Noradrenalin- und Adrenalingehalt des Rattenherzens bei experimenteller Niereninsuffizienz

Impulse interval-dependent effect of sympathetic nerve stimulation on evoked acetylcholine release from the rabbit perfused atria preparation.

The aim of the present study was to explore possible prejunctional effects mediated by impulse activity of sympathetic terminals on evoked acetylcholine release in an organ innervated by the autonomic ground plexus. Rabbit atria were isolated with the extrinsic right vagus and sympathetic nerves intact and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline and fractionation of the radioactivity on cation exchange columns. The overflow of endogenous noradrenaline was measured by HPLC and electrochemical detection. The vagus nerve was stimulated at 2 Hz for 3 min four times at intervals of 10 min. During the second …

Release of endogenous 3,4-dihydroxyphenylethylamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland. Effects of electrical stimulation and of inhibition of monoamine oxidase and reuptake.

: Isolated rat neurointermediate lobes were incubated in vitro. The release of 3,4-dihydroxyphenylethylamine (dopamine, DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and methoxyphenylethanol (MOPET) was determined by HPLC with electrochemical detection. Under resting conditions, the outflow of metabolites was 35–50 times that of DA. HVA accounted for 50%, DOPAC for 45%, and MOPET for 5% of the metabolites. Although an equivalent of 40–50% of the tissue DA content was released per hour as metabolites, the tissue DA content was not reduced after 110 min of incubation. The spontaneous outflow of DA and its metabolites was not affected by the DA uptake inhibitor GBR 12921 (1…

Die Konzentration von Noradrenalin und Adrenalin in den einzelnen Abschnitten des Herzens

1. A method for the assay of noradrenaline and adrenaline in small pieces of heart tissue is described. The amines were extracted with acid ethanol and separated by paper chromatography. The regions containing the amines were eluted and the amount of amines in the eluates was determined by bioassay. Noradrenaline was assayed on the blood pressure of the pithed rat. Adrenaline was assayed on the isolated atropinized rat's uterus stimulated with oxytocin. 2. The identity of the substances tested by bioassay with noradrenaline and adrenaline was confirmed by a number of chemical and pharmacological tests. 3. The concentration of catechol amines in different parts of the heart was studied in ca…

Die Hemmung der Noradrenalin-Aufnahme des Herzens durch Reserpin und die Wirkung von Tyramin

Die positiv inotrope Wirkung von Theophyllin, Adrenalin und Strophanthin am Papillarmuskel bei Sch�digung durch Dinitrophenol, Azid, Chinin und Barbiturat

�ber die Wirkung von Acetylcholin auf die mechanischen und elektrischen Eigenschaften des denervierten Rattenzwerchfells unter dem Einflu� verschiedener Pharmaka

Untersuchungen �ber die Einwirkung von verschiedenen Pharmaka auf die Spontanrhythmik des isolierten H�hneramnion

1. Das isolierte Huhneramnion nach Baur eignet sich gut, um Fragen nach der Entstehung der Erregung, deren Weiterleitung und Koordination, dem Angriffspunkt und der Wirkungsweise von Pharmaka zu prufen, da es sich um ein nervenfreies, rhythmische Kontraktionen ausfuhrendes Organ handelt, das praparativ leicht zu handhaben ist. 2. Auf die erregende Wirkung von Acetylcholin, Nicotin und Bariumionen sind d-Tubocurarin, Decamethonium, Atropin, Hexamethonium und Pentamethonium ohne Einflus. 3. Papaverin und Chinin hemmen die genannten erregenden Verbindungen reversibel. 4. Bariumionen fuhren zu Storungen in der Regelmasigkeit der rhythmischen Kontraktionen. Die Deutung dieses Effektes wird in de…

Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracain und Psicain auf die Noradrenalin-Freisetzung aus dem Herzen

Unterschiede zwischen Tyramin und Dimethylphenylpiperazin in der Ca++-Abhängigkeit und im zeitlichen Verlauf der Noradrenalin-Freisetzung am isolierten Kaninchenherzen

On the perfused rabbit heart a constant infusion of tyramine released noradrenaline continuously and independently of the external Ca++ concentration. In contrast, noradrenaline release by DMPP was only transient and required the presence of Ca++.

Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart

1. Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 μM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method. 2. Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8 μM, chlorpromazine 5.0 μM, desipramine 5.0 μM, dibenzepine 34.7 μM, doxepin 4.7 μM, imipramine 4.7 μM, noxiptiline 9.1 μM and opipramole 9.2 μM. The incidence of arrhythmias increased with the concentrat…

Der Einflu� von Monojodessigs�ure auf das Aktionspotential des Rattenzwerchfells

1. The action of iodoacetic acid (IA) was studied on the isolated rat diaphragm at 20–22° C. Membrane and action potentials were led off with intracellular microelectrodes. 2. IA causes a contracture which is complete in 4 hours. As long as t he contracture develops, the membrane potential remains constant. A contracture identical with that seen in a normal preparation can be produced by IA in the presence of isotonic K2SO4. 3. The amplitude of the action potential is only slightly reduced during the first two hours after addition of IA. The duration of the action potential is significantly increased. Finally, action potentials with a plateau are obtained which resemble those of normal vent…

�ber die getrennte Abh�ngigkeit des Stoffwechselverhaltens und der Schilddr�senhyperplasie von den ?- und ?-Zellen der Adenohypophyse bei der Ratte nach gemeinsamer Verabreichung von Thyreostatika und SH-gruppenhaltigen Substanzen

Short- and long-latency muscarinic inhibition of noradrenaline release from rabbit atria induced by vagal stimulation.

