bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth regulation of LLC‐PK1 cells: lack of effect of Na+‐loading
Authors: ÖSTLUND E. , LARSSON S. H. , WROBLEWSKI R. , WROBLEWSKI J. , APERIA A.
Published: December 2008

To gain more information about the growth regulation of renal epithelial cells, we examined the growth stimulatory effect of serum and intracellular sodium in the renal epithelial cell line, LLC‐PK1. In subconfluent LLC‐PK1 cells serum‐starved for 5 days and exposed to [3H]thymidine for 24 h, 22.9% of the cells synthesized DNA. Stimulation with 10% foetal calf serum (FCS) caused an almost three‐fold increase in the fraction of labelled nuclei (62.2%). Serum‐starved LLC‐PK1 cells exposed to 10% FCS responded with an increased abundance of c‐jun transcripts. The maximal expression of the c‐jun transcripts occurred at 60 min and declined 120 min after serum stimulation. It has been suggested that an increase in Na+influx plays a role in the growth regulation of renal epithelial cells. This prompted us to study the effect of intracellular Na+loading on the growth response of LLC‐PK1 cells. Serum‐starved LLC‐PK1 cells were incubated in a low K+medium or exposed to Nystatin. Incubation in a low K+medium or with Nystatin resulted in a marked increase in intracellular Na after only 5 min. A low K+medium did not significantly influence the intracellular pH. No effect was observed on DNA synthesis or the abundance of c‐jun transcripts in LLC‐PK1 cells. Nor did Na+loading enhance the growth stimulatory effect of serum. The results suggest that an increase in intracellular sodium does not directly regulate the growth of renal epithelial cells.
Effects of reduced CSF Na concentration and osmolality on haemodynamic and humoral responses to hypotensive haemorrhage in conscious sheep
Authors: ULLMAN J. , HJELMQVIST H. , RUNDGREN M.
Published: December 2008

The effects of iso‐ and hypo‐osmotic reduction of the CSF [Na+] on the tolerance to blood loss and concomitant cardiovascular and humoral responses were studied in conscious sheep. Animals only subjected to haemorrhage served as controls. The changes in CSF composition were induced by intracerebroventricular infusions of 0.3 m mannitol, respectively, 0.04 m NaCl. In the former instance the CSF [Na+] was reduced by 18 mm whereas a lowering by 13 mm concomitant with decreased CSF osmolality (mean change 25 mOsm kg‐1) was seen in response to the NaCl solution. Apart from a slight lowering of the cardiac output during the infusion of 0.3 m mannitol preceding haemorrhage, the changes in CSF composition did not have any significant haemodynamic effects in the normovolaemic animal, or altered the cardiovascular responses to a subsequent hypotensive haemorrhage. The amount of blood needed to be withdrawn to obtain the predefined degree of hypotension did not differ significantly between treatment groups. The plasma vasopressin and angiotensin II concentrations were consistently increased by the hypotensive haemorrhage, but the magnitude of the vasopressin response was significantly reduced when the CSF [Na+] was lowered. We conclude that lowered CSF [Na+] and/or osmolality, in contrast to increased CSF [Na+], does not influence the tolerance to blood loss or the accompanying haemodynamic changes in sheep, in spite of an attenuated vasopressin response.
Noradrenaline contributes to modulation of the carotid sinus baroreflex in the nucleus tractus solitarii area in the rabbit
Authors: YAMAZAKI T. , NINOMIYA I.
Published: December 2008

The authors examined the contribution of the noradrenergic system to central cardiovascular regulation in the dorso‐medial region of the medulla oblongata, including the nucleus tractus solitarii (NTS) area, in anaesthetized rabbits. First, to determine the modulation of the carotid sinus baroreflex system by a‐blocker, which blocks the action of noradrenaline, the open loop relationship between isolated carotid sinus pressure (CSP) and renal nerve activity (RNA) was examined before and after injection of a‐blocker (phentolamine, 10 μg, bilateral). α‐Blocker injected to the NTS area caused a decrease in RNA at low CSP level (40–50 mmHg), and RNA response remained higher at high CSP levels (130 mmHg), in comparison with control. Baroreflex sensitivity was attenuated significantly from 10.9 ± 2.2 to 5.0 ± 0.5% (mmHg‐1). The data show that the NTS area is one of the important sites in central modulation of the carotid sinus baroreflex function. It is suggested that the noradrenergic system in the NTS area contributed to facilitating carotid sinus baroreflex function. Second, using the dialysis technique, a dialysis probe was implanted in the dorso‐medial region of the medulla oblongata, including the NTS area, and perfused with Ringer's solution. Dialysates were collected from this region and noradrenaline (NA) output was determined by high‐performance liquid chromatography/electrochemical methods. Drug‐induced hypotension caused a 30% decrease in arterial pressure and an increase in dialysate NA levels from 6.8 ± 0.2 to 9.0 ± 0.4 pg sample‐1. The results show that noradrenaline in the NTS area is involved in the regulation of arterial pressure through the central modulation of arterial baroreflex function.
Effects of adrenergic stimulants on the splenic diameter, haemoglobin content and haematocrit in anaesthetized dogs: determination of the adrenoceptor subtype responsible for changes in the splenic diameter
Authors: OJIRI Y. , NOGUCHI K. , CHIBANA T. , SAKANASHI M.
Published: December 2008

