bluuebunny/crossref_metadata_2025 huggingface dataset:
Tubular response to hormones is blunted in weanling rats
Authors: KARLÉN J. , RANE S. , APERIA A.
Published: December 2008

The renal responses to atrial natriuretic peptide (ANP), parathyroid hormone (PTH) and arginine vasopressin (AVP) were studied in anaesthetized weanling and adult rats with clearance methods. In rats receiving PTH, thyroparathyroidectomy (TPTX) was performed prior to the study. The results showed that GFR remained unchanged in both age groups during infusion with ANP, AVP and PTH after TPTX as well as with TPTX alone. During ANP infusion, the urine flow rate increased from 0.01 ± 0.002 to 0.029 ± 0.004 ml (100 g body wt)‐1 min‐1 (P< 0.001) and the fractional sodium excretion increased from 0.48 ± 0.1 to 3.0 ± 0.4% (P< 0.001) in the adult rats; no significant changes were observed in the weanling rats. Phosphate excretion was not influenced by ANP in either age group. After TPTX, both net and fractional phosphate excretion decreased in both age groups. During PTH infusion in TPTX rats, both net and fractional phosphate excretions increased significantly in the adult rats but were unchanged in the weanling rats. In rats of the same age, the renal concentrating capacity and urinary excretion of prostaglandin E2 (PGE2) were determined after dehydration. The renal concentrating capacity was lower, and the renal excretion of PGE2 was higher, in the weanling than in the adult rats. Furthermore, the concentrating mechanism seems not to be influenced by indomethacin treatment in either age group. It is concluded that the tubular responses to ANP and PTH are blunted in the immature kidney and that the renal excretion of PGE2 is not an important factor in the regulation of the concentrating capacity in the weanling rat.
Effects of pinacidil on isolated human corpus cavernosum penis
Authors: HOLMQUIST F. , ANDERSSON K.‐E. , HEDLUND H.
Published: December 2008

Intracavernous injection of vasoactive agents causing vasodilatation is widely recognized in the diagnosis and treatment of erectile dysfunction. However, papaverine, the drug most commonly used for this purpose, may produce priapism and fibrotic lesions, and alternatives without these disadvantages are desirable. In this study we investigated the effects of pinacidil, a vasodilator drug supposed to act through the opening of K+ channels, on isolated human corpus cavernosum penis. Besides abolishing spontaneous contractile activity, pinacidil effectively relaxed preparations precontracted by noradrenaline 10‐6 M and inhibited contractions induced by electrical field stimulation of nerves. Furthermore, pinacidil depressed contractions induced by low‐K+ solutions (≤ 20 mM) and concentration‐dependently increased the efflux of 86Rb from preloaded tissue. The results suggest that pinacidil is effective in relaxing isolated human erectile tissue, probably by way of increased K+ permeability and subsequent hyperpolarization. Clinical testing seems justified in order to find out if K+‐channel openers can be used in the pharmacological treatment of impotence.
Duodenal alkaline secretion in rabbits: influence of artificial ventilation
Authors: HOLM L. , FLEMSTRÖM G. , NYLANDER O.
Published: December 2008

The effect of artificial ventilation on duodenal alkaline secretion and blood flow was studied in sodium pentobarbital‐anaesthetized rabbits. A duodenal segment (˜ 3 cm) was cannulated in situ and continuously perfused with isotonic saline, and the bicarbonate secretion was titrated by pH‐stat. Compared with the spontaneous breathing state, artificial ventilation improved the respiratory status of the animal, increasing Po2 and decreasing both PCO2 and plasma bicarbonate. Duodenal blood flow as measured with laser‐Doppler flowmetry was not altered but the alkaline secretion was reduced. Pretreatment with the α2‐adrenoceptor antagonist yohimbine (0.5 mg kg‐1 i. v., followed by 0.5 mg kg‐1 h‐1 i. v.) or the ganglionic blocker hexamethonium (10 mg kg‐1 i. v.) did not affect the decline in duodenal alkaline secretion in response to artificial ventilation. Nor did these pretreatments affect the changes in plasma bicarbonate and PCO2 or significantly alter the blood flow. Increasing PCO2 in the respirator air increased the plasma PCO2 and bicarbonate concentration as well as the duodenal bicarbonate secretion. Pretreatment with the carbonic anhydrase inhibitor acetazolamide (80 mg kg‐1 i. v.) reduced the bicarbonate secretion, and artificial ventilation induced a further reduction. Increasing PCO2 in the respirator in the animals pretreated with acetazolamide did not affect the bicarbonate secretion. Duodenal alkaline secretion was thus always reduced on artificial ventilation. The mechanism for this reduction does not seem to involve the sympathetic nervous system or the blood flow, but appears to be the consequence of alterations in the plasma concentration of bicarbonate and the plasma PCO2.
Occurrence and effects of endothelin in guinea‐pig cardiopulmonary tissue
Authors: FRANCO‐CERECEDA A. , MATRAN R. , LOU Y.‐P. , LUNDBERG J. M.
Published: December 2008

Endothelin‐like immunoreactivity (‐LI) was present in the guinea‐pig cardiopulmonary tissues with the associated autonomic neural supply. The highest levels were found in the stellate ganglion (15 pmol g‐1) followed by the vagus nerve, pulmonary artery, lung and right atrium of the guinea‐pig. Endothelin I, but not endothelin III, induced an increase in contractile force and frequency followed by an atropine‐resistant inhibition of right atrial contractility at higher concentrations. Exposure to endothelin I caused a pronounced, long‐lasting coronary vasoconstriction as revealed by a decrease in perfusate outflow. In addition, both heart and contractile force were attenuated. Guinea‐pig bronchi in vitro contracted upon exposure to endothelin I and III, but only endothelin I caused contraction of pulmonary arteries. The C‐terminal hexapeptide of endothelin I did not influence right atrial, bronchial or pulmonary artery contractility. Endothelin I increased the mean arterial pressure and insufflation pressure and decreased the heart rate in the guinea‐pig in vivo.

