bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta‐adrenergic blockade and training in healthy men—effects on central circulation
Authors: SVEDENHAG J. , HENRIKSSON J. , JUHLIN‐DANNFELT A. , ASANO K.
Published: December 2008

The effect of chronic β‐adrenergic blockade on central circulatory adaptations to physical training was investigated. 16 healthy sedentary males (20–31 yrs) trained on cycle ergometers 40 min/day, 4 days a week for 8 weeks at a work load that during the last 5 weeks corresponded to 75% of the pretraining VO2max. In a single blind way, 8 subjects were during the training period treated with the β‐adrenergic receptor blocker propranolol (160 mg/day), while the remaining 8 received placebo tablets. Pretraining tests were performed before the start of medication and posttraining tests were performed 6 days after the last day of training and medication. The training program resulted in a similar increase (8%) in VO2max in both groups (p<0.01). The resting heart rate (‐4 beats/min;p<0.05) as well as the exercise heart rate at a moderate work load (120 W: ‐11 beats/min;p<0.01) decreased with training, and no significant difference was seen between the 2 groups. At a high work load (180 W), however, the heart rate decreased significantly more with training in the placebo group as compared with the β‐blockade group (‐19 vs.‐7 beats/min;p<0.05). The oxygen pulse (VO2/HR) increased in both groups at 120 W (+6%;p<0.01). At 180 W the oxygen pulse increased only in the placebo group (+8%;p<0.05). The estimated stroke volume at 120 and 180 W, as determined by impedance cardiography, did not change significantly with training although there was a tendency towards an increase in the placebo group only. The resting left ventricular wall thickness and diameter, as determined by echocardiography, did not change significantly with training in either group.—In conclusion, the present study indicates that a moderate degree of β‐adrenergic blockade does not prevent or impair the training‐induced increase in the maximal oxygen uptake. During submaximal work, however, the circulatory adaptation may be less apparent if training has been performed during partial blockade of the sympathoadrenal system.
Cation exchange—a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)?
Authors: UVNÄS BÖRJE , ÅBORG CARL‐HUGO
Published: December 2008

Supervision of phenylethylamine‐, noradrenaline‐or histamine‐charged weak (carboxyl) cation‐exchangers (IRC‐50 and Duolite CS‐100) with isotonic NaCl caused a release of the amines. Similarly, bovine chromaffin granules and nerve granule preparations from bovine splenic nerve, rat vas deferens and rat corpus striatum released their amine(s) upon superfision with the same solution. The courses of release from the synthetic and biogenic materials showed very similar characteristics and fitted the same exchange equations. The observations support the view that the matrices of the biogenic amine‐storing granules have the properties of weak cation‐exchanger materials with carboxyls as the cation‐binding groups, and that the NaCl‐induced release of the biogenic amines is due to cation exchange (Na+⇌Amine+). The possibility that amine release in vivo is based on cation exchange is discussed.
Pharmacological characterization of postjunctional α‐adrenoceptors in isolated human omental arteries and veins
Authors: STEEN STIG , SKÄRBY TOR V. C. , NORGREN LARS , ANDERSSON KARL‐ERIK
Published: December 2008

The α‐adrenoceptors in human omental arteries and veins were characterized and compared. In the arteries both prazosin (pA29.48) and rauwolscine (pA27.19) displaced the noradrenaline (NA) concentration‐response (cr) curve towards higher concentrations without reduction of maximum. Neither clonidine, nor oxymetazoline had any consistent contractile effects. Phenylephrine had a lower potency than NA, but a similar intrinsic activity. In the veins, both prazosin (pA29.72) and rauwolscine (pA28.11) displaced the NA cr‐curve towards higher concentrations, but also significantly depressed maximum. Clonidine and oxymetazoline contracted veins from 3 out of 7 and 4 out of 6 patients, respectively. Their pD2‐values were similar to that of NA, but their intrinsic activities were significantly lower. NA was more potent than phenylephrine in these vessels, and there was no significant difference in intrinsic activity. The results suggest that in human omental arteries, the postjunctional a‐adrenoceptors are mainly of the α1‐type, even if a small population of α2‐adrenoceptors cannot be excluded. In omental veins, there seems to be a functionally important population of postjunctional α2‐adrenoceptors occurring together with a population of α1‐adrenoceptors.
Adenosine and adenosine analogues increase blood flow in oral mucosa
Authors: GAZELIUS BERTIL , SIDHAGEN BJÖRN , FREDHOLM BERTIL B.
Published: December 2008

The effect of adenosine and some related compound was studied on blood flow in feline oral mucosa. Changes in the rate of disappearance of 125Iodide (k‐value) from a local depot in the oral mucosa was used to determine changes in the mucosal blood flow. Infusion of adenosine caused a dose‐dependent increase of blood flow. Two stable adenosine analogues, adenosine 5′‐ethylcarboxamide (NECA) and l‐phenylisopropyl‐adenosine (l‐PIA), were 20 and 10 times more potent than the parent compound. Dipyridamole (2 mg/kg), which blocks adenosine uptake, significantly enhanced the potency of adenosine. Theophylline (10 mg/kg) inhibited the vasodilatory effect of adenosine and of the adenosine analogues. The result suggest that adenosine may be involved in the regulation of blood flow in the oral mucosa.
Effect of renal nerve stimulation on the activity of the tubuloglomerular feedback mechanism
Authors: HERMANSSON K. , KÄLLSKOG Ö. , WOLGAST M.
Published: December 2008