Changes in splenic diameter measured by sonomicrometry in response to various adrenergic stimulants were estimated together with simultaneously measured arterial haemoglobin content (HGB) and haematocrit (HCT) in anaesthetized dogs. Splenic diameter decreased following intravenous injections (i.v.) of adrenaline, noradrenaline and phenylephrine and splenic nerve stimulation associated with increases in arterial HGB and HCT, which were significantly attenuated by prazosin i.v. After prazosin i.v., adrenaline i.v. increased splenic diameter significantly, but noradrenaline i.v. did not. Isoprenaline i.v. increased splenic diameter transiently, followed by a decrease that was abolished by prazosin i.v. During occlusion of splenic arteries and veins, adrenaline i.v. and phenylephrine i.v. did not cause any change in arterial HGB and HCT. Injection to splenic artery (i.a.) of phenylephrine induced a significant decrease in splenic diameter that was attenuated by prazosin i.a. but not by yohimbine i.a. Clonidine i.a. did not change splenic diameter. The present results indicate that splenic contraction, which is mediated through α1‐adrenoceptor activation, causes a significant increase in arterial HGB and HCT.
Breakdown of membrane choline‐phospholipids induced by endogenous and exogenous muscarinic agonist is potentiated by VIP in rat submandibular gland
Authors: DUNÉR‐ENGSTRÖM M. , FREDHOLM B. B.
Published: December 2008

The outflow of tritium from rat submandibular gland fragments, pre‐labelled with [3H]choline, following electrical or pharmacological stimulation was studied. Electrical stimulation of the tissue increased the outflow of tritium in a frequency dependent manner. Atropine treatment decreased the electrically‐induced release, indicating that the outflow did not reflect acetylcholine from nerve endings, but was largely brought about by postsynaptic receptors. In agreement with this hypothesis, treatment with noradrenaline or carbachol induced a dose dependent increase in tritium outflow from the gland fragments which could be blocked by prazosin or atropine, respectively. Moreover, analysis of the tissue‐associated tritium revealed an incorporation primarily in the lipid fraction of the tissue (almost 80%), of which about 90% was in phosphatidylcholine, indicating that this was the source of the tritium outflow.

Pre‐incubation with vasoactive intestinal polypeptide (VIP), which coexists with acetylcholine in the parasympathetic neurons innervating the submandibular gland, increased the carbachol‐induced tritium overflow significantly. The effect of VIP could be imitated by the adenylyl cyclase stimulator forskolin, which increased the carbachol‐stimulated tritium efflux in a dose dependent manner.

Taken together, our results suggests that muscarinic‐ and α1‐receptor agonists may activate a phospholipase coupled to phosphatidylcholine hydrolysis in the rat submandibular gland. Endogenous acetylcholine released from parasympathetic nerve endings appear to activate this mechanism. Furthermore, VIP treatment, and the concomitant cAMP‐accumulation, potentiates the acetylcholine induced phosphatidylcholine hydrolysis, demonstrating a new type of interaction between the classical transmitter acetylcholine and the co‐stored neuropeptide VIP.
The influence of afterload on uniformity of segment shortening in feline left ventricles. Importance of cross‐fibre contraction
Authors: HEXEBERG E. , BIRKELAND S.
Published: December 2008

Previous studies have shown that the combined increase of preload and afterload leads to a more uniform wall contraction. As our previous information with a stable afterloaded situation showed considerable increase of left ventricular end‐diastolic pressure, we have as yet no information of how afterload per se effects uniformity of segment shortening. We therefore analysed maximal systolic shortening of cross‐oriented segments for three consecutive beats during abrupt elevation of afterload in 12 open‐chest cats. Peak left ventricular systolic pressure increased during the three beats from 154 ± 5mmHg (mean ± SEM) to 167 ± 5 mmHg and 186 ± 5 mmHg. Left ventricular end‐diastolic pressure remained unchanged. Maximal systolic shortening was reduced for both segments with increasing afterload, in longitudinal segment (LONG) from 7.6 ± 1.1 to 6.1 ± 1.0% (P < 0.005), and more pronounced for circumferential segments (CIRC) from 12.2 ± 0.7 to 8.3 ± 0.9% (P < 0.0005). Uniformity of maximal systolic shortening, LONG/CIRC, increased from 0.63 ± 0.08 in the first beat to 0.73 ± 0.10 and 0.82 ± 0.12 in the following beats (P < 0.02). We conclude that uniformity of contraction for cross‐oriented segments in the anterior left ventricular wall is increased during increased afterload. We propose that this can be explained by reduction of the effect of cross‐fibre contraction with increasing afterload.
Significance of increased atrial pressure on stroke volume during atrial fibrillation in anaesthetized pigs
Authors: LEISTAD E. , CHRISTENSEN G. , ILEBEKK A.
Published: December 2008

During atrial fibrillation synchronized atrial contraction is lost and cardiac output declines. Concomitantly, atrial pressure increases. The significance of the increase in atrial pressure on stroke volume was examined before and after blood volume expansion. Atrial fibrillation was induced by rapid atrial pacing in seven anaesthetized, open‐chest pigs. The increase in right atrial pressure subsequently was counteracted by an appropriate constriction of the inferior vena cava. To avoid the confounding effect of a rapid and irregular heart rate, ventricular rate was kept constant by separate His bundle pacing after complete atrioventricular block.

When atrial fibrillation was induced, right and left atrial pressure at the top of the v‐wave increased both during normovolaemia and during hypervolaemia. Concomitantly, stroke volume declined. When the increase in atrial pressure was prevented during atrial fibrillation, stroke volume declined further: by 35 (21–50) and 9 (2–17)% (difference: P= 0.01), during normo‐ and hypervolaemia, respectively.