1. The influence of the time interval between vagal and sympathetic nerve stimuli on the magnitude of muscarinic inhibition of noradrenaline release was studied in the isolated perfused rabbit atria preparation. The transmitter stores were labelled with [14C]choline and [3H]noradrenaline. 2. The right cardiac postganglionic sympathetic nerves were stimulated at 3 Hz for 3 min three times at intervals of 10 min. The [3H]noradrenaline outflow evoked by the second stimulation equalled the averaged means of the log values of amine outflows evoked by the first and third stimulations. 3. During the second sympathetic stimulation the right vagus nerve was stimulated (3 Hz, 3 min) in such a way tha…

Cholinesterase activity and exposure time to acetylcholine as factors influencing the muscarinic inhibition of [3H]-noradrenaline overflow from guinea- pig isolated atria

Guinea-pig isolated atria were incubated and loaded with [3H]-noradrenaline. The release of 3H and of [3H]-noradrenaline was induced by field stimulation (6-9 trains of 150 pulses at 5 Hz). The stimulation-evoked overflows of 3H and of [3H]-noradrenaline were determined. In the absence of an inhibitor of acetylcholinesterase, acetylcholine (12 min preincubation before nerve stimulation, up to 10 microM) failed to inhibit the evoked [3H]-noradrenaline overflow. In the presence of atropine, an increase by acetylcholine of evoked release was observed in the same atria. In contrast, the selective muscarinic agonist methacholine significantly decreased the evoked overflow. The inhibition was ant…

Muscarinic inhibition of [3H]-noradrenaline release on rabbit iris in vitro: effects of stimulation conditions on intrinsic activity of methacholine and pilocarpine

1. Rabbit isolated irides were loaded with [3H]-noradrenaline and superfused with Tyrode solution. The inhibition by the muscarinic agonists (+/-)-methacholine and pilocarpine of the [3H]-noradrenaline overflow into the superfusate evoked by field stimulation (pulses of 1 ms duration, 75 mA) was measured as an index of activation of presynaptic muscarinic receptors. 2. The fractional rate of release per pulse during the first stimulation period (S1) was low with 360 pulses at 3 Hz, intermediate with 360 pulses at 10 Hz and high with 1200 pulses at 10 Hz. Upon repetitive stimulation (7 periods at 20 min intervals), the fractional rates of release per pulse during S7 no longer differed, sugge…

Versuche zur Bestimmung des wahren K-Efflux im Rattenzwerchfell

In an isolated muscle loaded with 42K the potassium efflux through the muscle fibre membrane can be calculated from the rate constant of the loss of 42K into an inactive bathing solution. The calculation can only be valid if the amount of 42K leaving all the individual fibres is equivalent to the amount of 42K entering the bathing solution from the surface of the whole muscle. It seems possible that 42K ions which have already left a muscle cell can be taken up again into a muscle fibre before diffusing into the bathing solution. Thus the calculated potassium efflux might be smaller than the real efflux.

The effect of dopamine on the overflow of endogenous noradrenaline from the perfused rabbit heart evoked by sympathetic nerve stimulation.

1. The effects of dopamine and two dopamine receptor antagonists (pimozide, flupenthixol) on the release of endogenous noradrenaline evoked by electrical stimulation of the postganglionic sympathetic nerves and their influence on cardiac performance were measured in isolated perfused rabbit hearts. 2. Dopamine 0.2μM decreased noradrenaline overflow and ventricular tension development in response to nerve stimulation. 3. Dopamine 2μM increased spontaneous noradrenaline output and tension development. The noradrenaline overflow in response to nerve stimulation was greatly enhanced. This action was only partly reversed by wash out of exogenous dopamine, indicating de novo synthesis and facilit…

Adrenerge α- und β-Receptoren und ihre spezifischen Hemmstoffe

Die wichtigsten pharmakologischen Befunde, die zur Klassifizierung der adrenergen α- und β-Receptoren gefuhrt haben, werden besprochen. Hemmstoffe der α-Receptoren werden bereits seit langerer Zeit zu therapeutischen Zwecken verwandt. Ausfuhrlicher werden die Hemmstoffe der β-Receptoren behandelt, die erst in den letzten Jahren Eingang in die Klinik gefunden haben. Die pharmakologischen Wirkungen, Nebenwirkungen und therapeutischen Indikationen der Receptorenhemmstoffe werden besprochen.

Die Wirkung von Pharmaka auf die Elimination von Noradrenalin aus der Perfusionsfl�ssigkeit und die Noradrenalinaufnahme in das isolierte Herz

Muscarinic inhibition of potassium-induced noradrenaline release and its dependence on the calcium concentration.

1. Noradrenaline release from the isolated rabbit heart was evoked by perfusion with a medium containing 135 mM potassium and 17 mM sodium ions (high K+-low Na+). 2. The noradrenaline output in response to high K+-low Na+ was dose-dependently decreased by methacholine (0.625-320 muM) and this effect was reserved by atropine 1.44 mM. 3. Lowering the calcium concentration of high K+-low Na+ from 1.8-0.1125 mM decreased the noradrenaline output by 85%. The effect of methacholine, expressed as % inhibition of noradrenaline release, was potentiated by lowering of the calcium concentration. 4. Both at normal and lowered calcium concentrations the inhibitory action of methacholine was larger from …

�ber den Wirkungsmechanismus von Reserpin

Der Einflu� von Reserpin auf die Wirkung der ?Neuro-Sympathomimetica?