The influence of renal nerve stimulation on the tubuloglomerular feedback mechanism was studied on anaesthetized rats. The analyses was made by comparing the single‐glomerular filtration rate (SNGFR) measured from late proximal tubules with SNGFR measured from distal tubules in the same nephron. In the former situation the flow to the macula densa cells is interrupted and in the latter the macula densa is influenced by the flow passing by. In the control situation the SNGFR measured proximally was 47.7 ± 2.2 nl · min‐1 (mean ± SE) and 40.1 ± 1.8 measured distally indicating an activated tubuloglomerular feedback. During renal nerve stimulation (2–3 Hz), the SNGFR fell to 38.5 ± 2.3 and 33.5 ± 1.7 when measured proximally and distally, respectively. The results indicate that the tubuloglomerular feedback mechanism is unaffected by renal nerve stimulation.
Penetration of some compounds through blood‐brain and blood‐testis barriers in chronically hypertensive rats
Authors: PÖRSTI ILKKA , YLITALO PAULI
Published: December 2008

Acute hypertension impairs the function of biological barriers, e.g. that of blood‐brain barrier. We tested the hypothesis that chronic hypertension might influence the penetration of compounds through blood‐brain and blood‐testis barriers. With this in mind, the penetration of relatively small radioactive compounds (14C‐2‐methyl‐4‐chlorophenoxyacetic acid = 14C‐MPA, 14C‐sucrose and 14C‐antipyrine, 5 μCi/kg intravenously) into the brain, liquor space and testis was compared in male normotensive (Wistar and chronically hypertensive SH rats (11–22 months old). In chronic hypertension after 14C‐MCPA and 14C‐sucrose administration the penetration of radioactivity into the brain, cerebrospinal fluid and testis had significantly decreased or showed evidence of decrease, while after 14C‐antipyrine administration the penetration remained unchanged. Penetration of Evans blue‐albumin complex into the brain was studied by giving intravenous injection of Evans blue (5% solution) which is firmly bound to serum albumin. Extravasation of dye‐protein complex into the brain showed no difference between Wistar and SH rats. The results suggest that chronic hypertension does not increase the penetration of compounds into the brain and testis but rather, reduces it.
β1‐and β2‐adrenoceptor‐mediated secretion of amylase from incubated rat parotid gland
Authors: CARLSÖÖ B. , DANIELSSON Å. , HENRIKSSON R.
Published: December 2008

The present in vitro investigation was undertaken in an attempt to obtain further information on β‐adrenoceptor specificity and action in the rat parotid gland, with regard to amylase secretion. The β1‐selective agonist prenalterol was roughly 800 times more potent than the β2‐agonist terbutaline, and about 5 times more effective than noradrenaline in evoking amylase release. Propranolol was the most effective inhibitor of amylase release in all experiments. The β1‐selective antagonist metoprolol and H104/08 were also effective blockers of maximal noradrenaline‐and prenalterol‐induced release. The inhibition curves displayed biphasic shapes when amylase secretion was induced by noradrenaline, but not when prenalterol was the secretagogue. The β2‐antagonist H35/25 was without effect on maximal noradrenaline‐and prenalterol‐stimulated secretion. The amylase release evoked by submaximal concentration of terbutaline was inhibited by the two antagonists H35/25 and IPS 339. In another series of experiments propranolol and metoprolol clearly shifted the noradrenaline concentration‐response curve to the right, whereas H35/25 was without effect. The results further demonstrate the major importance of the β1‐adrenoceptor (noradrenaline‐activated) in eliciting amylase release from the rat parotid gland. However, it is also suggested that the β2‐adrenoceptors (terbutaline‐activated) may to some extent serve the same function.
Ephaptic impulse transmission between ventricular myocardial cells in vitro
Authors: SUENSON M.
Published: December 2008

Impulse transmission between closely appositioned cylindrical myocardial preparations, from the ferret, was studied in vitro. One preparation was driven, and when the longitudinal extracellular potential difference between electrodes 800 μm apart was made larger than 30–60 mV by increasing the resistance of the extracellular space, ephaptic (i.e. non synaptic) impulse transmission from one preparation to another occurred. In 2 out of 8 pairs of preparations examined the impulse transmission was bidirectional. The latency of the transmission varied from 9 to 369 ms. Various rate dependent blocks (sometimes associated with a Wenckebach phenomenon) were observed at stimulation frequencies above 1 Hz. The experimental situation has pathophysiological properties relevant to the analysis of the genesis of arrhythmias. Ephaptic interaction may be involved in the shaping of the wavefront of excitation under both normal and pathological conditions.
Phasic variations of extracellular potassium during fictive swimming in the lamprey spinal cord in vitro
Authors: WALLÉN PETER , GRAFE PETER , GRILLNER STEN
Published: December 2008

The lamprey spinal cord in vitro can generate the motor pattern underlying locomotion, which can be recorded with suction electrodes in the ventral roots. To test if the extracellular level of potassium changed during rhythmic activity, potassium‐sensitive microelectrodes were used to systematically (every 25 μm) explore the level of extracellular potassium [K+]e in different loci in the transverse plane of the spinal cord. During fictive locomotion the baseline level of [K+]e increased with 0.08–0.4 mM in the grey matter. As a rule phasic variations of up to 0.2 mM, correlated to each ventral root burst, were superimposed on the tonic deviation of [K+]e. Changes in this range may cause a moderate depolarization of the spinal neurones and might also affect other neuronal functions including the rhythm‐generating circuits.
Nocturnal variation in plasma levels of gastrin and somatostatin‐like immunoreactivity in man
Authors: UVNÄS‐MOBERG KERSTIN , WETTERBERG LENNART
Published: December 2008