Thus, the increase in atrial pressure counteracts the decline in stroke volume after induction of atrial fibrillation and thereby represents an important compensatory mechanism. This mechanism is more important with normal blood volume than during hypervolaemia.
Distribution of recurrent inhibition in the human upper limb
Authors: KATZ R. , MAZZOCCHIO R. , PÉNICAUD A. , ROSSI A.
Published: December 2008

The distribution of homonymous and heteronymous recurrent inhibition among the motor nuclei innervating the main muscles of the human upper limb has been investigated in 25 healthy subjects.

Homonymous recurrent inhibition was studied with a specially designed electrophysiological method with paired H‐reflexes, previously described by Bussel & Pierrot‐Deseilligny (1977), combined with a pharmacological study using a cholinergic agonist, the l‐acetylcarnitine (Rossi & Mazzocchio 1991). These methods were used to investigate the Flexor Carpi Radialis (FCR), Extensor Carpi Radialis (ECR), Opponens Pollicis (OP) and Abductor Digiti Minimi (ADM) motor nuclei. In the Deltoid, Triceps, Flexor Carpi Ulnaris (FCU) and Extensor Carpi Ulnaris (ECU) motor nuclei in which it was impossible to evoke clearly distinguishable H‐reflexes, homonymous recurrent inhibition was studied with the PSTH technique: homonymous recurrent inhibition was found in Deltoid, Triceps, FCR, FCU, ECR, ECU motor nuclei but not in OP and ADM motor nuclei.

Heteronymous recurrent inhibition was studied with the PSTH technique in the Deltoid, Biceps, Triceps, FCR, ECR, FCU, ECU, Flexor Digitorum Communis (FDC), Extensor Digitorum Communis (EDC) motor nuclei as well as those innervating the intrinsic muscles of the hand. The following results were obtained: (1) motor neurones innervating muscles acting at digits do not receive any heteronymous recurrent inhibition; (2) motor neurones innervating muscles acting at the wrist give recurrent inhibition to motor nuclei of proximal muscles but do not receive any recurrent projections from the latter; and (3) motor neurones innervating proximal muscles (acting at shoulder or elbow) are interconnected by recurrent inhibition and receive heteronymous recurrent projections from some wrist muscles but not from intrinsic hand muscles.
Variable effects of β‐adrenoceptor blockade on muscle blood flow during exercise
Authors: GULLESTAD L. , HALLÉN J. , SEJERSTED O. M.
Published: December 2008

The role of β‐adrenoceptors in exercise‐induced muscle hyperaemia was investigated. Exercise was performed with a small and a large muscle mass: knee extension (KE) and bicycle exercise (BE). Seven healthy subjects performed light and maximal KE and eight subjects performed stepwise dynamic BE to exhaustion before and after acute i.v. administration of propranolol (0.15 mg kg‐1). Leg blood flow was measured by a bolus dye dilution technique. During KE at low and high power leg blood flow was reduced by 8.7 and 10.5% after propranolol was administered, mean arterial blood pressure (MAP) was reduced at low, but not at high power resulting in increased leg vascular resistance (LVR) during high intensity. During BE propranolol reduced leg blood flow and increased LVR at low power, but not at high power. At high BE intensity LVR did not change with increasing power and was slightly decreased after propranolol was administered. In this situation oxygen uptake was close to maximum and the concentration of catecholamines was 3–5 times higher compared with KE. There was no significant effect of propranolol on lactate release or arterial‐femoral venous (a‐fv) differences for adrenaline or noradrenaline. We conclude that β‐adrenoceptors modulate local vasodilation in skeletal muscles during exercise independently of local muscle energy demand, but that the effect is highly dependent on active muscle mass since a‐adrenergic activity during maximal BE seemed to disguise any effect of propranolol on LVR.
Rhythmic contractions of isolated small arteries from rat: role of calcium
Authors: GUSTAFSSON H. , NILSSON H.
Published: December 2008

In order to investigate the mechanisms behind rhythmic contractions in small arteries of the mesenteric arcade from Wistar rats, the calcium dependency of the oscillations in response to noradrenaline activation was tested on isolated vessels. Application of 1 μM ryanodine or 30 μM TMB‐8 (procedures known to inhibit Ca2+release from intracellular stores) totally abolished the rhythmic activity, even though the antagonists had opposite effects on the amplitude of the contractile response to noradrenaline. Verapamil (1 μ) or felodipine (1 μ M) (agents known to inhibit influx of extracellular Ca2+) also abolished the oscillations and reduced the maximal noradrenaline response by about 40%. Reducing the extracellular Ca2+concentration to 0.1 DIM reduced the amplitude of the noradrenaline response to a similar extent as 1 nM felodipine, but did not eliminate the oscillations. This may indicate that the effect of calcium entry blockers was to eliminate the voltage‐dependency of Ca2+inflow rather than just reducing the Ca8+level. Manoeuvres that would increase the cytosolic Ca2+concentration (exposure to caffeine or to the calcium agonist BAY‐K 8644) increased the frequency of the oscillations. These observations indicate an important role, not only for voltage‐operating channels, but also for intracellular calcium stores in the generation of rhythmic contractions in these small arteries. Oscillations appear to be generated by an interplay between membrane activation and intracellular calcium stores.
Time‐dependently enhanced pressor responses in rat lungs after chronic exposure to high altitude
Authors: ASANO K. , SAKAI A.
Published: December 2008

