bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of M & B 17803A, a new β‐adrenoceptor blocking agent, on the cardiovascular responses to tilting and to isoprenaline in man
Authors: CUTHBERT M. F. , OWUSU‐ANKOMAH K. 
Published: July 2012

Summary
dl‐1‐(2‐acetyl‐4‐n‐butyramidophenoxy)‐2‐hydroxy‐3‐isopropylaminopropane hydrochloride (M & B 17803A) was given to four healthy volunteers in single oral doses of up to 300 mg. There were no subjective effects and no significant alterations in the heart rate, systolic and diastolic blood pressure in the seated position or in the forced expiratory volume or in the electrocardiogram within 6 h of the dose. There were no abnormalities in haematological tests and estimations of the serum glutamyloxaloacetic transaminase.
Oral doses of both M & B 17803A and propranolol inhibited the increase in heart rate which occurs on tilting from the supine to the 80° head up position. The results suggest that the degree of β‐adrenoceptor blockade produced by M & B 17803A (100 and 300 mg) is comparable to that of propranolol (10 and 40 mg) respectively. Propranolol is 7·5–10·0 times as potent as M & B 17803A when compared by this method. There were no significant changes in the systolic or diastolic blood pressure after any of the treatments, in either of the positions studied.
M & B 17803A was also effective in inhibiting the increase in heart rate produced by the intravenous infusion of isoprenaline and in two subjects the degree of β‐adrenoceptor blockade produced by M & B 17803A (300 mg) was comparable to that of propranolol (40 mg). M & B 17803A is a competitive β‐adrenoceptor blocking agent and the duration of the pharmacological activity of both M & B 17803A and propranolol appeared to be very similar as assessed by this method.
In separate experiments with small oral doses of M & B 17803A no evidence of a selective action on myocardial β‐adrenoceptors was obtained from the study of changes in heart rate and diastolic blood pressure (sphygmomanometric recording).
Central components of the renin‐angiotensin system
Authors: HAYDEN J. , TARGETT MARGARET A. 
Published: July 2012

Summary
Re‐establishment of renal blood flow after total renal ischaemia of 4 h duration causes a pressor response in pentobarbitone anaesthetized rats and cats.
The pressor response is related to the release of renin from the ischaemic kidney.
Spinal section at any cervical level or stellate ganglionectomy abolishes the pressor response but spinal section caudad to the thorax or vagotomy and treatment with hexamethonium have no effect.
Spinal section and stellate ganglionectomy interfere with the release of renin and with the pressor response to angiotensin.
Uptake kinetics and metabolism of 7–3H‐dopamine in the isolated perfused rat heart
Authors: HELLMANN G. , HERTTING G. , PESKAR B. 
Published: July 2012

Summary
The isolated, perfused rat heart accumulates dopamine by two distinct uptake mechanisms characterized by different kinetic constants and different patterns of metabolite production (Uptake 1: Km 0.69 × 10−6M and Vmax (1.45 × 10−9 mol/g)/min; Uptake 2: Km 5.9 × 10−4M and Vmax (0.14 × 10−6 mol/g)/min).
The metabolic fate of dopamine taken up by the isolated, perfused rat heart depends on the concentration of dopamine in the perfusion medium. At a very low perfusion concentration (0.047 × 10−10 mol/ml) most of the radioactivity is stored as unchanged dopamine and the main metabolite is noradrenaline. With increasing perfusion concentrations deamination becomes the main metabolic pathway, deaminated metabolites accounting for more than 50% of the total radioactivity after perfusion with 2,614.4 × 10−10 mol/ml for 16 minutes. The O‐methylated, and the O‐methylated deaminated metabolites are of minor importance at all perfusion concentrations.
The resistance to wash out of the dopamine taken up by the isolated, perfused rat heart is dependent on the perfusion concentration used. At a concentration of 66.9 × 10−10 mol/ml, 50% of the total activity is washed out during an 8 min wash period. Within the same time interval there is no wash out when a perfusion concentration of 0.042 × 10−10 mol/ml is used.
It is concluded that the metabolic fate of dopamine taken up at various perfusion concentrations reflects the distribution of dopamine within intra‐ and extraneuronal compartments in the hearts.
In pursuit of the α‐adrenoceptor: a fine‐structural and electron autoradiographic study using 3H‐phenoxybenzamine and smooth muscle from the cat and guinea‐pig
Authors: GRAHAM J. D. P. , IVENS CAROLINE , LEVER J. D. , McOUISTON R. , SPRIGGS T. L. B. 
Published: July 2012

