bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hypoxia on glucose metabolism in human skeletal muscle during exercise
Authors: KATZ A. , SAHLIN K.
Published: December 2008

The effect of respiratory hypoxia on muscle glucose metabolism during short‐term dynamic exercise has been investigated. Eight men cycled for 5 min at 120 ± 6 W (mean ± SE), which corresponded to 50% of maximal O2 uptake during normoxia (N), breathing air (N) on one occasion and 11 % O2 (hypoxia ‐ H) on the other. Biopsies were taken from the quadriceps femoris muscle before and after exercise. Oxygen uptake during exercise was not affected by H. The arterial blood glucose concentration during N exercise remained constant, but increased from 4.62 ± 0.11 mmol l‐1 at rest to 5.22 ± 0.19 mmol l‐1: at the end of H exercise (P < 0.05 vs N exercise). The intracellular glucose content at rest was low and did not change during N exercise, but was four times higher after exercise during H vs N (P < 0.01). Glucose 6‐P increased under both conditions but significantly more during H (P < 0.01), while glucose 1,6‐P2 was not significantly different between treatments either at rest or after exercise. It is concluded that: (1) glucose uptake by skeletal muscle during short‐term exercise during H is not associated with a stoichiometric glucose utilization; (2) the inhibition of hexokinase during H (evidenced by increase in muscle glucose) is due primarily to the increase in glucose 6‐P; and (3) glucose 1,6‐P2 is of minor importance for the regulation of contraction‐mediated flux through hexokinase in human skeletal muscle.
Transmission of externally applied negative pressure to the underlying tissue. A study on the upper arm of man
Authors: LUNDVALL J. , LÄUNNE T.
Published: December 2008

The transmission to the underlying tissue of externally applied negative pressure (2–50 mmHg) was studied in 15 male volunteers on a segment of the upper arm 8 cm in length enclosed in a clear plastic cylinder sealed hermetically against the skin. Pressure recordings were obtained from the anterior and posterior tissue compartments from sites along the entire tissue segment exposed to negative pressure at depths from the skin surface ranging from 5 to 62 mm. Reduction of pressure in the cylinder caused rapid decline, and cessation of external negative pressure rapid recovery, of tissue pressure. In the steady‐state phase of negative tissue pressure, the applied external pressure change was in the great majority of experiments transmitted fully or almost fully to the tissue, regardless of from which position along the tissue segment and from which tissue depth pressure was recorded and regardless of the magnitude of the applied negative pressure. The described findings suggest that a defined reduction of atmospheric pressure leads to a similar alteration of vascular transmural pressure and that the technique of external negative pressure can be used for not only qualitative but also quantitative studies of local circulatory reactions evoked by such transmural pressure changes.
Atrial natriuretic peptide (ANP): response to NaCI is attenuated in rat atria in vitro after hypophysectomy
Authors: ARJAMAA O.
Published: December 2008

The present study documents the effects of hypophysectomy on the NaCl‐stimulated release and on the basal secretion rates of ANP from rat atria in vitro. Three weeks before the experiments rats were subjected to hypophysectomy or to a corresponding sham operation. Atria were excised and superfused in an organ bath with a physiological buffer solution (PBS, 294 mosmol kg‐1). After a control period of 5 min, superfusion was made with hyperosmotic NaCI (330 mosmol kg‐1) for 10 min, and then again with PBS, but now for 15 min. Atria were paced with field stimulation (4 Hz, 20 V, 1 ms) and the resting tension was kept at 5 mN. The sham‐operated animals responded with a significant increase (P < 0.05) in the secretion rate of ANP (from 137 ± 13 pg ml‐1 [n = 35] to 235 ± 24 [n = 34], means + SE) to the NaCI stimulus. The hypophysectomy blunted the ANP response to hyperosmotic NaCl. In addition, basal secretion rate was signficantly (P < 0.001) lower in the hypophysectomized than in the sham‐operated animals during the whole experiment. Gel filtrations revealed that, during the hyperosmotic NaCI, both groups secreted exclusively ANP 1–28. We conclude that hypophysectomy blunts the basal as well as stimulus‐induced in‐vitro release of ANP from rat atria.
Temporal relationship between blood flow changes and release of ions and metabolites from muscles upon single weak contractions
Authors: KIENS B. , SALTIN B. , WALLØSE L. , WESCHE J.
Published: December 2008

The temporal changes in muscular blood flow and in the release of ions and metabolites have been studied during and after short‐lasting isometric contractions

Blood velocities in the human femoral artery were measured using pulsed bidirectional Doppler ultrasound equipment during single contractions of the quadriceps muscle group. Contractions of 5 s and 30 s duration and at a tension of 10% MVC (maximal voluntary contraction) were investigated. Even the contractions of 5 s duration caused conspicuous post‐contraction increases in femoral arterial flow.

.

The following substances were analysed in the femoral vein during and following the contractions: potassium, lactate, inorganic phosphate, calcium, sodium, oxygen and haemoglobin. Following contractions of 5 s duration, an increase in the venous potassium concentration (by 0.9mM) was found, but there was no change in concentration of any of the other substances analysed. Following contractions of 30 s duration a more marked increase in the venous potassium concentration (by 1.5 mM) was found, and in addition substantial changes in venous lactate concentration and oxygen saturation. There were small but statistically significant changes in the concentrations of inorganic phosphate and calcium, but no change in the sodium concentration.

