bluuebunny/crossref_metadata_2025 huggingface dataset:
Potent vasoconstrictor effects and clearance of endothelin in the human forearm
Authors: PERNOW J. , HEMSÉN A. , LUNDBERG J. M. , NOWAK J. , KAIJSER L.
Published: December 2008

The vascular effects of endothelin‐1 in humans were investigated by infusion into the brachial artery of healthy volunteers. Endothelin‐1 (5–500 pmol min‐1) evoked potent and long lasting increase in forearm vascular resistance (FVR) and reduction in venous compliance, suggesting constriction of both resistance and capacitance vessels. The threshold for effect on forearm vascular resistance was at a calculated plasma concentration of 614 pmol 1‐1. Endothelin‐1 was on a molar basis 10–20 times more potent than noradrenaline as constrictor of both resistance and capacitance vessels. The increase in forearm vascular resistance induced by endothelin‐1 lasted more than 30 min and that by noradrenaline less than 3 minutes. The endothelin‐I‐like immunoreactivity collected in the venous effluent during the infusion was 10–26% of the calculated arterial plasma concentration, indicating local removal of endothelin. After the infusion of endothelin‐1 the urine concentration of prostacyclin metabolite increased significantly, indicating release of prostacyclin, whereas the concentration of thromboxane metabolite did not increase. It is concluded that endothelin‐1 is a highly potent constrictor of human resistance and capacitance vessels, that it causes release of prostacyclin and that circulating endothelin‐1 is efficiently removed by the forearm in vivo.
Regional extraction of endothelins and conversion of big endothelin to endothelin‐1 in the pig
Authors: HEMSÉN A. , PERNOW J. , LUNDBERG J. M.
Published: December 2008

Endothelin‐like immunoreactivity (ET‐LI), mean arterial blood pressure (MABP) and vascular resistance in the spleen, kidney and femoral vascular bed were measured during intravenous infusions (20 pmol. kg‐1. min) of endothelin‐2 (ET‐2), endothelin‐3 (ET‐3), big endothelin‐1 (big ET) and sarafotoxin 6b in the pig. All peptides (especially endothelin‐2 and sarafotoxin 6b) caused vasoconstrictor effects in the kidney. Endothelin‐2, endothelin‐3 and sarafotoxin 6b also evoked significant increases in splenic and femoral vascular resistance. The relative vasoconstrictor response to endothelin‐2 was larger in the kidney and spleen than in the femoral vascular bed whereas the opposite was observed for endothelin‐3. A high degree of plasma clearance for endothelin‐like immunoreactivity was observed. Thus, for ET‐2 and ET‐3 about 70% of arterial endothelin‐like immunoreactivity was removed over the kidney while over the spleen and femoral vascular bed an extraction of 50% for plasma endothelin‐2 and 30–40% for endothelin‐3 was observed. Big endothelin‐1 was only extracted by 34% over the kidney and not at all in the splenic or femoral vascular bed. The metabolic plasma half‐lifes of endothelin‐2 and endothelin‐3 in vivo were in the same range, 1–2 minutes, whereas the half‐life of big endothelin‐1 was 9 minutes. HPLC‐characterization of the plasma endothelin‐like immunoreactivity during and after big endothelin‐1‐infusion as well as measurements using a specific endothelin‐1 antiserum revealed formation of endothelin‐1 from circulating big endothelin‐1 in vivo but not in plasma in vitro. It is concluded that there exists specificity concerning the vasoconstrictor effects and the removal of endothelin‐peptides from the circulation, both mechanisms being most prominent in the kidney. Big endothelin‐1 has a much longer metabolic half‐life, less regional clearance and poor vasoconstrictor activity compared with endothelin‐1. Furthermore, endothelin‐1 is formed from circulating big endothelin‐1 probably by an endothelin‐converting enzyme.
Respiratory sinus arrhythmia is reversed during positive pressure ventilation
Authors: YLI‐HANKALA A. , PORKKALA T. , KAUKINEN S. , HÄKKINEN V. , JÄNTTI V.
Published: December 2008

In order to study the relationship between heart rate and depth of anaesthesia, respiratory sinus arrhythmia (RSA) was investigated during enflurane and isoflurane anaesthesia in 28 patients (15–39 years). Positive pressure ventilation (six breaths min‐1) was used. Respiratory sinus arrhythmia was evaluated during light anaesthesia, deep anaesthesia (burst suppression in EEG) and light anaesthesia again by using signal averaging technique. In most patients, decrease of the heart rate was seen during inspiration (positive tracheal pressure), and increase during expiration. Respiratory sinus arrhythmia did not disappear in deep anaesthesia. Inter‐individual variation in the magnitude and phase relationship of respiratory sinus arrhythmia was considerable, and was not associated to the level of anaesthesia.
The efflux of 86Rb and [3H]5‐HT from human platelets during continuous perfusion: Effects of potassium‐induced membrane depolarization and thrombin stimulation
Authors: ANDERSSON T. L. G. , VINGE E.
Published: December 2008