Summary
Electron microscopical evaluation of sets of serial fine sections of pancreatic arteriolar muscle of the cat showed no significant difference between the number of pinocytotic vesicles per unit length of smooth muscle cell membrane in ‘synaptic’ and ‘non‐synaptic’ regions.
With high resolution autoradiography, 3H‐phenoxybenzamine was found to be distributed over the cytoplasm and nuclei of smooth muscle cell profiles of guinea‐pig vas deferens, although no localization in relation to discrete morphological organelles was evident.
‘Specific protection’ of α‐adrenoceptors using 606 μM noradrenaline resulted in a significant diminution in the binding of 3H‐phenoxybenzamine as evidenced by a decrease in silver grain concentrations over smooth muscle cell profiles in autoradiographs.
The significance of these findings in relation to the site and distribution of α‐adrenoceptors is discussed.
Effect of (±) dihydroxy ephedrine and (±) dihydroxy pseudoephedrine on adrenergic transmission in mesenteric arteries
Authors: MALIK K. U. 
Published: July 2012

Summary
The effect of (±) dihydroxy ephedrine (DHE), (±) dihydroxy pseudoephedrine (DHPE) and isoprenaline on the vasoconstrictor responses of the perfused mesenteric arteries of the rat produced by stimulation of their periarterial sympathetic fibres, and in the responses to injected noradrenaline, has been studied.
DHE and DHPE inhibited the responses to nerve stimulation and increased the responses to injected noradrenaline.
Isoprenaline slightly decreased the basal perfusion pressure and reduced the responses to both nerve stimulation and injected noradrenaline. Since these effects of isoprenaline were abolished by propranolol, they are presumably mediated by β‐receptors.
The inhibitory effect of DHE and DHPE on the responses to nerve stimulation was not abolished by propranolol.
The results suggest that DHE and DHPE impair adrenergic transmission by partially replacing the adrenergic neurotransmitter, thereby acting as a false neurotransmitter.
Diffusion of labelled substances through isolated rat diaphragm
Authors: BROOKES N. , MACKAY D. 
Published: July 2012

Summary
The rate of diffusion of [14C] sucrose through rat diaphragm muscle is dependent on the period of preliminary soaking of the muscle in Krebs solution at 36° C. The ratio of the length of the diffusion path through the diaphragm to its geometrical thickness appears to fall from 4.39 ± 0.38 (S.E. of the mean) to 2.23 ± 0.18 after about 6 h of soaking.
The area of the diaphragms available for diffusion is apparently constant at 0.3–0.4 of their total area.
The measured thickness of the diaphragms increases by about 20% on soaking.
Entry of [131I] iodide into the muscle fibres is detected as a fall in both steady state and non‐steady state rates of diffusion through the diaphragm.
Entry of [14C‐methyl] decamethonium into the muscle cells is not evident from such diffusion studies in normal Krebs solution.
Relationship between the anti‐inflammatory and irritant properties of inflammatory exudate
Authors: ATKINSON D. C. , HICKS R. 
Published: July 2012

Summary
Using the rat paw oedema assay procedure a comparison was made between the anti‐inflammatory and irritant properties of the inflammatory exudate obtained from polyester sponges implanted subcutaneously in adrenalectomized rats. Where necessary, comparison was also made with a known counter‐irritant, carrageenin.
A significant correlation between the anti‐inflammatory and irritant properties of sponge exudate was observed when each parameter was determined in relation to dose. A similar result was obtained with carrageenin.
A comparison of the two activities of sponge exudate samples harvested at various times following sponge implantation did not give a significant correlation although in each case significant anti‐inflammatory activity was accompanied by marked irritation.
Time‐effect curves of the two activities of sponge exudate showed a significant correlation over the time period examined. However, no such correlation was obtained using carrageenin.
Both activities of sponge exudate were retained following dialysis.
These findings are discussed in relation to a counter‐irritant mode of action for sponge exudate.
Interaction between prostaglandins E and F given intradermally in the rat
Authors: CRUNKHORN PEARL , WILLIS A. L. 
Published: July 2012

Summary
Increases in permeability observed after intradermal injection of prostaglandins PGE1 or PGE2 (0.1 μg) into rats were greatly reduced when they were given in admixture with PGF2α. This effect was not seen with PGF1α at doses of 0.5–1 μg.
Effects of the histamine releasing agent compound 48/80 (25 ng) were inhibited by PGF2α (0.5 μg) but not by PGFlα (0.5 μg).
Responses to histamine (1 μg), 5‐hydroxytryptamine (0.1 μg) and brady‐kinin (1 μg), which have a direct action on the microvasculature, were not significantly altered by PGF2α (0.5 μg).
It is concluded that PGF2α probably acts by interfering with the release of mast cell histamine by PGEl, PGE2 and compound 48/80.
Investigations of the mode of action of a new antidysrhythmic drug, Kö 1173
Authors: SINGH B. N. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