In conclusion, endothelin‐LI is present in the cardiovascular, respiratory and nervous tissues of the guinea‐pig and endothelin induces strong coronary and pulmonary vasoconstrictor effects. The effects on atrial contractile force and frequency are concentration‐dependent with stimulation at lower and inhibition at higher concentrations. Based on the diversity in response to endothelin III in the bronchi compared to atrium and pulmonary artery, it may be suggested that different receptor populations exist in bronchial and cardiovascular muscle, although the cellular localization and forms of endothelin present in guinea‐pig cardiopulmonary tissue remain to be established.
Endothelin‐induced vasoconstriction and release of atrial natriuretic peptides in the rat
Authors: ÖHMAN K. P. , HOFFMAN A. , KEISER H. R.
Published: December 2008

Endothelin‐1 (ET‐1) was given to male Sprague‐Dawley rats in i. v. bolus injections to evaluate its effects on blood pressure and the release of atrial natriuretic peptides (ANP). In awake rats ET‐1 (0.3, 1 and 3 nmol kg‐1 body wt) transiently reduced mean arterial pressure (MAP) and increased heart rate (HR), followed by a prolonged increase in MAP. The magnitude of these changes and the duration of the increase in MAP were dose‐related. The increase in MAP was completely blocked by verapamil, reversed by sodium nitroprusside, slightly reduced by rat atrial natriuretic factor (103–126) and unaffected by saralasin. The initial fall in MAP was also unaltered by these agents. In all groups HR changes were mirror‐images of MAP. In anaesthetized rats ET‐i (1 nmol kg‐1 body wt) induced a sustained release of ANP. Right atrial pressure increased transiently and then fell below baseline. When the increase in MAP was blocked with sodium nitroprusside, ET‐1 still produced an increase in ANP. In conclusion we find that repeated i. v. administration of ET‐1 induces immediate vasodilatation, without signs of tachyphylaxis, followed by long‐lasting severe vasoconstriction. Baroreceptor function seems to be unchanged. ET‐1 appears to induce ANP release by a direct action on atrial myocytes, independent of right atrial and systemic arterial pressure. We hypothesize that endothelin may be a mediator of stretch‐induced release of ANP.
Inhibitors of lipoxygenase increase the ovulation rate in the in‐vitro perfused luteinizing hormone‐stimulated rabbit ovary
Authors: HELLBERG P. , HOLMES P. V. , BRÄNNSTRÖM M. , OLOFSSON J. , JANSON P. O.
Published: December 2008

In order to determine whether leukotrienes, products of the lipoxygenase pathway, are involved in ovulation, pairs of rabbit ovaries were treated with the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and caffeic acid (CA) while being perfused in vitro. The control ovaries from each rabbit received luteinizing hormone (LH) (1.5–2.25 μg ml‐1) while the contralateral ovaries were treated with LH + NDGA (100μM) or LH + CA (100 μM). The numbers of ovulations from both the LH + NDGA‐ and LH + CA‐treated ovaries were significantly higher (P < 0.05) than from their respective LH‐stimulated controls. Treatment with NDGA alone in the perfusate did not cause any ovulation, while CA alone caused one ovulation from one of six ovaries perfused. Ovarian tissue levels of prostaglandins after 7 h of perfusion with LH + NDGA or with LH alone showed that, in five of the six ovaries perfused in this group, the tissue levels of PGE2, 6‐keto‐PGFlα and PGF2α were higher in the presence of NDGA. The mean differences were significant (P < 0.05) for prostacyclin but not significant (P > 0.05) for PGE2 and PGF2α.

Our interpretation of the findings is that, when used for blocking the lipoxygenase pathway, NDGA and CA increase the substrate availability for the cyclo‐oxygenase pathway of arachidonic acid metabolism, resulting in a net increase in prostaglandins. The increased ovarian levels of prostaglandins, especially prostacyclin, may cause the observed increase in ovulation rate. Consequently, although the leukotrienes may be involved in the mechanism of ovulation in the rabbit, their effects appear to be less pronounced than those of prostaglandins.
Sympathetic activity influences the vascular axon reflex in the skin
Authors: HORNYAK M. E. , NAVER H. K. , RYDENHAG B. , WALLIN B. G.
Published: December 2008

The interaction between changes of skin blood flow evoked by centrally mediated reflexes and local axon reflexes was studied in healthy subjects. Axon reflexes were evoked on the dorsum of the hand by transcutaneous electrical stimulation and reflex changes of blood flow by changes of ambient temperature, deep breath and emotional stress. Skin blood flow was measured by two laser‐Doppler flowmeters, the probes of which were situated 6–8 mm from the stimulating electrode (monitoring net flow responses) and several centimetres away (monitoring generalized reflex responses only). The axon reflex responses were markedly diminished by body cooling but did not change during body warming. In warm subjects, a deep breath and emotional stress caused transient reductions of the flow response evoked by the electrical stimulation. Regional anaesthesia of the nerve(s) innervating the stimulated skin area led to marked increases of axon reflex responses in cold subjects, but no changes occurred in warm subjects. The anaesthesia also eliminated the transient flow reductions evoked by deep breaths and emotional stress. Since the applied stimuli are known to change skin sympathetic activity, it is concluded that sympathetic (presumably vasoconstrictor) impulses destined for the skin may reduce axon reflex responses.
Variations in left ventricular volume alter myocardial oxygen consumption more at low than at high inotropy
Authors: ANDERSEN F. R. , ILEBEKK A. , KIIL F.
Published: December 2008