In order to study the ionic efflux or granule release from human platelets following pulse exposure to various stimuli, a method for continuous perfusion of platelets was developed. The method was applied to compare the effects of membrane depolarization and thrombin stimulation on the release of 86Rb and [3H]5‐HT. Washed and preloaded human platelets were placed on a membrane filter in a temperature controlled polypropylene chamber, and subsequently perfused with buffer. After an initial washout period the efflux of 86Rb or [3H]5‐HT reached steady, low levels. K+ induced concentration dependent increases in 86Rb efflux, corresponding to a depolarization of the membrane potential, whereas the efflux of [3H]5‐HT was unaltered. Thrombin induced concentration dependent increases in the efflux of both 86Rb and [3H]5‐HT. Pretreatment with K+ 12 or 30 mm did not alter the [3H]5‐HT efflux induced by thrombin 0.1 U ml‐1. Scanning electron micrographs of platelets on the filter showed that the unstimulated platelets had regular shape, whereas after addition of thrombin there was formation of pseudopods and minor aggregates. The effect of potassium‐induced membrane depolarization on platelet aggregation was also studied. High concentration of K+ did not induce aggregation or shape change during 2 or 10 minutes of incubation. K+ had little or no effect on aggregation induced by ADP 2μM or thrombin 0.4 U ml‐1. The results from release experiments and aggregation tests argue against an immediate coupling between membrane potential and platelet reactivity.
Does chronic hypoxaemia induce transformations of fibre types?
Authors: HILDEBRAND I. L. , SYLVÉN C. , ESBJÖRNSSON M. , HELLSTRÖM K. , JANSSON E.
Published: December 2008

The study comprised nine patients with chronic obstructive lung disease. Quadriceps muscle biopsies were studied with respect to fibre type composition before and after haemodilution that brought haemoglobin (Hb) to within normal limits. Ten days elapsed between the two biopsy occasions. The arterial oxygen tension (Pao2) and saturation (5ao2) were depressed to 8.4 pL 2.0kPa and 89pL11% in the patients with chronic obstructive lung disease and increased to 9.2 pL 2.1 and 91pL8% with haemodilation. The type II fibre proportion was 71 pL 12% before haemodilation and significantly higher than normal (reference group, see Aniansson et al. 1981). Following haemodilation the proportion of type II fibres decreased significantly to 60 pL14%. The proportion of type II fibres was directly related to the haemoglobin content before, but not after, haemodilation and was inversely related to Pao2 and 5ao2 both before and after haemodilation. In conclusion, hypoxaemia may be a factor underlying the high proportion of type II fibres found in patients with chronic obstructive lung disease.
Hyperresponsiveness to tussive stimuli in cigarette smoke‐exposed guinea‐pigs: a role for capsaicin‐sensitive, calcitonin gene‐related peptide‐containing nerves
Authors: KARLSSON J.‐A. , ZACKRISSON C. , LUNDBERG J. M.
Published: December 2008

Environmental pollutants may induce airway hyperresponsiveness to bronchoconstrictor stimuli, but if there is a concomitant change in other defensive reflexes, like the cough reflex, is not known. We have examined how two weeks' exposure to cigarette smoke influences airway sensitivity to inhaled irritants acting mainly through capsaicin‐sensitive sensory neurons (citric acid, capsaicin) or rapidly adapting stretch receptors (cigarette smoke, histamine). Guinea‐pigs were exposed, over a period of one hour, to cigarette smoke or room air, twice daily for 2 weeks. Twenty‐four hours after the end of the smoke exposure coughing produced by nebulized citric acid (0.40 M) and capsaicin (30 μM) was enhanced 3.7 (P < 0.001) and 2.S (P < 0.05) times, respectively, whereas the cigarette smoke‐induced cough was unchanged. The enhanced responsiveness gradually returned to normal over a period of three weeks and was not mediated by cyclo‐oxygenase products since it was not affected by indomethacin (3 μmol kg‐1). In contrast, the broncho‐constrictor responses to citric acid, capsaicin, cigarette smoke and histamine (0.70 mM) were not altered by inhalation of cigarette smoke. Smoke‐exposed animals had a significantly (P < 0.05) increased amount of calcitonin gene‐related peptide‐like material (CGRP, contained in capsaicin‐sensitive sensory neurons) in tracheal tissue, suggesting that chronic irritation stimulates peptide synthesis. The amount of neuropeptide Y‐like material (in autonomic motor nerves) in pulmonary tissue was not changed indicating some ‘specificity’ in the irritative effect of smoke. It is concluded that prolonged exposure to cigarette smoke produces a tussive hyperresponsiveness that seems to involve specifically capsaicin‐sensitive, CGRP‐containing sensory neurons mediating cough. The present data demonstrate the development of a ‘sensory’ hyperresponsiveness, separate from airway hyperresponsiveness to bronchoconstrictor agents.
Dual effects of vasoactive intestinal peptide (VIP) on leucocyte migration
Authors: BONDESSON L. , NOROLIND K. , LIDÉN S. , GAFVELIN G. , THEODORSSON E. , MUTT V.
Published: December 2008