Summary
Kö 1173, 1‐(2′,6′‐dimethyl‐phenoxy)‐2‐amino‐propane, was equal to lignocaine in potency as a local anaesthetic on stripped frog sciatic nerve at pH 7·5.
In anaesthetized guinea‐pigs in which ventricular fibrillation had been produced by an intravenous infusion of ouabain, intravenous administration of Kö 1173 caused reversion to sinus rhythm in ten out of ten animals. The mean dose of Kö 1173 required was 3·3 mg (15·3 μmol)/kg. When the ouabain infusion was continued, ventricular fibrillation did not recur, and the lethal dose of ouabain was greater than in controls.
Pretreatment with Kö 1173, however, did not influence the toxicity of ouabain infusion, implying great brevity of action.
Kö 1173 given intravenously caused a bradycardia which was maximal in 2–3 min, and which did not last more than 5 minutes.
Kö 1173 reduced the maximum driven frequency of isolated rabbit atria, raised electrical threshold, slowed conduction velocity and depressed contractions.
Kö 1173 reduced the maximum rate of depolarization of intracellularly recorded rabbit atrial and ventricular potentials, but did not affect the resting potential or the duration of the action potential.
Relationship between the chemical structure of prostaglandins and their vasoactivities in dogs
Authors: NAKANO J. 
Published: July 2012

Summary
The relationship between the chemical structure and the direct vasoactivity of different prostaglandins administered intra‐arterially was studied in the dog hindlimb preparation.
All of the prostaglandins studied, except PGF1α and PGF2α, caused a dose related decrease in the femoral arterial perfusion pressure in dogs in which the femoral arterial blood flow was kept constant, indicating the direct vasodilator action of these prostaglandins.
Among the prostaglandins studied, PGE1 is the most potent vasodilator. Comparing the chemical structure and vasodilator action of PGE1 with those of different prostaglandins, the following conclusions can be made:
The formation of the Δ5 double bond in PGE1 causes no change in its vasodilator activity, whereas the saturation of the Δ13 double bond of PGE1 slightly reduces its activity.
The alterations in the orientation and length of the carboxyl and alkyl side chains reduce markedly the vasodilator action of PGE‐ and PGA‐compounds.
The presence of a carbonyl group at C9 is the most important requirement for the potent vasodilator action of PGE1. On the other hand, the presence and S‐configuration of a hydroxyl group at C15 are essential for the intrinsic action at the receptor sites in the vascular smooth muscle, but may not be responsible for the vasodilator action.
The esterification of PGE1 or PGE2 and a triple bond formation and the replacement of C7 with oxygen in prostaglandin appear to reduce or abolish their vasodilator action.
Clinical investigation of an antagonist at α‐ and β‐adrenoceptors‐AH 5158A
Authors: COLLIER J. G. , DAWNAY N. A. H. , NACHEV CH. , ROBINSON B. F. 
Published: July 2012

Summary
The α‐ and β‐adrenoceptor blocking action of AH 5158A was investigated in man using the veins of the hand, the arterial bed of the forearm, and certain responses of the circulation as a whole.
In the veins, locally infused AH 5158A resulted in specific and competitive antagonism of the constrictor response to locally infused noradrenaline and of the dilator response to isoprenaline.
Brachial artery infusions of AH 5158A resulted in competitive antagonism of the arterial blood flow changes produced by local infusions of noradrenaline and isoprenaline.
Systemic infusion of AH 5158A (0·5–0·9 mg/kg) produced clear blockade of the heart rate response to systemic infusion of isoprenaline. It also attenuated the response to exercise at 80 watts for 4 min; mean arterial pressure during exercise was reduced by 16% and heart rate by 18%. Blockade lasted at least 1 hour.
AH 5158A caused small changes in arterial pressure and heart rate at rest supine, but had no effect on the response of pressure and rate to tilting.
Selective inhibition by glycine of some somatic reflexes in the cat
Authors: DHAWAN B. N. , SHARMA J. N. , SRIMAL R. C. 
Published: July 2012

