron of the crayfish
Authors: RYDQVIST R. , ZHOU J.‐Y.
Published: December 2008

The outward current in the stretch receptor neuron of the crayfish Pucifastacus leniusculus was analysed using a two‐micropipette potential‐clamp technique. The outward current was shown to be carried by K+. When the sodium‐dependent inward current was blocked by tetrodotoxin a fast‐activating potassium current was revealed, resembling the delayed rectifier. The time‐course of activation (Tn) was dependent on potential and had a mean value of 1 ms at potential steps of to mV. The activation followed a second‐order process according to the Hodgkin‐Huxley model. The potential dependence of activation (nα) followed a sigmoid curve, nα= 1/{1 +exp [(E ‐ En) / a]} with half‐maximal activation potential En= ‐31 mV and a= ‐13 mV.

When long pulses were applied, the potassium current showed marked inactivation with a fast time constant of 0.5 s that was potential independent and a slow component that was slightly potential dependent. The minimum value for the slow time constant was 4 s for steps to about o mV. The potential dependence of inactivation followed a sigmoid function kα= 1/{1 +exp [(E ‐ Ek)/a]} with Ek= ‐ 39 mV and a= 11 mV. No transient potassium outward current (IA) was found in the crayfish stretch receptor neuron. In experiments on tail currents after depolarizing potential steps of different duration, it was found that the reversal potential changed in the positive direction when the duration of the pre‐pulse increased. This could be due to K+ accumulation in a space close to the neuronal membrane. The potassium current during depolarizing potential steps in the crayfish stretch receptor is similar to the delayed current found in other cells, for example the frog myelinated nerve, but different from many other invertebrate neurons.
Characterization of the cardiovascular actions of endothelin in vivo: comparisons with neuropeptide Y and angiotensin II
Authors: PERNOW J.
Published: December 2008

The cardiovascular actions of the endothelium‐derived peptide endothelin were investigated and characterized in vivo. Intravenous bolus administration of endothelin (4–200 pmol kg‐1) in the anaesthetized and chlorisondamine‐pre‐treated pig caused a dose‐dependent increase in mean arterial blood pressure (MABP) with a threshold effect at 20 pmol kg‐1 without affecting heart rate. Endothelin induced dose‐dependent and long‐lasting renal vasoconstriction. A slight effect was observed at 4 pmol kg‐1 and the maximal response at zoo pmol kg‐1 was a 648 ± 210% increase in renal vascular resistance. The potency of endothelin in increasing MABP and renal vascular resistance was, on a molar basis, similar to that of angiotensin II and six times higher than that of neuropeptide Y. Administration of the calcium antagonist nifedipine (loo μg kg‐1 i.v.) markedly inhibited the endothelin‐induced increases in MARP and renal vascular resistance. The renal vasoconstrictor responses to angiotensin II and neuropeptide Y were similarily reduced by nifedipine (100 μg kg‐1). A lower dose of nifedipine (10 μg kg‐1) slightly attenuated the response to angiotensin II but not that to endothelin or neuropeptide Y. It is concluded that i.v. endothelin induces potent increases in systemic blood pressure and renal vasoconstriction in the pig. Nifedipine reduces the vasoconstrictor response to endothelin but not more than the responses to angiotensin II and neuropeptide Y.
Repeated hypotension induced by nitroprusside and haemorrhage in sheep: effects on vasopressin release and recovery of arterial blood pressure
Authors: JONASSON H. , HJELMQVIST H. , RUNDGREN M.
Published: December 2008

The arginine vasopressin (AVP) release in response to repeated hypotension caused by intravenous (i.v.) infusion of sodium nitroprusside (SNP) or haemorrhage was studied in conscious euhydrated sheep. Parallel determinations of renal excretion and plasma concentration of AVP were made in experiments involving two consecutive 10‐min i.v. infusions of SNP (about 35 μg kg‐1 min‐1) with a 3‐h interval between and repeated the next day. The AVP response to the second SNP administration was significantly reduced, but partial recovery was observed in response to the initial infusion the next day. Maximal fall in mean arterial blood pressure (MABP) and its recovery pattern did not differ in response to any of the four SNP infusions. In contrast, impaired recovery of the MABP together with markedly reduced AVP response was seen as a consequence of a hypotensive haemorrhage repeated after 3 h, but not when the interval between haemorrhages was extended to 24 h. The haemorrhage‐induced increase in plasma renin activity was not affected by variations in the interval between experiments. It is concluded that the massive AVP liberation normally seen as an effect of acute isovolaemic hypotension becomes markedly reduced upon a renewed fall in the MABP occurring within 3 h. An iteration of hypotensive haemorrhage accentuates this fatigue of the hormonal response, which may contribute to the impaired recovery of the MABP.
Field potential analysis of the cortical projection of the central lateral nucleus in the cat
Authors: SHYU B. C. , OLAUSSON B. , RYDENHAG B.
Published: December 2008