Variations in left ventricular (LV) wall tension during changes in LV end‐diastolic volume significantly affect myocardial oxygen consumption (MVO2). In the present study we examined if the reduction in M VO2) per beat accompanying a decline in LV end‐diastolic volume at constant LV systolic pressure (LVSP) is dependent on the level of myocardial inotropy. In six anaesthetized open‐chest pigs, the blood volume was expanded by i. v. infusion of a Ringer solution. At constant heart rate (by atrial pacing) and LVSP (by adjustments of a proximal aortic snare), LV end‐diastolic volume was reduced in steps by withdrawals of blood. This procedure was performed at high inotropy (during a continuous intracoronary infusion of isoproterenol, 0.40 ± 0.08 μg min‐1), and at low inotropy (after i. v. injection of 3.4 ± 0.2 mg propranolol).

LVSP was about 25 mmHg higher at high than at low inotropy. The fall in LV tension was therefore greater during blood volume reductions at high than at low inotropy because the fall in LV end‐diastolic volume was almost identical and was initiated from the same level at both high and low inotropy. Nevertheless, the slope of the MVO2/LV end‐diastolic volume relationship was significantly (P < 0.05) less steep at high (1.26 ± 0.30 μmol 100 g ‐1 mm‐1) than at low inotropy (2.06 ± 0.48 μmol 100 g‐1 mm‐1). MVO2 per beat fell by only 0.79 ± 0.17 μmol 100 g‐1 (from 6.03 ± 0–4±5 μmol 100 g‐1 = 13.8 ± 3.1%) at high inotropy compared with 1.21 ± 0.19 μmol 100 g‐1 (from 3.79 ± 0.29 μmmol 100 g‐1 = 30.5 ± 3.4%) at low inotropy.

The greater reduction in MVO2 per beat at low inotropy was associated with a reduction in LVdP/dt of 24 ± 4%, whereas LVdP/dt remained unchanged at high inotropy. Thus, the changes in MVO2 per beat and LVdP/dt were closely correlated (r = 0.94), and because the reduction in contractility was present only after propranolol administration it appeared to be induced by mechanisms other than variations in β‐adrenergic stimulation.
Actions of endothelin on isolated corpus cavernosum from rabbit and man
Authors: HOLMQUIST F. , ANDERSSON K.‐E. , HEDLUND H.
Published: December 2008

The effects of endothelin, a vasoconstrictor peptide produced by vascular endothelial cells, were investigated in isolated rabbit and human corpus cavernosum (CC). Preparations from both rabbit and man were potently contracted by endothelin in a concentration‐dependent manner. The contractions developed slowly, could not be reversed despite frequent washings, and were only partly inhibited by the Ca2+ channel blocker nimodipine. Even in Ca2+‐free medium containing the chelator EGTA a small contractile component persisted. In rabbit CC, the contractions in Ca2+‐free medium were not affected by nimodipine, the Ca2+‐channel agonist BAY K 8644, or by depletion of intracellular Ca2+ stores sensitive to noradrenaline (NA) and caffeine, but were almost abolished by the protein kinase C inhibitor H7. In both rabbit and man, carbachol and vasoactive intestinal polypeptide concentration‐dependently relaxed preparations contracted by endothelin. The relaxations induced by carbachol were antagonized by atropine. Endothelin enhanced concentration‐dependently the contractions induced by exogenously applied NA in rabbit CC. The enhancement was more pronounced at low concentrations of NA.

This study shows that endothelin potently contracts isolated penile erectile tissue. The contraction seems to be mediated mainly by influx of Ca2+ through the cell membrane, which partly occurs through a pathway other than voltage‐operated calcium channels. However, involvement of other mechanisms cannot be excluded. The results suggest that endothelin can play a role in penile erectile mechanisms.
The effect of hydration status on plasma vasopressin release during physical exercise in man
Authors: VIINAMÄKI O.
Published: December 2008

The effect of hydration status on plasma vasopressin release was studied in six healthy volunteers undergoing a 15‐min bicycle ergometer exercise. The hydration states were dehydration, produced by a 14‐h abstinence from fluids, euhydration, and hyperhydration caused by drinking 20 ml kg‐1 water 2 h before the exercise. The exercise load was individually adjusted to 70% of maximal oxygen uptake. Exercise resulted in a significant increase in plasma vasopressin only during euhydration, in spite of the marked increase in plasma osmolality in all hydration states. The vasopressin concentrations during hyperhydration were significantly lower than during euhydration. Plasma volume and serum sodium were significantly affected by the exercise. The highest responses were obtained in euhydration and the lowest in hyperhydration. On this basis, the body's drive towards normal homeostasis and to the best ability to respond to the challenges of the environment is rational.
Mucosal/submucosal blood flow in the small intestine in pigs determined by local washout of 133Xe and microsphere techniques
Authors: MORTENSEN P. E. , OLSEN J. , SEJRSEN P. , BÜLOW J. , EDELFORS S.
Published: December 2008