Die Hemmung der Aufnahme vonα-Methylnoradrenalin in das Herz durch sympathomimetische Amine

Hearts of rabbits were isolated and perfused with Tyrode solution containing 10 ng/ml (−)-α-methyl noradrenaline. The uptake by the heart ofα-methyl-noradrenaline was calculated by estimating the amount of amine removed from the perfusion fluid while passing through the heart. In control experiments the mean removal ofα-methyl noradrenaline was 43,7 ± 1,6% of the amount infused. The rate of removal remained constant throughout the time period of the experiment, i.e. 20 min.

Uptake of [3H]dopamine into dopaminergic and noradrenergic neurones of the isolated neurointermediate lobe of the rat hypophysis. Effects of desipramine and nomifensine.

The isolated neurointermediate lobe (NIL) of the rat hypophysis accumulates [3H]dopamine from the incubation medium. Column chromatographic analysis showed that 92% of the tissue radioactivity was contained in the catecholamine fraction. [3H]Dopamine represented 70% and [3H]noradrenaline 30% of the [3H]catecholamines. Desipramine (1 microM) prevented the formation of [3H]noradrenaline without affecting the storage of [3H]dopamine. Nomifensine (10 microM) blocked the storage of [3H]dopamine and [3H]noradrenaline. Thus, in the NIL, [3H]dopamine is taken up into dopaminergic and noradrenergic neurones. In the latter, [3H]dopamine is converted to [3H]noradrenaline, indicating a significant dopa…

Die Aufnahme von ?-Methylnoradrenalin in das isolierte Kaninchenherz und seine Freisetzung durch Reserpin und Guanethidin in vivo

Die Wirkung von Harmalin auf die Konzentration von Noradrenalin und Adrenalin im Herzen

A single injection of harmaline increases the noradrenaline and adrenaline concentration in the rat heart. The maximum effect is obtained after about 40 min.

Effects of several muscarinic agonists on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart

Summary 1 The effects of several muscarinic agonists on atrial tension development, ventricular rate and noradrenaline release from terminal sympathetic fibres evoked by electrical nerve stimulation (SNS) and 1,1-dimethyl-4-phenylpiperazinium (DMPP) were measured in isolated perfused rabbit hearts. 2 Hexamethonium, in a concentration which almost abolished the release of noradrenaline by DMPP, had no effect on the release produced by SNS, confirming that the stimulation was postganglionic. 3 The order of potency for inhibition of atrial tension development was N-methyl-1,2,5,6, tetrahydro-nicotinic acid prop-2-yne ester (MH-1)>oxotremorine > acetylcholine > methacholine > carbachol > furtre…

�ber die Wirkung hypotoner Salzl�sungen auf das Rattenzwerchfell

Es wird die Wirkung hypotoner Salzlosungen auf das isolierte Rattenzwerchfell beschrieben. Auf 5/10–6/10 der Isotonie verdunnte Tyrodelosungen fuhren an Muskeln, die bereits langere Zeit im Versuch sind, zu einer dauernden Verstarkung der elektrisch ausgelosten Kontraktionen („hypotoner Effekt“). Mit Saccharose auf Warmbluterisotonie erganzte hypotone Salzlosungen zeigen diesen Effekt nicht. Vermehrung des Kaliums oder Calciums im Austausch gegen Natrium bei erhaltener Hypotonie hemmt den „hypotonen Effekt“, Senkung der Badetemperatur hebt ihn ebenfalls auf.

Aufnahme von Guanethidin in Gewebe nach sympathischer Denervierung und Vorbehandlung mit Reserpin

Aufnahme von threo-Corbadrin und seine Freisetzung als falsche sympathische �bertr�gersubstanz

Der Einflu� von BAL und Methionin auf die Schilddr�senhyperplasie nach chronischer Gabe von Methylthiouracil

Bei 45 tagiger Verabreichung wurde an Ratten der Einflus von BAL (30 mg/kg) und Methionin (3 g/kg) auf die durch Methylthiouracil (MTU, 25 mg/kg) verursachten Stoffwechsel-, Schilddrusengewichts-und-aktivitatsanderungen untersucht. Die Ergebnisse sind statistisch gesichert.

Die Noradrenalin-Abgabe aus dem isolierten Kaninchenherzen bei sympathischer Nervenreizung und ihre pharmakologische Beeinflussung

Co-transmitter mediated facilitation by sympathetic nerve stimulation of evoked acetylcholine release from the rabbit perfused atria preparation.

Rabbit atria were isolated with the extrinsic right sympathetic and vagus nerves attached and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline and fractionation of the radioactivity on cation exchange columns. Sympathetic nerve stimulation (SNS, 2 Hz, 3 min) carried out together with vagus nerve stimulation (VNS, 2 Hz, 3 min), but each SNS pulse preceding a vagal one by 19 ms, caused a facilitation of acetylcholine overflow of about 60% versus independent controls in the absence of SNS. Antagonists of putative neurotransmitters were tested to find out the prejunctional mediator involved in the facilitation. The …

Über den Zusammenhang zwischen histologischer Struktur und funktionellem Verhalten des Skelettmuskels

A stimultaneous investigation of the function and the histological structure of two different muscles of the rat showed no relation between the arrangement of the fibrilles in the muscle cell and the function of the muscle. Such a relation between structure and function was assumed byKruger on the basis of histological investigations, but our findings do not support this hypothesis.