Somatostatin and gastrin‐like immunoreactivity was measured in peripheral venous plasma at 22, 24, 02, 04 and 06 hours in 10 experiments performed on 6 healthy volunteers. In five of the experiments the subjects had been pretreated with propranolol 20–40 mg three times daily for one week. At 22 h gastrin and somatostatin levels averaged 153 and 143 pg/ml without treatment with β‐blockers and 93 and 74 with such treatment. Gastrin and somatostatin levels fell during the course of the night to ˜ 10 and 60% of the 22 h value, respectively. Somatostatin levels reached their lowest value at 02 h (50%) of the 22 h value. Treatment with β‐blockers tended to decrease gastrin as well as somatostatin levels over the whole experimental period, but did not influence the gradual decline of gastrin and somatostatin levels occurring during the night or the 02 h dip in somatostatin levels. It is suggested that the nocturnal dip in somatostatin secretion is vagally mediated and that the peak in acid output occurring at this hour is due to the decreased output of gastric somatostatin. The fact that the nightly dip in somatostatin secretion coincides with the peak output of the pituitary hormones prolactin and growth hormone is discussed.
Inhibition of transcellular NaCI reabsorption in dog kidneys during hypercalcemia
Authors: SEJERSTED OLE M. , STEEN PETTER ANDREAS , KIIL FREDRIK
Published: December 2008

Reduced concentrating and diluting capacity of the kidney in acute and chronic hypercalcemia may partly be due to inhibition of transcellular sodium reabsorption (RNa) in the thick ascending limb of Henle's loop. To examine this hypothesis, local heat production and RNawere measured during normo‐and hypercalcemia at comparable glomerular filtration rate (GFR) in volume expanded, anesthetized dogs. Changes in proximal RNawhich might occur during CaCl2infusion, were minimized by infusing acetazolamide (75 mg/kg body wt iv). When ultrafiltrable calcium was increased from 1.12±0.09 to 2.95±0.10 mmol/1, cortical heat production was unchanged, whereas outer medullary heat production fell by 32±4%. RNawas reduced by 32±6%. Bicarbonate reabsorption did not change but calcium reabsorption and potassium excretion increased significantly. The potassium content of cortex and outer medulla increased during hypercalcemia, whereas ouabain, an inhibitor of Na+K+‐ATPase reduces the potassium content. We conclude that hypercalcemia does not inhibit transcellular RNain the diluting segment by a direct effect on the Na+K+‐ATPase or the mitochondria, but by interfering with the coupled NaCI transport across the luminal cell membrane.
Total and regional renal blood flow during complete unilateral ureteral obstruction
Authors: WAHLBERG JAN , KARLBERG LARS , PERSSON A. ERIK G.
Published: December 2008

Regional renal blood flow was investigated after 1,2, 12 and 24 h of unilateral ureteral obstruction in rats. Total renal and cortical blood flow rates were determined by the microsphere technique and regional medullary blood flow by the 86‐Rb extraction method. The kidneys were microdissected into cortex and medulla, which was further divided into the outer stripe and the inner stripe of the outer zone, and the inner zone. In the obstructed kidneys cortical blood flow increased by 33% after 1 h of obstruction, but was normalized after 2 h. After 12 and 24 h this flow was significantly decreased (55% and 65% of control respectively). The pattern of total renal blood flow was similar to that of cortical blood flow. In the outer stripe there was an initial increase (44%) after 1 h, but later no significant deviations from control values were found. After 1 h of obstruction the blood flows in the inner stripe and the inner zone were not significantly different from control values. A significantly decreased blood flow was seen in the inner stripe after 2 h (57% of control) and in the inner zone after 12 h (58% of control). A significant recovery of the blood flow had occurred in the inner stripe and the inner zone after 24 h of obstruction. In the contralateral, non‐obstructed kidney no significant changes were found, besides an increased innerstripe blood flow after 24 h of UUO.
Effect of increased knee joint pressure on oxygen tension and blood flow in subchondral bone
Authors: GRØNLUND J. , KOFOED H. , SVALASTOGA E.
Published: December 2008

We have investigated the influence of acute changes in the knee joint pressure of rabbits on the oxygen tension and the regional blood flow in the subchondral bone. The intra‐articular pressure was increased by infusion of a sodium chloride solution into the joint cavity, and the associated change in the subchondral oxygen tension was measured by mass spectrometry. The mass spectrometer was also used to detect, qualitatively, changes in the regional blood flow. When the joint pressure was increased from the habitual level to 75 mmHg, the average subchondral oxygen tension was reduced from about 39 to about 30 mmHg and, at the same time, the regional blood flow was reduced significantly.
Somatostatin release and plasma molecular somatostatin components in man
Authors: BURHOL PER G. , LYGREN IDAR , JENSSEN TROND G. , FLORHOLMEN JON , JORDE ROLF
Published: December 2008

The present paper describes a sensitive, precise and specific radioimmunoassay method for measurements of plasma somatostatin; significant rises in plasma somatostatin following a test meal, intraduodenal infusion of fat and HCl, and intravenous injection of insulin; and separation of immunoreactive plasma somatostatin into two components probably representing bound and free molecular forms of somatostatin both in fasting and postprandial human plasmas.
Indoleaminergic mechanisms in brain vessels; Localization, concentration, uptake and in vitro responses of 5‐hydroxytryptamine
Authors: EDVINSSON L. , BIRATH E. , UDDMAN R. , LEE T. J.‐F. , DUVERGER D. , MacKENZIE E. T. , SCATTON B.
Published: December 2008