In 11 anaesthetized pigs a laparotomy was performed and the mucosal and submucosal blood flow rate in the small intestine of the pig was determined by a local application of 133Xe and by 6.5‐μm radioactive microspheres. The 133Xe washout plotted in a semilogarithmic diagram showed a multiexponential configuration. As localization studies of 133Xe in the intestinal mucosa showed a constant high concentration of 133Xe in the luminal part of the mucosa due to shunting by diffusion, the initial slope of the 133Xe washout was used for blood flow determination in the mucosa/submucosa. There was a good relationship between blood flow determined by the two techniques. The correlation coefficient, R, between the two techniques was 0.89.
Change in the pattern of behavioural specialization of neurons in the motor cortex of the rabbit following lesion of the visual cortex
Authors: ALEXANDROV YU. I. , GRINCHENKO YU. V. , JARVILEHTO T.
Published: December 2008

In order to find out whether damage of the visual cortex (area 17) of the brain results in a functional reorganization of the motor cortex, experiments were carried out with freely moving rabbits performing a food acquisition task in an experimental cage. Two rabbits served as controls, while in three rabbits the visual cortex was bilaterally damaged. Analysis of the activity of 575 neurons in the control and operated rabbits after the recovery of the original instrumental food acquisition behaviour revealed a marked difference in the behavioural specialization of the neurons in the motor cortex of two operated rabbits compared with the control animals. Although the same types of units as in the control rabbits could be found in the operated rabbits (M neurons activated in relation to body and limb movements, S neurons activated in relation to food seizure and L neurons activated in relation to learned food acquisition task), the number of S units was about half of that in the controls and the number of L units about double. The relative number of activations of the neurons in the operated rabbits was significantly less frequent during the food seizure and more frequent during the learned behaviour. This difference indicates a change in the pattern of behavioural specialization of the neurons in the motor cortex due to the damage of the visual cortex. In this reorganization, the motor cortex became more like (but not identical to) visual and limbic cortices that normally contain noticeably more L neurons than the motor cortex. The number of neurons activated in relation to the behaviour in the operated rabbits, as compared with the control animals, was smaller in the upper and larger in the lower layers of the motor cortex. This may indicate recruitment of new neurons from the lower cortical layers.
Prostaglandin E2 binding sites in human renal tissue: characterization and localization by radioligand binding and autoradiography
Authors: ERIKSSON L.‐O. , LARSSON B. , HEDLUND H. , ANDERSSON K.‐E.
Published: December 2008

The prostaglandin E2 (PGE2) binding site in human kidney was characterized in membrane preparations from cortex, outer medulla and inner medulla using radioligand binding techniques. The localization of the binding sites for [3H]PGE2 was visualized autoradiographically. In the membrane suspensions, the highest level of specific [3H]PGE2 binding was detected in the outer medulla (5max = 335 ± 28 fmol mg‐1 protein) followed by the inner medulla (Bmax = 258 ± 21 fmol mg‐1 protein) and the cortex (Bmax = 143 ± 22 fmol mg‐1 protein). The binding was of high affinity with KD values between 3.7 and 6.2 nM in the various regions. Unlabelled prostaglandins competed for the [3H]PGE2 binding sites in the following rank order of potency: PGE2 ≅ PGE1 > PGF2α ≅ PGA2 > PGB2 > PGI2 ≅ PGD2. Autoradiographs revealed that a high density of [3H]PGE2 (2 nM) binding sites were located on the distal tubule, particularly on the thick ascending limbs of Henle. Lower densities of [3H]PGE2 binding sites were found on the medullary collecting ducts and possibly on the thin loops of Henle. In contrast, no specific [3H]PGE2 binding could be found on the proximal tubule, glomeruli or on blood vessels. This distribution is in accordance with the assumed site of action for the salt and water regulatory function of PGE2.
ATP content in single fibres from human skeletal muscle after electrical stimulation and during recovery
Authors: SÖDERLUND K. , HULTMAN E.
Published: December 2008

The ATP content was measured in type I and type II fibres from human vastus lateralis muscle at rest, after electrical stimulation and during recovery. At rest the mean values were 25.2 ± 4.02 and 25.9 ± 3.62 mmol kg‐1 dry muscle (mean ± SD) for type I and type II fibres respectively. Normal distribution curves were found for both types I and II fibres. After intermittent electrical stimulation for 83 s (1.6 s Stimulation, 1.6 s pause) with occluded blood flow, the force generation decreased to 22± of the initial value and the muscle tissue showed a mean decrease in ATP to 14.8 and in phosphocreatine to 5.44 mmol kg‐1 dry muscle; lactate increased to 128.9 mmol kg‐1 dry muscle. The ATP content in isolated fibres was equally decreased in both fibre types to 16 mmol kg‐1 dry muscle. In 11± of the fibres the ATP content was lower than 10 mmol kg‐1 dry muscle. After 15 min rest with intact blood circulation ATP was completely resynthesized in type I fibres and to 91± in type II fibres.
Myelin basic protein stimulates insulin and glucagon secretion from rat pancreatic islets in vitro and in vivo
Authors: KOLEHMAINEN E. , KNIP M. , LEPPÄLUOTO J.
Published: December 2008

The effect of myelin basic protein on insulin and glucagon secretion from rat pancreatic islets was studied in vivo and in vitro. The myelin basic proteins isolated from bovine, human and rat brains all stimulated insulin secretion in a similar fashion. In a static incubation of isolated pancreatic islets, myelin basic protein at doses of 15.6–250 μg in a 0.5‐ml reaction volume (1.7 times 10‐8 to 2.7 times 10‐5 M) significantly stimulated hormone release. Maximal stimulation, obtained at the 250‐μg dose, was 6.5‐fold greater than control for insulin secretion and 6.7‐fold greater than control for glucagon secretion. In the case of glucagon no saturation was observed, but saturation was obvious for insulin release at doses of myelin basic protein of 62.5–250μg, larger doses causing permeabilization of the islet membranes as indicated by leakage of acid phosphatase. At a 100‐μg dose the time course of insulin secretion induced by myelin basic protein indicated a fast initial release, and after the first 2 h only a little more insulin was released. At the lower doses of myelin basic protein (11 and 33μg) the secretion rate was nearly constant after the first hour. Significant stimulation of glucagon release by myelin basic protein was seen after 60 min, the rate of release being roughly constant at 33‐and 100‐μg doses thereafter. At the 11‐μg dose significant stimulation of hormone release was observed only after a 4‐h incubation. Lowering the temperature from 37 to 27 and 20°C reduced both basal and stimulated hormone secretion, the extent of stimulation over the basal level remaining the same at all temperatures only for insulin secretion at a dose of myelin basic protein of 100 μg.

A dose of 10 mg myelin basic protein injected intravenously into anaesthetized rats resulted 15 min after injection in a circulating concentration of myelin basic protein of 34.7 μg ml‐1 (1.7 times 10‐6 M) as measured by our radioimmunoassay. It stimulated insulin secretion (P < 0.01), having no significant effect on plasma glucagon levels.

Since myelin basic proteins have been shown to display fusogenic properties in cell‐free membrane systems, we propose that myelin basic protein exerts its hormone‐releasing effect by aggregating and fusing the hormone‐containing vesicles to the cell plasma membranes.
Viscoelastic properties of the slowly adapting stretch receptor muscle of the crayfish
Authors: RYDQVIST B. , SWERUP C. , LANNERGREN J.
Published: December 2008

The viscoelastic properties of the muscle associated with the slowly adapting stretch receptor organ of the crayfish (Astacus astacus) were studied by recording the tension response to various length changes. When steady‐state length changes were applied to the muscle, the tension developed in a non‐linear way, increasing slowly for small extensions and rapidly when extension increased. Muscle tension responses to ramp‐and‐hold extensions were characterized by a transient peak followed by a gradual decline in tension. At the onset of the ramp the tension increased rapidly, similar to the response seen in resting skeletal muscle. The relation between peak dynamic tension and extension was non‐linear. In a log‐log plot the relation was linèar with a mean slope of 1.4. At small extensions (< 5%) the slope seemed to be lower. The experimental results have been analysed in relation to a viscoelastic model consisting of a Voigt element in series with a non‐linear spring. The model could describe both the static length‐tension relation and the dynamic response, but different parameters for the springs had to be used for the two cases. When the measured tension response was transformed by an exponential function of the squared tension, in accord with recent findings on stretch‐activated channels, a good agreement was obtained with the time course of the receptor currents. Adaptation is thus likely to be caused by both the mechanical properties of the receptor muscle and the characteristics of stretch‐activated channels of the neuron.
Effects of magnesium on isolated human fetal and maternal uteroplacental vessels
Authors: SKAJAA K. , FORMAN A. , ANDERSSON K.‐E.
Published: December 2008

The effects of Mg2+were studied in human umbilical arteries, stem villous arteries and maternal intramyometrial arteries. The vessels were dissected and mounted in organ baths, and isometric tension was recorded. In all fetal preparations investigated, Mg2+(0.5–6.0 mM) in a concentration‐related way decreased pD2values for prostaglandin F2αresponses. The maximum response to prostaglandin F2awas depressed in umbilical arteries, but remained unaffected in stem villous artery preparations. In stem villous arteries pretreated in Ca2+‐free medium, increasing concentrations of Mg2+markedly depressed the response to Ca2+after stimulation with K+ or prostaglandin F2αsuggesting that Mg2+inhibited transmembrane calcium influx and interfered with intracellular calcium effects. In both stem villous and intramyometrial arteries, increasing concentrations of Mg2+increased EC50values for responses to K+, whereas Emaxvalues were unaffected. Mg2+produced relaxation of agonist‐induced contractions by up to 60% in stem villous arteries and up to 40% in intramyometrial artery preparations. The relaxant effect of Mg2+did not seem to be mediated through the endothelium or through changes in the synthesis of prostanoids, since endothelial disruption and treatment with indomethacin left the responses to Mg2+unaffected.

Relaxation of vessels important for resistance regulation in the human uteroplacental vascular bed may be of benefit when uteroplacental blood flow is impaired, and the present results support the established use of magnesium sulphate in the treatment of pre‐eclampsia.
Ageing alters the myosin heavy chain composition of single fibres from human skeletal muscle
Authors: KLITGAARD H. , ZHOU M. , SCHIAFFINO S. , BETTO R. , SALVIATI G. , SALTIN B.
Published: December 2008

The myosin heavy chain composition of single fibres (n = 1088) was analysed with an electrophoretic technique in biopsy material from m. vastus lateralis (n = 5) and m. biceps brachii (n = 4) of young (23–31 years old) and elderly men (68–70 years old). In m. vastus lateralis, elderly subjects had a higher proportion of fibres showing a coexistence of myosin heavy chain types I and IIa (20 ± 3% vs 8 ± 1%, P < 0.05) and of myosin heavy chain types IIa and IIb (33 ± 2% vs> 12 ± 4%, P < 0.05). In contrast, the young subjects had a higher proportion of fibres containing only myosin heavy chain type I (50±5% us 33 ± %, P < 0.05) and type IIa (26 4 3% vs> 12 ± 2%, P < 0.05). A similar pattern of myosin heavy chain expression was found in single fibres from m. biceps brachii, with the exception that the elderly subjects had a lower proportion of fibres with coexistence of types IIa and IIb (23 ± 1% vs 34 ± 20, P < 0.05) and a higher proportion of fibres containing only myosin heavy chain type IIa (25 ± 5 % us> 12 ± 20, P < 0.05). Three fibres from m. biceps brachii contained all three isoforms. These results indicate that coexistence of myosin heavy chain isoforms in single fibres is present in skeletal muscles of young adults, and that there is an increased occurrence of this phenomenon with ageing. Whether this reflects an ongoing transition process or a ‘dynamic equilibrium’ between the fibre populations is presently unsettled.
Different‐sized mRNAs from GH4C1 cells induce a TRH‐dependent electrical response in Xenopus laevis oocytes
Authors: WRIGHT M. S. , KARLSEN H. E. , PAULSSEN E. J. , MEYERHOF W. , HØGSET A. , GAUTVIK K. M.
Published: December 2008