To investigate the de‐acclimatization process with respect to pulmonary vaso‐reactivity after high‐altitude exposure, we performed a study of changes in pressor responses over time in salt‐perfused lungs from rats that had been exposed to high altitude (HA, n=41, 20 weeks at actual 2400 m). Comparisons were made with the lungs of rats kept at low altitude (n=8, kept at 610 m). We studied HA rats from the time just after removal from high altitude to 2 weeks after the exposure. The pressor responses of HA lungs to both 0.5 μg‐angiotensin II and 5 min airway hypoxia (3% O2) just after the exposure did not differ from those of controls, but their responses began to increase within 12 h, and reached a maximum 3 days after exposure ended. The increase was time‐dependent. We conclude that pulmonary vasopressor responses are enhanced time‐dependently during the very early stages of de‐acclimatization after high‐altitude exposure.
Developmental changes in action potential properties of the guinea‐pig myocardium
Authors: AGATA N. , TANAKA H. , SHIGENOBU K.
Published: December 2008

Developmental changes in action potential properties were examined in electrically driven (1 Hz) left atria and right ventricles from foetal, neonatal and adult guinea‐pig hearts, using standard micro‐electrode recording techniques. In both left atria and right ventricles, the overshoot, resting potential and maximum upstroke velocity of the action potential increased progressively with age until birth, and then remained almost unchanged. Action potential duration (APD) changed markedly with age during foetal and neonatal periods. In left atria, APD at 50% repolarization initially decreased until foetal day 50, and then increased until the adult period. In right ventricles, APD initially increased until approximately foetal day 45, then decreased for 5 days following birth, thereafter it increased again. In addition, after‐hyperpolarization was observed only in left atria of younger foetuses. Thus we have demonstrated that in the guinea‐pig myocardium developmental changes in action potential properties occur more extensively during the foetal period than during the postnatal period.
Renal Na+, K+‐ATPase in Dahl salt‐sensitive rats: K+ dependence, effect of cell environment and protein kinases
Authors: NISHI A. , BERTORELLO A. M. , APERIA A.
Published: December 2008

Na+, K+‐ATPase in renal epithelial cells plays an important role in the regulation of Na+ balance, extracellular volume and blood pressure. The function of renal Na+, K+‐ATPase in Dahl salt‐sensitive (DS) rats, an animal model for salt‐sensitive hypertension, and Dahl salt‐resistant (DR) rats has been studied. In Na+, K+‐ATPase partially purified from renal cortex, affinities and the Hill coefficients for Na+ and K+ activation were similar in DS and DR rats. Only one component of low ouabain affinity site was found in both strains, indicating the presence of the al isoform. Protein kinase C and cAMP‐dependent protein kinase phosphorylated Na+, K+‐ATPase α subunit in DS and DR rats, and the phosphorylation by protein kinase C was associated with an inhibition of enzyme activity. The kinetic parameters for K+ activation were also studied in a preparation of basolateral membranes and were found to be similar in DS and DR rats. In a preparation of cortical tubule cells, Na+, K+‐ATPase activity was determined as ouabain‐sensitive oxygen consumption (OS Qo2). Maximal OS Qo2, measured in Na+ loaded cells, was the same in DS and DR rats. The K06 for K+ was significantly lower in DS than DR rats (0.163 ±0.042 vs. 0.447 + 0.061 mM, P < 0.05), indicating that factors regulating Na+, K+‐ATPase activity in intact cells are altered in DS rats. Kinetic parameters for Na+ activation in cells were the same in both strains.

In summary, the function of renal Na+, K+‐ATPase molecule is not altered in DS rats. The intracellular systems that regulate renal Na+, K+‐ATPase activity might be different in DS and DR rats.
Role of the L‐arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins
Authors: KIRKEBY H. J. , SVANE D. , POULSEN J. , T0TTRUP A. , FORMAN A. , ANDERSSON K.‐E.
Published: December 2008

In human penile corpus cavernosum strips, pre‐contracted by noradrenaline, electrical stimulation of nerves evoked non‐adrenergic, non‐cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10‐6M, NG‐nitro‐L‐arginine (L‐NNA) 10‐7‐10‐4M, and oxyhaemoglobin 10‐5M, but not by methylene blue (MB) 10‐5M. Acetylcholine‐induced relaxations were also inhibited by L‐NNA 10‐4M and oxyhaemoglobin 10‐5M, but were unaffected by pyrogallol 10‐4M, MB 10‐6M, and tetrodotoxin 10‐6M. MB 5 × 10‐4‐10‐4M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10‐7‐10‐4M and sodium nitroprusside 10‐9‐10‐4M caused concentration‐dependent relaxations. The NO‐induced relaxations were inhibited by oxyhaemoglobin 10‐5M, and the concentration‐response curve for sodium nitroprusside was shifted to the right by MB 10‐5M. The response to sodium nitroprusside was unaffected by L‐NNA 10‐4M, oxyhaemoglobin 10‐5M, and pyrogallol 10‐4M. In circumflex veins, pre‐contracted by noradrenaline, no NANC‐mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium‐dependent relaxations, which were insensitive to L‐NNA 10‐4M and oxyhaemoglobin 10‐5M. NO and sodium nitroprusside caused concentration‐dependent relaxations; the concentration‐response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10‐5M. Removal of the endothelium left the NO‐ and sodium nitroprusside‐induced relaxations unchanged.