The time‐course and magnitude of the changes in venous potassium concentration fit well with the idea that potassium is important in the initiation and regulation of the functional hyperaemia in contracting muscles.
Characterization of antigenic structures in autoimmune atrophic gastritis with pernicious anaemia. The parietal cell H,K‐ATPase and the chief cell pepsinogen are the two major antigens
Authors: MÅRRDH S. , SONG Y.‐H.
Published: December 2008

Using isolated cells and subcellular fractions from pig gastric mucosa, antigenic structures with specific binding of IgG from sera of patients with auto‐immune atrophic gastritis were characterized by means of immunoblotting and enzyme‐linked immunosorbent assay. In immunoblotting experiments using mucosal cells as the antigen source, two dominating bands of 94 and 41 kDa were found. The two major antigens were identified as the H,K‐ATPase (94 kDa), which constitutes the parietal cell acid pump, and pepsinogen (41 kDa) located in the chief cells. There was also a small but significant binding of antibodies to a preparation of Na,K‐ATPase, an enzyme which is about 60% homologous to H,K‐ATPase. Commercial preparations of hog gastric pepsinogen and pepsin bound pernicious anaemia IgG with equal efficacy. When sera from seven patients with the diagnosis pernicious anaemia were tested, all were found to contain auto‐antibodies against H,K‐ATPase as well as pepsinogen. In intact, isolated H,K‐ATPase‐containing vesicles the cytosolic part of the ATPase molecule is facing the outside of the vesicles. Both intact and trypsinized vesicles were incubated with patient sera and with a monoclonal antibody against H,K‐ATPase. Pernicious anaemia IgG was found to bind to a cytosolic, trypsin‐resistant structure, but the binding of the monoclonal antibody was lost upon trypsinization. The present results indicate that intracellular structures of the gastric mucosa, due to cell damage, may be exposed to immune‐competent cells, which do not recognize these structures as ‘self’.
Vasoactive intestinal peptide (VIP) may reduce the removal rate of cytosolic Ca2+ after transient elevations in clonal rat lactotrophs
Authors: SAND O. , CHEN B. , LI Q. , KARLSEN H. E. , BJØRO T. , HAUG E.
Published: December 2008

The prolactin‐producing rat anterior pituitary GH4C1 cells possess Ca2+‐activated K channels which are activated by physiological elevations of the cytosolic Ca2+ concentration even at membrane potentials more negative than the normal level of about ‐ 50 mV. Whole‐cell current recordings showed a marked outward tail current following depolarizing voltage steps to o mV from a holding potential close to the normal membrane potential. The half‐time of this tail current was about 1.3 s after a 4‐s depolarization step. The GH4C1 cells also possess voltage‐activated Ca channels, and we conclude that this tail current is a Ca2+‐activated K+ current for the following reasons:

(hd) The reversal potential for the tail current was close to thhd K+ equilibrium potential for a range of transmembrane K+ gradients.

(2) The tail current was blocked by a Ca2+ antagonist, and the voltage dependence of this current closely mirrored the voltage dependence of the isolated Ca2+ current.

The time‐course of the decline of the tail current thus reflects the removal rate of the Ca2+ entering the cytosol through voltage‐dependent Ca channels during the depolarizing voltage step. VIP stimulates prolactin secretion from GH4C1 cells, and this peptide prolonged the half‐time of the tail current by about 47% in 63% of the cells. This indicates that VIP may prolong the transient cytosolic Ca2+ elevations following the action potentials in these cells. Such a mechanism might be an important factor for the control of the cytosolic Ca2+ level, and hence hormone secretion.
Growth hormone‐releasing factor induces a biphasic modulation of K+ permeability in perfused cultured rat somatotrophs
Authors: OHLSSON L. , LINDSTRÖM P.
Published: December 2008

Ohlsson, L. & Lindström, Phd 1989. Growth hormone‐releasing factor induces a biphasic modulation of K+ permeability in perfused cultured rat somatotrophs. Acta Physiol Scand 137, 237–241. Received 22 May 1989, accepted 16 June 1989. ISSN 0001–6772. Department of Histology and Cell Biology, University of Umeå, Sweden.

Growth hormone‐releasing factor (GKF) induced a biphasic response in 86Rb outflow in rat somatotrophs. An early inhibition was observed at all GRF concentrations tested, 1 pm‐10 nm, and this was followed by a later increase. The increase in 86Rb outflow rate came earlier at high GRF concentrations and GRF had a dose‐related effect on the magnitude of the increase. The effects of GRF on 86Kb outflow were observed also in the absence of extracellular calcium. Peak growth hormone release preceded peak 86Rb outflow rate. The timing of the effects of GRF on potassium outflow is consistent with the hypothesis that reduced potassium outflow is involved in somatotroph depolarization leading to increased exocytosis, followed by a later increase in potassium outflow leading to repolarization.,
Effects of continuous positive‐ and negative‐pressure breathing on the pattern of breathing in man during exercise
Authors: RAER R. , EIKEN O.
Published: December 2008

Breathing pattern and static lung volumes were studied in 10 subjects at rest and during incremental‐load cycle ergometry under three different conditions, viz. with normal pressure in the airways (control) and during continuous positive‐ and negative‐pressure breathing (CPPB, CNPB) of +15 and ‐15 cmH2O. End‐expiratory, end‐inspiratory and mid‐expiratory volumes were increased by CPPR and decreased by CNPB; these effects were especiallv pronounced at rest and during mild exercise, Both at rest and during exercise mean inspiratory flow (VT/T1) was exaggerated by CPPB and attenuated by CWB. At rest these changes were due mainly‐ to concomitant changes in tidal volume (VT) which was increased by CPPB and decreased by CNPR, while inspiratory time duration (T1) was relatively unaffected by pressure breathing. The transition Crom rest to loadless pedalling induced an increase in VT but no change in T1 in the control condition, whereas in the CPPB and CNPB conditions T1 decreased and VT remained unaltered. This CPPB‐ and CNPB‐induced change in the volume‐time threshold relationship at the onset of pedalling is attributed to increased stretch receptor activity in the extrathoracic portion of the trachea as a result of the increments in transmural pressure. During the course of exercise there was an inverse relationship between the slope of the VT‐T1 curve and the mid‐expiratory volume in that the slope was greater in the control than in the CPPB condition and greatest during CNPB, suggesting that in exercise hyperpnoea the VT‐T1 relationship is also determined by pulmonary and/or thoracic mall stretch receptors capable of sensing the absolute lung volume.,
The cold pressor test: effects on sympathetic nerve activity in human muscle and skin nerve fascicles
Authors: FAGIUS J. , KARHUVAARA S. , SUNDLOF G.
Published: December 2008

