bluuebunny/crossref_metadata_2025_split huggingface dataset:
AN ELECTROPHYSIOLOGICAL ANALYSIS OF THE EFFECTS OF AMINE‐UPTAKE BLOCKERS AND α‐ADRENOCEPTOR BLOCKERS ON ADRENERGIC NEUROMUSCULAR TRANSMISSION
Authors: BENNETT M.R. , MIDDLETON J. 
Published: July 2012

An electrophysiological study has been made of the effects of either blocking noradrenaline (NA) uptake or α‐adrenoceptors on conduction in adrenergic preterminal axons and on NA release.
The excitatory junction potential (e.j.p.) evoked by a single stimulus increased slightly in duration (maximum 20%) in the presence of high concentrations of desipramine or cocaine (> 1 μg/ml) but there was no change in the spontaneous miniature excitatory junction potential (m.e.j.p.s); the single compound preterminal action potential was decreased in amplitude by a maximum of 10%. The e.j.p., m.e.j.p. and the terminal action potential were not altered by lower concentrations of these drugs (< 1 μg/ml).
The increased decline of the e.j.p. amplitude observed during the first few hundred impulses at high frequencies (10 Hz) in the presence of desipramine or cocaine was accompanied by a similar decline in the amplitude of the preterminal compound action potential, suggesting that the latter gave rise to the former.
These observations suggest that the action on post‐synaptic α‐adrenoceptors of NA released by single impulses is terminated by diffusion, and that any NA which is subsequently taken up into nerves is metabolized.
All the α‐adrenoceptor blocking drugs tested reversed the normal depression in e.j.p. amplitude observed during the first few hundred impulses at high frequencies to facilitation; this was unaccompanied by any changes in the preterminal compound action potential.
α‐Adrenoceptor blocking drugs did not alter the potentiating effect which a conditioning impulse had on the amplitude of the e.j.p. evoked by a subsequent test impulse. The facilitated release of NA during trains of impulses was quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train.
It is suggested that if there is an auto‐inhibition of NA release, then it is unlikely that the pre‐ and post‐synaptic α‐adrenoceptors are identical.
THE PENETRATION OF DAPSONE, RIFAMPICIN, ISONIAZID AND PYRAZINAMIDE INTO PERIPHERAL NERVES
Authors: ALLEN B.W. , ELLARD G.A. , GAMMON PATRICIA T. , KING R.C. , McDOUGALL A.C. , REES R.J.W. , WEDDELL A.G.M. 
Published: July 2012

Dapsone, rifampicin, isoniazid and pyrazinamide were shown to penetrate readily into the sciatic nerves of the dog and sheep.
These findings suggest that the continued persistence of viable drug‐sensitive leprosy bacilli in the peripheral nerves of patients treated for long periods with either dapsone or rifampicin is not due to inadequate intraneural drug penetration.
VASCULAR DOPAMINE RECEPTORS IN THE CANINE HINDLIMB
Authors: BELL C. , CONWAY E.L. , LANG W.J. , PADANYI R. 
Published: July 2012

Increases in femoral blood flow were produced by intra‐arterial injections of dopamine (5–50 μg) in some but not all anaesthetized dogs studied, following treatment with the α‐adrenoceptor antagonist, phentolamine.
The dilator effect of dopamine was not due to inhibition of adrenergic vasomotor tone as it was not affected by pharmacological procedures which completely abolished the activity of vasomotor nerves.
Blockade of vascular β‐adrenoceptors using propranolol reduced the flow increases produced by dopamine much less than it did those produced by isoprenaline.
Responses to dopamine were significantly depressed by intra‐arterial administration of ergometrine (0.5 mg). This dose of ergometrine did not reduce femoral dilator responses to acetylcholine, histamine, isoprenaline, bradykinin or 5‐hydroxytryptamine.
It is concluded that the femoral vascular bed in the dog contains specific vasodilator receptors for dopamine. Ergometrine appears to be a selective antagonist of dopamine at these receptors.
THE EFFECTS OF HISTAMINE AND SOME HISTAMINE‐LIKE AGONISTS ON BLOOD PRESSURE IN THE CAT
Authors: OWEN D.A.A. 
Published: July 2012