The results confirm previous observations that relaxations of human corpus cavernosum induced by both NANC nerve stimulation and exogenous acetylcholine involve an agent derived from L‐arginine. No NANC response to electrical stimulation was found in circumflex veins, where acetylcholine induced an endothelium‐dependent relaxation, apparently independent of the L‐arginine/nitric oxide pathway.
The effect of high‐intensity training on purine metabolism in man
Authors: HELLSTEN‐WESTING Y. , BALSOM P. D. , NORMAN B. , SJODIN B.
Published: December 2008

The effect of intermittent high‐intensity training on the activity of enzymes involved in purine metabolism and on the concentration of plasma purines following acute short‐term intense exercise was investigated. Eleven subjects performed sprint training three times per week for 6 weeks. Muscle biopsies for determination of enzyme activities were obtained prior to and 24 h after the training period. After training, the activity of adenosine 5′‐phosphate (AMP) deaminase was lower (P < 0.001) whereas the activities of hypoxanthine phosphoribosyl transferase (HPRT) and phosphofructokinase were significantly higher compared with pre‐training levels. The higher activity of HPRT with training suggests an improved potential for rephosphorylation of intracellular hypoxanthine to inosine monophosphate (IMP) in the trained muscle. Before and after the training period the subjects performed four independent 2‐min tests at intensities from a mean of 106 to 135 % of Vomax. Venous blood was drawn prior to and after each test. The accumulation of plasma hypoxanthine following the four tests was lower following training compared with prior to training (P < 0.05). The accumulation of uric acid was significantly lower (46% of pre‐training value) after the test performed at 135% of Fo2mM (P < 0.05). Based on the observed alterations in muscle enzyme activities and plasma purine accumulation, it is suggested that high intensity intermittent training leads to a lower release of purines from muscle to plasma following intense exercise and, thus, a reduced loss of muscle nucleotides.
Static and dynamic pulmonary compliance during upright immersion
Authors: TAYLOR N. A. S. , MORRISON J. B.
Published: December 2008

Elastic properties of the lung are typically assessed using the static pressure‐volume relaxation manoeuvre. Although dynamic methods have produced equivalent results in normal healthy subjects, their use under obstructive pulmonary disease states and during certain conditions has been questioned. Static (Cst(1)) and dynamic (Cdyn(1)) pulmonary compliance were measured in eight subjects in air (control) and during immersion. Cdyn(1) decreased from 2.94 to 1.61 1 kPa‐1 following immersion, during which subjects breathed air supplied at mouth pressure (P < 0.05), while Cst(1) remained approximately equivalent (3.16 and 4.07 1 kPa‐1 respectively, P >0.05). When immersed subjects were supplied with breathing gas at lung centroid pressure (PLC), Cdyn(1) returned to control status (2.89 1 kPa‐1; P > 0.05), while Cst(l) remained stable at 3.60 1 kPa‐1 (P > 0.05). The difference between Csta) and Cdynm(1) may imply that flow‐resistive properties are included within the latter measurement. It is recommended that Cdyn(1), under these conditions, be interpreted as an index of peripheral airway patency, rather than as an assessment of lung elasticity.
Enhancement of depolarization‐induced contractions after endothelium denudation is not related to an impaired production of nitric oxide or prostacyclin in the rabbit basilar artery
Authors: PETERSSON J. , RYMAN T. , HOGESTATT E. D.
Published: December 2008

Enhancement of the extracellular potassium ion (K+) concentration combined with endothelial injury have been suggested to occur during cerebral ischaemia‐reperfusion and vasospasm after subarachnoid hemorrhage. The effect of potassium (K+) depolarization was therefore investigated in isolated segments of the rabbit basilar artery with and without an intact endothelial cell layer. Addition of potassium chloride to the organ bath induced a concentration‐dependent contraction. Endothelial denudation of the artery resulted in an unstable baseline tension and a leftward shift of the K+concentration‐response curve. The K+concentration eliciting half maximum contraction decreased from 26 mmol l‐1in the presence to 12 mmol l“1in the absence of an intact endothelium. Nimodipine (3 × 10‐7mol l‐1) or exposure to a calcium‐free medium abolished the spontaneous as well as K+‐induced contractions. A^‐nitro‐L‐arginine (10‐4mol l‐1), indomethacin (3 × 10‐6mol l‐1) and glibenclamide (10‐5mol I‐1) did not affect the contractile response to K+in intact arteries. However,Nw‐nitro‐D‐arginine increased the baseline tension, and this effect could not be reproduced withNw‐nitro‐D‐arginine. Pinacidil (10‐6mol l‐l) abolished the spontaneous contractile activity in endothelium‐denuded arteries and reduce the K+sensitivity to the same level as in intact arteries. Tetraethylammonium (3 mmol l‐1) and ouabain (10‐5mol I‐l) increased the basal tension and shifted the K+concentration‐response curve to the left. Calcium‐induced contractions in preparations exposed to a calcium‐free, 124 mmol l‐lK.+solution did not differ between endothelium‐denuded and intact arteries. It is suggested that the endothelium of the rabbit basilar artery releases a hyperpolarizing factor, distinct from nitric oxide or a cyclooxygenase product, which attenuates the vasoconstrictor effect of K+depolarization.
Effects of luminal stimuli on polyamine metabolism in the small intestine of the rat: the role of enteric nerves
Authors: ANSSON M. J. , NILSSON B.‐O. , ROSENGREN E. , EKSTROM J. , LUNDGREN O.
Published: December 2008

The aim of this study was to investigate to what extent polyamine metabolism in the small intestine of the rat is controlled by the enteric nervous system. Polyamine metabolism was followed by measuring the activity of ornithine decarboxylase (ODC) and in some instances also the content of polyamines (putrescine, spermidine and spermine). ODC activity in the intestine was increased when intraluminal pressure was increased and 3 h after placing cholera toxin in the intestinal lumen. Cholera toxin also increased the tissue putrescine content. Atropine or hexamethonium given i.v. did not influence the evoked changes of ODC activity. The pressure induced changes were not decreased by placing lidocaine on the serosal surface. On the other hand, the ODC activity of control segments were decreased by hexamethonium or atropine. The presence of glucose in the intestinal perfusate did not augment tissue ODC activity, neither did the heat stable enterotoxin from Escherichia coli (STa). It is concluded that the effect on polyamine metabolism evoked by luminal pressure or cholera toxin seems not to be mediated via nerves, while nerves seem to influence ODC activity during control conditions. The experiments with enterotoxins suggest that cAMP is the intracellular second messenger controlling intestinal ODC activity.
Kinetics of ATP‐ and noradrenaline‐mediated sympathetic neuromuscular transmission in rat tail artery
Authors: BAO J. X. , GONON F. , STJÄURNE L.
Published: December 2008