Micro‐electrode multi‐unit recordings of muscle nerve sympathetic activity (MSA) involved in cardiovascular homeostasis or skin nerve sympathetic activity (SSA) involved in thermoregulation were made in the right peroneal nerve of 48 healthy volunteers during performance of the cold pressor test, i.e. immersion of one hand in ice water (zko.5 “C) for I min. Eleven subjects underwent the same procedure on a second MSA recording occasion. As a rule, immersion evoked an increase in MSA, with a gradual decrease on emersion. The response showed a wide range of variation between and within subjects; the intra‐individual difference between first and second immersion on the same recording occasion was up to sevenfold, and from first to second recording up to fivefold. The increase in MSA correlated with the degree of discomfort from the ice water. In nine subjects with a large increase in MSA on ice water immersion, intracutaneous painful electrical stimulation to a level equalling the discomfort from the ice water was added, but it was not accompanied by any change in MSA. The increase in MSA was accompanied by and correlated quite well with an increase in blood pressure. Intra‐arterial blood pressure recordings showed that MSA occurred at pressure levels normally associated with total inhibition of MSA, and that an inverse linear relationship between diastolic blood pressure and MSA at rest was abolished during the ice water immersion. SSA showed no consistent change with ice water immersion.

I t is concluded that the cold pressor test is a powerful activator of MSA, i.c. baroreceptor‐governed vasoconstrictor outflow; that MSA contributes to the blood pressure elevation with this manoeuvre; that MSA operates at another blood pressure level during the manoeuvre and that the baroreflex inhibitory level consequently is changed; and that the response is not a reaction to pain only.
Changes of high‐energy phosphorous compounds in skeletal muscle during glucose‐induced thermogenesis in man. A 31P MR spectroscopy study
Authors: THOMSEN C. , JENSEN K. E. , ASTRUP A. , BULOW J. , HENRIKSEN O.
Published: December 2008

By the use of invasive techniques, skeletal muscle has been shown to contribute to thermogenesis induced by glucose in humans. In an attempt to study this phenomenon by a non‐invasive method, this study investigated intracellular high‐energy phosphorous compounds in calf muscle by “P MR spectroscopy during an oral glucose load in healthy lean subjects. The inorganic phosphate concentration increased gradually (P < 0.0;) after glucose intake. The phosphocreatine/inorganic phosphate rate decreased (P < 0.0;) and the estimated ADP concentration increased. ATP and intracellular pH remained unchanged after the glucose administration. N o changes were seen in the control experiments. The processes responsible for the decreased energy‐ state of the skeletal muscle cell may be an obligatory conversion of glucose to glycogen. Also, facultative processes, such as sodium/potassium pumping and substrate cycles stimulated by the sympatho‐adrenal system, may be partly responsible.
The metabolic relation between hypoxanthine and uric acid in man following maximal short‐distance running
Authors: WESTING Y. HELLSTEN , EKBLOM B. , SJÖDIN R.
Published: December 2008

Hellstn Westing, Y., Ekblom, B. & Sjödin, R. 1989. The metabolic relation between hypoxanthine and uric acid in man following masimal short‐distance running. Acta Physiol Scand 1–37, 341–345. Received 10 March 1989, accepted 24 June 1989. ISSN 0001–0772. Department of Physiology III, Karolinska Institute, and Swedish Defence Research Establishment, Stockholm, Sweden.

This study was performed to asscss the metabolic relation between hypoxanthine and uric acid following short‐distance maximal running. Eleven trained males, mean age 22 years (16–31), were instructed to run 800 m in the shortest time possible. Bood samples were collected before warm‐up, before the run, immediately after the run and periodically up to 24 h following the run. Blood lactate was determined after warm‐up, and at 5, 10, and 30 min following the run. Mean Vo2 mas for the subjects was 65.8 (4.7) (SD) ml kg‐1 min‐1 and mean oxygen demand for the running was 118 (8)%, of Vo2 may. Plasma hl‐poxanthine levels rose from 3.3 (1.4) to a peak of 48.2 (19.0)μmol l‐1 at to min following the run and at 180 min had almost returned to pre‐tun levels Plasma uric acid levels rose from a pre‐run value of 267 (34) to a peak value of 131 (87) μmol l‐1 at 45 min following the run. Uric acid concentrations had not returned to normal at 10 h following the run. The hlood lactate level peaked at j min with 13.7 (2.0) mmol l‐1. The results obtained in this study indicate a metabolic relationship between the formation of hypoxanthine and the formation of uric acid. The data also indicate that xanthine osidase is active following short‐distance intensive running.
Volume regulation in mouse pancreatic islet cells as studied by a new technique of microperifusion
Authors: ENGSTRÖM K. G. , SANDSTRÖM P.‐E.
Published: December 2008