A previous field potential study has indicated a monosynaptic projection of fibres from the central lateral nucleus (CL) to the mid‐suprasylvian gyrus (MSSG). The present study, which is based on an analysis of current source density (CSD), aims to investigate further the sites of major localized synaptic activities in different layers of the MSSG after electrical stimulation in the CL. An initial positive surface potential was evoked in the MSSG with a latency of 3–5 ms and followed by a large negative potential with a peak latency of 8–15 μs. The initial positivity was only found in the rostral part of the MSSG, which corresponds to area 5. The positivity reversed in deeper layers. The CSD analysis showed a sink at a depth from 650 to 1050 μ. A corresponding source was found more superficially at 400–600 μ. This indicates that CL fibres have an excitatory synaptic termination on the soma or proximal dendrites of neurons in layers III and IV. The surface negative potential reversed at the border between layers II and III, suggesting a superficial CL projection. The CSD analysis of potentials in superficial layers showed a sink appearing between the pial surface and a depth of 350 μm, and a source lying in layers below. This indicates a depolarization of apical dendrites of cells in layers II and III. The superficial sink appeared in a large part of the MSSG. Application of a solution of 0.5% gamma‐aminobutyric acid (GABA) on the surface of the cortex blocked the superficial sink and source and revealed a prominent sink current in layers III and IV in agreement with a deep termination of CL fibres. Application of a solution of 25 mM DL‐2–amino‐5–phosphono‐valeric acid (APV) abolished CL‐evoked cortical responses indicating that N‐methyl‐D‐aspartate (NMDA) receptors are involved in the cortical activation. The CSD analysis confirms that CL has a wide superficial projection to the MSSG. It also confirms a deeper monosynaptic projection from CL to area 5.
Large capacity in man for effective plasma volume control in hypovolaemia via fluid transfer from tissue to blood
Authors: LUNDVALL J. , LÄNNE T.
Published: December 2008

Compensatory absorption of extravascular fluid from skeletal muscle and skin into the circulation in response to experimental hypovolaemia was studied by plethysmographic technique in the upper arm of man. Lower body negative pressure (LBNP) of 90 cmH2O, applied for 10 min, served to produce rapid and prominent hypovolaemic stress as indicated by prompt decrease in central blood volume (external recording of [99Tcm]erythrocyte activity) followed by marked tachycardia. The arm concomitantly showed an initial mobilization of regional blood, an increased vascular resistance, and a continuous net transcapillary fluid absorption, i.e. similar responses as reported in animals upon haemorrhage. The absorption of extravascular fluid, validated by simultaneous analyses of changes in tissue volume and in regional blood volume [99Tcm]erythrocyte activity), was rapid and averaged 0.13 ml min‐1 100 ml‐1 soft tissue during the 10 min of LBNP exposure. In some subjects with symptoms and signs of pronounced circulatory stress fluid was transferred twice as fast. Separate experiments indicated that the rapid fluid flux was causally linked to the existence in the studied tissue of a large transcapillary hydraulic conductance. It is concluded that man possesses a surprisingly great capacity for compensatory circulatory refill via fluid transfer from tissue to blood. The data in fact suggest that in true states of hypovolaemia as much as 500 ml might be gained into the circulation in only 10 min.
The occurrence of gastric and duodenal autoantibodies in peptic ulcer disease
Authors: SONG Y.‐H. , MÅRDH S.
Published: December 2008

The possible relationship between peptic ulcer and the occurrence of auto‐antibodies was investigated by means of an enzyme‐linked immunosorbent assay (ELISA). Sera from 24 patients with active duodenal ulcer were analysed using cells and subcellular fractions from pig gastric and duodenal mucosa for binding of immunoglobulins. Four sera (17%) reacted with a homogenate from duodenal mucosa. Nine sera (38%) were found to contain auto‐antibodies against gastric mucosal cells. The cell‐reactive autoantibodies were shown to bind preferentially to parietal cells and chief cells. In these cells the antigens were identified as H, K‐ATPase and pepsinogen respectively. Six sera were positive against purified H,K‐ATPase; 12 sera were positive against pepsinogen, and only one of these sera reacted with both H,K‐ATPase and pepsinogen. The results show that auto‐antibodies are formed in a large fraction of patients (18/24; 75%) with peptic ulcer disease. The present study further demonstrates that enrichment of antigenic structures is required for obtaining a satisfactory sensitivity in the assay.
Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors
Authors: HOFFMANN P. , SKARPHEDINSSON J. O. , DELLE M. , THORÉN P.
Published: December 2008

In a previous study, prolonged low‐frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long‐lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5‐HT) systems were involved. More recently, we have shown that the 5‐HT1 receptors are involved in the post‐stimulatory decrease in blood pressure.