Electrophysiological, electrochemical and mechanical recordings were employed to study the kinetics of the release and clearance of adenosine 5′‐triphosphate (ATP) and noradrenaline (NA) as sympathetic co‐transmitters and of the neurogenic and non‐neurogenic contractions in rat isolated tail artery. The life‐time of ATP and NA released by a single pulse or 10 pulses at 50 Hz was brief (< 100 ms, or < 3 s, respectively); the neurogenic contractile responses occurred largely after the transmitters had been removed from the extracellular space. The ATP‐induced neurogenic contractile responses to a single pulse or 10 pulses at 50 Hz were similar in time‐course to the responses to direct muscle stimulation at low voltage; both seemed to be caused by activation of nifedipine‐sensitive voltage‐gated L‐type Ca2+ channels. The a,‐ and a2‐adrenoceptor‐mediated components of the NA‐induced neurogenic contractile response to 10 pulses at 50 Hz were more delayed and prolonged and determined by properties of the post‐receptor mechanisms. The per pulse release of both ATP and NA faded rapidly during long high‐frequency trains. So did the ATP level at the receptors and the ATP‐induced neurogenic contraction. The NA levels and the contractile responses induced via a,‐ and ^‐adrenoceptors were much better maintained during ongoing stimulation at 20 Hz but relaxed rapidly afterwards, suggesting that nerve activity suppressed, and ce'ssation of nerve activity reactivated NA clearance.
Myosin heavy chain isoforms in single fibres from m. vastus lateralis of soccer players: effects of strength‐training
Authors: ANDERSEN J. L. , KLITGAARD H. , BANGSBO J. , SALTIN B.
Published: December 2008

The myosin heavy chain (MHC) composition of single fibres (n= 2171) was analysed with an electrophoretic technique in biopsy material from m. vastus lateralis of two groups of soccer players before and after a 3‐month period of either strength‐ (n= 8) or non‐training (control) (n= 6). Traditional myofibrillar ATPase histochemistry demonstrated a decrease in type IIA fibres with strength‐training (35.4 ± 2.1 vs. 26.7 ± 2.4% (P < 0.05)). This was not observed in the non‐training group (25.7 ± 4.6 vs. 23.8 ± 1.7%). One‐dimensional electrophoresis on muscle homogenates showed no significant change in the amount of MHC isoforms in either of the two groups. The MHC isoform I IB was undetectable in all but three samples. No changes in the proportions of fibres containing any of the MHC isoforms were observed. Fibres containing only MHC isoform I IB were found in very small numbers (only 11 out of 2171). Before the experimental period, between 6 and 10% histochemical type IIB fibres were found in both groups. This was identical with the proportion of fibres showing co‐existence of MHC isoforms IIA and IIB, but in contrast to the very few fibres containing only MHC isoform IIB. This suggests that nearly all histochemical type IIB fibres of the soccer players display co‐existence of both MHC isoform IIA and IIB. No major change in the muscle fibre area of the two groups was observed. The strength‐training group increased mean power output in a short‐term dynamic knee‐extensor test after strength‐training (119 ± 6.6 vs. 136.5 ± 4.7 W (P < 0.01)), whereas no change was observed in the non‐training group (151.2 ± 4.5 vs. 148.4 ± 6.5 W).
Effects of blood‐volume distribution on the characteristics of the carotid baroreflex in humans at rest and during exercise
Authors: EIKEN O. , SUN J. C. L. , MEKJAVIC I. B.
Published: December 2008

Seven supine subjects were studied at rest and during mild to moderate dynamic leg exercise with and without unloading of the cardiopulmonary baroreceptors accomplished by exposing the lower portion of the body to a subatmospheric pressure of 20 mmHg (Lower Body Negative Pressure, LBNP). The function of the cardiac branch of the carotid baroreflex was studied over its full operational range by measuring R‐R intervals during application of pulse synchronous graded pressures (40 to – 65 mmHg) in a neck‐chamber device. Raising the carotid transmural pressure (systolic arterial pressure minus neck‐chamber pressure) induced increasing R‐R intervals in all conditions. In conformity with previous results from our laboratories it was found that the maximal rate of change in relative R‐R intervals and the corresponding transmural pressure were higher during exercise than at rest, indicating that exercise increased the carotid baroreflex sensitivity and shifted its optimal buffering range to higher arterial pressures. LBNP did not affect the characteristics of the reflex at rest nor during exercise. It is concluded that reduced central venous pressure with consequent selective cardiopulmonary receptor disengagement exerts no influence on the carotid baroreflex control of heart rate (HR), as tested over the entire arterial pressure‐effector response relation, either at rest or during mild‐moderate exercise.
Thromboxane‐like actions of prostaglandin D2 on the contractility of the rat colon in vitro
Authors: DIENER M. , GABATO D.
Published: December 2008

Prostaglandin D2 (PGD2) concentration‐dependently induced a contraction of the longitudinal muscle of the intact isolated rat colon in vitro. The effect of PGD2 increased continuously from the anal to the oral end of the colon. The action of PGD2 was not inhibited but rather enhanced by the neurotoxin, tetrodotoxin, and by the PGD2 antagonist, AH 6809. In contrast, the thromboxane A2 antagonist, SK&F 88046, concentration‐dependently inhibited the PGD2 effect. The action of PGD2 was mimicked by the stable thromboxane A2 derivative, carbocyclic thromboxane A2, indicating that PGD2 exerts its action on the smooth muscle by stimulation of thromboxane receptors.