A new technique was designed to analyse whether pancreatic islet cells are able to regulate their volume in anisotonic media. The projected cell area of individual cells was continuously observed, and the corrcsponding volume calculated during microperifusion with media of diffrent osmolarities. In isotonic medium (317 niosmol) the cell volume was stable during perifusion and decreased by 17 or 25% when the osmolarity was increased (sucrose) to 417 or 517 mosmol. Reducing the medium osmolariti to 285 mosmol resulted in a volume reduction of ahout 7%. No evidence for cell volume regulation was observed in these media. Homever, reducing the medium osmolarity to 262 niosmol induced an immediate and rapid cell swelling of approximately 14% after which the initial cell volume was regained Mithin 9 min. The data suggest that the pancreatic islet cells are equipped with mechanisms for regulatory volume decrease that appear to he actibated when the cell volume is increased above a certain limit.
Calcium dependency of the post‐stimulatory potentiation of the neurogenic response in small mesenteric arteries from the rat
Authors: SJÖRLOM‐WIDFELDT N. , NILSSON H.
Published: December 2008

We have previously shown that the contraction of small mesenteric arteries in response to nerve stimulation is enhanced by preceding high‐frequency stimulation. We have now investigated the calcium dependency of this post‐stimulatorp potentiation. Small arteries (inner diameter 150–250 μm) from normotensive rats were dissected free from surrounding tissue, and segments were mounted in a myograph where the wall tension was measured at well‐defined circumferences. Nerve stimulation was performed by field stimulation.

A single stimulation of the nerve caused a contraction of 2.6 ± 0.25%, of maximal adrenergic response. After a high‐frequency nerve stimulation with 16 Hz and 480 pulses the response to a single nerve stimulation was enhanced 6.6 ± 1.3 times. The potentiation decayed with a time constant of 93.7 ± 20.0 s. The amplitude of the post‐stimulatory potentiation was dependent on the extracellular calcium concentration during the conditioning stimulation. In a solution containing 2.5 mM calcium the single twitch was enhanced 6.6 times while after exposure to reduced calcium (0.5 mm) it was only enhanced twice.

The contraction caused by a short burst of high‐frequency nerve stimulation (20 Hz and 10 pulses) was potentiated four times by a conditioning stimulation (16 Hz and 480 pulses), and this potentiation seemed to be independent of the extracellular calcium concentration during the conditioning stimulation.

Thus the magnitude of the post‐stimulatory potentiation of single nerve stimulations is linearly related to the extracellular calcium concentration during the conditioning nerve stimulation. For the potentiation of the response to burst stimulation no relation was found between the potentiation and extracellular calcium.
Alkaline secretion by Necturus proximal duodenal mucosa
Authors: BRIDÉN S. , FLEMSTRÖM G.
Published: December 2008

Proximal duodenum from the amphibian Necturus was stripped of muscle layers and the mucosa was mounted as a tube for studies of alkali transport or as a flat sheet for intracellular impalement by voltage‐sensitive glass micro‐electrodes. The mucosa alkalinized the unbuffered luminal perfusate at a high rate (34 μequiv. Cm‐1 h‐1) and developed a transepithelial electric potential difference of 5.7 mV (lumen negative). Transport was inhibited by 2,4‐dinitrophenol (10‐4 M) and by furosemide (10‐3 M) and SITS (10‐3 M) on the serosal but not on the mucosal side, indicating dependence on tissue metabolism and on serosal membrane Cl‐/HCO3‐ exchange. Prostaglandin E2 (107‐105 M) and dibutyryl cyclic AMP (10‐6‐10‐4 M) had no effects on the secretion or transepithelial electrical potential difference. Removal of serosal HCO‐3 decreased luminal alkalinization by 75%, indicating a contribution by passive migration of HCO‐3, and/or a dependence of transcellular transport on the nutrient supply of this ion. Administration of HCO‐3 (17.8 mM) to the luminal perfusate affected neither the transepithelial nor transmembrane electrical potential differences nor the resistance ratio. It is thus unlikely that the luminal membrane possesses any major HCO‐3 conductance.
Renal and circulatory effects of medullipin I, as studied in the in‐vivo cross‐circulated isolated kidney and intact Wistar‐Kyoto (WKY) rat
Authors: KARLSTRÖM G. , ARNMAN V. , BERGSTRÖM G. , MUIRHEAD E. E. , RUDENSTAM J. , GÖTHBERG G.
Published: December 2008

The renal medulla harbours powerful humoral antihypertensive mechanisms, as earlier explored in unclipping experiments on renal hypertensive rats or in normotensive isolated kidneys cross‐circulated at increased perfusion pressures from ‘donor rats’, in which renal function also seemed to be affected. Injection of the renomedullary factor medullipin I (Med I; formerly ANRL) mimics these haemodynamic responses, and Med I seems to be one of the most important mediators of the depressor effects.

The present study was performed to analyse further the haemodynamic and, particularly, the renal effects of Med I, using anaesthetized intact WKY rats and constant‐pressure perfused (90 mmHg) isolated WKY kidneys, cross‐circulated by these intact ‘donor’ rats. Mean arterial pressure (MAP), heart rate (HR) and renal function were followed for one 30‐min period before and two 30‐min periods after injection of 1 mg Med I (M; n = 7) or an equal volume of saline as control (C; n = 13).