The interferance of muscarinic receptors with the noradrenaline release from sympathetic nerve endings caused by nicotinic agents.

RELEASE BY SYMPATHETIC STIMULATION OF ALPHA-METHYLNORADRENALINE STORED IN THE HEART AFTER ADMINISTRATION OF ALPHA-METHYLDOPA.

Dans les cœurs de lapins traites par l'α-methyldopa, la depletion de la noradrenaline s'accompagne d'une fixation importante d'α-methylnoradrenaline. Sous l'effet de stimulation sympathique ou d'iodure de dimethylphenyl-piperazinium, ces cœurs liberent conjointement de la noradrenaline et de l'α-methylnoradrenaline.

Isoprenaline and forskolin increase evoked vasopressin release from rat pituitary

Isolated neurointermediate lobes of rat pituitaries were incubated in Krebs solution. The vasopressin release evoked by electrical stimulation (0.2 ms, 80 V, 15 Hz, 10 s trains at 10 s intervals for a total of 10 min) was completely inhibited by tetrodotoxin. Isoprenaline increased the evoked vasopressin release to a maximum of 60% (EC50 10 nM) and this effect was antagonized surmountably by propranolol. Forskolin increased the vasopressin release by 98%. These results suggest the presence within the neurohypophysis of a beta-adrenoceptor-linked adenylate cyclase facilitating vasopressin secretion.

Freisetzung von Alpha-Methylnoradrenalin durch sympathische Aktivität beim Menschen nach Verabreichung von Alpha-Methyldopa

Nach dem Ergebnis von Tierversuchen wird Alpha-Methyldopa im Organismus zu Alpha-Methyldopamin dekarboxyliert. Dieses Amin wird dann zu Alpha-Methylnoradrenalin hydroxyliert und in sympathischen Nerven zusammen mit dem naturlichen Ubertragerstoff Noradrenalin gespeichert (Carlsson u. Lindqvist, 1962). Da Alpha-Methylnoradrenalin bei elektrischer oder pharmakologischer Reizung sympathischer Nerven zusammen mit Noradrenalin freigesetzt wird (Musduoll u. Maitre, 1963), bezeichnet man es auch als „falschen“ sympathischen Ubertragerstoff. Einer Hypothese von Day U. Rand (1964) zufolge wird auch am Menschen bei antihypertensiver Therapie mit Alpha-Methyldopa das Alpha-Methylnoradrenalin gebildet …

The effects of methacholine and calcium deprivation on the release of the false transmitter, ?-methyladrenaline, from the isolated rabbit heart

1. Anaesthetized rabbits were infused for 20 min with 85 μg · kg−1 · min−1 (±)-α-methyladrenaline. The hearts dissected 15 min after the infusion contained 1.49 μg/g α-methyladrenaline; the endogenous noradrenaline content was correspondingly decreased. 2. Hearts from α-methyladrenaline-infused animals were isolated with the right sympathetic nerves intact and perfused. Ventricular rate, right atrial and right ventricular tensions were recorded using the transverse method. 3. Electrical stimulation (10 Hz, 1 ms, 1 min) of sympathetic nerves, perfusion with the nicotinic drug, p-aminophenethyltrimethylammonium (PAPETA) or perfusion with 54 mM KCl (high K+) solution evoked an output of both α…

A muscarinic mechanism inhibiting the release of noradrenaline from peripheral adrenergic nerve fibres by nicotinic agents.

Modulation by fenoldopam (SKF 82526) and bromocriptine of the electrically evoked release of vasopressin from the rat neurohypophysis. Effects of dopamine depletion.

1. Single neurointermediate lobes were fixed by their stalks to a platinum wire electrode and incubated in Krebs-bicarbonate solution. Vasopressin release into the medium was determined by a radioimmunoassay. Vasopressin secretion was increased by electrical stimulation (15 Hz, 10 s trains with 10 s intervals for 10 min). 2. Fenoldopam (SKF 82526) had a dual effect on vasopressin release, 30 nM decreasing (by 30%) and 3 μM increasing (by 32%) the evoked vasopressin secretion. The facilitatory effect of fenoldopam was antagonized in a concentration-dependent manner by flupenthixol but not by sulpiride. Sulpiride (1 μM) prevented the inhibitory effect of fenoldopam (30 μM). 3. After pretreatm…

Atropine-resistant effects of the muscarinic agonists McN-A-343 and AHR 602 on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart

Abstract 1 The effects of 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) and N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) on cardiac performance and noradrenaline release from terminal sympathetic fibres were measured in isolated perfused hearts of rabbits. 2 In the presence of sufficient atropine to block muscarinic receptors, high concentrations of McN-A-343 and AHR 602 caused no cardiac stimulation and there was no increase in the resting output of noradrenaline into the perfusates. 3 McN-A-343 and AHR 602 increased both the mechanical responses and the transmitter overflow evoked by electrical stimulation of the sympathetic nerves (SNS) but inhibi…

Der Einflu� von BAL, Methionin und Cystin auf die Schilddr�senhyperplasie nach kurzfristiger Gabe von Methylthiouracil

In einer 16tagigen Versuchsreihe wurde an Ratten der Einflus von BAL (15 mg/kg), Methionin (3 g/kg) und Cystin (3 g/kg) auf die durch 100 mg/kg Methylthiouracil (MTU) hervorgerufenen Stoffwechsel-, Schilddrusengewichts- und -aktivitatsanderungen untersucht. Folgende Ergebnisse konnten statistisch gesichert werden:

Die Wirkung von Acetylcholin auf den K- und Na-Flux und ihre pharmakologische Beeinflussung am denervierten Rattenzwerchfell

Absence of muscarinic modulation of vasopressin release from the isolated rat neurohypophysis

1. Isolated rat neurohypophyses were incubated in Locke solution at 37°C and the vasopressin output into the medium determined by bioassay. 2. Potassium chloride 60 mM caused a 9-fold increase in the rate of vasopressin release that was abolished when calcium chloride was omitted from the Locke solution. 3. Acetylcholine 5.5×10−4 M neither alone nor in the presence of atropine 2.9×10−6 M changed the “resting” release of vasopressin. 4. Neither acetylcholine 5.5×10−4 M nor oxotremorine 10−4 and 3×10−4 M altered the vasopressin release evoked by potassium chloride 60 mM. 5. In contrast to the peripheral adrenergic nerve fibres, the secretory terminal fibres of the neurohypophysis do not appea…

The use of the de deckere-ten hoor preparation for study of nicotinic and potassium-evoked dopamine ?-hydroxylase release from the rabbit heart

1. Dopamine β-hydroxylase (DBH) and noradrenaline were determined both in the venous effluent (perfusate) and in the transmyocardial fluid (TMF) collected from the apex of the rabbit isolated heart which was prepared according to De Deckere and Ten Hoor (1977) and perfused with Tyrode's solution at 20 ml/min. 2. Perfusion for 2 min with the nicotinic drug, p-aminophenethyl-trimethylammonium (PAPETA), both in the absence of presence of atropine evoked noradrenaline overflow into the perfusate and TMF that was maximal in the 0–2 min sample and declined from maximum with a t1/2 of 0.6 min. DBH was released into TMF with the maximum from 2–4 min and a t1/2 of decline of 5.6 min. 3. High K-low N…

Ver Gleichende Untersuchungen �ber die Wirkung von Purink�rpern auf die Kontraktionskraft des Herzens

The effects of several muscarinic antagonists on pre- and postsynaptic receptors in the isolated rabbit heart

In order to reveal possible differences between pre- and postsynaptic muscarine receptors, seven antagonists were tested for their affinities on these receptor sites in the rabbit isolated perfused heart. Methacholine was used as an agonist to inhibit the noradrenaline overflow evoked by electrical stimulation (3 Hz, 3 min) of the sympathetic nerves (presynaptic parameter) and to decrease the systolic tension development of the right atrium (postsynaptic parameter). The affinity of an antagonist was expressed as pA2. A decreasing order of potency was obtained with ipratropium, scopolamine, atropine, trihexyphenidyl, amitriptyline, and gallamine, both for pre- and postsynaptic responses. The…

Die Wirkung von Guanethidin und Hexamethonium auf die Aufnahme zirkulierenden Noradrenalins in das Herz

Nicotine receptors do not modulate the 3H-noradrenaline release from the isolated rat heart evoked by sympathetic nerve stimulation.

Isolated rat hearts with the right sympathetic nerves attached were perfused at a constant flow rate of 7 ml/min with Tyrode's solution. (-)-3H-Noradrenaline (final concentration 10–13.9 nM) was infused for 10 min to label the noradrenaline stores. After wash-out the sympathetic nerves were stimulated electrically (3 Hz, 180 impulses, 1 ms, 20–30 mA) three times (S1–S3) at intervals of 15 min. 3H-Noradrenaline and its metabolites were determined by liquid scintillation counting according to Graefe et al. (1973). Both, nicotine 50 μM and p-aminophenethyltrimethylammonium (PAPETA) 30 μM, enhanced the 3H-noradrenaline overflow in the absence of nerve stimulation. The effect of PAPETA was bipha…

Nachweis von α-Methylnoradrenalin im Harn von Hypertonikern während einer Behandlung mit α-Methyldopa

Wahrend einer antihypertensiven Therapie mit α-Methyldopa wird im Harn α-Methylnoradrenalin ausgeschieden; gleichzeitig sinkt die Noradrenalin-Ausscheidung ab. Diese Veranderungen sind der Blutdrucksenkung zeitlich korreliert.

Wirkung von Reserpin auf im Herzen gespeichertes α-Methylnoradrenalin

Cholinergic-Adrenergic Presynaptic Interactions on the Heart in the Millisecond Range as Studied With the Pulse-to-Pulse Method

A method has been devised to study the interactions of cholinergic and adrenergic nerves in the rabbit atria, a tissue known to be densely innervated by both vagus and sympathetic nerve fibres. The atria were isolated and perfused via the ascending branches of the coronary arteries. The acetylcholine (ACh) stores were labelled with [14C]-choline and the noradrenaline (NA) stores with [3H]-NA. The radioactive compounds were separated on columns and determined by scintillation spectrometry.