The effects of histamine on blood pressure have been compared with the effects caused by four histamine‐like agonists in anaesthetized cats.
It has been confirmed that the depressor responses to histamine involve both H1‐ and H2‐receptors: depressor responses also follow the administration of selective H1‐ and H2 ‐receptor agonists.
2‐Methylhistamine, in doses up to 1 × 10−7 mol/kg, lowers blood pressure by interaction with H1‐receptors. Larger doses of 2‐methylhistamine also lower blood pressure but this may involve H2‐receptors.
4‐Methylhistamine, in doses up to 1 × 10−7 mol/kg, lowers blood pressure by interaction with H2‐receptors. Larger doses of 4‐methylhistamine also lower blood pressure but this may involve H1‐receptors.
2‐(2‐Aminoethyl)pyridine and 2‐(2‐aminoethyl)thiazole both lower blood pressure by interaction with H1‐receptors only.
The potential value and limitations of these compounds as tools to investigate the cardiovascular effects of histamine are discussed.
HISTAMINE RECEPTORS IN PERIPHERAL VASCULAR BEDS IN THE CAT
Authors: FLYNN SHEILA B. , OWEN D.A.A. 
Published: July 2012

The vasodilator activity of histamine has been studied in anaesthetized cats.
Histamine causes dose‐dependent vasodilatation in the vasculature of the hind‐limb and mesentery, perfused with blood at constant flow.
Experiments using the selective antagonists mepyramine and metiamide indicate the involvement of both H1‐ and H2‐receptors in the vasodilator responses to histamine. Mepyramine (2.5 × 10−6 mol/kg), causes displacement of the histamine dose‐response curve. This displacement is maximum with a dose‐ratio of about 10. Further dose‐dependent displacement of the dose‐response curve occurred after metiamide (4 × 10−7 mol kg−1 min−1 and 2 × 10−6 mol kg−1 min−1), although these does of metiamide had no effect on histamine responses in the absence of mepyramine.
Vasodilator responses could also be elicited by the selective H1‐receptor agonists, 2‐methylhistamine, 2‐(2‐aminoethyl)pyridine and 2‐(2‐aminoethyl)thiazole and the selective H2‐receptor agonist, 4‐methylhistamine.
The selectivity of mepyramine and metiamide as histamine receptor antagonists was confirmed by their failure to reduce the vasodilator responses to acetylcholine, isoprenaline and bradykinin.
RAPID REDUCTION OF PROSTAGLANDIN 15‐HYDROXY DEHYDROGENASE ACTIVITY IN RAT TISSUES AFTER TREATMENT WITH PROTEIN SYNTHESIS INHIBITORS
Authors: BLACKWELL G.J. , FLOWER R.J. , VANE J.R. 
Published: July 2012

The capacity of rat kidneys to metabolize prostaglandins is rapidly lost when de novo protein synthesis is reduced by cycloheximide and puromycin. Enzyme activity declines to about half control values 45–75 min after a single dose of cycloheximide. Prostaglandin metabolism by the lung is also diminished.
These inhibitors apparently act by preventing the synthesis of new prostaglandin 15‐hydroxy dehydrogenase enzyme.
The RNA synthesis inhibitor actinomycin D has no effect on metabolism.
It is concluded that prostaglandin dehydrogenase is a short‐lived enzyme in the cell whose replacement depends upon de novo protein (but not RNA) synthesis. The implications of this finding are discussed.
BIOASSAY OF HISTAMINE IN THE PRESENCE OF PROSTAGLANDINS
Authors: GRYGLEWSKI R.J. , KORBUT R. 
Published: July 2012