In the intact ‘donor’ WKY, MAP and HR remained largely constant in C during the three periods, being 126 ± 5, 125 ± 5, and 120 ± 5 mmHg, while MAP fell in the M group after Med I, from 121 ± 5 to 107 ± 7 and 107 ± 5 mmHg (P <0.05), and also HR tended to decrease in M. Renal resistance (RR) fell while renal plasma flow (RPF) and glomerular filtration rate (GFR) increased significantly (P < 0.05) after Med I in the M donor rats despite their MAP reduction. However, in the constant‐pressure perfused, cross‐circulated kidneys the RR, RPF and GFR changes were clearly more pronounced (P < 0.01) and also diuresis, natriuresis, osmolar excretion and osmolar clearance increased significantly after Med I (P <0.01). In conclusion, the present results support the view that Med I not only has important and long‐lasting depressor effects but also affects renal function in important ways, inducing vasodilatation and increasing GFR, RPF, diuresis and sodium‐osmolar excretion.
Mechanism of erythrocyte trapping in ischaemic acute renal failure
Authors: BAYATI A. , CHRISTOFFERSON R. , KÄLLSKOG Ö. , WOLGAST M.
Published: December 2008

Forty‐five minutes of warm ischaemia and 20 min of recirculation in the rat kidney was found to result in (1) a massive transient extravasation of plasma upon recirculation and (2) an increase in plasma‐lymph transport of proteins during the first hours after onset of circulation. This was accompanied by trapping of erythrocytes, as determined with 51Cr‐labelIed erythrocytes, in the capillaries, mainly in the inner stripe of the outer medulla. At scanning electron microscopy of vibratome sections, the trapping appeared as aggregates of polygonally shaped erythrocytes. It is concluded that 45 min of ischaemia and 20 min of recirculation results in an increase in the permeability of the renal capillaries. This increase leads to extravasation of capillary plasma with consequent local haemoconcentration, causing an increase in vascular resistance and in capillary hydrostatic pressure. This elevated pressure will, in turn, lead to perpetuating extravasation of plasma, further haemoconcentration and so on, eventually resulting in dense packing of polygonal erythrocytes, obstructing the blood flow. It is believed that oxygen‐derived free radicals generated in the early recirculation phase contribute to the increase in macromolecular permeability, since the scavenger bovine superoxide dismutase and allopurinol, a xanthine oxidase inhibitor, were found to prevent this unfavourable chain of events.
The long‐term outcome of post‐ischaemic acute renal failure in the rat. I. A functional study after treatment with SOD and sucrose
Authors: BAYATI A. , KÄLLSKOG Ö. , WOLGAST M.
Published: December 2008

The long‐term outcome in rat kidneys subjected to 45 min of warm ischaemia with no treatment and after administration of 20 mg superoxide dismutase (SOD) and of SOD combined with 2 ml of a 12% sucrose solution was studied by the micropuncture technique. It was found that, although in the acute phase SOD prevented trapping of erythrocytes in the medullary vasculature and that SOD + sucrose also prevented the formation of tubular obstruction, the long‐term results as studied 1 week and 1 month after the primary ischaemic insult were virtually identical. This was due to the formation of new obstructions, during the first week, mainly in the thick ascending limb of Henle's loop. After 1 month the proximal tubular free‐flow pressure and the single‐nephron filtration rate had returned to normal. However, since the total glomerular filtration was only one‐third of that under normal conditions, it would seem that two‐thirds of the nephrons had undergone complete degeneration. This degeneration was probably the result of persistent tubular obstruction. The tubular degeneration was also accompanied by a reduction in urine osmolality and potassium secretion.
The long‐term outcome of post‐ischaemic acute renal failure in the rat. II. A histopathological study of the untreated kidney
Authors: BAYATI A. , NYGREN K. , KÄLLSKOG Ö. , WOLGAST M.
Published: December 2008

Histopathological changes in kidneys subjected to 45 min of isothermic unilateral ischaemia in the acute phase and 1 week and 1 month after primary damage were studied at the electron microscopic level. During the first week after recirculation long homogeneous cylinders, probably consisting of Tamm‐Horsfall protein, developed in the medullary parts of the nephron, and after 1 month of recirculation there were two types of nephrons: (1) nephrons with a normal histological appearance and (2) degenerated nephrons. The latter group gave rise to crypts in the outer cortical area. It is hypothesized that the generation of the long Tamm‐Horsfall cylinders in the thick ascending limb of the loop of Henle plays an important role in the long‐term outcome of the kidney after the primary damage. The persistent blockade caused by these cylinders will lead to precipitation of the ultrafiltrate, resulting in long cell‐protein cylinders in the proximal parts of the nephron. This precipitation will proceed in the retrograde direction, reaching the mother glomeruli, eventually leading to total degeneration of the nephron.
Studies of cholera toxin‐induced changes of alkaline secretion and transepithelial potential difference in the rat intestine in vivo
Authors: TANTISIRA M. H. , FÄNDRIKS L. , JÖNSSON C. , JODAL M. , LUNDGREN O.
Published: December 2008

A pH‐stat technique was used to investigate the effects of cholera toxin (CT) on alkaline secretion from denervated intestines (jejunum, ileum, colon) in anaesthetized rats. Transepithelial potential difference (PD) was also followed in some experiments. CT, given intraluminally, caused a marked increase in jejunal alkaline secretion, whereas only a small effect was observed in the ileum and no apparent effect was noted in the proximal colon. The pronounced increase in jejunal alkaline secretion was found to be inhibited by 10–25% by hexamethonium (10 mg kg‐1 body wt i. v.) and similarly by serosal application of lidocaine, whereas atropine (0.25 mg kg‐1 body wt i. v.) had no effect. Thus the cholera toxin‐induced alkaline secretion in the jejunum is attributed mainly to a non‐nervous mechanism. The small effect of CT on ileal alkaline secretion observed in this study contrasts with the high ileal bicarbonate concentration reported in cholera by authors who estimated the concentration from the total carbon dioxide/bicarbonate contents. This discrepancy may be explained by a CT‐evoked increased transport of the coupled Na+/H+ and Cl/HCO3‐ exchangers, which cannot be measured with the pH‐stat technique used in this study.
Sex‐linked variation in creatine kinase release, and its dependence on oestradiol, can be demonstrated in an in‐vitro rat skeletal muscle preparation
Authors: AMELINK G. J. , KOOT R. W. , ERICH W. B. M. , VAN GIJN J. , BÄR P. R.
Published: December 2008