Cholinergic–Adrenergic Presynaptic Interactions in the Heart and Characterization of the Receptors Involved

ABSTRACT The rabbit perfused atria preparation with the extrinsic sympathetic and vagus innervation intact has been used to study the mutual interactions between the two branches of the autonomic nervous system by measuring the respective transmitter overflow rates upon electrical stimulation. Using this method the stimuli exciting vagus and sympathetic nerves can be applied at selected time intervals which provides an advantage over the common method of field stimulation where all kinds of neurons are stimulated simultaneously. In the absence of drugs, presynaptic interactions resulting in a decreased noradrenaline overflow occurred when the vagal stimuli preceded the sympathetic ones by 3…

The Tuberohypophyseal Dopamine System: Dopaminergic Modulation of Vasopressin Release. Characterization of Release and Metabolism of3H-Dopamine

Dopamine (DA) fibres originating in the arcuate nucleus project into the neural and intermediate lobes (N-IL) of the pituitary gland. It has been shown that DA and DA agonists decrease the electrically evoked vasopressin release from the isolated N-IL, an effect antagonized by D2 selective DA antagonists (see Holzbauer et al., 1983). However, there are also observations suggesting that there is an additional facilitation of the evoked vasopressin release via D1 receptors. Thus, SKF 82526 (6-chloro-7,8-drhydroxy-1-(p-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-benzazepine mesylate) concentrationdependently decreased (max. 30 % at 30 nM) and increased (max. 40 % at 3 µM) the electrically evoked vaso…

Die Trennung von Erregungsvorgang und Kontraktion am Skelett und Herzmuskel durch 2,4-Dinitrophenol

Die Freisetzung von Noradrenalin aus dem perfundierten Kaninchenherzen

Dopaminergic modulation of evoked vasopressin release from the isolated neurohypophysis of the rat

1. Neurointermediate lobes of rat pituitaries were incubated in Locke or Krebs solution, and the vasopressin released into the medium was assayed on the blood pressure of the pithed rat or by a radioimmunological procedure. Release of vasopressin over resting levels was evoked either by incubation with 60 mM KCl (high K) solution or by electrical stimulation of the pituitary stalk. Two different kinds of electrical stimulation were carried out. Procedure A (1 ms, 10 Hz, 5 times for 1 min within 10 min) induced a vasopressin overflow which was greatly calcium-dependent but only insignificantly sensitive to tetrodotoxin (TTX). Procedure B (0.2 ms, 15 Hz, 10 s trains with 10 s intervals for 10…

Die Wirkung thiolopriver Substanzen auf Membran-und Aktionspotential des Rattenzwerchfells

Vor einiger Zei t wurde uber die Ver~nderungen des Membranpo ten t i a l s des i so l ier ten Ra t t enzwerchfe l l s du rch th io lopr ive Subs t anzen be r i ch t e t (MUSCKOLL 1956). Diese Versuche wurden einersei ts un te r nommen, u m eine e lekt rophys io logische Kl~Lrung der versch iedenen Ph£nomene herbeizufuhren , die a m isol ier ten Muskel oder auch in v ivo durch Quecks i lberd iure t ica au f t r e t en (siehe dazu KIYSCHI~SXY, M]mCXER, WESTERMA~N u. LULLMA~N). Andererse i t s schien es von In te resse fes tzuste l len, ob den K o n t r a k t u r e n , die durch d ie th io lopr iven Subs tanzen hervorgerufen wurden, auch zei t l ich koord in i e r t e Depo la r i sa t ionen de…

�ber den Einflu� der extracellul�ren Kalium-Konzentration auf den Kalium-Flux des Rattenzwerchfells

Die Behandlung der experimentellen Quecksilbervergiftung mit 2,3 Dimercaptopropions�ure

Die Wirkungen von 2,3 Dimercaptopropionsaure (DMPS) und 2,3 Dimercaptopropanol (BAL) auf die Sublimatvergiftung der Maus wurden miteinander verglichen. Ferner wurde an Kaninchen und Hunden der Einfiuβ von DMPS und anderen Substanzen auf die akuten, durch das Natriumsalz des 3-Oxymercuri-2-methoxy-propylamids des Salicylsaureglykolsaureathers = Salyrgan an Herz und Blutdruck hervorgerufenen Veranderungen untersucht.

Der Einfluss von Acetylcholin auf die42Kalium-Abgabe postnataler, denervierter und reinnervierter Skeletmuskulatur

The loss of42K from the isolated rat diaphragm into the bathing solution is increased by acetylcholine, (a) 3 to 4 days after birth, (b) 7 to 14 days after sectioning of the phrenic nerve. The42K loss is not altered by acetylcholine in the diaphragm of adult rats and after the denervated diaphragm has become reinnervated.

Studies on the formation of ?-methylnoradrenaline in hypertensive patients treated with ?-methyldopa

Noradrenaline depleting and blood pressure lowering activity of threo-corbadrine

Abstract Threo-corbadrine caused a long-lasting depletion of noradrenaline in the heart and in mesenteric vessels and lowered the blood pressure of normal and renal hypertensive rats. It is suggested that threo-cobadrine decreases vascular tone by acting peripherally as a substitute adrenergic transmitter.

Der Kalium-Flux des normalen und denervierten Rattenzwerchfells

Die Verteilung von Noradrenalin und Adrenalin im Herzen der Katze, des Kaninchens und der Ratte

The concentration of noradrenaline in different parts of the heart was estimated in cats, rabbits, and rats. In each heart, the concentration of noradrenaline was much higher in the right atrium than in the left atrium and higher in the right ventricle than in the left one.