Summary
The effects of intracerebroventricular or intrathecal administration of glycine on some somatic reflexes in chloralosed cats were investigated.
Glycine produced marked inhibition of the flexor reflex (FR) and crossed extensor reflex (CER) at low doses (2·5–5·0 mg) but even large doses (up to 400 mg) had no effect on the facilitation or inhibition of the patellar reflex produced by stimulation of either the reticular formation or the sciatic nerve. The linguomandibular reflex (LMR) could be blocked by 10–20 mg glycine.
Glycine antagonized strychnine‐induced facilitation of FR, CER and LMR and was 5–6 times as active as γ‐aminobutyric acid in this respect.
The possibility of glycine being a transmitter in spinal pathways is discussed.
Effects of a focal penicillin lesion on responses of rabbit cortical neurones to putative neurotransmitters
Authors: CLARKE G. , HILL R. G. 
Published: July 2012

Summary
Epileptogenic foci were generated in rabbit cerebral cortex by the topical application of penicillin.
Responses to iontophoretically applied putative neurotransmitters were compared in cortical neurones firing spontaneously with those driven by applied excitant substances, both before and after establishing the penicillin focus.
In the presence of the spiking focus, currents of γ‐aminobutyric acid, which normally produced 100% depression of neuronal firing, were ineffective.
In the same situation, currents of (±)‐homocysteic acid, glutamate and acetylcholine produced predominantly depolarization block responses, and hence depression of firing.
It is concluded that an epileptogenic focus can alter the responses of rabbit cortical neurones to microiontophoretically applied neurotransmitter substances. Possible mechanisms for the spread of seizure activity are discussed.
Interaction of prostaglandin E1 and calcium in the guinea‐pig myometrium
Authors: EAGLING ELIZABETH M. , LOVELL H. G. , PICKLES V. R. 
Published: July 2012

Summary
Prostaglandin E1 (PGE1) increased the responses of guinea‐pig myometrium in a low calcium medium to added Ca2+, acetylcholine, vasopressin, Ba2+ and Sr2+. The concentration of PGE1 used (50 pg/ml) was clearly below the threshold for direct spasmogenesis. In the presence of PGE1 the doses necessary for half‐maximal contractions were decreased by factors of 2·6 for Ca2+, 2·4 for acetylcholine, and 3·7 for vasopressin. The responses to Ba2+ or Sr2+, though studied less extensively, were found to be affected in much the same manner.
The K+ depolarized myometrium in a low Ca2+ medium contracts in response to added Ca2+. These responses also were increased by low concentrations of PGE1, but the effective concentration of PGE1 was indistinguishable from that for direct spasmogenesis.
Possible mechanisms for the interaction of PGE1 and Ca2+ in the myometrium are discussed. It is tentatively suggested that these findings may be relevant to the physiological control of human myometrium.
Distribution and excretion of N‐[14C]‐methyl labelled m‐hydroxybenzyltrimethylammonium ions in mice
Authors: BARLOW R. B. , READING H. W. , YATES CELIA M. 
Published: July 2012

Summary
Radioactivity in the plasma, livers, and brains of mice was measured at intervals of 10 min to 24 h after the intraperitoneal injection of 14C labelled m‐methoxy‐ and m‐hydroxy‐ benzyltrimethylammonium ions.
Well over 10% of the dose of either of these quaternary compounds was found in the liver and plasma within 10 min of the injection, but they were rapidly excreted or metabolized, having a half life of between 1 and 2 hours.
Small amounts of radioactivity were detectable in brain, and were not due to contamination of brain samples by blood, after doses of 14–16 μmol/kg (approximately 4 mg iodide/kg) and upwards. After doses of 4–6 μmol/kg (approximately 1 mg iodide/kg), however, radioactivity in the brain was barely detectable.
Any behavioural effects reported to occur in mice treated with these lower doses of m‐hydroxybenzyltrimethylammonium, which include improved performance in a test of avoidance learning, are unlikely to be due to an action within the central nervous system. Learning may be more influenced by the peripheral effects of drugs than has hitherto been appreciated.
Effects of the inhibition of noradrenaline uptake and synthesis on the maintenance of the response to continuous nerve stimulation in the central artery of the rabbit ear
Authors: KALSNER STANLEY 
Published: July 2012