Between 18 (distal colon) and 38% (proximal colon) of the preparations exhibited spontaneous phasic myogenic contractions. The thromboxane antagonist, SK&F 88046, completely suppressed these spontaneous contractions. The combined lipoxygenase/ cyclo‐oxygenase inhibitors nordihydroguaiaretic acid and sulfasalazine mimicked the action of SK&F 88046, whereas the cyclo‐oxygenase inhibitor, indomethacin, was ineffective. These results suggest that endogenously produced metabolites of arachidonic acid, e.g. thromboxane A2, contribute to the generation of spontaneous muscle contractions in vitro. The failure of indomethacin to suppress muscular activity, however, requires further studies.
Visco‐elastic properties of the rapidly adapting stretch receptor muscle of the crayfish
Authors: RYDQVIST B. , PURALI N. , LÄNNERGREN J.
Published: December 2008

The visco‐elastic properties of the receptor muscle associated with the rapidly adapting stretch receptor organ of crayfish (Pacifastacus Leniusculus) were studied by recording the tension responses to various length changes. Steady‐state length changes resulted in a non‐linear tension development in the receptor muscle. The tension increased slowly for small extensions and more rapidly when extension increased. Muscle tension responses to ramp‐and‐hold extension were characterized by a transient peak followed by a gradual non‐exponentional decline in tension. At the onset of the ramp the tension increased rapidly, similar to what has been observed in the muscle of the slowly adapting receptor (SM). The steeper rise in tension during the first part of the ramp indicating higher initial stiffness, resulted in a ‘hump’ when large extensions (> 15%) were applied. The results show that the rapidly adapting receptor muscle has a more pronounced dynamic component; the ratio between the amplitude of the peak and the steady state response was larger in the rapidly than in the slowly adapting receptor muscle. Accordingly, different values for the elements of a visco‐elastic model of the muscle had to be set for the two types of receptors. The different properties of the rapidly and slowly adapting receptor muscles are in line with the differences in the overall adaptive behaviour of the organ and give further support to the idea that mechanical factors contribute to the adaptive properties.
Hypertension and thirst outlasting renal vasoconstriction as effects of a brief elevation of systemic angiotensin II in sheep
Authors: ERIKSSON S. , ANDERSSON B. , GUNNARSSON U. , RUNDGREN M.
Published: December 2008

The influence of 10 min intracarotid (i.e.) and intravenous (i.v.) infusions of angiotensin II (Ang II; 20 pmol kg‐1 min‐1) on carotid blood pressure (cBP) and renal blood flow (RBF) was studied in unanaesthetized ewes without and with pre‐treatment with the α1‐and β‐adrenoceptor blocker labetalol. RBF was also monitored during 30 min intracerebroventricular (ICV) infusions of Ang II at 2 pmol kg‐1 min‐1.

The i.e. infusions of Ang II induced about 50 mmHg rise in cBP. A steep decline occurred during 5 min post‐infusion, followed by a much slower reduction with the cBP remaining above control level at 40 min post‐infusion. The pressure elevation induced by i.v. Ang II was less pronounced but exhibited a similar pattern. Labetalol significantly reduced the pressor response to i.e. as well as i.v. Ang II.

The i.e. and i.v. infusions of Ang II conspicuously reduced the RBF regardless of whether the ewes were labetalol‐treated or not. At 5 min after the infusions RBF had returned to control level. The ICV infusions did not influence the RBF.

Ang II i.e. elicited thirst in 50% of the ewes with the urge to drink remaining at 40 min post‐infusion. The dipsogenic response was not reduced by labetalol pre‐treatment.

The results imply that no cerebral component contributes to the reduction in RBF induced by systemic Ang II. However, a centrally mediated action seems to be the cause of the long‐lasting post‐infusion cBP elevation and dipsogenic response. It suggests that, once bound at brain sites, Ang II may have a sustained action, alternatively may initiate cerebral processes of long duration.
Analysis of the pressure‐flow characteristics of isolated perfused rat kidneys with inhibited tubular reabsorption
Authors: JOHNSSON E. , RIPPE B. , HARALDSSON B.
Published: December 2008

The renal hemodynamics were studied in an isolated perfused rat kidney model modified for investigations of the glomerular permeability characteristics. The tubular reabsorptive activity was inhibited by perfusion at low temperature (8 oC) in the presence of furosemide and nitroprusside resulting in a dramatic increase in the filtered load of fluid and solute reaching the tubules and hence in tubular pressure. The glomerular filtration rate (GFR), arterial pressure (PA) aid needle pressure (intrarenal tissue pressure, PiR) were continuously recorded and the glomerular hydrostatic pressure was estimated by an arterial occlusion technique.

The pre‐ to postglomerular resistance ratio was calculated from the pressure vs. GFR relationships for two perfusates having differing oncotic pressures (π= 5.5 and 77 = 20 mmHg), from which estimations of glomerular hydrostatic pressures (PGC) were concomitantly made. Thus, increases in An could be exactly counterbalanced by equally large increases in Pac for any given GFR, the needle and Bowman's capsule pressures being dependent on GFR but not on plasma colloid oncotic pressure.