In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 ±10% (P < 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h.

One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post‐stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5‐HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5‐HT1&2 receptor antagonist) abolished the post‐stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205–930 (5‐HT2 and 5‐HT3 blocking agents respectively).

In another group of experiments, the serotonin receptor antagonists were administered post‐stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels.

Thus, intact 5‐HT systems were necessary to elicit the analgesia to muscle stimulation and the response was mediated by the 5‐HT1 receptor. However, the results indicate that serotonin is not required to maintain the analgesia once it has been elicited.
Cardiovascular responses to carotid sinus baroreceptor stimulation during moderate to severe exercise in man
Authors: STRANGE S. , ROWELL L. B. , CHRISTENSEN N. J. , SALTIN B.
Published: December 2008

Our objective was to assess the importance of arterial baroreflexes in maintaining vasoconstriction in active muscle during moderate to severe exercise. Eight subjects exercised for 8–15 min on a cycle ergometer at three levels (averages 94, 194, 261 W) requiring 40–88 % of Vo2 max. Four times during each exercise level pulsatile negative pressure (– 50 mmHg) was applied over the carotid sinuses for 30 s; suction was applied at each ECG R‐wave for 250–400 ms. Before and during each neck suction, femoral venous blood flow (FVBF) was measured by constant infusion thermal dilution. At 94 W neck suction significantly reduced blood pressure (BP) (15 mmHg) and heart rate (HR) (7 beats min‐1), and raised leg vascular conductance (LVC) (11.4%) without changing FVBF. At 194 W, neck suction reduced BP (9 mmHg), HR (4 beats min‐1) and FVBF (5.1%, 240 ml min‐1), and raised LVC (5.2%). At 261 W, LVC was unchanged by neck suction, but BP and FVBF both fell (9 mmHg and 650 ml min‐1 or 7.4%). We conclude that competing local vasodilation and sympathetic vasoconstriction control muscle blood flow during moderate exercise, and vasoconstrictor tone can be withdrawn by baroreceptor stimulation. High levels of vasoconstrictor outflow to muscle in severe exercise may not originate from baroreflexes.
Effect of intracerebroventricular deuterium oxide on water intake and AVP release induced by intravenous infusion of angiotensin II in sheep
Authors: HJELMQVIST H. , RUNDGREN M.
Published: December 2008

The effect of intracerebroventricular (i. e. v.) infusion (0.02 ml min‐1) of deuterium oxide (D2O), with NaCl added to isotonicity, on the water intake and arginine vasopressin (AVP) release caused by intravenous (i. v.) infusion of angiotensin II (All) (4.8 nmol min1) was studied in euhydrated sheep. The i. e.v. infusion of D2O, which started 80 min before commencement of the All infusion, induced a water diuresis in four out of six animals and a measurable decrease in plasma AVP concentration. The i. v. infusion of All effectively stimulated the AVP release and the response was unaffected by prior and simultaneous i. c.v. administration of D2O. However, the water intake measured 2 min after cessation of the All administration was reduced by 50% when D2O was infused i. c.v. compared to that seen after simply the All infusion. The inhibitory effect of D2O on All‐induced drinking disappeared rapidly after discontinuation of D2O administration. Compensatory increased drinking was seen during the first post‐infusion hour, resulting in an equivalent cumulative intake of water at 60 min post‐infusion in the two types of experiments. The present results support the idea that at least some of the cerebral effects of circulating All on fluid balance are medicated via targets which are simultaneously accessible to influences from the blood and the cerebrospinal fluid.
Gastrin releasing peptide stimulates the secretion of insulin, but not that of glucagon or somatostatin, from the isolated perfused dog pancreas
Authors: HERMANSEN K. , AHRÉN B.
Published: December 2008

Gastrin releasing peptide (GRP) is an intrapancreatic peptide, but its physiological function is unknown. Previously, the peptide has been shown to increase plasma levels of insulin and glucagon in vivo in dogs, but no studies on the possible direct actions on islet hormone secretion from the dog pancreas have been undertaken. Therefore, we examined the effects of a 10‐min perfusion of synthetic porcine GRP at four different dose rates over a wide range (0.1–50 nmol l‐1) on the islet hormone release from the isolated dog pancreas (n = 5–6 in each group) at 5.5 mM glucose. We found that, at all four concentrations tested, GRP rapidly and markedly stimulated insulin secretion. The stimulation was, however, transient: the increased insulin secretion returned to basal levels within 7–8 min despite the ongoing GRP perfusion for 10 min. In contrast, GRP did not affect the pancreatic secretion of glucagon or somatostatin. We conclude that GRP stimulates insulin secretion by a direct pancreatic action without affecting the secretion of glucagon or somatostatin.
Uptake of ascorbic acid by freshly isolated cells and secretory granules from the intermediate lobe of ox hypophyses
Authors: ZHOU A. , MATSUMOTO T. , FARVER O. , THORN N. A.
Published: December 2008

Mechanically isolated cells from the intermediate lobe of ox hypophyses contained 40.6 ± 3.7 nmol mg‐1 protein (mean ± SE, n = 5) of ascorbic acid. They accumulated radioactivity time dependently, on incubation with L‐[14C]ascorbic acid in an ionic medium dominated by NaCl. No definite saturation of uptake occurred when mechanically isolated cells were incubated with increasing ascorbic acid concentrations up to 0.6 mM. But if such cells were purified on a Percoll gradient, a clear saturation of uptake could be observed. Acetylsalicylic acid reduced the uptake markedly. When cells loaded with L‐[14C]ascorbic acid were homogenized and placed on a Percoll gradient, the radioactivity was recovered in several subcellular fractions. Decrease of the Na+ concentration or presence of ouabain in the medium did not cause noticeable changes in uptake by non‐purified cells, whereas uptake by purified cells was clearly sodium‐dependent. Phloridzin inhibited uptake.

Secretory granules from pars intermedia contained 40.0 ± 3.8 nmol mg‐1 protein of ascorbic acid (mean ± SE, n = 3) and could accumulate L‐[14C]ascorbic acid rapidly in a KCl‐dominated medium. The uptake was not saturable with ascorbic acid concentration and was not influenced by the presence of 1 mM ATP + 1 mM Mg2+ in the medium.

The concentration of copper and iron in isolated cells was comparable to that in isolated neurohypophysial nerve terminals, whereas the concentration of zinc was considerably higher in the pars intermedia cells. The concentration of Cu, Zn, Fe and Co in secretory granules from pars intermedia was higher than in secretory granules from neurohypophyses.
Inhibition of the Cortisol response to systemic angiotensin II by forebrain lesions involving the anterior wall of the third ventricle
Authors: JUNKERGÅRD J. , ANDERSSON B. , JÓNASSON H.
Published: December 2008

The influence of bilaterally narrow, medial forebrain lesions on the increase in plasma Cortisol concentration normally seen in response to intravenous angiotensin II was studied in five goats. For comparison, the pre‐ and post‐lesion Cortisol responses to intravenous endotoxin were also evaluated. The Cortisol response to angiotensin was extinguished in two goats, whereas a slightly attenuated response to endotoxin was still obtained post‐lesioning. In these animals the lesions embraced the subfornical organ (SFO), the organum vasculosum of the lamina terminals (OVLT) and the interjacent anterior wall of the third ventricle. In two other goats, in which the SFO was completely destroyed but the OVLT remained largely intact, the lesions caused about 50% reduction of the Cortisol response to angiotensin without any concomitant reduction of the response to endotoxin.

It is concluded that ACTH‐cortisol release in response to systemic angiotensin II is not mediated exclusively by receptors for the octapeptide confined to the SFO. Angiotensin receptors in the OVLT seem to be equally important in this respect.
Influence of splanchnic intravascular volume changes on cardiac output during muscarinic receptor stimulation in the anaesthetized dog
Authors: MORSE M. A. , BELL L. , RUTLEN D. L.
Published: December 2008

The direct influence of systemic muscarinic receptor stimulation on total splanchnic intravascular volume and the splanchnic organs responsible for the total splanchnic volume change associated with muscarinic receptor stimulation in the animal with an intact circulation are unknown. Furthermore, the subsequent effect of these volume changes on cardiac output is not known. Thus, acetylcholine was infused at 5μg kg‐1 min‐1 in 25 anaesthetized dogs in which nicotinic blockade of the ganglia was achieved with mecamylamine, while total and regional splanchnic intravascular volume changes were determined with a radionuclide imaging technique. Total splanchnic volume decreased by 4.9 ± 1.0% (P < 0.0001), splenic volume decreased by 10.3 ± 2.0% (P < 0.0001), hepatic volume increased by 5.8 ± 1.4% (P < 0.01), extrahepatosplenic volume increased by 6.6 ± 1.6% (P < 0.01) and cardiac output increased from 1960 ± 190 to 2290 ± 230 ml min‐1 (P < 0.001). After splenectomy (n= 13), the hepatic and extrahepatosplenic volume increments were abolished, and the increase in cardiac output was not attenuated (1600 ± 260 102040 ± 370 ml min‐1). After subsequent evisceration (n= 5), the cardiac output increment associated with acetylcholine was still not attenuated. Acetylcholine‐associated splanchnic volume changes were abolished after muscarinic receptor blockade with atropine. Thus, muscarinic receptor stimulation causes a decrease in total splanchnic volume due entirely to a decrease in splenic volume. The splanchnic volume changes do not influence cardiac output.