Vasoactive intestinal peptide, at different concentrations, was tested on the migration of leucocytes by using the sealed capillary migration test. Vasoactive intestinal peptide, at 10‐7–10‐9 M, inhibited, while at 10‐12–10‐14 M, stimulated mononuclear leucocyte migration. The migration of polymorphonuclear leucocytes was inhibited by vasoactive intestinal peptide at 10‐6–10‐9 M, a stimulation was found at 10‐13–10‐14 M. The inhibiting effect of vasoactive intestinal peptide on leucocyte migration was abolished when vasoactive intestinal peptide was split into C‐ and N‐terminal fragments, while a stimulating effect was retained in the N‐terminal fragment, at 10‐14 M, for mononuclear cells. Helodermin and peptide T, as well as two other members of the secretin‐glucagon family, secretin and gastric inhibitory peptide, had no effect on the migration. When VIP antiserum was tested, it had an inhibiting effect, which was not seen with control serum, supporting a physiological effect of the lower vasoactive intestinal peptide concentrations. Vasoactive intestinal peptide seems to have dual effects on mononuclear and polymorphonuclear leucocyte migration and, generally, intact vasoactive intestinal peptide seems to be needed for these effects.
Transmural fibre direction in the anterior wall of the feline left ventricle: theoretical considerations with regard to uniformity of contraction
Authors: HEXEBERG E. , MATRE K. , LEKVEN J.
Published: December 2008

Previous studies of non‐uniform performance of a myocardial region have indicated that measurement of local contraction is vectorial. Myocardial performance in one direction mainly, but not exclusively, depends on performance of the wall fibres in this same direction irrespective of wall depth. In this study we therefore determined fibre direction across the anterior wall of the left ventricle in twelve cats. Based on the fibre configuration a simple model is developed to analyse and predict the degree of uniformity of contraction. Fibre direction shifted continuously across the wall, from almost alignment with global apex‐to‐base axis in the endocardium (90d̀), to close to the equatorial direction (0d̀) in the midwall, and finally to about ‐ 50d̀ in the epicardial layer. The model predicts less uniformity with reduction of preload, and in the event of subendocardial ischaemia, which fits well with experimental data. Analysis of uniformity based on the integrated vectorial contribution of all myocardial layers thus provides a way to quantify regional uniformity/non‐uniformity as a regulatory mechanism of cardiac function.
Right ventricular coronary blood flow patterns during aortic pressure reduction in renal hypertensive dogs
Authors: SMOLICH J. J. , WEISSBERG P. L. , FRIBERG P. , KORNER P. I.
Published: December 2008

We measured right ventricular coronary blood flow with radioactive microspheres during graded aortic pressure reduction in 13 normal dogs and in 13 renal hypertensive dogs with left ventricular hypertrophy. Under anaesthesia and controlled loading conditions, mean aortic pressure was lowered from control (128 mmHg in normal and 146 mmHg in hypertensive dogs) to approximately 100, 90 and 80 mmHg. In normal dogs, right ventricular blood flow was not affected by this pressure reduction, consistent with effective right ventricular autoregulation. In hypertensive dogs, however, right ventricular blood flow was maintained between a mean aortic pressure of 146 and 90 mmHg (range 75–79 ml min‐1 100 g‐1) but fell by 18% to 63 ml min 100 g‐1 at a mean aortic pressure of 80 mmHg (P < 0.005). We conclude that autoregulation of right ventricular blood flow was preserved in chronic hypertension but that, compared to normal dogs, the lower limit of autoregulation was reset to a higher pressure level. Moreover, the similarity of right ventricular‐to‐body weight ratios in the two groups implied that this change was a consequence of hypertension‐induced structural changes in the coronary vasculature.
Strenuous prolonged exercise elevates resting metabolic rate and causes reduced mechanical efficiency
Authors: Bahr R. , Opstad P. K. , Medbø J. I. , Sejersted O. M.
Published: December 2008

Resting O2 consumption, net mechanical efficiency during cycling exercise and excess postexercise O2 consumption (EPOC) was measured bin 15 army cadets after 3 or 4 days of continuous simulated combat exercises (estimated energy demand: 40 MJ day‐1), no organized sleep and virtually no food intake (stress experiment). They exercised for 30 minutes at a work load corresponding to about 50% of maximal O2 uptake. An identical test using the same absolute work load was repeated when the cadets were completely recovered from the combat course (control experiment). Resting O2 consumption increased by 15% from 279±7 mlmin‐1 (control) to 320±8 ml min‐1 (stress, P < 0.001). Mechanical efficiency decreased from 24.6±0.4% (control) to 20.9±0.2 % (stress, P < 0.001). EPOC1hincreased from 0.58±0.411 (control) to 2.24±0.461 (stress, P < 0.05). Glucose infusion during exercise (0.20 g kg‐1 body weight) had no effect on mechanical efficiency or EPOC. About 1/5 of the increase in exercise O2 uptake can be explained by a substrate shift from carbohydrates to fat, as evidenced by a reduction in R‐value during exercise from 0.90±0.012 (control) to 0.80±0.010 (stress). Hence, after severe physical stress combined with sleep deprivation and food restriction, O2 uptake is increased both at rest and during submaximal exercise.
Potential‐dependent potassium currents in the rapidly adapting stretch receptor neuron of the crayfish
Authors: RYDQVIST B. , PURALI N.
Published: December 2008

The outward current was analysed in the rapidly adapting stretch receptor neuron of the crayfish Pacifastacus leniusculus with a two‐micropipette potential clamp technique and K+‐selective microelectrodes in an attempt to establish if the properties of this current could explain the difference in adaptive behaviour compared to the slowly adapting receptor. A fast activating outward current carried by K+ was revealed. The time constant of activation (tn) was dependent on potential and had a mean value of 0.5 ms at potential steps to 0 mV. Activation followed a second‐order process according to the Hodgkin‐Huxley model. The potential dependence of activation (n∞) followed by a sigmoid curve n∞= l/{l + exp[(E —En)/a]} with a half maximal activation potential En= ‐44 mV and a = ‐13 mV.