Immunocytochemical studies have revealed the presence of 5‐HT‐containing nerve fibres in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guineapig, rabbit and cat. Biochemical measurements (using HPLC) revealed substantial concentrations of 5‐HT and 5‐HIAA in the pial vessels of the rat, rabbit, cat and man, the amounts corresponding well with the density of the perivascular nerve supply. The uptake of 3H‐5‐HT was studied in arteries removed from the circle of Willis in rats. Maximum uptake was reached after 15 min of incubation at 37°C and plateaued at 30 min. The reaction was temperature‐dependent and found to be absent if performed at O°C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by approximately 90% upon administration of 5‐HT, whereas vessels from guinea‐pig, rabbit, cat and man were contracted by 40 to 60% relative to 124 mM K+. The EC50 values in the different species varied by between 1.×10‐7 M (rat) and 3×10‐9 M (dog). The 5‐HT‐induced contractions were blocked by the 5‐HT antagonists, methysergide, methergoline and ketanserin. Transmural nerve stimulation (TNS) of the rabbit basilar artery revealed a tetrodotoxin sensitive constriction whereas TNS of cat and dog middle cerebral arteries caused a tetrodotoxin‐sensitive relaxation. The relaxation was not significntly attenuated until high doses of methergoline (3× 10‐6 M) or ketanserin (3×10‐5 M) had been given. The contraction obtained upon electrical field stimulation of the rabbit basilar artery was reduced by the 5‐HT antagonists only in concentrations of 10‐6 M and above.
Endothelial surface sulfhydryl‐groups in blood‐brain barrier transport of nutrients
Authors: HERVONEN HEIKKI , WALL OSKAR STEIN
Published: December 2008

The sulfhydryl‐inhibitors p‐chloromercuribenzoic acid (PCMB) and p‐chloromercuribenzene sulfonic acid (PCMB‐S) were used to study the mechanism of nutrient transport across the blood‐brain barrier (BBB) in the rabbit. The vascular endothelium of the left hemisphere was exposed to these agents at 10–4M concentration for 35 sec by intracarotid perfusion. The non‐perfused right hemisphere served as intact control.3H‐methyl‐O‐glucose,14C‐cycloleucine and L‐DOPA were used as tracers for carrier‐mediated nutrient transport, and3H‐norepinephrine,14C‐sucrose and horseradish peroxidase were given to demonstrate abnormal extravasation. Assays of symmetrical samples from left and right hemispheres showed that PCMB‐S reduced the uptake of cycloleucine and methylglucose in the perfused hemisphere down to 14.1 ±2.3% and 33.2±2.2%, respectively, without deranging the barrier to the other tracers. PCMB also diminished the uptake of the nutrient tracers, but simultaneously induced extravasation of the normally barred tracers, an effect similar to that induced by mercuric ions in corresponding earlier studies. Our findings indicate that sulfhydryl‐groups located on the surface of the luminal membrane of the brain endothelial cells, where they are accessible to PCMB‐S binding, are essential for the blood‐brain barrier transport of important nutrients.
Different nerve responses in consecutive sections of the arterial system
Authors: NILSSON HOLGER
Published: December 2008

Isometric responses to nerve stimulation and to applied noradrenaline were compared in isolated ring preparations of three consecutive types of rat arteries, viz. the aorta, the superior mesenteric artery and 200‐μm branches of the latter. Intramural nerves were activated by graded electrical field stimulation; obtained responses were blocked by tetrodotoxin, phentolamine or prazosin. Also direct muscle activation could be accomplished, using impulses of long duration. In the aorta responses to nerve stimulation were sluggish, could reach only 30–40% of the maximal noradrenaline response and single impulses were ineffective. In the small resistance arteries, neurogenic responses matched the maximal noradrenaline responses and distinct, rapid contractions occurred to single nerve impulses. The superior mesenteric artery was intermediate in these respects. By contrast, on direct muscle activation all vessels responded to single impulses with rapid contractions that differed little in velocity. Pharmacological inhibition of transmitter reuptake increased noradrenaline sensitivity most in the small arteries, but nerve responses were most enhanced in the superior mesenteric artery. These regional differences, probably reflecting decreasing neuromuscular distance with decreasing vessel size, imply that generalizations concerning the relation between responses to nerve stimulation and to exogenous noradrenaline cannot be made from one vascular model only.
Characterization of the prostanoid receptors and of the contractile effects of prostaglandin F2ain human pial arteries
Authors: USKI TORE K. , ANDERSSON KARL‐ERIK , BRANDT LENNART , LJUNGGREN BENGT
Published: December 2008

The contractile and relaxant effects of various prostanoids were studied on isolated human pial arteries. Contractions were elicited with the following order of potency: U46619≅U44069>PGB2>PGF2a>PGE2≅PGD2>PGF1a≥TXB2, indicating that prostanoid‐induced contractions probably are mediated by a thromboxane‐sensitive receptor. Relaxation of PGF2a‐contracted arteries was induced with the order of potency: PGE2> PGE1>PGD2≅PGD1. Vessels contrated by K+were relaxed only by PGE,. Since PGI2was previously found to be more potent than all the prostanoids tested in the present study, relaxant responses are probably mediated via a PGI2‐sensitive receptor. The roles of free extracellular and cellularly bound calcium for the contractile effects of PGF2aand K+were estimated by incubating the arteries for various times in calcium‐free medium containing 10‐5M EGTA. Incubation for 5–10 min abolished K+‐induced contractions, whereas after 40 min of incubation PGF2astill induced contractions that reached 70% of control. The PGF2a‐induced contraction was biphasic in 8 out of 10 preparations. The second phase could be eliminated by increasing the EGTA‐concentration to 10‐4M, as well as by nifedipine pretreatment. In calcium‐free, high K+medium calcium‐induced contractions were elicited at lower concentrations in the presence of PGF2a. The results suggest that PGF2a‐induced contractions in human pial arteries are relatively independent of free extracellular calcium. PGF2amay promote trans‐membrane influx of calcium, as well as release calcium from seemingly superficially located cellular stores.
Actions of centrally administered neuropeptide Y on EEG activity in different rat strains and in different phases of their circadian cycle
Authors: ZINI I. , PICH E. MERLO , FUXE K. , LENZI P. L. , AGNATI L. F. , HÄRFSTRAND A. , MUTT V. , TATEMOTO K. , MOSCARA M.
Published: December 2008