Creatine kinase (CK) release from male and female rat soleus muscles was studied for 4.5 h in vitro, under basal conditions and after electrical stimulation. Basal CK release was greater from male than from female muscles, and CK release from male muscles increased significantly when the muscle tension in the in‐vitro set‐up was increased. CK release after electrical stimulation was also more marked in male soleus muscles. Pretreatment of male rats and ovariectomized female rats with oestradiol for 3 weeks attenuated the enzyme efflux, but ovariectomy 24 h before in females, or oestradiol administration 24 h before in males, did not affect the release of CK in vitro. The data show that sex‐linked differences in CK efflux are still present, under both basal and stimulated conditions, when muscles are isolated from the intact animal, and that hormone treatment of the intact animal affects these properties in the isolated muscle in vitro.

(Experiments with rats were performed under supervision of a legally appointed administrator.)
Atrial natriuretic factor (ANF 103–126) enhances volume‐ and pressor‐induced heart rate response in the conscious rat
Authors: MARKS E. S. , ÖHMAN K. P. , KEISER H. R.
Published: December 2008

The reduction in blood pressure due to ANF(103–126) fails to elicit reflex cardioacceleration in the conscious rat. To examine baroreflex sensitivity, the effect of ANF(103–126) on the heart period (HP) response to rapid central volume expansion and to alterations in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside was assessed. ANF(103–126) significantly augmented the bradycardic response induced by acute volume expansion from 426 ± 21 to 391 ± 23 beats min‐1 versus 421 ± 23 to 405 ± 24 without ANF(103–126). Baroreflex sensitivity was defined by the ratio of the change in heart period to the maximal change in mean arterial pressure. The dose of ANF(103–126) utilized did not affect basal heart rate or the magnitude of the mean arterial pressure response to phenylephrine but did significantly enhance the nitroprusside‐induced decrease in mean arterial pressure. Baroreceptor sensitivity to phenylephrine was significantly increased by ANF(103–126): 0.997 ± 0.07 (ms mmHg‐1) during ANF(103–126) vs 0.613 ± 0.08 during vehicle. The total duration of the heart rate response to phenylephrine was also prolonged. In contrast, ANF(103–126) did not alter the baroreceptor sensitivity (1.45 ± 0.3 vs 1.43 ± 0.2 ms mmHg‐1) or duration of heart rate response to nitroprusside. In the conscious rat, ANF(103–126) modifies the heart rate response to changes in mean arterial pressure and acute central volume expansion. This action appears to be dependent on stimulation of cardiac vagal afferents.
Cardiovascular and endocrine responses to haemorrhage in the pig
Authors: JACOBSEN J. , SØFELT S. , SHEIKH S. , WARBERG J. , SECHER N. H.
Published: December 2008

Heart rate (HR), mean arterial pressure (MAP), indices of sympathetic and parasympathetic activity (plasma concentrations of adrenaline, noradrenaline and pancreatic polypeptide, PP), vasopressin (VP) and aldosterone (ALDO) were measured in six pigs during continuous bleeding resulting in hypovolaemic shock, from which five survived. Three stages of haemorrhage could be defined.

Stage I. Resting MAP was 85 ± 6 mmHg and increased to 96 ± 5 mmHg with a blood loss of 275 (range 250–300) (10 (9–12)% of the estimated blood volume) concomitant with an increase in HR from 105 ± 5 to 113 ± 6 beats min‐1 (P < 0.05).

Stage II. After a blood loss of 375 (300–500) ml (15 (13–16)%) MAP fell to 62 ± 9 mmHg and HR to 95 ± 5 beats min‐1 (P < 0.05).

Stage III. A blood loss of 1113 (825–1450) ml (44 (30–52)%) resulted in a MAP of 50 ± 4 mmHg and an increase in HR to 206 ± 3 beats min‐1 (P < 0.05). Adrenaline increased from 0.3 ± 0.1 to 0.8 ± 0.3 (stage II) and 3.6 ± 1.1 nmol l‐1 (stage III) (P < 0.05); noradrenaline from 0.4 ± 0.1 to 1.5 ± 0.4 (stage II) and 5.9 ± 1.7 nmol l‐1 (stage III) (P < 0.05); PP from 6.2 ± 1.6 to 13.3 ± 2.3 (stage II) and 20.9 ± 7.8 pmol l‐1 (stage III) (P < 0.05). VP changed only marginally, but ALDO increased from 496 ± 54 to 623 ± 76 pmol l‐1 (stage III) (P < 0.05). The results suggest that a high HR and intense sympathetic activity is seen during severe haemorrhage in the pig while vagal slowing of the heart and moderate hypotension are prominent when bleeding amounts to approximately 15% of the estimated blood volume.
A transient acidification linked to intracellular Ca2 in anti‐μ‐stimulated human B‐lymphocytes
Authors: SCHØYEN H. , IVERSEN J. G. , SMELAND E. B. , HEIKKILÄ R.
Published: December 2008