When long pulses were applied the outward potassium current decreased with two time constants, one that was potential independent (0.2 s) and one that was potential dependent (2–8 s). The latter could be explained by accumulation of K+ in the extracellular space of the neuron. The potential dependence of inactivation followed a sigmoid function k∞= 1/{1 +exp[(E —Ek)/+ a]} with Ek= ‐36 mV and a = 13 mV. The inactivation properties are different from those of the classical fast transient (IA) current. The transport system for the outward potassium current during depolarizing potential steps in the rapidly adapting stretch receptor is similar to the current found in the slowly adapting receptor neuron. However, the activation is faster and seems to occur at potentials more negative than in the slowly adapting receptor. These differences can contribute to but not entirely explain the difference in adaptive behaviour between the slowly and rapidly adapting receptor.
Bradykinin‐induced oedema formation proceeds from B2 receptor stimulation and is potentiated by concomitantly released prostaglandins
Authors: NEPPL H. , NEUHOF H. , AFFLERBACH F. , NEPPL J. LLACH PUIG , BERGHÖFER A.
Published: December 2008

Bradykinin, a stimulator of B1 and B2 receptors, significantly increased PGI2 synthesis and fluid extravasation, as assessed by the increase of organ weight when injected intra‐arterially into the artificially perfused rabbit hindquarters preparation. Diclofenac pretreatment prevented PGI2 synthesis and significantly reduced fluid extravasation. Oedema formation and PGI2 synthesis were also significantly reduced by a simultaneous infusion of papaverine. Selective stimulation of B1‐type receptors with des‐Arga‐bradykinin was not accompanied by edema formation nor PGI2 synthesis but by a significant rise in vascular resistance. The combined application of bradykinin and the selective B1 receptor antagonist des‐Arg9‐‐[Leu8]‐bradykinin also resulted in oedema formation and PGI2 synthesis, the extent, however, being significantly reduced in comparison to the application of bradykinin only. The data suggest that bradykinin‐induced oedema proceeds from B2 receptor stimulation and is potentiated by simultaneous stimulation of B1 receptors. The kinin‐induced fluid extravasation seems to be augmented by concomitantly generated prostaglandins.
Selectivity of ruthenium red in inhibiting bronchoconstriction and CGRP release induced by afferent C‐fibre activation in the guinea‐pig lung
Authors: LOU Y.‐P. , KARLSSON J.‐A. , FRANCO‐CERECEDA A. , LUNDBERG J. M.
Published: December 2008

Ruthenium red (3 × 10‐4 M) aerosol attenuated the cough induced by nebulized citric acid in conscious guinea‐pigs. Citric acid‐induced coughing is mediated via capsaicin‐sensitive neurons. However, cigarette smoke‐induced coughing, which involves capsaicin‐resistant mechanisms, was not affected by ruthenium red. In conclusion, ruthenium red selectively inhibits the capsaicin, resiniferatoxin and citric acid‐induced excitation of the sensory nerves as revealed by calcitonin gene‐related peptide‐like immunoreactivity release, bronchoconstriction and coughing, suggesting that these agents share a common mechanism of action.
The microsphere technique in anaesthetized and awake pregnant guinea‐pigs: reproducibility of repeated blood flow measurements
Authors: JANSSON T.
Published: December 2008

Repeated microsphere injections are extensively employed for measurements of uteroplacental blood flows in experimental animals. However, this technique has not been systematically validated in pregnancy. In the present series of experiments the effects of three consecutive microsphere injections on central haemodynamics and regional blood flows were studied in 43 late pregnant guinea‐pigs. In group A (n= 13) experiments were carried out in the awake chronically catheterized animal. In group B (n = 8) animals were studied under anaesthesia. In two additional anaesthetized groups reference withdrawal rate (C, n = 7) and the amount of injected spheres (D, n = 7) were increased 2–3 fold. Cardiac output, mean arterial blood pressure, heart rate as well as regional blood flows to placenta, ovaries, kidneys, heart, liver and carcass remained unaltered in all protocols. Myoendometrial blood flow increased in group A and C and a similar pattern could be demonstrated in group B and D but was not statistically significant. Adrenal blood flow was enhanced in groups A and C and brain blood flow increased in group C and D. The gastrointestinal tract especially the stomach was sensitive to repeated microsphere injections since blood flow reductions were apparent in all groups but were statistically significant only for groups A and D. In group E (n= 8), the three microsphere labels were injected simultaneously. The coefficients of variability for these blood flow measurements were in the range of 3.6–6.8% for different organs. It is concluded that repeated microsphere injection is an ideal method to measure placental blood flow. However, the technique may provide inaccurate results with respect to the myoendometrium and gastrointestinal tract.
The effects of hypobaric hypoxia (50.6 kPa) on blood components in guinea‐pigs
Authors: OSADA H.
Published: December 2008

One hundred and five male (Hartley) guinea‐pigs weighing 350–380 g and 30 splenectomized guinea‐pigs were exposed to simulated hypobaric hypoxia of 50.6 kPa (equal to an altitude of 5486 m) for 14 days. The partial pressure of oxygen was set at half that at sea level.