The effects of centrally administered neuropeptide Y (NPY) on the sleep‐wakefulness cycle have been studied by analyzing its action in different strains of rats with or without spontaneous hypertension and during two different phases of the circardian cycle. Normal adult Sprague‐Dawley (SD), Wistar‐Kyoto (WKy) and spontaneous hypertensive (SH) rats were used. By means of EEG electrodes the recording of the fronto‐parietal electrocorticogram and the electromyogram could be made. Stainless steel cannula were also implanted into the lateral ventricle. The effects of an intraventricular injection of NPY (1.25 nmol/rat) was compared with the effects of the vehicle (saline) alone. The EEG patterns were classified as desynchronized, mixed or synchronized. In the SD rats NPY produced behavioural signs of sedation and a significant reduction of synchronizeded EEG activity as well as significant increase of synchronized and mixed EEG activities in comparison with the saline treated rats. In the WKy rats NPY administration produced an increase of synchronized EEG activity during evening sessions. In SH rats NPY produced a significant increase of desynchronized EEG activity and a decrease in mixed EEG activity indicating an awakening effect of the peptide. In view of the NPY innervation of the locus ceruleus, it therefore seems possible that the neuronal and hormonal regulation of the locus ceruleus noradrenaline nerve cells is different in the two strains of rats. It also seems possible that the ability of NPY to increase wakefulness in hypertensive animals is related to abnormal changes in the α2‐adrenoreceptors taking place in SH rats.
The release of (3H)‐GABA from the rabbit retina
Authors: AGARDH ELISABET , BAUER BIRGITTA
Published: December 2008

The neuronal and glial release of (3H)‐GABA from rabbit retina has been studied. The results indicate, that neither are there any glutamate, aspartate or glycine receptors on the GABA accumulating neurons, nor any GABA autoreceptors. (3H)‐GABA was found to be released by 40 mM K+ from retinal neurons, but not from glia, and the release was not dependent on extracellular Ca++. This indicates a release from a non vesicular transmitter pool. Ouabain has been proposed as a pharmacological tool for studying the release of (3H)‐GABA located in neuronal cytoplasm. However, it induced an increased release of (3H)‐GABA from both neurons and glia and it is therefore unlikely that it can be used for the specific purpose of studying release from neuronal cytoplasm.
Thyrotropin‐releasing hormone (TRH) causes sympathetic activation and cerebral vasodilation in the rabbit
Authors: KOSKINEN LARS‐OWE , BILL ANDERS
Published: December 2008

The effects of TRH on regional blood flow were studied in rabbits under urethane anesthesia. Four types of experiments were performed with the following results. (1) I.v. injection of 2 mg/kg b. w. TRH in animals with unilateral cervical sympathotomy caused a rise in mean arterial blood pressure from 10.0±0.5 to 13.3±0.5 kPa. Total cerebral blood flow, measured with labeled microspheres, increased from 75±5 to 126±16 g/min/100 g tissue on the intact side. There was a similar increase on the side with symphathotomy. The greatest increase, about 70%, was observed in cortical gray matter, caudate nucleus and thalamic region. There were marked reductions in blood flows in the spleen, gastric mucosa, skin and skeletal muscle. Mydriasis occurred on the side with an intact sympathetic supply. (2) I.v. infusion of 0.06 mg/kg b. w. per min TRH in animals with unilateral cervical sympathotomy and stabilized blood pressure increased total cerebral blood flow from 84±10 to 139±7 g/min/100 g. Blood flows to the masseter muscle, submandibular gland and facial skin but not to the eye or tongue were markedly reduced on the side with an intact sympathetic supply while little or no effect was observed on the side with sympathotomy. (3) Unilateral peripheral stimulation of the sympathetic chain at 1 Hz after bilateral sympathotomy caused a reduction in blood flows in the tongue, masseter muscle, submandibular gland and facial skin in animals with stabilized blood pressure. No potentiation of the stimulation effect was observed during TRH infusion. (4) The arteriovenous difference in oxygen saturation in the brain decreased from 39.1±2.8 to 26.4±3.7% after i. v. injection of 2 mg/kg b. w. TRH. The results indicate that TRH caused cerebral vasodilation in excess of that required by possible changes in cerebral metabolism. The vasoconstriction in the head region and the mydriasis was caused mainly by an increase in the activity of the cervical symphathetic nerves.
Different effects of glibenclamide and the structural analogue HB 699 on the45Ca2+uptake byob/ob‐mouse islets
Authors: NORLUND LENA , SEHLIN JANOVE
Published: December 2008

The effects on45Ca2+uptake of HB 699, an acyl‐amino‐alkyl benzoic acid derivative, was compared to those of glibenclamide in incubations using the La3+wash technique. HB 699 enhanced the45Ca2+net uptake in a concentration range (10–200 μM) where insulin release was also stimulated. Glibenclamide showed maximum stimulation of45Ca2+net uptake already at 1 μM. HB 699 did not clearly stimulate the short‐term45Ca2+uptake whether or not the islets were preincubated with the drug. It is suggested that HB 699–induced insulin release is mediated, at least partly, by increased mobility of β‐cell Ca2+.
Effects of standard diuretics and ortho‐vanadate on sodium transport across isolated frog skin
Authors: ERIKSSON ÖRJAN
Published: December 2008

Frog (Rana temporaria) skins were studied in an Ussing type lucite chamber adapted to diminish tissue edge damage. The transepithelial electrical potential difference, short circuit current and direct current (DC) resistance of skins mounted in this chamber were 56, 20 and 24% higher, respectively, than those of skins mounted in a conventional chamber. Amiloride, triamterene, ouabain and ortho‐vanadate inhibited short circuit current and net mucosal to serosal flux of 22Na. Amiloride and triamterene had rapid onsets of action and were effective only when administered to the mucosal (pond) side of the skin. Ouabain and ortho‐vanadate had slower onsets of action and were effective only when administered to the serosal side of the skin. Steady state of effects of these drugs was not reached within the three‐hour period of the experiments. The inhibitory effect of ortho‐vanadate was blocked by adding a disulfonic stilbene derivative (DIDS) to the serosal side of the skin. Serosal prostaglandin E2 stimulated the short‐circuit current and decreased the DC resistance. Thiazides, acetazolamide and loop diuretics had no effects on Na+ transport by frog skin. Thus, frog skin seems to be a useful model only in studies of the mode of action and the structure‐activity relationship of diuretic which act by inhibiting sodium entry or Na+‐K+‐ATPase activity.
The effect of indomethacin on the local cerebral blood flow increase induced by somato‐sensory stimulation
Authors: DAHLGREN NILS , ROSÉN INGMAR , NILSSON BENGT
Published: December 2008

The local cerebral blood flow in cerebral cortical and subcortical regions of the rat brain was studied with the14C‐iodoantipyrine autoradiographic technique at rest and during strong non‐noxious stimulation of the nose. Patterns of local blood flow changes evoked by stimulation with and without pretreatment of indomethacin, a potent cyclooxygenase inhibitor were determined. Stimulation produced a marked heterogeneous enhancement of CBF. Indomethacin did not prevent this effect although the absolute flow levels were considerably lower in indomethacin‐treated animals. Indomethacin was especially effective in reducing the cerebral cortical blood flow response to stimulation whereas the subcortical response was much less affected.
Site and magnitude of the tubular inhibitory effect of expanding the extracellular volume in dogs
Authors: LANGBERG HARALD , HARTMANN ANDERS , HOLDAAS HALLVARD , KIIL FREDRIK
Published: December 2008

Ethacrynic acid inhibits energy‐requiring transcellular NaCl reabsorption without affecting NaHCO3reabsorption. Acetazolamide inhibits NaHCO3and most of the remaining NaCl reabsorption in the proximal tubules (bicarbonate‐dependent reabsorption) but raises distal transcellular NaCl reabsorption. After administration of both diuretics, the remaining bicarbonate‐dependent and transcellular reabsorptions become constant until glomerular filtration rate (GFR) is almost halved. The inhibitory effect of expanding the extracellular volume (ECV) until plasma volume and GFR increased 30–40% was examined in anesthetized dogs. Examinations at comparable GFR obtained by altering arterial perfusion pressure showed that the inhibitory effect of ECV expansion was attenuated by administering acetazolamide. Ethacrynic acid amplified the inhibitory effect which for sodium and chloride reabsorption amounted to 6–7% of the filtered load at comparable GFR. An inhibitory effect of ECV expansion of bicarbonate reabsorption was disclosed only after raising plasma bicarbonate concentration. Thus, the small inhibitory effect of massive ECV expansion is confined to proximal tubular bicarbonate‐dependent reabsorption and is of the same magnitude as previously demonstrated in experiments of similar design by raising plasma pH by only 0.07 unit. Since ouabain inhibits transcellular NaCl reabsorption, a natriuretic hormone is more likely to be an inhibitor of carbonic anhydrase than of Na, K‐ATPase.
Repetitive measurements of intracranial pressure in awake rabbits
Authors: GYRING JENS A. , BRØNDSTED HANS E.
Published: December 2008

Previous measurements of the intracranial pressure in experimental animals suffer from acute and subacute effects of cannulation. In order to obtain reliable, repetitive or continuous values, we measured the intracranial pressures in awake rabbits with a new permanent adjustable ventricular cannula that included a separate entrance to the subarachnoid space. The mean intraventricular pressure ten days after the operation was 5.2±1.1 mmHg (SD) (70 animals). Manipulation of the cannula system and infusion of artificial cerebrospinal fluid did not damage the blood‐brain barrier (indicated by extravasation of Evans Blue). The intracranial pressure was constant for as long as 6 months and as many as 22 separate measurements and infusions. The cerebrospinal fluid cells and protein content did not change in animals with permanent cannulae and in animals perfused with 2–4 ml artificial cerebrospinal fluid. In 30 animals the ventricular cannula functioned for 10–180 (median 65) days and the subarachnoid entrance for 11–23 (median 16) days.
Buffer capacity and lactate accumulation in skeletal muscle of trained and untrained men
Authors: SAHLIN K. , HENRIKSSON J.
Published: December 2008