Mitogen‐induced cellular proliferation is in many cell types preceded by rapid changes in intracellular pH and free Ca2+ concentration. We studied the patterns of pH and Ca2+ changes in normal resting human B‐lymphocytes after exposure to and‐μ antibodies and the monoclonal antibody 1F5, reactive with the CD20 antigen, both able to activate resting B‐lymphocytes to enter the G1 phase of the cell cycle. Monitoring intracellular pH with the pH‐sensitive, fluorescent dye, 2',7'‐bis(carboxyethyl)‐5,6‐carboxy‐fluorescein, we demonstrated that poly‐ and monoclonal anti‐μ antibodies induced a rapid (maximum change within 2 min) intracellular acidification of 0.06 pH units followed by a slower (10–15 min) alkalinization towards, or slightly above, the resting pH of 6.88. The acidification response was amiloride‐resistant, whereas the return to baseline was sensitive. Intracellular free Ca2+ was measured by using the fluorescent Ca2+ dye, indo‐i. Exposure of cells to anti‐/i resulted in a rapid increase (maximum change within 2 min) in cytoplasmic Ca2+ of 340 nM and a slower decline in fluorescence back to baseline of about 180 nM. In contrast to anti‐μ, 1F5 caused no change in cytoplasmic Ca2+ and pH. However, the Ca2+ ionophore ionomycin at low concentrations mimicked the Ca2+ response as well as the pH response to anti‐μ. In Ca2+‐free solutions the intracellular Ca2+ stores are usually rapidly depleted and, indeed, the Ca2+ and pH responses to anti‐μ were reduced after 5 min and almost abolished after 35 min under such conditions. Our data therefore suggest that the anti‐μ‐induced rapid acidification is the result of increased intracellular Ca2+ and dependent on it.
Force and EMG signal patterns during repeated bouts of concentric or eccentric muscle actions
Authors: TESCH P. A. , DUDLEY G. A. , DUVOISIN M. R. , HATHER B. M. , HARRIS R.T.
Published: December 2008

Healthy males (n= 14) performed three bouts of 32 unilateral, maximal voluntary concentric (CON) or eccentric (ECC) quadriceps muscle actions on separate days. Surface electromyography (EMG) of the m. vastus lateralis (VL) and m. rectus femoris (RF) and torque were measured. Integrated EMG (IEMG), mean (MPF) and median power frequencies and torque were averaged for seven separate blocks of four consecutive muscle actions. Torque was greater (P < 0.05) for ECC than for CON muscle actions at the start of exercise. It did not decline throughout ECC exercise, but decreased (P < 0.05) markedly for each bout and over bouts of CON exercise. Thus, torque overall was substantially greater (P < 0.05) for ECC than for CON exercise. At the start of exercise IEMG of VL or RF was greater (P < 0.05) for CON than for ECC muscle actions. This was also true for overall IEMG activity during exercise. The IEMG increased (P < 0.05) modestly for both muscles during each bout of CON or ECC muscle actions, but did not change for the VL over bouts. The IEMG of RF decreased (P < 0.05) modestly over CON but not ECC exercise bouts. At the beginning of the first bout of exercise the IEMG/torque ratio was twofold greater (P < 0.05) for CON than ECC muscle actions. The ratio of IEMG/torque increased (P < 0.05) markedly during CON but did not change during ECC exercise. Thus, by the end of the third bout there was a fivefold difference (P < 0.05). The MPF decreased (P < 0.05) substantially in each CON bout with only a partial recovery between bouts. In contrast, MPF remained the same within each bout and over bouts of ECC exercise. These results indicate that the ability to maintain force during repeated bouts of maximal voluntary muscle actions at a relatively high angular velocity is remarkably greater for eccentric than for concentric exercise. It is suggested that the factors responsible for fatigue and for changes in the EMG signal pattern during concentric exercise do not materialize during, or are different for, eccentric exercise as performed here.
The influence on the breathing pattern in man of moderate levels of continuous positive and negative airway pressure and of positive end‐expiratory pressure during air and CO2 inhalation
Authors: ELLINGSEN I.
Published: December 2008

The purpose of this study was to determine in man the effect on the breathing pattern of continuous positive (CPAP), continuous negative (CNAP) and positive end‐expiratory (PEEP) airway pressure during air breathing and CO2 inhalation. Six subjects were exposed to CPAP, CNAP and PEEP 0.5 kPa, while five subjects were exposed to CPAP and CNAP 0.8 kPa.

End‐expiratory lung volume increased during CPAP 0.8 kPa and decreased during CNAP 0.8 kPa. CPAP induced more extensive changes in the ventilatory pattern, and the changes in each parameter were larger than observed during CNAP and PEEP at the same pressure level. In contrast to previous reports we found the effect of CO2 inhalation combined with the effect of pressure breathing to be not stronger than additive. Even moderate CPAP induced alveolar hyperventilation with marked reduction in arterial PCO2 (PaCO2) when breathing air. With increasing fraction of CO2 in the inspiratory gas, the difference in PaCO2 between CPAP and no CPAP disappeared. PEEP also affected the breathing pattern in that it induced an increase in mean inspiratory flow and mean expiratory flow and a reduction in inspiratory duration. Occurrence of ventilatory pauses depended on whether mouthpiece or facemask was used. CPAP and CNAP did not influence the occurrence of pauses, while PEEP prolonged post‐expiratory pauses.