Poly(A)+ RNA from the GH4C3 rat pituitary cell line elicited a thyrotropin releasing hormone response in Xenopus luevis oocytes which could be measured as a change in membrane current by the voltage‐clamp method. Oocytes injected with poly(A)+ RNA from GH42C1 cells which do not bind thyrotropin releasing hormone or with buffer solution alone did not show this response. Size fractionation of total poly(A)+ RNA by sucrose density‐gradient centrifugation shows two response maxima representing various mRNA fractions larger than 18s. These results indicate the presence of thryotropin releasing hormone receptor mRNA heterogeneity where the smallest mRNA is at least 2 kb.
Increase in the proportion of fast‐twitch muscle fibres by sprint training in males
Authors: JANSSON E. , ESBJÖRNSSON M. , HOLM I. , JACOBS I.
Published: December 2008

Fifteen male physical education students were studied. The subjects trained for 4–6 weeks, 2–3 days per week, on a mechanically braked bicycle ergometer. A training session consisted of repeated 30‐s ‘all‐out’ sprints on a Wingate bicycle ergometer, on which the brake band of the flywheel was loaded with 75 g kg‐1 body wt, with rest periods of 15–20 min between consecutive sprints. Thigh muscle biopsies were taken before and after the training period and were analysed for fibre types using a myofibrillar ATPase stain. The proportion of type I fibres decreased from 57 to 48% (P < 0.05) and type IIA fibres increased from 32 to 38% (P < 0.05). This study indicates that it is possible to achieve a fibre type transformation with high‐intensity training. The effect of two‐legged ‘sprint’ training on muscle fibre type composition may be related to a changed pattern of muscle fibre activation (e.g. an increased stimulation frequency). A change in fibre activation frequency may induce an increased synthesis of type II fibre myosin (fast myosin). Hormonal influences such as enhanced adrenergic stimulation of the muscle fibres cannot be excluded as a contributing factor, however.
Reabsorption and intracellular transport of cytochrome c and lysozyme in rat kidney
Authors: HYSING J. , TOLLESHAUG H. , CURTHOYS N. P.
Published: December 2008

Renal uptake and degradation of cytochrome c and lysozyme were investigated, using preparations that were labelled by means of covalent coupling of either protein to iodinated tyramine‐cellobiose. Following proteolytic digestion, the label remains ‘trapped’ within intracellular organelles. Within 15 min after intravenous injection, 43% of the [1251]tyramine‐cellobiose‐cytochrome c and 29% of the [1311]tyramine‐cellobiosd ysozyme were recovered in the kidneys. Isopycnic sucrose‐gradient frac‐tionation indicates that the two proteins initially exhibit closely similar intracellular distributions, being associated with vesicles of an equilibrium density slightly lower than that of plasma membranes. However, within 5 min after injection, the two proteins exhibit distinctly different distribution profiles. The [1251]tyramine‐cellobiose‐cytochrome c is localized predominantly in the lysosomal fraction of the gradient. The [1311]tyramine‐cellobiose‐lysozyme is also translocated to the lysosomal fraction, but at a much lower rate. For both proteins, the rates of intracellular degradation correlate with their rates of translocation. The observed difference in their kinetics of intracellular movement suggests that the two proteins are translocated at different rates into transport vesicles.
Transient appearance of vacuoles in fatigued Xenopus muscle fibres
Authors: LÄNNERGREN J. , WESTERBLAD H. , FLOCK B.
Published: December 2008

In the preceding paper we showed that post‐contractile depression is accompanied by an increased light scattering in the light microscope, which suggests an association between morphological changes and the force reduction. In the present paper the morphology of fatigued fibres has been studied using electron microscopical techniques. Fibres fixed in glutaraldehyde during maximum post‐contractile depression (about 20 min after fatiguing stimulation) contained a large number of vacuoles. Fibres fixed earlier displayed generally swollen and in some cases vesiculated mitochondria, but only a few vacuoles. Fixation methods aiming at visualizing the T‐tubular system revealed apparent communications between T‐tubules and vacuoles; apart from this the T‐tubular system, as well as the triadic junctions, appeared to be normal. We consider it most likely that the vacuoles primarily originate from damaged mitochondria, but other possibilities cannot be excluded. Further, a simple causal relation between the observed ultrastructural changes and the force depression is not obvious. Rather we suggest that post‐contractile depression is caused by additional changes in the triadic junctions, which were not detected with the present techniques.
Contractile effects of endothelin‐I and localization of endothelin binding sites in rabbit lower urinary tract smooth muscle
Authors: GARCIA‐PASCUAL A. , LARSSON B. , ANDERSSON K.‐E.
Published: December 2008

In isolated rabbit bladder and urethral smooth muscle, endothelin‐1 caused concentration‐related, slowly developing contractions that were difficult to wash out. Relative to contractions induced by K+ (124 mM), contractions in bladder preparations reached a higher amplitude than in urethral preparations. There was a marked tachyphylaxis to the effects of the peptide. The endothelin‐l‐induced contractions were not significantly affected by phentolamine or indomethacin in the urethra, or by scopolamine or indomethacin in the bladder. Incubation for 30 min in a Ca2+‐free solution abolished the endothelin‐l‐induced contractions. Nifedipine did not affect the actions of endothelin‐1 in the urethra but had a marked inhibitory action on its effects in the bladder. In the presence of endothelin‐1, Ca2+‐induced contractions were significantly blocked by nifedipine in the bladder but not in the urethra.