Buffer capacity (β) of skeletal muscle has been determined in trained (n=7) and in sedentary subjects (n=8). The trained subjects were active in ball games where a high degree of anaerobic energy utilization is required. Percentage fibre type occurrence in the thigh muscle was not significantly different in the two groups. However, there was a tendency towards a higher proportion of type I (slow‐twitch) fibres (61.5±11.6% vs. 50.2±12.5%) and a lower proportion of type IIB fibres (2.1±3.5% vs 14.1±16.3%) in the trained subjects. The proportion of the cross‐sectional area of the muscle biopsies that was made up of type I or type II fibres was not different in the two groups. All subjects performed an isometric contraction of the knee extensors to fatigue at 61% of their maximal voluntary contraction force. Muscle biopsies were taken from the quadriceps femoris muscle at rest and immediately after contraction. The buffer capacity of muscle was calculated from: β= (Muscle lactate (work)‐Muscle lactate (rest))/(Muscle pH (rest) ‐Muscle pH (work)). A higher buffer capacity (p<0.05) was observed in the trained subjects (β=194±30 mmolxpH‐1xkg‐1 dry wt.) compared to the sedentary group (β=164±20) (mean±SD). An unexpected finding was that muscle lactate after contraction to fatigue was lower (30%, p<0.01) and muscle pH was higher (6.80±0.06 vs. 6.61±0.12, p<0.01) in the trained subjects than in the sedentary controls. Creatine phosphate stores were almost completely depleted in both groups. Post‐exercise lactate values were related to the proportion of type II fibres in the muscle (p<0.01). There was, however, no statistical correlation betwe β and fibre type occurrence (p>0.05). In summary, the present results indicate that skeletal muscle buffer capacity can be changed by training in man. Furthermore, it is concluded that the lower lactate accumulation and pH decline after an isometric contraction to fatigue that was observed in the trained compared to the sedentary subjects is related to the training per se. However, the tendency towards a lower type I (slowtwitch) fibre percentage in the trained subjects is likely to have contributed to the observed differences.
Further studies on renal nerve stimulation induced release of noradrenaline and dopamine from the canine kidney in situ
Authors: BRADLEY THOMAS , HJEMDAHL PAUL
Published: December 2008

The renal venous outflow of dopamine and noradrenaline were studied in the canine kidney in situ in connection with renal nerve stimulation (RNS). RNS (0.5‐4 Hz) caused frequency‐dependent increases in the outflow of both catecholamines, which could be detected already at 0.5 Hz. The ratio dopamine/noradrenaline in renal venous plasma (approximately 0.15) was not influenced by varying the RNS parameters but was significantly enhanced (to about 0.25) by pretreatment with guanethidine according to a procedure previously used to demonstrate renal dopaminergic vasodilatation. The unstimulated kidney removed conjugated dopamine (which represents 98–99% of the total dopamine in plasma). During RNS the conjugated dopamine outflow to renal venous blood increased, but measurements of conjugated dopamine were less reliable than measurements of free dopamine to assess dopamine release from the kidney. When studying the renal nerve contributions to the renal venous outflow of dopamine and noradrenaline more accurate estimates may be obtained by correcting for the removal of catecholamines delivered to the kidney in arterial plasma. Such corrections were performed with endogenous adrenaline or radiolabelled noradrenaline. The two methods of correction yielded similar results and showed that RNS reduced catecholamine extraction in the kidney. The high ratio of dopamine/noradrenaline in kidney tissue (with a preferential distribution of dopamine to the cortex) and the dopamine outflow to renal venous plasma during RNS support the existence of specific dopaminergic nerves in the dog kidney.
Transport of branched‐chain amino acids in brain slices of developing and adult rats
Authors: PAJARI M.
Published: December 2008

The accumulation of labelled leucine, isoleucine and valine by cerebral slices of developing and adult rats was studied. The accumulation increased with age by 15–25%. It was strongly (from 52 to 86%) inhibited by a 100‐fold excess of phenylalanine, tryptophan and another branched‐chain amino acid, but moderately activated by GABA and glutamate. The inhibitions evoked by leucine and isoleucine were slightly stronger in young than in adult rats. The corresponding 2‐oxoacid analogs of leucine, isoleucine and valine were also inhibitory but less effective. The 30‐min accumulation of 3H‐labelled branched‐chain amino acids was ostensibly higher than the increase in their total concentrations in incubated slices, which apparently bespeaks lively homoexchange of endogenous intracellular and labelled extracellular amino acids.
Intimacy of the neuroeffector junction and resistance to α‐adrenoceptor‐blockade of the neurogenic contractile response in vasa deferentia from guinea pig and rat
Authors: HAMMARSTRÖM MARGARETA , SJÖSTRAND NILS O.
Published: December 2008

The effect of phentolamine on the neurogenic contractile response in vasa deferentia from rat and guniea pig was studied during Wallerian degeneration. This response was also investigated after partial denervation (surgery or chemical sympathectomy by guanethidine treatment) in vasa deferentia from guinea pig. During Wallerian degeneration the response showed a gradual increase in sensitivity to phentolamine and was abolished in the late stages. The neurogenic contractile response of the partially denervated vas deferens was blocked by low concentrations of phentolamine. It is concluded that decreased intimacy of the neuroeffector junctions leads to increased susceptibility to α‐adrenoceptor blockade of the contractile response to nerve stimulation. It is further concluded that the motortransmission in the vas deferens is essentially adrenergic. The resistance to α‐adrenoceptor blockade of the initial phase of the contractile response to nerve stimulation of intact vasa deferentia from guinea pig and rat might well be explained by the “proximity theory” of Dale & Gaddum although participation of supplementary mediators cannot be excluded.
Characterization of two different calcium entry pathways in small mesenteric arteries from rat
Authors: HÖGESTÄTT EDWARD D.
Published: December 2008

The effects of Ca2+removal, nifedipine, and La3+on contractions induced by 124 mM K+and 10 μM noradrenaline (NA) were investigated in small mesenteric arteries from rat. Ring segments of the arteries were suspended between two steel wires in a 2.5 ml muscle bath, and the mechanical activity recorded “isometrically”.The tonic components of the contractile responses to both K+and NA were critically dependent on the presence of Ca2+in the bath solution. Nifedipine effectively relaxed K+‐contracted arteries, whereas those activated by NA were considerably less affected by the drug. Application of NA to arteries depolarized by K+in the presence of nifedipine induced a sustained tonic contraction, which was only approximately 20% smaller than that elicited by NA in “standard” Krebs solution, implicating pharmacomechanical coupling. Unlike nifedipine, La3+inhibited K+‐ and NA‐induced contractions to approximately the same extent. Re‐application of Ca2+to “Ca2+‐depleted” preparations exposed to K+and/or NA induced concentration‐dependent contractions. The experimental results suggested that the effects of K+and NA on the membrane permeability to Ca2+were additive. The Ca2+‐induced contractions were more inhibited by nifedipine in K+‐depolarized than in NA‐exposed artereis. It is concluded that K+and NA utilize partly different Ca2+entry pathways to increase the myoplasmic Ca2+concentration in rat mesenteric arteries. Whereas K+seems to promote the influx Ca2+by activation of Ca2+channels sensitive to the membrane potential, the nature of the receptor‐operated Ca2+entry pathway remains to be established.
Changes in neuromuscular performance and muscle fiber characteristics of elite power athletes self‐administering androgenic and anabolic steroids
Authors: ALÉN M. , HÄKKINEN K. , KOMI P.V.
Published: December 2008

The influence of androgenic‐anabolic steroid‐induced changes in measures of body composition, muscle fiber characteristics and various aspects of the neuromuscular performance of the leg extensor muscles was investigated in five experimental and six control power athletes during the 24‐week programmed strength training followed by the additional six week training without hormone drugs. The mean values of the dosages of self‐administration during the 24‐week period were 31.0pL14.3 mg/day for anabolic steroids (methandienone, stanozolol, nandrolone) and 178.4pL82.7 mg/week for testosterone. During the 24‐week hormone period the experimental group gained in fat‐free weight (p<0.01) and in the mean muscle fiber areas (p<0.01) of the vastus lateralis muscle while the corresponding gains in the control group were minor (NS).The increases of maximal isometric force in the experimental and control groups were 14.7% (p<0.01) and 6.1% (NS), respectively, and the values obtained in average load‐vertical jumping height curves were improved significantly (p<0.05) only in the experimental group. Increases of 18.2% (p<0.001) and 12.9% (p<0.01) took place in the squat lift in the experimental and control groups, respectively. Both groups demonstrated similar (p<0.05) improvements in isometric fast force production. During the additional six week programmed training without hormone drugs significant (p<0.05) increases were observed in the experimental group in addition to maximal isometric force and the squat‐lift but also in isometric fast force production, while the corresponding changes in the control group were minor (NS).It is suggested that strength training in combination with administration of androgenic‐anabolic steroids causes improvements in selected neuromuscular parameters. These changes may be greater than those of caused by the strenght training alone.
Neither vasoactive intestinal peptide (VIP) nor purine derivatives may mediate non‐adrenergic tracheal inhibition
Authors: KARLSSON J.‐A. , PERSSON C.G.A.
Published: December 2008

Neurogenic responses in isolated electrical field stimulated guinea‐pig tracheas include a prominent relaxation that is only partially inhibited by propranolol. The possibility that either purine derivatives or VIP could be a non‐adrenergic inhibitory neurotransmitter was examined. Relaxant characteristics of adenosine, ATP, adenine and VIP in tracheas with different degrees of contraction were compared to those of maximal non‐adrenergic nerve stimulation. Spontaneous tone and carbachol (5.5 μM and 55 μM)‐contracted tracheas were inhibited 77.5±5.0% (n=9), 24.7±2.8% (n=11) and 14.5±5.0% (n=10), respectively, by electrical nerve stimulation. At the three states of contraction exogenous VIP, but not adenosine, ATP, or adenine, produced relaxations similar to those of electrical nerve stimulation. In carbachol‐contracted tracheas with maximally effective concentrations present of adenosine (3 mM), adenine (3 mM) or VIP (23.3 μM), the non‐adrenergic neurogenic inhibitory response remained intact. The neurogenic inhibitory response was also unaffected by the presence of theophylline and indomethacin which blocked relaxatory effects of adenosine and ATP, respectively. The results suggests that neither the purine derivatives, nor VIP are involved in the non‐adrenergic, neurogenic inhibition in the guinea‐pig trachea.
Facilitation of transmission at the crayfish neuromuscular synapse by a convulsant phenol
Authors: KAILA K. , HEINONEN E. , ÅKERMAN K.E.O.
Published: December 2008

The effects of the convulsant drug 4‐C1 phenol on synaptic transmission were studied in the opener muscle of the crayfish walking leg.4‐C1 phenol was found to increase the amplitude of the excitatory postsynaptic potential without affecting the resting potential or input resistance of the muscle fiber. The drug did not change the frequency of spontaneous miniature postsynaptic potentials in K+‐depolarized fibers. The postsynaptic voltage response to bath‐applied glutamate (the excitatory transmitter compound) was decreased while the C1“‐conductance increase related to the action of bath‐applied γ‐aminobutyric acid (the inhibitory transmitter) was not affected. In the light of previous results obtained on crayfish axons it is concluded that convulsant phenols induce an increase in the evoked release of transmitter by increasing the duration of the presynaptic depolarization through a block of voltage‐dependent potassium channels.