The white blood cell count increased significantly on day 3 of the simulated high altitude experiment but returned to normal on day 7, whereas the red blood cell count increased continuously. To study the effect of high altitude exposure on platelets, the platelet count in the splenectomized group was compared to that in a non‐splenectomized group. Investigation of the resistance of red blood cell membranes to osmotic pressure under hypobaric conditions revealed a shift of the onset of haemolysis in the hyperosmotic direction.

These findings may help to increase our understanding of the biochemical mechanisms of adaptation to hypobaric hypoxia.
On the role of polyamines in bone resorption induced by parathyroid hormone
Authors: LJUNGGREN Ö. , FREDHOLM B. B. , LERNER U. H.
Published: December 2008

In order to elucidate the possible role of polyamines in the mobilization of mineral from long‐term bone cultures stimulated with parathyroid hormone we have measured the activity of ornithine decarboxylase in osteoblasts, the levels of polyamines in calvarial bone and determined the effect of added polyamines and inhibitors of polyamine biosynthesis on calcium mobilization.

Parathyroid hormone (10nmoll‐1) stimulated omithine decarboxylase activity by approximately 50% in both cultured bone cells of osteoblastic phenotype, UMR 106 and in mouse calvarial osteoblast‐like cells. In mouse calvaria the levels of putrescine and spermidine were increased by parathyroid hormone after 24 hours. The levels of spermine were very low and were unchanged by parathyroid hormone.

The two polyamine synthesis inhibitors alpha‐difluoromethylornithine (DFMO; 2 mmol 1‐1) and methylglyoxal‐bis‐guanylhydrazone (MGBG; 50 μ mol 1‐l) did not significantly affect the mobilization of 45Ca from parathyroid hormone‐stimulated bones. All three polyamines, putrescine, spermidine and spermine, inhibited the mobilization of 45Ca induced by parathyroid hormone in a dose‐dependent manner. The inhibition induced by putrescine was reversible.

In summary, we have shown that parathyroid hormone increases the accumulation of polyamines in bone, but the effect is small. Furthermore, inhibition of polyamine biosynthesis does not reduce parathyroid hormone‐induced mineral mobilization and the addition of polyamines leads to a reduced rather than a stimulated mineral mobilization. Thus, polyamines do not seem to be critically involved in the changes in bone resorption induced by parathyroid hormone. However, polyamines are themselves potent inhibitors of parathyroid hormone effects and an examination of the mechanism underlying this effect may help to define critically important elements in the signal transduction from parathyroid hormone receptor to bone resorption.
Myogenic responsiveness in rat hindquarter vessels during constant‐flow and constantpressure perfusion in vitro; effects of various potassium concentrations and of endothelial nitrous oxide blockade
Authors: JOHNSSON E. , FOLKOW B. , KARLSTRÖM G.
Published: December 2008

An in vitro constant‐flow, alternatively constant‐pressure, perfusion method for studying microvascular myogenic responsiveness in otherwise intact rat hindquarters was used to explore how three types of influences affect the pressure‐flow induced enhancements of myogenic tone: (1) Changes of potassium concentration over the range 2–50 mmol; (2) Whether myogenic responsiveness, which is fairly weak during these conditions of high shear rates, is enhanced by blockade of endothelial prostacycline and nitrous oxide formation; (3) Whether some of the drawbacks of the constant‐flow technique, like rapid edema formation, is offset by a constant‐pressure variant.

The result can be summed up as follows. (1) Myogenic responsiveness is also during in nitro conditions markedly influenced by even modest potassium concentration changes around the physiological resting level, e.g. showing a fourfold difference between potassium concentrations of 2.5–4.5 mmol. It was entirely suppressed above 7–8 mmol potassium concentration but also when potassium concentration values above 20 mmol increasingly depolarize and constrict the resistance vessels. (2) While blockade of prostacycline synthesis was without effect, suppression of endothelial nitrous oxide production could increase myogenic responsiveness up to fourfold, suggesting that shear‐stress dependent release of this agent serves to suppress myogenic activity. These effects were, however, quite variable suggesting that also other endothelial inhibitory influences are involved. (3) The constant‐pressure variant reduces some of the methodological drawbacks, particularly the oedema formation which can be further reduced by increasing perfusate colloid osmotic pressure. However, interferences by the mentioned, partly unknown endothelial mechanisms still tend to suppress myogenic responsiveness to a varying extent, which hampers quantitative analyses particularly of other inhibitory influences.
Fibrin(ogen) degradation product peptide 6A increases femoral artery blood flow in dogs
Authors: SALDEEN K. , NICHOLS W. , LAWSON D. , ANDERSSON R. , SALDEEN T. , MEHTA J.
Published: December 2008

To determine the effects of peptide 6A (a fibrinogen‐degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50pmoles) caused a short‐lasting dose‐dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 μmoles min‐1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 ± 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A‐induced increase in femoral blood flow. Inin vitroexperiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6‐keto‐PGF1α in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A‐induced relaxation was abolished by de‐endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium‐derived relaxing factor. PGI2release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.
Segmental heterogeneity of the rat colon in the response to activators of secretion on the cAMP‐, the cGMP‐ and the Ca2+‐pathway
Authors: NOBLES M. , DIENER M. , MESTRES P. , RUMMEL W.
Published: December 2008

The electrolyte transport was compared in proximal and distal segments of the rat colon under control conditions and after induction of secretion on the CAMP‐, the cGMP‐ and the Ca2+‐pathway.