Urethral preparations at resting tension responded to electrical stimulation by tetrodotoxin‐sensitive, frequency‐dependent contractions sensitive to α‐adrenoceptor blockade. Pretreatment with endothelin‐1 (10‐9′ M) produced a significant increase in the nerve‐induced contractions but had no significant effect on contractions induced by exogenous noradrenaline. Endothelin‐1 did not affect spontaneous or stimulation‐induced efflux of 3H‐labelled noradrenaline in urethral smooth muscle. Preparations contracted by endothelin‐1 were frequency‐dependently relaxed by electrical stimulation. The peptide had no significant effect on the responses induced by electrical stimulation in the bladder preparations.

In both bladder and urethra, [125]endothelin‐l binding sites were found mainly in the outer longitudinal muscle layer, in vessels and in the submucosa. The highest density of binding sites appeared to be in vessels and the outer muscle layer in both types of muscle.

The results suggest that in the rabbit both bladder and urethral smooth muscle contain binding sites for endothelin. The peptide has contractant effects dependent on extracellular calcium in both types of tissue, but voltage‐operated calcium channels seem to involved in activation only of bladder smooth muscle. The functional importance of endothelin‐1 in the rabbit lower urinary tract remains to be elucidated.
Augmented sympathetic nerve activity in response to stressors in young borderline hypertensive men
Authors: MATSUKAWA T. , GOTOH E. , UNEDA S. , MIYAJIMA E. , SHIONOIRI H. , TOCHIKUBO O. , ISHII M.
Published: December 2008

To determine whether there may be an abnormality in sympathetic nerve activity in response to physical and psychological stressors, we microneurologically recorded muscle sympathetic nerve activity in 11 normotensive and 9 borderline hypertensive, age‐matched men. Supine blood pressure, plasma levels of epinephrine and norepinephrine and muscle sympathetic nerve activity were measured before and during a cold pressor test or a mental arithmetic test. The resting basal values of muscle sympathetic nerve activity, blood pressure and plasma epinephrine were significantly higher in the borderline hypertensives than in the normotensives (P < 0.05). Plasma norepinephrine levels tended to be higher in the borderline hypertensives than in the normotensives but not to a significant extent (P < 0.10). The cold pressor test produced significantly exaggerated pressor and muscle sympathetic nerve responses (P < 0.05) with a trend towards an increase in plasma norepinephrine (P < 0.10) in the borderline hypertensives as compared with normotensives. The mental arithmetic test produced significantly enhanced pressor and plasma epinephrine responses in the borderline hypertensives as compared with the normotensives (P < 0.05). During the mental arithmetic test the muscle sympathetic nerve activity decreased significantly in the normotensives P(< 0.05) but not in the borderline hypertensives. These findings indicate that in people with borderline hypertension an abnormality exists in sympathetic nerve activity at rest and in response to stressors.
Comparison between isoprenaline infusions and bolus injections to assess β‐adrenoceptor function in man, with special reference to cardiac contractility and the influence of autonomic reflexes
Authors: MARTINSSON A. , MELCHER A. , LINDVALL K. , HJEMDAHL P.
Published: December 2008

The present study was performed to characterize cardiovascular responses to isoprenaline and the influence of autonomic reflexes on these reponses. Nine healthy volunteers received infusions and bolus injections of isoprenaline before and after ‘autonomic blockade’ produced by intravenous atropine 0.04 mg kg‐1 and clonidine 300 μg. Heart rate, blood pressures, systolic time intervals and various echocardiographic measures of cardiac contractility were registered. No significant differences in responsiveness to isoprenaline were seen when infusions were repeated on the same day without ‘autonomic blockade’. After ‘blockade’, Δ responses at 1 nmol 1‐1 isoprenaline (infusions) were increased for diastolic blood pressure and decreased for systolic blood pressure and stroke volume. Bolus injections of 2 μg isoprenaline caused enhanced Δ responses after ‘autonomic blockade’ of diastolic blood pressure, left ventricular diameter in systole, ventricular circumferential fibre shortening, mean posterior wall velocity (Vmean pw), stroke volume, systemic vascular resistance, electromechanical systole (QS2) and pre‐ejection period. Systolic blood pressure decreased, in contrast to a small increase without ‘blockade’. These findings are explained by differences in haemodynamic effects of isoprenaline and by the dependence of responses on reflexes when isoprenaline is administered in different ways. When heart rate was increased by bolus doses of atropine, in the presence of β‐blockade (propranolol), pre‐ejection period and left ventricular diameter in systole were unaffected, and Vmean pw and ventricular circumferential fibre shortening showed only small increases (compared with alterations induced by isoprenaline). However, left ventricular ejection time, QS2 and ejection time (by echocardiography), were markedly dependent on heart rate alterations. Thus, pre‐ejection period, left ventricular diameter in systole Vmean pw and ventricular circumferential fibre shortening are parameters which can be useful in order to evaluate cardiac β‐adrenoceptor sensitivity in vivo in man.
Measurement of hepatic protein synthesis in unrestrained mice‐evaluation of the ‘flooding technique’
Authors: LUNDHOLM K. , TERNELL M. , ZACHRISSON H. , MOLDAWER L. , LINDSTRÖM L.
Published: December 2008

Controversy exists regarding the validity of various techniques for estimating rates of protein synthesis in viva. In the present report, we have compared estimates of hepatic protein synthesis in normal mice with a pulse labelling of [1‐14C]leucine and calculated hepatic protein synthetic rates in a conventional two‐pool model and in a five‐pool compartment analysis. Results obtained with pulse labelling were also compared to those obtained in animals receiving a flooding dose of 1.5 μmol L‐phenylalanine and 0.4 μCi [U‐14C]phenylalanine per gram of body weight or 1.0 μmol L‐leucine and 0.4, μCi [I‐14C]leucine per gram of body weight. Estimates of protein synthesis were calculated with plasma free amino acid, liver acid‐soluble fraction and acylated tRNA specific radioactivities as being representative of the precursor pool for protein synthesis.