The experimental interventions resulted in a pronounced elevation of PiR as compared with in vivo conditions, while the PGC values were in a normal range, resulting in reduced glomerular filtration pressures. Furthermore, the clearance of albumin varied with the oncotic pressure in agreement with the notion of heteroporosity.
Serum hormones and strength development during strength training in middle‐aged and elderly males and females
Authors: HÄKKINEN K. , PAKARINEN A.
Published: December 2008

Effects of a 12‐week progressive strength training period on serum concentrations of testosterone, Cortisol and sex‐hormone‐binding globulin (SHBG) as well as on strength development of the leg extensor muscles were investigated in nine middle‐aged males (M50; range 44–57 years) and in nine middle‐aged females (F50; range 43–54 years) as well as in 10 elderly males (M70; range 64–73 years) and in 11 elderly females (F70; range 66–73 years). Substantial increases took place in maximal isometric strength during the 12‐week training period both in M50 (from 2834 ±452 to 3941 ±772 N; P < 0.001) and in F50 (from 2627±725 to 3488± 1017 N; P < 0.001) as well as in M70 (from 2591 ±736 to 3075±845N; P < 0.01) and in F70 (from 1816 ± 427 to 2483 ±408 N; P< 0.001). The relative increases in strength during the 12‐week training period did not differ significantly between the groups. However, during the last 4 weeks of the training none of the groups demonstrated further increases in strength but it actually decreased in F50 (P < 0.05), M70 (P < 0.01) and in F70 (P < 0.05). No systematic changes were observed during the training in the mean concentrations of serum total testosterone, free testosterone, Cortisol, and SHBG, nor in testosterone/ Cortisol and testosterone/SHBG ratios. However, the individual levels of serum testosterone and testosterone/cortisol ratio and the individual changes in strength during the last four most intensive training weeks of the 12‐week period were in significant positive linear correlation in F70 (r = 0.57; P < 0.05) and in M70 (r = 0.61; P < 0.05). The present findings demonstrate that considerable gains may take place in strength during progressive strength training both in middle‐aged and elderly people. The findings also point out the importance of the anabolic hormonal level for the trainability of muscle strength of an individual during prolonged strength training especially in elderly males and females. This indicates a need to plan strength training programmes carefully with regard for to the overall volume and the length of each training period to optimize the training process in elderly people both in preventive purposes and in rehabilitation.
Effects of intensified endurance training on the concentration of Na, K‐ATPase and Ca‐ATPase in human skeletal muscle
Authors: MADSEN K. , FRANCH J. , CLAUSEN T.
Published: December 2008

Thirty‐nine moderately endurance trained males increased their normal training programme of 2.2 h week‐1 with an average training intensity of 65 % of maximum heart rate (HRmax) to 2.7 h week‐1 and a mean intensity of 78% of HRmax. Performance tests and measurements of the total concentrations of Na,K‐ATPase (3H‐ouabain binding) and Ca‐ATPase, fibre type distribution and fibre area were performed in biopsies from the vastus lateralis muscle before and after increased training. The 6 weeks of training elevated Vo2max from 54.9 + 3.1 to 58.3±3.0 ml 02 min‐1 kg‐1 (P < 0.0001). Exercise time to exhaustion at 86% of Fo2max (pre‐training) increased from 35 ±8 to 61 + 17 min (P < 0.0001). The concentration of Ca‐ATPase was unaffected by the intensified training (6.74 ± 1.03 vs. 6.68+ 1.07 nmol g wet wt‐1), but the concentration of Na,K‐ATPase increased from 307±43 to 354 + 59 pmol g wet wt ' (P < 0.0001). The relative distribution of FT‐fibres was correlated with the concentration of Ca‐ATPase (r = 0.72, P < 0.0001). The data support the view that intensive training induces an upregulation of the concentration of skeletal muscle Na,K‐ATPase, but no change in the total capacity for reaccumulation of Ca2+ into the SR. There was no correlation between the concentrations of Na,K‐ATPase, Ca‐ATPase and indices of endurance performance.
Contribution of liver nerves, glucagon, and adrenaline to the glycaemic response to exercise in rats
Authors: VAN DIJK G. , BALKAN B. , LINDFELDT J. , BOUWS G. , SCHEURINK A. J. W. , AHRÉN B. , STEFFENS A. B.
Published: December 2008

The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of somatostatin in combination with adrenodemedul–lation. Blood samples were taken for measurements of blood glucose, plasma free fatty acids (FFA), adrenaline (A), noradrenaline (NA), insulin and glucagon. Liver denervation by itself did not influence glucose levels during exercise. Infusion of somatostatin in SHAM animals, which inhibited the exercise–induced glucagon response, led to enhanced sympathoadrenal outflow (measured as plasma A and NA) and a reduced blood glucose during exercise, suggesting that glucagon serves as a powerful mediator of the glycaemic response during swimming. Infusion of somatostatin in LDX animals failed to enhance plasma NA levels and led to a more pronounced reduction in blood glucose levels. This indicates that liver nerves do contribute to the glycaemic response to exercise when glucagon secretion is suppressed. Reduced blood glucose levels after adrenodemedullation revealed that adrenal A is another important mediator of the glucose response to exercise. Infusion of somatostatin in adreno–demedullated SHAM or LDX animals was not accompanied with increased NA outflow, suggesting that adrenal A is necessary to allow the compensatory increased outflow of NA from sympathetic nerves. In conclusion, the study shows that pancreatic glucagon and adrenal A are the predominant factors influencing the glycaemic response to exercise, whereas a role of the sympathetic liver nerves becomes evident when glucagon secretion is suppressed.