bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF ADRENOCEPTOR BLOCKADE ON PLASMA CATECHOLAMINE LEVELS DURING ADRENALINE INFUSION
Authors: BRITTON B.J. , IRVING M.H. , WOOD W.G. 
Published: July 2012

The present experiments investigate the effects of phenoxybenzamine and propranolol, singly and in combination, on plasma catecholamine levels in sheep receiving a three‐hour adrenaline infusion.
Five groups of five anaesthetized sheep were studied for a period of 3 h each. One group acted as a control and received only a saline (0.9% w/v NaCl solution) infusion. A second group received a constant infusion of adrenaline (2 μg kg body weight−1 min−1). A third group received a similar adrenaline infusion, having been premedicated with phenoxybenzamine (1 mg/kg body weight). A fourth group received a similar adrenaline infusion following premedication with (±)‐propranolol hydrochloride (7 μg/kg body weight). The fifth group received the adrenaline infusion following premedication with both the α‐ and β‐blocker in the above doses.
Plasma catecholamines were measured on blood samples taken at seven intervals before, during and following the infusion.
Control animals receiving only a saline infusion remained physiologically and biochemically stable throughout the experimental period.
Adrenaline infusion in animals not receiving adrenoceptor blocking drugs caused a rise in plasma adrenaline levels from a low basal value of 1 μg/litre to a maximum level of 19.8 μg/litre. Animals premedicated with phenoxybenzamine exhibited a similar response.
Animals premedicated with propranolol before the infusion of adrenaline did not demonstrate as marked a rise of plasma adrenaline levels as the two previous groups. The maximum mean plasma adrenaline level recorded in this group was 6.88 μg/litre.
Animals premedicated with phenoxybenzamine and propranolol before the infusion of adrenaline showed only a small rise in plasma adrenaline levels compared with animals receiving adrenaline infusion alone. The maximum mean plasma adrenaline level in the group was only 3.43 μg/litre.
The studies demonstrate that by an unknown mechanism β‐adrenoceptor blockade with (±)‐propranolol, either alone or in combination with phenoxybenzamine, lowers the plasma adrenaline response evoked by adrenaline infusion.
POTENTIATION OF THE RESPONSE TO VASOPRESSIN (PITRESSIN) BY TREATMENT WITH A COMBINATION OF CHLORPROPAMIDE AND CHLOROTHIAZIDE IN BRATTLEBORO RATS WITH HEREDITARY HYPOTHALAMIC DIABETES INSIPIDUS
Authors: LAYCOCK J.F. , LEWIS A.F. 
Published: July 2012

The effect of a combination of chlorpropamide and chlorothiazide in Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI) treated with low doses of vasopressin (Pitressin tannate in oil) was investigated with particular reference to the time course of response from the initiation of treatment.
Analysis of the relationship between water intake and body weight indicated no real correlation and body weight accounted for only 4.4% of the variation in water intake. It was therefore decided to use whole body responses as the index in preference to the response per unit body weight.
The daily administration of 5 mg chlorpropamide combined with chlorothiazide in the drinking water (4 mg/l) to Pitressin‐treated DI rats potentiated the response to small doses of vasopressin (25 and 50 mu Pitressin/24 hours). Water intake was reduced by the drug combination by an average of 12.35 ml/24 h, but only on the second day of treatment was the decrease of any real magnitude (30 ml/24 h but otherwise 9 ml/24 h or less). Analysis of urine volume measurements gave similar results to those obtained for water intake and the potency ratio measured in terms of free water clearance was 1.26 (agreeing closely with the ratio for water intake which was 1.24).
A reduction in the solute excretion was observed only in those DI rats treated with the higher dose of Pitressin (50 mu/24 h) combined with the two drugs.
Possible reasons for the discrepancy between the effect of the combination of chlorpropamide and chlorathiazide on water metabolism in the DI rat and the DI patient are discussed.
MODIFICATION BY CAPSAICIN AND COMPOUND 48/80 OF DYE LEAKAGE INDUCED BY IRRITANTS IN THE RAT
Authors: ARVIER P.T. , CHAHL LORIS A. , LADD R.J. 
Published: July 2012