Rates of hepatic protein synthesis obtained with pulse labelling and either leu‐tRNA or acid‐soluble fractions of liver leucine as the precursor for protein synthesis gave similar results (37 pL 5 vs 42 pL 5% per day) in a two‐pool model, but disagreed in a fivepool model (37 pL 5 us 6 pL 2% per day). Estimates based on plasma enrichment in leucine were only one fifth of values obtained with tRNA in labelling experiments. When the plasma pool with tracer amino acids was used to indicate the precursor labelling of protein synthesis, values obtained with the flooding dose of either phenylalanine or leucine agreed with those obtained with pulse labelling and enrichment in tRNA (30 pL 3 nmol min‐1 us 28 pL 4 nmol min‐1); with however no agreement when the enrichment in the liver mixed tissue pool was used (76 pL 5 nmol min‐1). Complete equilibration of the amino acid pools did not occur despite flooding.

Therefore, the flooding technique may only represent an approximate method to measure protein synthesis in vivo, although it gives absolute values that agree well with results from labelling techniques based on tRNA enrichment provided the plasma pool is used as the precursor enrichment.
Membrane‐bound carbonic anhydrase CA IV in the human kidney
Authors: LÖNNERHOLM G. , WISTRAND P. J.
Published: December 2008

The distribution of membrane‐bound carbonic anhydrase, CA IV, was studied in human kidneys by an indirect immunoperoxidase method using a rabbit polyclonal antibody directed against human kidney CA IV. Clear staining of CA IV was found in the apical cell borders of some cells in the cortical and medullary segments of the collecting ducts, presumably the A type of intercalated cells. Weak staining for CA IV was located in the interior of a number of collecting duct cells and in the basolateral regions of the proximal convoluted tubules. However, no staining was found in the brush border of the same tubules. This is a surprising finding, since evidence for carbonic anhydrase activity has been found biochemically and histochemically both in isolated brush‐border and baso‐lateral membranes. Further work is needed to clarify this matter. The endothelium of the peritubular capillaries also stained for CA IV.
Neurochemical effects of nicotine on glutamate and GABA mechanisms in the rat brain
Authors: DE LA MORA M. PÉREZ , MEANDEZ‐FRANCO J. , SALCEDA R. , AGUIRRE J. A. , FUXE K.
Published: December 2008

The effects of nicotine on y‐aminobutyric acid (GABA) and glutamate mechanisms were studied in several rat brain regions both in vivo and in vitro. In vivo acuteintermittent injections of nicotine decrease GABA utilization in the hypothalamus and glutamate levels within the nucleus caudatus and the subcortical limbic forebrain (mainly tuberculum olfactorium and nucleus accumbens). Glutamic acid decarboxylase activity was slightly increased in several regions, when the rats were treated with a single convulsant dose of nicotine and killed at the moment of the convulsions but it was not affected by a single injection nor by intermittent acute administration of non‐convulsant doses of nicotine. In vitro nicotine elicited release of L‐[3H]glutamaftreo m synaptosomal preparations obtained from the frontoparietal cortex, nucleus caudatus and hypothalamus. The effect was dose‐dependent and it was not blocked by mecamylamine. It was also Ca2+ independent. The possibilities are discussed that the decreased GABA utilization in the hypothalamus may be related to certain neuroendocrine actions of nicotine and that the nicotine‐induced glutamate release might be involved in some of the physiological and toxicological effects of nicotine.
Effects of weaning on plasma levels of prolactin, oxytocin, insulin, glucagon, glucose, gastrin and somatostatin in sows
Authors: ROJKITTIKHUN T. , UVNÄS‐MOBERG K. , EINARSSON S. , LUNDEHEIM N.
Published: December 2008

The effect of total weaning (all piglets were weaned at 35 days of lactation) and fractionated weaning (the heavier half of the litter was weaned on day 33 of lactation and the remainder 2 days later) on plasma levels of prolactin, oxytocin, insulin, glucagon, glucose, gastrin and somatostatin in primiparous sows was studied. Twelve crossbred sows were grouped into six pairs according to farrowing date and litter size. The litter of one sow in each pair was weaned in two stages (treatment), and the other was conventionally weaned (control). Blood samples were collected via a permanent jugular vein catheter every 3 hours from 9 a. m. to 9 p. m. from day 31 of lactation until the third day of final weaning.

In response to total weaning (studied in the six control sows), plasma prolactin, glucagon and gastrin decreased significantly, whereas plasma insulin and somatostatin significantly increased. Basal concentrations of plasma oxytocin and glucose remained unchanged after weaning. Fractionated weaning did not result in any significant differences in the hormonal and glucose levels as compared with the total weaning. The possible role of prolactin in modulating insulin, glucagon and glucose concentrations as well as the possibility that oxytocin affects gastrin and somatostatin levels following weaning are discussed.