Die Wirkung von Reserpin auf die Konzentration von Adrenalin und Noradrenalin im Katzenherz

1. Cats were given single injections of 1.8 mg/kg reserpine intraperitoneally. After a time interval of 18 hours the animals were killed. The concentration of adrenaline and noradrenaline in the right and left atria and ventricles was estimated by a method reported previously. 2. Reserpine caused a similar loss of catechol amines from all parts of the heart. The concentration of noradrenaline was reduced by 93–97%, the concentration of adrenaline by 59–79%. 3. These observations suggest that the adrenaline of the heart behaves differently from that of sympathetic ganglia or postganglionic nerve fibres after an injection of reserpine. In ganglia and nerve fibres the adrenaline concentration …

The role of cytoplasmic (newly synthesized) dopamine for the spontaneous and electrically evoked release of dopamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated rat NILs were incubated in Krebs-HEPES solution. The release of dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous release of the sum of metabolites was about 40 times that of dopamine. The spontaneous outflow of dopamine metabolites was unaffected after inhibition of dopamine uptake (by GBR 12921) or after pretreatment with reserpine (5 mg/kg, 12 h before the experiments), but it was reduced by 50% after preincubation with the irreversible DOPA decarboxylase inhibitor, (MFMD, 10 microM, for 10 min). The combination of pretreatment with reserpine and preincubation with MFMD resulted in an 80% inhibition of the …

Wirkungen von threo-Corbadrin auf die Aminspeicher und den Blutdruck der Ratte

Storage and release of false transmitters after infusion of (+)- and (?)-?-methyldopamine

Rabbits were given an infusion of 10 mg/kg (−)- or 30 mg/kg (+)-α-methyldopamine and killed after 135 min. The noradrenaline content of the heart was decreased to 26±5 and 34±2%, respectively, of the control value. After infusion of the (+)-isomer the missing noradrenaline was replaced by (−)-α-methylnoradrenaline. Electrical stimulation of the sympathetic nerves or infusion of acetylcholine plus atropine caused an output of noradrenaline and (−)-α-methylnoradrenaline from the isolated heart. The two amines were released in the same proportion as they were stored in the heart and the total output of both amines equalled the output of noradrenaline from control hearts. Nerve stimulation caus…

Autoinhibition of noradrenaline release from the rat heart as a function of the biophase concentration. Effects of exogenous alpha-adrenoceptor agonists, cocaine, and perfusion rate.

1. Rat isolated perfused hearts with the right sympathetic nerves intact were loaded with 3H-(-)-noradrenaline. The nerves were stimulated with trains of 180 pulses at 3 Hz and at 10 min intervals. The overflow of 3H-noradrenaline and 3H-metabolites was determined by liquid scintillation spectrometry. 2. Clonidine (IC50 17 nM), oxymetazoline (IC50 63 nM), and α-methylnoradrenaline (apparent IC50 35 nM, determined in the presence of cocaine and propranolol) decreased the stimulation-evoked overflow of 3H-noradrenaline by 26, 49, and 78%, respectively, but not methoxamine up to 100 μM (propranolol present). Oxymetazoline and α-methyl-noradrenaline did not cause desensitization of the presynap…

The effect of methacholine on noradrenaline release from the rabbit heart perfused with indometacin

The experiments were undertaken in order to study the effect of inhibition of prostaglandin synthesis on the muscarinic inhibition of noradrenaline release evoked by sympathetic nerve stimulation. The right sympathetic nerves of the perfused rabbit heart were stimulated electrically. The noradrenaline output was enhanced after perfusion of the hearts with indometacin 3×10−5 M indicating blockade of the prostaglandin-mediated negative feedback control. Both in the presence and in the absence of indometacin methacholine 4×10−5 M decreased the noradrenaline output by a similar percentage. It is concluded that the muscarinic inhibition of noradrenaline release does not require the functional in…

A presynaptic excitatory M1 muscarine receptor at postganglionic cardiac noradrenergic nerve fibres that is activated by endogenous acetylcholine.

Rabbit atria were isolated with the extrinsic right vagus and sympathetic nerves intact and perfused with Tyrode solution. Noradrenaline overflow evoked by sympathetic nerve stimulation (SNS) at 3 Hz for 3 min was determined before, during, and after vagus nerve stimulation (VNS), also at 3 Hz and for 3 min. The VNS pulses preceded the SNS pulses by 3, 100 and 233 ms. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline. Pirenzepine 80 nmol/l failed to alter the muscarinic inhibition of noradrenaline overflow when the vago-sympathetic impulse intervals were 3 and 233 ms. At an interval of 100 ms VNS did not significantly inhibit noradrenaline ove…

Die Wirkung von Theophyllin, Coffein und Theobromin auf Kontraktionskraft, Erregbarkeit, Refrakt�rzeit und Spontanfrequenz des isolierten Herzmuskels der Katze

In the electrically driven papillary muscle of the cat's right ventricle theophylline, caffeine and theobromine exerted a positive inotropic action. Log. dose-effect regression lines for the three drugs were parallel; the effect of theophylline was significantly greater than those of caffeine and theobromine. The range of concentrations used was 1/32–1/2 mM/1.

Die Wirkung von Acetylcholin, Dekamethonium und d-Tubocurarin am isolierten Rattenzwerchfell in Abh�ngigkeit von der Denervationsdauer

An 41 isolierten Zwerchfellpraparaten der Ratte wurde zu verschiedenen Zeitpunkten nach Exharese des N. phrenicus die Wirkung von Acetylcholin (Ach), Decamethonium (C 10) und d-Tubocurarin (dTc) untersucht. Die Reaktionen des Muskels zeigten eine charakteristische Abhangigkeit von der Denervationsdauer. Ach verursachte eine Verminderung der Hubhohe elektrisch ausgeloster Einzelzuckungen, Kontraktur und Kontraktur-Ruckstand. Die Wirkung von C 10 ahnelte der von Ach weitgehend. Dagegen fuhrte Gabe von dTc zu einer Senkung der „Grundlinie“ und zur Verminderung der Hubhohe der Einzelzuckungen.