Baseline short‐circuit current was decreased by indometacin and tetrodotoxin in the distal colon, indicating a spontaneous production of neuronally acting prostaglandins. In contrast, baseline short‐circuit current in the proximal colon was decreased only by indometacin, but not by tetrodotoxin. Unidirectional flux measurements revealed that in the distal colon sodium and chloride were absorbed, while the proximal colon secreted chloride.

A morphological comparison between the distal and proximal epithelium revealed that the zonulae occludentes and the microvilli were longer in the distal colon. The size of the Golgi apparatus was several times larger in the crypt than in the surface region without differences between proximal and distal colon.

Distal segments were more sensitive to an activator of the Ca2+‐pathway, carbachol, or activators of the CAMP‐pathway such as forskolin and a CAMP‐analogue. In contrast, the activation of the cGMP‐pathway by a cGMP‐analogue or by the heat‐stable enterotoxin of E. coli (STa) was more effective in the proximal colon. The results give evidence for a segmental specificity with regard to the intracellular pathways responsible for the activation of secretion.
Acute effects of alcohol on unit activity in the motor cortex of freely moving rabbits: comparison with the limbic cortex
Authors: ALEXANDROV Y. I. , GRINCHENKO Y. V. , LAUKKA S. , JARVILEHTO T. , MAZ V. N.
Published: December 2008

Unit activity was recorded from the motor cortex of eight freely moving rabbits in order to examine the acute effect of ethanol (1 g kg‐1) on organization of unit activity and to compare it with our earlier results from the limbic cortex. The rabbits performed a food‐acquisition task in the experimental cage. Unit activity was recorded during behaviour in the control experiment followed by the alcohol experiment on the next day. After ethanol, behavioural mistakes and the duration of the behavioural cycle significantly increased. In the control experiments activation of 58% of the units had no constant relation to the phases of the behavioural cycle (non‐involved units), whereas 42% of the units were constantly activated during certain phases (involved units). Two per cent of the latter units were activated in relation to newly learned behavioural acts (e.g. pedal pressing; L units), 28% in relation to food seizure and/or grinding (S units) and 12% in relation to certain movements during different behavioural acts (M units). Ethanol had no effect on the number of active units and the same relation between the number of non‐involved and involved units or between the number of different types of involved units was found. However, the number of involved units decreased in the upper and increased in the lower cortical layers. Also the number of units with low background frequency increased, although the frequency within activations did not change. In our earlier study the number of active units in the limbic cortex decreased after ethanol by one third and the relation between the number of L and M units was reversed. Thus, acute effects of ethanol on unit activity in the motor and limbic cortex differ in the number of active units and in their behavioural specialization pattern, both of which change in the limbic, but not in the motor cortex. However, also in the latter the set of involved units changed and manifested as changes in the number of these units in the upper and lower cortical layers. Consequently, the differences between the effects of ethanol on the motor and limbic cortex are not simply quantitative, but ethanol changes the behavioural role of these two cortical areas in qualitatively different ways.
Children in sauna: hormonal adjustments to intensive short thermal stress
Authors: JOKINEN E. , VÄLIMÄKI I. , MARNIEMI J. , SEPPÄNEN A. , IRJALA K. , SIMELL O.
Published: December 2008

Hormonal response to Finnish sauna bath was investigated in 20 prepubertal children (age 5–10 years). Blood leukocyte count, plasma potassium, serum aldosterone, growth hormone and prolactin concentrations increased; plasma volume, plasma sodium, catecholamines, serum antidiuretic hormone, atrial natriuretic peptide (ANP), cortisol, and thyrotropin concentrations remained unchanged during sauna bath. One hour after sauna, serum thyrotropin, atrial natriuretic peptide and blood glucose concentrations decreased, whereas the rest of the hormones remained unchanged. Our results implicate that maintenance of homeothermia resulted in moderate hormonal changes in children during Finnish sauna bath which indicate similar adequate hormonal thermoregulatory adjustment as previously documented in adults.
Flashed pattern‐induced activity in the visual system: I. The short latency evoked response recorded from the cat visual cortex
Authors: SJÖSTRÖM A. , ABRAHAMSSON M. , NORRSELL K. , HELGASON G. , ROOS A.
Published: December 2008

Previous methods for estimating visual acuity have used the visual evoked response conventionally the late visual evoked response components or the steady‐state potential. The present experiments were undertaken to evaluate the possible use of short latency flashed pattern evoked responses in estimating pattern dependent activity in the cat visual system.

Recordings were made from the skull bone and the dura above the primary visual cortex and intracortically.