We conclude that CPAP, CNAP and PEEP induce active ventilatory responses in man and that strong mechanisms are involved during CPAP since PaCO2 is markedly reduced.
Regulation of splanchnic organ size during muscarinic receptor stimulation in the anaesthetized pig
Authors: RUTLEN D. L. , VENGEN Ø. A. , ILEBEKK A.
Published: December 2008

To determine the mechanisms responsible for changes in splanchnic organ size during muscarinic receptor stimulation, acetylcholine was infused at 5 μg kg‐1 min‐1 in 11 anaesthetized pigs which had previously undergone carotid denervation and cervical vagotomy. Blood pressure decreased by 42 ± 4 mmHg (P< 0.005), portal vein pressure decreased by 1.0 ± 0.3 mmHg (P< 0.01), IVC pressure increased by 0.2 ± 0.1 mmHg (P< 0.01), hepatic arterial flow increased by 10 ± 6 ml min‐1 (NS), portal vein flow decreased by 89 ± 20 ml min‐1 (P< 0.005), splenic segment length (SSL) decreased by 0.52 ± 0.11 mm (P< 0.005) (control 12.49 ± 1.27) (measured with ultrasonic crystals) and hepatic segment length (HSL) increased by 0.29 ± 0.06 mm (P< 0.005) (control 13.94 ± 1.16). Aortic constriction to decrease the splanchnic distending pressure by an amount comparable to that achieved with the acetylcholine‐associated decrease in portal flow caused a similar decrease in SSL and increase in HSL. Graded constriction of the portal vein or IVC, to increase SSL or HSL respectively, in the presence and absence of acetylcholine demonstrated no change in splenic or hepatic compliance with acetylcholine. Ligation of the splenic vasculature reduced the acetylcholine‐associated HSL increase from 0.41 ± 0.09 to 0.20 ± 0.07 mm (P< 005). Acetylcholine infused directly into the portal vein did not alter HSL. Atropine abolished all acetylcholine‐associated haemodynamic changes. Thus, muscarinic receptor stimulation does not appear to act directly on splanchnic capacity vessels. Splenic dimension decreases due to a decrease in splanchnic flow and pressure, and hepatic dimension increases due to an increase in IVC pressure and redistribution of volume from the spleen.
Endothelin has no positive inotropic effect in guinea‐pig atria or papillary muscle
Authors: VOLKMANN R. , BOKVIST K. , WENNMALM Å.
Published: December 2008

Endothelin is a recently discovered, highly potent vasoconstrictor peptide. In isolated atria from rat and guinea‐pig, endothelin has been reported to elicit a positive inotropic effect. The purpose of the present study was to compare the effects of endothelin on electromechanical coupling in guinea‐pig atrial and ventricular muscle. In isolated, electrically driven specimens of atria and papillary muscle, action potentials and isometric contractions were recorded in the basal state and 30 min following non‐cumulative exposure to endothelin (100 nM). In the atria, endothelin reduced action potential overshoot and relaxation velocity, and increased resting tension. In the papillary muscle the peptide slightly shortened the duration of the action potential. Endothelin did not affect peak tension, either in the atria or in the papillary muscle. These data contrast with earlier reports on a positive inotropic effect of endothelin in guinea‐pig atria.
Failure of islet amyloid polypeptide to inhibit basal and glucose‐stimulated insulin secretion in model experiments in mice and rats
Authors: PETTERSSON M. , AHRÉN B.
Published: December 2008

Islet amyloid polypeptide (IAPP), also known as amylin, has previously been demonstrated to occur in amyloid deposits in pancreatic islets in type 2 diabetics, and, therefore, the peptide has been suggested to be involved in the pathogenesis of diabetes. The 37 amino acid peptide shows approximately 50% homology with the intrapancreatic neuropeptide calcitonin gene‐related peptide (CGRP), a peptide that inhibits insulin secretion. We therefore examined, in model experiments in mice and rats, if IAPP also exerts this effect. IAPP was given intravenously, at dose levels at which CGRP previously has been shown to inhibit insulin secretion. Thus, in mice, IAPP was injected at 0.85 and 4.25 nmol kg‐1, and in rats IAPP was infused at 17 or 68 pmol min‐1. However, neither basal nor glucose‐stimulated insulin release was inhibited by IAPP under these experimental conditions. We also investigated if IAPP (10‐1 to 10‐6 M), when incubated in vitro with isolated, overnight‐cultured rat islets, could affect insulin secretion induced by glucose (3.3, 8.3 or 11.7 mM). However, also in vitro no effect by IAPP on insulin release was observed. Hence, in mice and rats, IAPP does not inhibit insulin secretion under experimental conditions identical to those previously used to demonstrate an inhibition by CGRP. Therefore, we conclude (1) that the homologous amino acid sequence within IAPP and CGRP does not seem to be sufficient for inducing inhibition of insulin release in mice and rats and (2) that the possible involvement of IAPP in the pathogenesis of diabetes type 2 still remains speculative.
Urinary bladder and urethral responses to pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptide in the anaesthetized dog
Authors: ANDERSSON P. O. , SJÖGREN C. , UVNÄS B. , UVNÄS‐MOBERG K.
Published: December 2008

The effects on the urinary bladder and urethra of pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptides (VIP) were investigated in the anaesthetized dog. Both pelvic and hypogastric nerve stimulation elicited a twofold increase in urinary bladder blood flow and a clear‐cut increase in bladder venous effluent VIP concentration. Hypogastric nerve stimulation induced an initial, partly α‐adrenergic and partly non‐adrenergic, non‐cholinergic, contraction of the urinary bladder followed by a relaxation. The urethra response was a maintained a‐adrenergic contraction. Pelvic nerve stimulation elicited a bladder contraction with an initial non‐cholinergic peak, whereafter the bladder pressure was maintained at a lower level, an effect which was mainly cholinergic in origin. The urethral response was an initial non‐adrenergic, non‐cholinergic contraction followed by a maintained cholinergic contractile response. Afferent pelvic nerve stimulation led to an efferent activity that seemed to be a combination of activity in pelvic and hypogastric pathways to the urinary bladder and the urethra. VIP (10 nmol) injected i. v. induced a relaxation of the urinary bladder and the urethra, together with a fall in systemic blood pressure. However, despite high plasma concentrations, no vasodilatation was elicited in the urinary bladder. Thus, the main target for the VIP release during pelvic and hypogastric nerve stimulation is probably not the bladder vasculature, but instead perhaps the bladder smooth muscle proper.