Zur Frage des Vorkommens von Isopropylnoradrenalin in Herz und Nebenniere

1. Extracts of adrenal glands and heart tissue of the cat were prepared and chromatographed on paper. The regions corresponding to the RF values of noradrenaline, adrenaline and isoprenaline (isopropylnoradrenaline) were eluted. The eluates were assayed on the blood pressure, the isolated auricle and the isolated uterus of the rat. Differential assay on these preparations proved to be specific and extremely sensitive for isoprenaline. 2. There was no evidence for the occurrence of isoprenaline in the adrenal medulla or the heart of the cat. The method used is sufficiently sensitive to detect 0,2% of isoprenaline in the total catechol amines of the heart and 0,007% in the adrenals.

Effect of cocaine and related drugs on the uptake of noradrenaline by heart and spleen

Noradrenaline uptake by heart and spleen after intravenous infusion of noradrenaline was measured in the pithed rat. Cocaine, given before the infusion, inhibited the noradrenaline uptake in relation (a) to the dose administered and (b) to the amount of noradrenaline infused. There was an association between increase in the pressor response to a test dose of noradrenaline and inhibition of the uptake by the heart. Drugs related chemically to cocaine, such as alpha-cocaine, amethocaine, and atropine, did not alter the noradrenaline uptake or potentiate the blood pressure response to noradrenaline. The noradrenaline uptake by the heart was unchanged after dibenamine, but blocked by the dichlo…

�ber das Verhalten der Cholinesterase und des Gewichtes denervierter Rattenzwerchfelle

Es wird das Verhalten des Gewichtes und der Cholinesteraseaktivitat denervierter Rattenzwerchfelle untersucht. Der Zeitraum erstreckt sich vom 1. Tag nach Denervation bis zur Reinnervation. Wahrend das Gewicht des denervierten Zwerchfelles zuerst einen Anstieg zeigt (+38% am 5. Tag nach Denervation), sinkt der Cholinesterasegehalt schnell ab (−60% am. 5. Tag nach Denervation). Etwa am 20. Tag nach Denervation beginnt die Atrophie des Zwerchfelles, das nach 6 Wochen einen 50%-Gewichtsverlust aufweist. Die Cholinesteraseaktivitat im Hemidiaphragma bleibt unverandert niedrig. Reinnervierte Zwerchfelle verhalten sich wie normale Kontrollen. Die Aktivitat der Pseudocholinesterase wird von der De…

The effects of the tricyclic antidepressants desipramine, doxepin and iprindole on the isolated perfused rabbit heart.

1. The right sympathetic nerves of isolated perfused rabbit hearts were stimulated electrically (1 msec, supramaximal strength, 15 sec) with increasing frequencies (0.25–20 Hz) at 3 min intervals before and 20 min after starting perfusion with desipramine, doxepin or iprindole. Ventricular rate, right atrial and right ventricular tensions were recorded using the transverse method. 2. Sympathic nerve stimulation caused ventricular arrhythmias in the presence of desipramine (3.3 and 5.0 · 10−6 M) and doxepin (1.6−4.7×10−6 M) but failed to produce arrhythmias in hearts not exposed to drugs, or after iprindole, cocaine and atropine. 3. When desipramine or doxepin was added to Tyrode solution co…

The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition

Abstract 1 Rat isolated perfused hearts with the right sympathetic nerves attached were loaded with [3H]-(-)-noradrenaline. The nerves were stimulated with up to 40 trains of 10 pulses every min at 1 Hz, and the evoked increases of [3H-]noradrenaline overflow into the perfusate, of right atrial tension development and ventricular beating frequency were measured. 2 Oxymetazoline inhibited the evoked transmitter overflow (IC50: 10 nM) and decreased the postsynaptic responses in a concentration-dependent manner. It behaved as a full against in abolishing the evoked transmitter overflow. 3 Yohimbine up to 1 microM neither enhanced the evoked [3H]-noradrenaline overflow nor the postsynaptic para…

Sympathetic Nerve Stimulation on the perfused rat heart. Affinities of N-methylatropine and pirenzepine at pre- and postsynaptic muscarine receptors.

Rat isolated hearts with the sympathetic nerves attached were perfused with (-)-3H-noradrenaline in order to label the storage vesicles of the adrenergic nerves. Release was induced either by electrical stimulation of the nerves (3 Hz, 1 min) or by perfusion with high K+ solution (54 mM). The overflow of 3H-noradrenaline and its metabolites was determined by liquid scintillation counting after separation of the compounds by column chromatography. The experimental conditions ensured a minor contribution of 3H-metabolites to the evoked total tritium overflow. The release of 3H-noradrenaline evoked by nerve stimulation or high K+ solution was decreased in the presence of the muscarinic agonist…

The effect of physostigmine on the vagally induced muscarinic inhibition of noradrenaline release from the isolated perfused rabbit atria.

1. Presynaptic cholinergic-adrenergic interactions were studied on isolated perfused rabbit atria with the extrinsic right vagus and sympathetic innervation intact. The transmitter stores were labelled with 14C-choline and 3H-noradrenaline. The radioactive compounds were separated on columns and determined by scintillation spectrometry. The stimulation-evoked overflow of both transmitters was calcium-dependent and abolished by tetrodotoxin. 2. Methacholine caused a concentration-dependent decrease of atrial tension development and 3H-noradrenaline overflow evoked by 3 Hz sympathetic stimulation. Vagus nerve stimulation (1–20Hz), although nearly abolishing tension development at 20Hz, decrea…