An Amberlite XAD‐2 column in a heated (37°C) jacket was incorporated in between two banks of bioassay organs superfused with Krebs bicarbonate solution in cascade. The column removed prostaglandins E1, E2 and F2α and also rabbit aorta contracting substance (RCS) and possibly slow reacting substance of anaphylaxis (SRS‐A).
The column gave free passage to histamine in concentrations up to 3000 ng/ml. The method described improves the accuracy of histamine bioassay in the presence of prostaglandins.
PROLONGED EFFECTS OF p‐CHLOROPHENYLALANINE ON THE BLOOD PRESSURE OF CONSCIOUS NORMOTENSIVE AND DOCA/SALINE HYPERTENSIVE RATS
Authors: BUCKINGHAM R.E. , HAMILTON T.C. , MOORE R.A. 
Published: July 2012

In deoxycorticosterone acetate (DOCA) saline hypertensive rats a single dose of p‐chlorophenylalanine methylester (PCPAME) (400 mg/kg i.p.) produced a significant fall in blood pressure (20–43 mmHg) which lasted for at least 8 days and was accompanied by a parallel depletion of brain stem 5‐hydroxytryptamine (5‐HT) but not of noradrenaline (NA).
In normotensive rats single doses of PCPAME (200 and 400 mg/kg i.p.) produced a significant hypotension (15–20 mmHg) after a latent period of 5 days. An initial pressor response (12 mmHg) was observed at the higher dose level only on day 3.
The hypotensive response to PCPAME (200 mg/kg i.p.) in normotensive rats was not modified by pretreatment with 5,6‐dihydroxytryptamine (5,6‐DHT; 50 μg i.c.v.) or 6‐hydroxydopamine (6‐OHDA; 3 × 250 μg intracerebroventricularly).
It is concluded that the hypotensive response to PCPAME in normotensive rats is independent of brain stem depletion of 5‐HT and is probably not mediated by the formation of a false transmitter substance acting via central noradrenergic inhibitory pathways. The mechanism involved in the antihypertensive response to PCPAME in DOCA/saline hypertensive rats has yet to be defined.
THE UPTAKE OF TRITIATED Δ1‐TETRAHYDROCANNABINOL BY THE ISOLATED VAS DEFERENS OF THE RAT
Authors: EGAN SANDRA M. , GRAHAM J.D.P. , LEWIS M.J. 
Published: July 2012

Weighed stripped vasa deferentia were incubated in Holman's solution containing (a) [14C]‐sorbitol 0.014 mM, (b) [3H]‐noradrenaline ([3H]‐NA) 12.31 nM, (c) [3H]‐tetrahydrocannabinol ([3H]‐Δ1‐THC) 1 μg/ml for 5, 10, 20 and 30 minutes.
Tissues were washed, dissolved in Protosol, counted by standard scintillation counting technique and ‘drug space’ expressed as ct min−1 mg−1 tissue/ct min−1 μl−1 bathing fluid.
Vasa incubated for 30 min with [14C]‐sorbitol were washed for varying lengths of time; 82% clearance had taken place after 2 washes of 5 minutes.
The uptake of [3H]‐NA was inhibited by the presence of desmethylimipramine (DMI) 10 nM in the bath or by pretreatment of rats with 6‐hydroxydopamine (6‐OHDA).
The uptake of [3H]‐Δ1‐THC was not inhibited by the presence of DMI. It was reduced but not abolished by 6‐OHDA pretreatment.
THE EFFECTS OF DIMERCAPTOSUCCINIC ACID ON THE EXCRETION AND DISTRIBUTION OF MERCURY IN RATS AND MICE TREATED WITH MERCURIC CHLORIDE AND METHYLMERCURY CHLORIDE
Authors: MAGOS L. 
Published: July 2012