Summary
. The central artery of the rabbit ear was perfused through its lumen in vitro, with a constant pressure technique, and stimulated continuously via its periarterial sympathetic nerves at the physiological frequency of 5 Hz.
. The vasoconstrictor response, which led initially to an almost complete cessation of intraluminal flow, deteriorated steadily over a period of hours. The involvement of presynaptic mechanisms in this effect was indicated by the finding that noradrenaline, administered extraluminally, produced a similar response before the onset of continuous stimulation and at a late stage when the constriction had decreased markedly. In addition, the noradrenaline precursor DOPA, restored the depressed responses towards their original values, indicating that failure involved depletion of mediator for release.
. Responses to continuous stimulation declined significantly faster after inhibition of tyrosine hydroxylase with α‐methyl‐p‐tyrosine. However, inhibition of the uptake of noradrenaline with cocaine did not enhance the decline of the response, even when the sensitization produced by the compound was taken into account.
. It is concluded that synthesis, along with the mobilization of stored mediator, rather than uptake and re‐use of noradrenaline maintain the effector response in the central artery of the rabbit ear stimulated continuously at a frequency within the physiological range.
The release of prostaglandins and rabbit aorta contracting substance (RCS) from rabbit spleen and its antagonism by anti‐inflammatory drugs
Authors: GRYGLEWSKI R. , VANE J. R. 
Published: July 2012

Summary
. Slices of rabbit spleen generate rabbit aorta contracting substance (RCS) and a prostaglandin of the E series when they are vibrated or stirred.
. The release of both substances is increased by arachidonic acid and inhibited by aspirin‐like drugs.
. When the spleen effluent containing RCS and prostaglandin E is incubated for a further 3 min, the prostaglandin concentration increases and the RCS concentration declines.
. RCS may therefore be an unstable intermediate in the biosynthesis of prostaglandins.
Degradation of angiotensin II by plasmin
Authors: DUDEK G. , LATALLO Z. S. , PROKOPOWICZ J. , WOROWSKI K. 
Published: July 2012

Summary
. Synthetic angiotensin II (Hypertensin, Ciba, Basel) was incubated with a water‐insoluble preparation of plasmin (E.C. 3.4.4.14) and the resulting products analysed by paper chromatography and N‐terminal amino‐acid analysis.
. Only the N‐terminal asparagine was split off from the peptide. This indicates that plasmin attacks the Asn‐Arg but not the Arg‐Val in angiotensin II molecule.
Some evidence of the active uptake of noradrenaline in the guinea‐pig isolated trachea
Authors: FOSTER R. W. , O'DONNELL STELLA R. 
Published: July 2012

Summary
. Guinea‐pig isolated trachea immersed in a low concentration (50 nm) of (—)‐3H‐noradrenaline accumulates radioactive material against an apparent concentration gradient.
. Compartmental analysis based on the decay curve of radioactive material content during washout and its comparison with that of 14C‐sorbitol shows that some extracellular noradrenaline is adsorbed. A considerable mass exists in a slowly exchanging compartment, i.e. is retained. This retention is inversely concentration dependent.
. Over a 25‐fold range of concentration the entry of either total radioactive material or noradrenaline followed Michaelis‐Menten kinetics.
. The uptake of radioactive material was sodium‐dependent and ouabainsensitive.
. The uptake was susceptible to metabolic poisons which deprive the tissue of all available energy but it was not exclusively associated with either oxidative or glycolytic energy supply.
. Although net uptake could not be distinguished from exchange with endogenous amine, other evidence has been obtained for an active noradrenaline transport system with properties similar to neuronal uptake.
Actions of levodopa on the blood pressure of conscious rabbits
Authors: CALNE D. B. , REID J. L. 
Published: July 2012

Summary
. In conscious rabbits, the rapid intravenous injection of levodopa alone does not have any significant effects on the blood pressure in doses up to 10 mg/kg.
. After inhibition of monoamine oxidase, levodopa induces a sustained pressor response.
. This response can be blocked by inhibition of extracerebral decarboxylase.
. Possible mechanisms for these interactions are discussed, together with their therapeutic implications in Parkinsonism.
β‐Adrenoceptor blocking properties and cardioselectivity of M & B 17,803A
Authors: BASIL B. , JORDAN R. , LOVELESS A. H. , MAXWELL D. R. 
Published: July 2012

Summary
. The β‐adrenoceptor blocking properties of (±)‐1‐(2‐acetyl‐4‐n‐butyramidophenoxy)‐2‐hydroxy‐3‐isopropylaminopropane hydrochloride (M&B 17,803A) have been compared with those of practolol and propranolol in the guinea‐pig, cat and dog.
. Following either intravenous or oral administration in the cat or dog, M&B 17,803A and practolol had similar potency in antagonizing isoprenaline‐induced tachycardia and both showed cardioselectivity, but both were less potent than propranolol.
. M&B 17,803A and practolol had approximately one hundredth the intravenous potency of propranolol in increasing the severity of anaphylactic bronchospasm in the conscious sensitized guinea‐pig.
. M&B 17,803A possessed less marked intrinsic sympathomimetic activity than practolol but, like propranolol, it had significant local anaesthetic properties and increased the refractory period of rabbit isolated atria.