Concentration‐related dye leakage produced by intracutaneous injections of irritants was measured in rats by an Evans blue technique.
In rats pretreated with a total dose of 50 mg capsaicin over 4 days, the response to capsaicin, formalin, HCl, KCl, prostaglandin E1, bradykinin and bradykinin with prostaglandin E1 (10−6 m) were greatly reduced, the responses to histamine and 5‐hydroxytryptamine were slightly reduced and those to adenosine 5′‐triphosphate (ATP) and compound 48/80 were unaffected.
Pretreatment with intracutaneous injections of compound 48/80 (0.5 μg, 24 and 48 h previously) recuded the responses to ATP, compound 48/80, HCl, KCl, prostaglandin E1, and bradykinin but did not affect those to histamine, 5‐hydroxytryptamine or bradykinin with prostaglandin E1 (10−6 m).
Responses to capsaicin and formalin produced spotted blueing extending over a large area and were suppressed by compound 48/80 in the smaller pretreated area only. Capsaicin responses were reduced with larger doses of compound 48/80 (total dose 15 μg).
It is concluded that the production of neurogenic oedema involves both sensory nerves and mast cells.
THE PHARMACOLOGICAL PROPERTIES OF THE CHOLINERGIC FALSE TRANSMITTER, N‐2‐ACETOXYETHYL‐N‐METHYLPYRROLIDINIUM, AND ITS PRECURSOR, N‐2‐HYDROXYETHYL‐N‐METHYLPYRROLIDINIUM
Authors: VON SCHWARZENFELD I. , WHITTAKER V. P. 
Published: July 2012

The pharmacological properties of N‐2‐hydroxyethyl‐N‐methyl pyrrolidinium (pyrrolcholine) and its acetate ester, recently shown to be a false transmitter at the cholinergic electromotor synapses in Torpedo marmorata, also those of the corresponding morpholinium compounds (morpholinecholine, acetylmorpholinecholine), have been studied on the guinea‐pig ileum, frog heart, frog rectus abdominis muscle, rat blood pressure, rat gastrocnemius muscle and dorsal muscle of the leech.
Acetylpyrrolcholine and acetylmorpholinecholine are full cholinoceptor agonists with dose‐response curves parallel to that of acetylcholine. They are, however, less potent. Acetylpyrrolcholine is relatively more potent as a muscarinic drug (molar potency about 30% of that of acetylcholine in the ileum but only 4% on the leech) whereas acetylmorpholinecholine is more strongly nicotinic. The unacetylated compounds are very weak agonists with potencies comparable to that of choline.
Pyrrolcholine in high concentration showed a distinct neuromuscular blocking effect in the rat gastrocnemius muscle preparation. It is likely that this is a direct effect and not due to uptake by the presynaptic nerve terminals followed by conversion to a false transmitter since it was not reduced by hemicholinium‐3, which is known to block uptake of choline and choline analogues by the presynaptic high affinity choline uptake system.
THE SELECTIVE ACTION OF β‐ADRENOCEPTOR BLOCKING DRUGS AND THE NATURE OF β1 and β2 ADRENOCEPTORS
Authors: COLEMAN A.J. , SOMERVILLE A.R. 
Published: July 2012

Purified membranes retaining a catecholamine responsive adenylate cyclase have been prepared from rabbit heart, lung and (pseudo‐pregnant) uterus.
These preparations have the characteristics of plasma membranes and both heart and lung respond to β‐adrenoceptor agonists in the order:(±)‐isoprenaline> (—)‐noradrenaline> (—)‐adrenaline> (+)‐isoprenaline> salbutamol.The sensitivity of the adenylate cyclase to β‐adrenoceptor stimulation is improved by pre‐treatment of the animals with reserpine and syrosingopine.
Dose‐ratios for several concentrations of propranolol (non‐selective β‐adrenoceptor blocker), practolol and atenolol (cardio‐selective β‐adrenoceptor blockers) have been measured on all three membrane preparations. Schild plots of log (dose ratio — 1) vs. log dose were virtually coincident for heart and lung with a dissociation constant (Kb) for propranolol very close to the pharmacological value. The ratio of Kb values was 0.65 for practolol and 1.23 for atenolol compared with pharmacological cardio‐selectivity ratios (measured on isolated atria and tracheal chain) of 67.6 and 110 respectively. The uterus/heart Kb ratio was 51.5 for atenolol. Inhibition of the uterus by practolol gave a Schild plot with slope significantly less than 1, indicating a different mechanism of action from the heart.
Kb values obtained by measuring adenylate cyclase stimulation in chopped tissue (including preparations of bronchial tree and alveolar tissue as well as whole lung) resembled the membrane values rather than those found in whole organs.
The results show that the pharmacological selectivity of practolol and atenolol is maintained at the receptor‐adenylate cyclase level, at least as far as heart and uterus are concerned, though the smaller selectivity ratios in the biochemical system suggest that receptor difference is not the only factor and that phase distribution of the drug may also be important. Membranes prepared from whole lung show an overall β1 response which may simply reflect the predominance of β1 cell types containing β1‐adrenoceptors over bronchial smooth muscle.
A COMPARISON OF THE EFFECTS OF SODIUM THIOCYANATE AND DANTROLENE SODIUM ON A MAMMALIAN ISOLATED SKELETAL MUSCLE
Authors: MOULDS R.F.W. 
Published: July 2012

A combination of electrical and pharmacological stimulation has been used to compare the effects of sodium thiocyanate and dantrolene sodium on the excitation‐contraction coupling (ECC) mechanism of the mouse soleus muscle.
Thiocyanate prolonged the ‘active state’ after electrical stimulation and increased the response to 8 mm caffeine and 80 mm KCl. Dantrolene had an opposite effect to thiocyanate on all the indices studied.
It is concluded that the mechanism of action of dantrolene is by inhibition of the release of the calcium ions involved in the ECC mechanism, probably at the level of the transverse tubules.
THE EFFECTS OF GLUCAGON, SECRETIN, PANCREOZYMIN AND PENTAGASTRIN ON THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG
Authors: RICHARDSON P.D.I. , WITHRINGTON P.G. 
Published: July 2012

The sympathetically‐innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were monitored continuously and the hepatic arterial vascular resistance (HAVR) calculated from these measurements.
Commercial preparations of secretin, pancreozymin, glucagon and pentagastrin were administered by intra‐arterial (i.a.) injection and infusion.
Secretin and pancreozymin by injection caused dose‐dependent hepatic arterial vasodilatation, and on a molar basis were both more potent than glucagon or pentagastrin.
Intra‐arterial infusions of secretin and pancreozymin caused hepatic arterial vasodilatation at calculated blood concentrations close to those measured under physiological conditions by other investigators. The vasodilatation was of the same duration as that of the hormone infusions.
Pentagastrin by i.a. injection caused dose‐dependent hepatic arterial vasodilatation; by i.a. infusion, vasodilatation occurred but there was marked ‘escape’ from the effects during the continued infusion.
As reported previously, glucagon by injection caused dose‐dependent hepatic arterial vasodilatation of long duration; by infusion, glucagon caused vasodilatation that persisted after the cessation of the infusion.
Glucagon infused i.a., inhibited the vasoconstrictor effects of i.a. noradrenaline, over the same range of infusions that caused hepatic arterial vasodilatation.
Secretin or pancreozymin did not antagonize the effects of noradrenaline on the hepatic arterial vascular bed at any doses used.
Pentagastrin did not antagonize the vasoconstrictor effect of noradrenaline whether hepatic arterial vasodilatation resulted from the pentagastrin infusion, or not.
These results are discussed with respect to the possible control of the hepatic arterial vascular bed by gastrointestinal hormones.
EFFECT OF ANTI‐THYROID AGENTS, METHIMAZOLE AND PROPYLTHIOURACIL, ON BRAIN NORADRENALINE CONTENT
Authors: HASHIZUME Y. , YAMAKI T. , HIDAKA H. 
Published: July 2012

Methimazole (1‐methyl‐2‐mercaptoimidazole, MMI) and propylthiouracil (6‐propyl‐2‐thiouracil, PTU) which are used in the therapy of hyperthyroidism were found to reduce brain noradrenaline (NA) content. Endogenous NA levels in rat brain were reduced from 1 to 6 h after intraperitoneal injection of MMI by doses in excess of 25 mg/kg and by PTU at a dose of 50 mg/kg. However, endogenous NA in the rat heart was only slightly reduced after 50 mg/kg of MMI, and was not affected by PTU (50 mg/kg).
Both MMI and PTU effectively inhibited the in vivo conversion of [3H]‐dopamine into [3H]‐noradrenaline ([3H]‐NA) in the brain of rats after a single intraperitoneal injection of doses above 10 mg/kg (MMI) and 25 mg/kg (PTU). This inhibition by MMI and PTU was dose‐dependent over the range of 10 mg/kg to 50 mg/kg, was highest after 2–3 h and continued for at least 6 h after their injection. The conversion rates returned to normal after 24 hours.
The results suggest that the reduction of brain NA by these drugs is, at least in part, due to the inhibition of brain dopamine β‐hydroxylase.
THE INTERACTION OF SOME BIS‐ARYLHYDROXYSULPHONIC ACIDS WITH A SITE OF KNOWN STRUCTURE IN HUMAN HAEMOGLOBIN
Authors: BROWN F.F. , GOODFORD P.J. 
Published: July 2012

1 Two bis‐arylhydroxysulphonic acids were previously designed to interact with the known molecular configuration of the 2,3‐diphosphoglycerate (DPG) receptor‐site of human haemoglobin. These compounds liberate oxygen from the haemoglobin similarly to DPG.2 Solutions of haemoglobin have now been observed under physiological conditions by nuclear magnetic resonance (n.m.r.) in the presence of DPG and of the compounds.3 Two peaks in the n.m.r. spectrum of haemoglobin are shifted when DPG is added to the solution.4 The same two peaks in the spectrum are affected by the compounds.5 The observations are compatible with the predicted interaction between the compounds and the haemoglobin receptor site.
SOME OBSERVATIONS ON THE MECHANISM OF BENZODIAZEPINE‐BARBITURATE INTERACTIONS IN THE MOUSE
Authors: CHAMBERS D.M. , JEFFERSON G.C. 
Published: July 2012

1 The prolongation of pentobarbitone sleeping times by five benzodiazepines, administered by prior intraperitoneal injection, was measured in mice. The pentobarbitone was injected either intraperitoneally or intracerebroventricularly. For each benzodiazepine, the prolongation was dose‐related and differences in potency between benzodiazepines were not marked.2 The percentage prolongation of sleeping times produced by most of the benzodiazepines was greater when the pentobarbitone was given intracerebroventricularly and was explained by a preferential addition of CNS depressant effects associated with this route.3 To test whether the action of intraperitoneally administered pentobarbitone had been influenced by a metabolic component, the effects of nitrazepam on drug metabolism, measured by changes in plasma phenazone levels in the mouse, were studied. Nitrazepam (32 mg/kg, i.p.) produced a 23% reduction in the rate of phenazone metabolism.4 Nitrazepam was also shown to have produced a transient fall in body temperature. Calculations based on Q10 values suggested that this hypothermia accounted, at most, for half the metabolic change measured.
DRUGS ALTERING INSULIN SECRETION: EFFECTS ON PLASMA AND BRAIN CONCENTRATIONS OF AROMATIC AMINO ACIDS AND ON BRAIN 5‐HYDROXYTRYPTAMINE TURNOVER
Authors: CURZON G. , FERNANDO J.C.R. 
Published: July 2012

1 An investigation was made into the effects of drugs which alter insulin secretion on the concentrations of tryptophan and other aromatic amino acids in plasma and brain and on 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) in train. Drugs used were streptozotocin, propranolol, tolbutamide and phentolamine.2 Tolbutamide and phentolamine increased the plasma insulin concentrations by 100% and 300% respectively but with little effect on the brain/plasma ratios for the aromatic amino acids. Previously propranolol was found to decrease plasma insulin by 50% without altering the above ratios. The ratios were decreased by streptozotocin but only when plasma insulin fell by more than 50%.3 Phentolamine and propranolol did not alter the brain/plasma ratios for the aromatic amino acids in streptozotocin‐treated rats.4 The results suggest that only large changes of insulin secretion e.g. those associated with food intake or aminophylline injection are likely to alter appreciably the brain/plasma ratios for the aromatic amino acids.5 Tolbutamide displaced tryptophan from its binding to plasma albumin and increased brain 5‐HIAA probably by inhibiting 5‐HIAA efflux from brain. The other drugs did not alter brain 5‐HT or 5‐HIAA concentrations.
SOME OBSERVATIONS ON THE ANORECTIC ACTIVITY OF PROSTAGLANDIN F2α
Authors: DOGGETT N.S. , JAWAHARLAL K. 
Published: July 2012

1 Intracerebroventricular injection of prostanglandin F2α (10‐40 μg) decreases food intake in a dose‐dependent manner in rats trained to consume their daily total food intake in a 2 h period.2 This anorexia is also observed in satiated rats, which had ad libitum access to food.3 The anorectic activity of prostaglandin F2α is not modified by changes in the internal environment of the body after food intake, such as increased blood glucose and insulin levels and decreased fatty acid levels, or by the presence or absence of food in the stomach, as is evident from the anorectic activity of prostaglandin F2α in partially satiated rats.4 The anorexia is not due to pain or irritative properties of prostaglandin F2α since induction of comparable pain with 3% acetic acid does not affect food intake in rats deprived of food for 22 hours.5 Anorectic doses of prostaglandin F2α when injected intraperitoneally cause hypothermia.6 The results suggest that the inhibitory activity of prostaglandin F2α on food intake is at both peripheral and central sites.7 Prostaglandin F2α‐induced anorexia is associated with the behavioural tranquillization that is seen after the ingestion of food.
THE EFFECT OF CLOPROSTENOL ON HUMAN LUTEAL STEROID AND PROSTAGLANDIN SECRETION in vitro
Authors: McDOUGALL A.N. , WALKER FELICITY M. MAULE , WATSON J. 
Published: July 2012

1 Human luteal tissue slices from days 18, 21 and 25 of the menstrual cycle were superfused in vitro with Medium 199 alone or containing cloprostenol (1 μg/ml). Concentrations of progesterone, oestradiol‐17β and prostaglandins F2α and E2 were determined in the superfusate samples.2 Secretion of steroids and prostaglandins was maintained at an approximately constant level throughout the experiments (21 h in one case) when the tissue was perfused with M199 alone.3 Superfusion with cloprostenol (1 μg/ml) resulted in an initial depression of progesterone and oestradiol‐17β but this was not maintained, levels returning to control values or showing an increase, while superfusion with cloprostenol continued. Cloprostenol is not therefore considered to be luteolytic at this dose and under these conditions for human luteal tissue in vitro.4 Superfusion with cloprostenol (1 μg/ml) also resulted in a large stimulation of secretion of endogenous prostaglandin F2α following a short lag phase. This stimulation was possibly due to the initial depression of progesterone secretion. A short‐lived stimulation of prostaglandin E2 secretion was also observed.5 The significance of the increase in prostaglandin E2 secretion and the interrelationships between the various changes observed with cloprostenol are difficult to interpret.
EFFECTS OF ATENOLOL ON REGIONAL MYOCARDIAL BLOOD FLOW AND ST SEGMENT ELEVATION IN THE CANINE MYOCARDIUM
Authors: BERDEAUX A. , BOISSIER J.R. , GIUDICELLI J.F. 
Published: July 2012

1 The effects of atenolol on regional myocardial blood flow (RMBF) and on ST segment elevation were studied both in normal and ischaemic regions of the myocardium in dogs. Some of the experiments were performed with cardiac pacing or after bilateral stellectomy.2 In the absence of cardiac pacing, atenolol (1 mg/kg, i.v.) induced a marked reduction in heart rate and contractile force and a decrease in RMBF, which was of the same magnitude in normal and ischaemic areas. There was no modification in the endo/epi flow ratio. ST segment elevation in ischaemic areas was significantly reduced.3 Bilateral stellectomy induced similar effects to those of atenolol. Atenolol after bilateral stellectomy exhibited no additional effects.4 In dogs submitted to cardiac pacing, atenolol no longer decreased RMBF and ST segment elevation.5 These results demonstrate that with atenolol, there is no correlation between bradycardia and the endo/epi flow ratio while there is one between bradycardia and reduction in ST segment elevation.
STUDIES ON THE CARDIOVASCULAR EFFECTS OF PINDOLOL IN DOCA/SALINE HYPERTENSIVE RATS
Authors: BUCKINGHAMM R.E. , HAMILTON C. , ROBSON D. 
Published: July 2012

1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS‐rats) is described. In DS‐rats, pindolol (10‐50 μg/kg) produced a dose‐dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 μg/kg) in DS‐rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by β‐adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 μg/kg) produced a further fall in blood pressure in DS‐rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 μg/kg) resulted in a reduction of neuronally‐induced tachycardia in pithed DS‐rats; neuronally‐evoked pressor effects were also antagonized by pindolol (50 μg/kg, orally).5 Whereas pindolol, 50 μg/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS‐rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS‐rats, an equivalent degree of cardiac β‐adrenoceptor blockade was produced by pretreatment with pindolol, 50 μg/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS‐rats, the tachycardia produced by intravenous isoprenaline, 3 μg/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol, 50 μg/kg, in DS‐rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525‐A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS‐rat are mediated by a metabolite(s) acting by stimulation of peripheral β‐adrenoceptors.