The visual evoked responses to patterned (checks) and non‐patterned light flashes of high intensity and short duration were recorded. The visual evoked response activity recorded from the cortical surface had an onset latency of 14–15 ms. The initial positive‐negative potential sequences of the responses were similar for patterned and non‐patterned stimuli, however a difference was recorded from 35–40 ms after stimulus. The smallest check size which separated a pattern from a non‐pattern VER was in the order of 10 min of arc. The results indicate that the short‐latency cortical VER may be used to estimate visual resolution.
The possible role of prostaglandin D2 in the long‐lasting airways vasodilatation induced by allergen in the sensitized pig
Authors: ALVING K. , MATRAN R. , LUNDBERG J. M.
Published: December 2008

Allergen‐induced nasal and bronchial vasodilatation and bronchoconstriction were studied in ascaris‐sensitized pigs with and without pretreatment with diclofenac sodium, to evaluate the contribution of prostanoids in these responses. The bronchoconstriction induced by allergen aerosol challenge was enhanced by diclofenac, whereas the duration of the bronchial vasodilatation was reduced from 80 to 30 min, without changing the maximal effect. However, both the maximal effect and the duration of the nasal vasodilatation were reduced upon nasal allergen challenge by 60% (P < 0.01) and from 72 to 16 min (P < 0.05), respectively. Bronchial challenge with the allergen also induced nasal vasodilatation of long duration and this response was highly sensitive to diclofenac pretreatment. I.v. injections of prostaglandins (PG) E1, E2, I2 and D2 revealed that only PGD2 induced vasodilatation of long duration in the airways without major effects on the systemic arterial blood pressure. Nebulization of PGD2 (0.7‐1.4 μmol) into the pig airways also induced marked vasodilatation of long duration (40 min), especially in the nasal circulation. The vasodilatory responses to PGD2 were not changed by systemic pretreatment with capsaicin or diclofenac. Challenge in the airways with platelet‐activating factor (PAF) produced bronchial and vascular responses similar to those seen with the allergen and the vasodilatory responses to PAF were partly sensitive to diclofenac.

We propose that a long‐lasting component of the allergen‐induced vasodilatation in the pig airways, especially in the nasal mucosa, may be caused by the release of PGD2, acting independently of sensory nerves. Allergen and PAF aerosol challenge in the lung may also induce the release of a vasodilatory prostaglandin, possibly PGD2, into the systemic circulation, thereby inducing nasal vasodilatation.
Effect of exercise on recovery changes in plasma levels of FFA, glycerol, glucose and catecholamines
Authors: BAHR R. , HØSTMARK A. T. , NEWSHOLME E. A. , GRØNNERØD O. , SEJERSTED O. M.
Published: December 2008

The prolonged effects of acute exercise on the plasma concentrations of FFA, glycerol, glucose and catecholamines were examined. Twelve young men performed exhaustive prolonged exercise on a cycle ergometer (80 minutes at 70–75% of Vo2 max), and in separate experiments they exercised for shorter durations (20, 40 and 80 minutes) and at lesser intensities (29, 50 and 75% of Vo2 max). Carbohydrate‐rich meals were given 2, 7 and 12 hours after exercise. Blood samples were taken while the subjects rested in bed during a 12–14–hour recovery period. Control experiments without exercise were also performed. In some subjects the plasma concentration of FFA after exhaustive exercise was increased to levels considered to be potentially hazardous, and the mean plasma level of FFA was increased for 6 hours and that of glycerol was increased for 2.5 hours after exercise. The plasma concentration of glucose was generally reduced for 12 hours after exhaustive exercise. Plasma catecholamines were increased for 2 hours after exhaustive exercise. We observed a preprandial increase in FFA and glycerol concentrations during recovery from exercise which was related to the duration and intensity of exercise. These findings indicate that the rates of FA utilization and TG–FA substrate cycling were increased in the recovery period after exercise, and that the magnitude of both depends on the duration and intensity of exercise.
Ability of omega‐3 fatty acids to restore the impaired glucose tolerance in a mouse model for type‐2 diabetes. Different effects in male and female mice
Authors: ISLIN H. , CAPITO K. , HANSEN S. E. , HEDESKOV C. J. , THAMS P.
Published: December 2008

Mice of both sexes were fed diets with 80 per cent animal or vegetable fat for 3 months. Half of the animals also received SuperEPA, which contains 61 % omega‐3 fatty acids. At the end of the feeding period the mice receiving animal fat had gained more weight than the controls and the mice receiving vegetable fat, and all fat diet groups, irrespective of sex or kind of diet, had become hyperglycaemic and had impaired intravenous glucose tolerance. The decay in plasma glucose during the tolerance tests was, however, significantly slower in the groups getting animal fat than in the groups getting vegetable fat. Supplementation with omega‐3 fatty acids only affected the male mice receiving the animal fat diet. Thus, these mice gained less weight, and both the hyperglycaemia and the impairment of the glucose tolerance were significantly less pronounced in this group than in the male mice fed animal fat without SuperEPA. In the groups eating fat diets, the plasma total cholesterol levels increased 50–100 per cent during the first 2 weeks of the experiment and then plateaued. In both sexes HDL‐cholesterol averaged approx. sixty‐five per cent of the total cholesterol content at the start of the experiment and was not changed significantly during the feeding period. It is concluded, that omega‐3 fatty acids do not seem to be suitable as a general means of ameliorating impaired glucose tolerance. It is further suggested that the fat‐fed mouse may be a useful animal model for further studies of the regulation of metabolism in type‐2 diabetes.
Effects of stimulation of the parasympathetic and sympathetic innervations in bursts on the syntheses of polyamines, DNA and protein in salivary glands of the rat: non‐adrenergic, noncholinergic responses
Authors: NILSSON B.‐O. , ROSENGREN E. , EKSTRÖM J.
Published: December 2008