All five rats in a group survived if dimercaptosuccinic acid (DMSA), a water soluble derivative of 2,3‐dimercaptopropanol (BAL), was given in doses of 10–40 mg/kg intraperitoneally 30 min, 4 and 24 h after administration of 2.4 mg/kg Hg as HgCl2, whereas three out of a group of five died if DMSA was not given. DMSA 20 mg/kg increased urinary excretion and decreased the body burden significantly more than 10 mg/kg DMSA, but further doubling of the dose had only marginal effects.
DMSA was able to reduce body burden and increase urinary excretion of Hg when intraperitoneal treatment started eight days after the subcutaneous administration of HgCl2.
DMSA was effective in decreasing body burden and the brain concentration of Hg in rats dosed orally with methylmercury (MeHgCl) when intraperitoneal treatment started with 40 mg/kg DMSA 24 h after Hg. Increase in the urinary excretion of mercury was responsible for the decrease in body burden.
DMSA was effective when given in the drinking water of rats or mice both against inorganic Hg and MeHgCl. In mice treated intraperitoneally with MeHgCl, DMSA 19.5 μg/ml in the drinking water caused a significant decrease in the body burden and increase in the excretion of Hg.
DMSA was about four times more efficient than d‐penicillamine in decreasing the body burden of Hg. As their toxicity is in the same range, the higher efficiency of DMSA offers a larger margin of safety for the mobilization of Hg.
EFFECT OF EXPERIMENTAL DIABETES, FOOD DEPRIVATION AND GENETIC OBESITY ON THE SENSITIVITY OF PITHED RATS TO AUTONOMIC AGENTS
Authors: FOY J.M. , LUCAS P.D. 
Published: July 2012

The sensitivities of alloxan and streptozotocin diabetic and hereditary obese pithed rats to acetylcholine, isoprenaline and noradrenaline were compared to those of controls.
Blood pressure and heart rate recordings made before dosing was started showed the streptozotocin‐treated animals to have a significantly reduced heart rate and increased pulse pressure as compared with controls.
Both diabetic groups were found to have reduced sensitivities to the pressor effect of noradrenaline, the depressor effect of acetylcholine, the positive chronotropic and inotropic effect of isoprenaline and the reduction in diastolic pressure induced by isoprenaline. The reduction in sensitivity was generally much greater in the streptozotocin diabetic animals.
The genetically obese rats were found to have similar sensitivities to all three agents as did their non‐obese litter mates.
When either diabetic group was deprived of food for 24 h preceding the tests the sensitivities were found to be raised significantly towards normal in almost all cases.
The results are contrasted with previous in vitro results and possible causative metabolic factors discussed. It is suggested that sensitivity changes are unevenly distributed within the cardiovascular system.
SELECTIVITY OF β‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON BRONCHIAL, SKELETAL, VASCULAR AND CARDIAC MUSCLE IN THE ANAESTHETIZED CAT
Authors: APPERLEY G.H. , DALY M.J. , LEVY G.P. 
Published: July 2012

The potencies of fifteen β‐adrenoceptor agonists of widely differing chemical structures were compared with that of (–)‐isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The β‐adrenoceptor antagonist potencies of propranolol and practolol were determined against (—)‐isoprenaline in the same model.
(—)‐Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003‐0.01 μg/kg and maximal or near maximal responses were produced by 0.3‐1 μg/kg. Trimetoquinol was also an essentially unselective agonist.
For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate.
The remaining agonist — AH 7616 (4‐hydroxy‐α1‐[[(1‐methyl‐3,3‐diphenyl‐propyl)amino]methyl]‐m‐xylene‐α1,α3‐diol, acetate) — was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5‐hydroxytryptamine (5‐HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5‐HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5‐HT antagonist action in addition to its β‐adrenoceptor agonist action.
The fifteen test agonists were longer acting than (—)‐isoprenaline and this was particularly true of trimetoquinol and soterenol.
The β‐adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10–12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure.
These findings suggest that it may not be possible to separate the bronchodilating and tremor‐enhancing properties of β‐adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual β‐adrenoceptor sub‐classification.
COMPARATIVE EFFECTS OF PROPRANOLOL AND PRACTOLOL IN THE EARLY STAGES OF EXPERIMENTAL CANINE MYOCARDIAL INFARCTION
Authors: MARSHALL R.J. , PARRATT J.R. 
Published: July 2012

The effects of propranolol and practolol, at equivalent myocardial β‐adrenoceptor blocking doses, (as assessed by the degree of shift of isoprenaline dose‐response curves) were investigated in anaesthetized greyhounds before and after acute coronary artery ligation.
When administered intravenously to the intact closed‐chest dog, propranolol (0.1 mg/kg) and practolol (0.5 mg/kg) caused similar decreases in heart rate, left ventricular dP/dt max, myocardial blood flow and cardiac output. Only propranolol increased peripheral vascular resistance.
When administered 2–3 h after acute coronary artery ligation, propranolol (0.1 mg/kg) significantly decreased blood flow in both normally perfused and ischaemic regions of the heart. There was also electrocardiographic evidence of further deterioration after propranolol; two out of seven animals died following this treatment.
Practolol (0.5 mg/kg) when administered after coronary artery ligation also decreased normal myocardial blood flow but flow in the ischaemic area remained unchanged. Evidence was obtained from electrocardiographic, myocardial temperature, myocardial O2 consumption and lactate measurements that the administration of practolol, in contrast to propranolol, benefited the ischaemic myocardium.
Analysis of the results suggests that this beneficial action of practolol may be related to at least two mechanisms. Firstly the ability of practolol to increase the period during diastole when perfusion of the subendocardium is possible, without decreasing the transventricular pressure during this period. Secondly that practolol does not unmask α‐adrenoceptor vasoconstriction in the ischaemic region.
THE EFFECTS OF PENTOBARBITONE AND PETHIDINE ON FOETAL BREATHING MOVEMENTS IN SHEEP
Authors: BODDY K. , DAWES G.S. , FISCHER R.L. , PINTER S. , ROBINSON J.S. 
Published: July 2012

Small doses of pentobarbitone (4 mg/kg i.v.) administered to sheep in the last third of pregnancy had little overt effect on the mothers. In the foetus they caused arrest of breathing movements, an alteration in the character of the electrocorticogram and cardiovascular changes which varied with gestational age.
In contrast, relatively large doses of pethidine (100–200 mg) administered to the mother had no consistent effect on normal foetal breathing movements, though they abolished the foetal response to hypercapnia.
The results are discussed in relation to foetal sleep state.
THE ROLE OF BOUND CALCIUM IN SUPER‐SENSITIVITYINDUCED BY COCAINE
Authors: GREENBERG R. , INNES I.R. 
Published: July 2012

Noradrenaline caused a small contraction of the cat isolated spleen strip bathed in a calcium‐free solution; this contraction was greatly potentiated by cocaine. This potentiation was also present in isolated spleen strips where noradrenaline stores were depleted by reserpine. The maximum response of the spleen strip to noradrenaline in the absence of extracellular calcium was also increased by cocaine.
The disodium salt of ethylenediaminetetraacetic acid (Na‐EDTA) but not Ca‐EDTA antagonized the potentiation of the response to noradrenaline by cocaine in a calcium‐free solution, and greatly reduced the magnitude of subsequent responses to noradrenaline and cocaine.
Strontium caused equivalent contractions of normal and reserpine‐treated spleen strips bathed in a calcium‐free solution. These responses were potentiated by cocaine.
Histamine caused a small contraction of the isolated spleen strip bathed in a Ca‐free solution. Cocaine failed to potentiate these very small histamine contractions, but did potentiate the contraction of these same strips in response to noradrenaline.
It is concluded that the potentiation of the response of the isolated spleen strip to noradrenaline by cocaine in the absence of extracellular calcium is due to a mechanism other than decreased neuronal uptake of noradrenaline. It is suggested that cocaine makes a bound store of calcium more available to promote contraction of the spleen strip by noradrenaline.
ADENOSINE ON MYOCARDIAL OXYGEN CONSUMPTION
Authors: GROSS G.J. , HARDMAN H.F. , WARLTIER D.C. 
Published: July 2012