The increase in the activity of ornithine decarboxylase, the key enzyme in the formation of polyamines, in the sublingual glands of the chloralose‐anaesthetized rat in response to stimulation of the parasympathetic innervation was enhanced by employing an intermittent pattern of nerve stimulation. 20 Hz in bursts delivered for 1 second every 10th second over a period of 3 hours increased the activity 1000‐fold, whereas a frequency of 2 Hz delivered continuously, and thus giving rise to the same total number of impulses as the burst stimulation, increased the enzyme activity only 50‐fold. Already 2 Hz in bursts caused the ornithine decarboxylase activity to increase. A parasympathetic non‐adrenergic, non‐cholinergic regulation of ornithine decarboxylase activity was shown in response to the two modes of stimulation. The increase to 2 and 20 Hz in bursts was 2‐ and 80‐fold, respectively, whereas it was 29‐fold to 2 Hz continuously. Increases in the concentration of the polyamine putrescine in response to burst stimulation of the parasympathetic nerve were found both in the absence and in the presence of atropine. The ornithine decarboxylase activity of the submaxillary gland was not affected by the parasympathetic stimulation. Stimulation of the sympathetic innervation was more effective in both types of glands, as to increases in the ornithine decarboxylase activity, when employing the continuous mode. In cultured tissue of the sublingual glands which, in vivo, had been subjected to parasympathetic stimulation in bursts (20 Hz), the syntheses of DNA and protein were increased as judged by the incorporation of radio‐labelled thymidine and leucine; in the presence of atropine the stimulation resulted only in increased synthesis of protein.
The ‘initial burst’ of human primary muscle spindle afferents has at least two components
Authors: EDIN B. B.
Published: December 2008

Ten muscle spindle primary afferents from the extensor digitorum communis muscle of man were studied with single unit afferent recordings. Responses to slow test stretches with three different pre‐history conditions were assessed to investigate the contribution of rapid stretches to the stretch sensitization phenomenon. In two of the conditions, the slow test ramps were preceded by rapid stretch after which the parent muscle of the receptor was either (a) kept short for 5 seconds or (b) kept long for 3.2 seconds and then returned to the short muscle length for 5 seconds. The third condition (c) consisted of a slow stretch from short to long muscle length followed by a rapid return to the short muscle length, in turn followed by 5 seconds at the short muscle length.

Afferent responses were depressed when the muscle had been kept at the long length after the rapid stretches (condition b) and enhanced when the muscle had been kept at the short length (conditions a & c). A prominent ‘initial burst’ was only present in the afferent discharge when the parent muscles of the primary endings had been kept short (condition a). A second, more prolonged burst was present for conditions (a) and (c) but was lacking or inconspicuous when the muscle had been kept long after rapid stretches (condition b). The rapid stretches in the stretch sensitization paradigm appear to be a primary factor not only for the enhanced responses of sensitized primary afferents but also for the depressed responses of desensitized primary afferents.
Participation of the GABAergic system of the turtle retina in the light adaptation process
Authors: KUPENOVA P. , VITANOVA L. , MITOVA L. , BELCHEVA S.
Published: December 2008

A comparative study was made of the ERG b‐ and d‐wave intensity‐response functions before and after GABAergic blockade by means of 0.4 mmol 1‐1 picrotoxin. A wide range of background intensities, including part of the high photopic range, were used. The intensity‐response functions of both the ERG waves fitted well to the Michaelis‐Menten equation (V/Vmax= In/(In+s̀n). A s̀‐value decrease and a Vmax and n increase were observed after picrotoxin treatment. The analysis of the intensity‐response functions shows that, under a wide range of backgrounds, the GABAergic neurons influence the on‐ and off‐response in the distal retina in a similar way. They decrease the gain and the contrast gain of the b‐ and d‐wave generating neuronal mechanisms and widen the intensity span of their responses under given background illumination. The GABAergic system is involved also in ‘response scaling’ in the on‐and off‐channels in the distal retina. A very important effect in this respect seems to be the equalization of the range of the responses to increment stimuli under different backgrounds.
Dyssynchrony of segment shortening in the anterior wall of the feline left ventricle
Authors: HEXEBERG E. , MATRE K. , BIRKELAND S. , LEKVEN J.
Published: December 2008

Non‐uniformity of regional contraction may be both spatial and temporal. This study was undertaken to deal with the temporal aspects of shortening and to quantify non‐uniformity with regard to timing. Nine cats were anaesthetized and artificially ventilated. Two pairs of ultrasonic crystals were situated in the anterior midwall of the left ventricle to measure regional shortening. One pair, longitudinal segment, was oriented to align with midwall fibres. The other pair, transverse segment, was placed perpendicular to the first one. Registrations in control state, during caval occlusion, and during aortic constriction were carried out with and without isoprenaline infusion. Cyclic events were analysed in terms of phase angle, 0–2π representing one heart cycle. Transverse segments showed marked shift of duration of shortening, from 1.19π± 0.06π (meanæM) in the control state to 0.40π± 0.14π during caval occlusion with isoprenaline infusion. Duration of shortening of longitudinal segments showed less prominent shift with mean values between 1.38π and 1.11π. Regional uniformity of timing, expressed as synchronization index, varied markedly with interventions (P < 0.0005). Dyssynchrony was most prominent during caval occlusion with mean values less than 0.6. A simple model of force generation for the two segments visualizes that segment shortening of the transverse segment is of shorter duration than the longitudinal segment and a common mechanism for temporal and spatial non‐uniformity within a region could be elaborated. This study quantifies both the time course of shortening and temporal non‐uniformity of two cross‐oriented segments within the same myocardial region.