A 3 min intracoronary infusion of adenosine (50 μg/min) produced a significant decrease in coronary artery perfusion pressure, left ventricular systolic pressure and myocardial O2 consumption in the isolated supported heart preparation of the dog perfused at a constant coronary blood flow. Heart rate was controlled at 150, 190 or 230 beats/minute.
Myocardial contractile force and maximal left ventricular dp/dt were not changed by adenosine infusion.
The absolute decrease in myocardial O2 consumption was greater at increasing heart rates whereas the decrease in coronary artery perfusion pressure and peak left ventricular systolic pressure were similar.
The results suggest that the reduction in myocardial O2 consumption produced by adenosine is not related to coronary vasodilatation or to a negative chronotropic or inotropic action, but may be due to a functional shunting of blood flow from high O2 extracting regions of the myocardium to low O2 extracting ones and/or to important effects on myocardial substrate utilization.
THE EFFECT OF CATECHOLAMINES ON THE INFLUX OF CALCIUM AND THE DEVELOPMENT OF TENSION IN DENERVATED MOUSE DIAPHRAGM MUSCLE
Authors: EVANS R.H. , SMITH J.W. 
Published: July 2012

The nature of the catecholamine‐induced contracture of chronically denervated mouse diaphragm muscle has been investigated and compared with the contractural response evoked by acetylcholine.
The time course of onset of catecholamine‐sensitivity in denervated diaphragm muscles was similar to the development of acetylcholine sensitivity. However, catecholamine contractures were absent in tissues denervated for periods longer than 90 days whereas acetylcholine‐sensitivity was still evident several months after denervation.
The catecholamine‐induced contracture of the denervated muscle was inhibited specifically by β‐receptor blocking drugs and was unaffected by α‐receptor blocking drugs and cholinoceptor antagonists.
Catecholamine‐induced contractures of denervated muscles, unlike contractures to acetylcholine, were dependent upon the presence of spontaneous fibrillation and the amplitude of spontaneous fibrillation was increased by catecholamines. Fibrillation was absent in the presence of tetrodotoxin (1 μm), 2,4‐dinitrophenol (10 μm), potassium cyanide (10 μm), ouabain (100 μm), in lithium chloride Ringer solution and at low temperature. Under these conditions catecholamine‐induced contractures, but not those to acetylcholine, were abolished.
Labelled calcium was found progressively to enter denervated muscle fibres and this entry of calcium was increased by catecholamines. It is suggested that this calcium entry may represent either an increased calcium permeability of denervated muscle fibres which is increased further by catecholamines or the presence of a calcium current that occurs during the fibrillatory potentials of denervated muscle.
EXTRA‐VESICULAR BINDING OF NORADRENALINE AND GUANETHIDINE IN THE ADRENERGIC NEURONES OF THE RAT HEART: A PROPOSED SITE OF ACTION OF ADRENERGIC NEURONE BLOCKING AGENTS
Authors: GIACHETTI A. , HOLLENBECK R.A. 
Published: July 2012

The binding and efflux characteristics of [14C]‐guanethidine and [3H]‐noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide.
Binding of both compounds occurred at extra‐vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [14C]‐guanethidine and [3H]‐noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment.
(+)‐Amphetamine accelerated the efflux of [14C]‐guanethidine and [3H]‐noradrenaline; this effect was inhibited by desipramine.
Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [14C]‐guanethidine but not that of [3H]‐noradrenaline.
Heart slices labelled with [3H]‐noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in the slices.
It is suggested that [14C]‐guanethidine and [3H]‐noradrenaline are bound at a common extra‐vesicular site within the adrenergic neurone. Binding of guanethidine to the extra‐vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission.