bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of heart rate on indices of myocardial contractility in the dog
Authors: Richmond D. R. , Angus J. A. , Goodman A. H. , Cobbin L. B.
Published: June 2007

1. Changes in heart rate were evoked by atrial pacing in anaesthetized dogs with no pretreatment and in dogs given reserpine or guanethidine for 72 h. The effect of alterations in heart rate were related to two indices of myocardial contractility: the maximal rate of change of left ventricular pressure (dp/dt), and an index which was independent of initial fibre length (dp/dt)/ITT, where IIT is integrated isometric tension.

2. An increase in heart rate in control dogs was accompanied by a rise in both dp/dt and (dp/dt)/IIT confirming that the Bowditch staircase does exist in the intact ventricle. The regression line relating heart rate to (dp/dt)/IIT was significantly steeper than that relating heart rate to dp/dt because the reduction in left ventricular preload at high heart rate tends to attenuate the rise in dp/dt.

3. Reserpine, but not guanethidine pretreatment was accompanied by either a slight decrease or no change in (dp/dt)/IIT during pacing.

4. Acute elevation of (dp/dt)/IIT by either calcium or isoprenaline infusion in reserpine pretreated dogs did not restore the Bowditch effect.

5. Acute depression of (dp/dt)/IIT by propranolol and pentobarbitone was accompanied by a greater rise in (dp/dt)/IIT with pacing in control dogs and a rise rather than a fall in reserpine‐pretreated dogs.
The cardiovascular effects of intraventricular 5,6‐dihydroxytryptamine in conscious hypertensive rats
Authors: Finch L.
Published: June 2007

1. Conscious experimental hypertensive rats injected intraventricularly with 5,6‐dihydroxytryptamine (50 μg) responded with a rapid and long‐lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration.

2. The acute actions of 5,6‐dihydroxytryptamine on the cardiovascular system were not modified by pretreatment with bromolysergide (0·5 mg/kg, i.p.), methysergide (2·5 mg/kg, i.p.) or intraventricular phentolamine (200 μg).

3. The results suggest that central serotonergic neurones play an important role in the regulation of blood pressure. However, the site of action remains to be investigated.
Interaction between drugs and potassium‐rich solutions in producing contraction in bovine tracheal smooth muscle: studies in normal and calcium‐depleted tissues
Authors: Kirkpatrick C. T. , Jenkinson Hilary A. , Cameron A. R.
Published: June 2007

1. The contracture normally induced in isolated bovine tracheal smooth muscle by potassium‐rich solution was abolished by removal of the extracellular calcium. The contraction returned when calcium was added to the solution in a concentration greater than 0·05 mmol/l.

2. The amplitudes of the potassium‐contracture, and of the contractile responses to histamine and acetylcholine in normal physiological solutions, declined at low temperatures (15–25°C). If drugs were added during the plateau phase of the potassium contracture, the extra tension developed above the contracture did not change with temperature.

3. Calcium‐depletion reduced the responses to drugs, and repeated application of the drugs in calcium‐free solution produced progressively smaller contractions, suggesting that an intracellular store of calcium was being used up.

4. Depolarization of calcium‐depleted tracheal muscle by high‐K+ solution without calcium produced responses to drugs which were larger than those in sodium‐based calcium‐free solutions. There was no potentiation in a solution in which sodium was replaced by sucrose, suggesting that potassium was not acting simply by replacing the sodium.

5. It is suggested that depolarization of the membrane by potassium makes available a fraction of bound calcium which was not available in calcium‐free sodium‐based solution.
The inhibition of renin secretion in the isolated rat kidney by clonidine hydrochloride (Catapres)
Authors: Vandongen R. , Greenwood Dianne M.
Published: June 2007

1. The effect of clonidine HCl on basal and isoprenaline‐stimulated renin secretion was examined in the isolated rat kidney.

2. Intrarenal infusion of clonidine at a dose level which did not increase renal perfusion pressure (1·9 nmol min−1 g−1), significantly lowered basal renin secretion without altering the stimulatory response to isoprenaline.

3. Increasing the dose of clonidine (3·4 nmol min−1 g−1) raised renal perfusion pressure, lowered perfusate flow rate and attenuated the response in renin secretion to isoprenaline.

4. Since the vasoconstrictor effect of clonidine is considered to be due to α‐adrenergic stimulation, this observation is similar to a previous study reporting suppression of renin secretion by vasoconstrictor infusions of catecholamines (Vandongen & Peart, 1974).

5. These studies demonstrate a direct intrarenal inhibitory effect of clonidine on renin secretion. It is suggested that this may contribute to the suppression of plasma renin levels observed in vivo following administration of this drug.
GLUTATHIONE ALTERATIONS IN RAT LIVER AFTER ACUTE AND SUBACUTE ORAL ADMINISTRATION OF PARACETAMOL
Authors: Buttar H. S. , Chow A. Y. K. , Downie R. H.
Published: June 2007

1. The effect on hepatic glutathione was studied in rats pretreated orally with various dosages of paracetamol (acetaminophen) for varying time intervals.

2. Paracetamol caused a dose‐dependent depletion of hepatic glutathione, the maximum depletion occurring 3 h after acute dosing, the levels returning to normal by 12 h after low doses (0.1 or 0.25 g/kg, p.o.) and by 72 h after the hghest doses (1 g/kg, p.o.).

3. Before returning to normal, the liver glutathione levels became significantly greater than the control values (35–40%) at 24 and 48 h in 0.5 and 1 g/kg paracetamol‐treated rats, respectively, suggesting thereby a ‘glutathione rebound action’ of paracetamol‐pretreatment.

4. In contrast with the acutely treated rats, the liver glutathione content remained unchanged when 0–5 g/kg paracetamol was administered twice daily for 7 consecutive days.

5. Fasting caused a significant reduction in hepatic glutathione, the glutathione stores were replenished within 6 h after feeding.

6. The results suggest that the hepatic glutathione levels are reversibly depleted by single large doses of paracetamol, while the glutathione depletory effect appears to decrease after the repeated administration of this hepatotoxic agent.
A STUDY IN MICE OF BROMO AND CHLORO ACYLUREA ANALOGUES OF THE SEDATIVE‐HYPNOTIC BROMUREIDES
Authors: Mrongovius R. I. , Rand M. J.
Published: June 2007

1. A series of 1‐(2‐chloroacyl)ureas, related to the sedative‐hypnotic drugs brom‐valetone and carbromal, was synthesized and tested in mice to determine central depressant and acute toxic effects. Four 1‐(2‐bromoacyl)ureas and two 3‐halo compounds were included for comparison.

2. Large variations in potency were seen between the compounds. Much of this can be ascribed to differences in lipophilicity. Among homologous 1‐(2‐chloroacyl)ureas, those with 6 acyl carbons had maximal potency. Among groups of structural isomers, the most potent were 2‐halo, 3‐alkyl substituted compounds.

3. The most potent compounds were also those with the largest ratios of hypnotic to lethal activity.

4. The variation in the onset and duration of action of these compounds enables a choice to be made for a compound with a particular set of characteristics.
CARDIOVASCULAR EFFECTS OF CARBACHOL AND OTHER CHOLINOMIMETICS ADMINISTERED INTO THE CEREBRAL VENTRICLES OF CONSCIOUS CATS
Authors: Day M. D. , Roach A. G.
Published: June 2007

1. The cholinomimetic substances acetylcholine, nicotine, tetramethylammonium chloride and carbachol were infused intracerebroventricularly (i.c.v.) into conscious, normotensive cats and their effects on behaviour, blood pressure and heart rate recorded.

2. Intracerebroventricular acetylcholine, nicotine and tetramethylammonium chloride each produced small, mainly stimulant, effects on the cardiovascular system which were not accompanied by any marked behavioural effects.

3. Intracerebroventricular carbachol at a dose of 30 μg produced marked and persistent cardiovascular stimulant effects accompanied by a striking rage/fear reaction. When the dose of carbachol was reduced to 7.5 μg the behavioural effects were no longer seen but marked cardiovascular stimulant effects remained.

4. The cardiovascular stimulant effects of i.c.v. carbachol were apparently mediated via the peripheral sympathetic system since they were abolished by peripheral adrenergic neurone blockade.

5. The blood pressure and heart rate increases produced by i.c.v. carbachol were blocked by prior i.c.v. treatment with atropine, hexamethonium, guanethidine, bethanidine or propranolol.

6. The data are consistent with an interaction between central cholinergic and catecholaminergic neural pathways involved in central regulation of blood pressure and further suggest the involvement of β‐adrenoreceptors in the responses to centrally‐administered cholinomimetics.
A PHARMACOLOGICAL INVESTIGATION OF SYNTHETIC SUBSTANCE P ON THE ISOLATED GUINEA‐PIG ILEUM
Authors: Bury R. W. , Mashford M. L.
Published: June 2007

1. The pharmacological properties of synthetic substance P have been studied on the guinea‐pig ileum and compared with those of acetylcholine and other agonists.

2. The effects of synthetic substance P in the presence of atropine, hexamethonium, mepyramine and certain of the drugs which antagonize serotonin are in close agreement with those reported for the naturally occurring peptide.

3. The spasmogenic action of substance P is not mediated by cholinergic mechanisms or release of prostaglandins, and does not appear to involve release of serotonin. The inability of tetrodotoxin to attenuate responses to substance P suggests that its spasmogenic action is not elicited through neural mechanisms. Thus, it is likely that substance P acts directly on the smooth muscle of the ileum.

4. Since substance P is present in the brain and can depolarize neurones, it may be a neurotransmitter. A screening of various centrally acting drugs, whose mechanisms of action are unclear, was undertaken to seek possible interactions with substance P. Pimozide was the most potent in depressing responses to substance P but none of the drugs caused the specific antagonism which would assist in elucidating a possible physiological role for substance P.
POSITIVE INOTROPIC ACTION OF GLYCERYL TRINITRATE AS OBSERVED IN THE BLOOD‐PEWUSED PAPILLARY MUSCLE PREPARATION OF THE DOG HEART
Authors: Himori Norio , Imai Yutaka , Taira Norio
Published: June 2007

1. The effects of glyceryl trinitrate on the coronary vasculature and on the contractility of the ventricular myocardium were investigated by the use of papillary muscle preparations of the dog, and that on the sino‐atrial node activity by the use of sino‐atrial node preparations of the dog. The papillary muscle preparation was cross‐circulated through the anterior septal artery and the sino‐atrial node preparation through the sinus node artery from a donor dog. The papillary muscles were driven at a rate of 120 beats/min. Drugs were injected close‐arterially.

2. Glyceryl trinitrate, in doses of 0.03–100 μg, produced dose‐related increases in blood flow and developed tension. An increase in developed tension caused by 100 μg of glyceryl trinitrate amounted to about 24% of the basal developed tension. Large doses of glyceryl trinitrate (100–300 μg) produced a negative inotropic effect after a positive one in some preparations.

3. The positive inotropic effect of glyceryl trinitrate was not modified by propranolol, excluding a possible participation of an adrenergic mechanism.

4. Glyceryl trinitrate in large doses failed to modify the positive inotropic effect of calcium chloride.

5. Glyceryl trinitrate in a wide range of doses (0.03–100 μg) had virtually no effect on sino‐atrial node activity.
A METHOD FOR LOCALIZING ATRIAL TYPE B RECEPTORS IN THE DOG
Authors: Fahim M.
Published: June 2007

1. The effect of ectopic stimulation of atria (premature ventricular contraction) on the activity of atrial type B receptors has been studied in dogs.

2. In sixteen open‐chest dogs, discharge from right or left atrial type B receptors (identified by their response to pulmonary artery occlusion) was recorded. Direct stimulation of either atrium produced an increase in the activity of the left atrial but a decrease in the right atrial receptors. The earlier during the ventricular systole that the premature ventricular contraction occurred the more marked was the effect.

3. In a separate series of fourteen closedchest experiments the right atrium was stimulated internally via the external jugular vein. The effects on the activity of the atrial type B receptors were similar to those observed during the open‐chest experiments.

4. It is concluded that in the dog the technique of internal stimulation of the right atrium without opening the chest can be used to distinguish between the right and left atrial type B receptors.
EFFECTS OF HISTAMINE BOLUS INJECTIONS AND CONTINUOUS INFUSIONS ON THE H1‐ AND H2‐RECEPTORS IN THE HINDLIMB VESSELS OF THE RABBIT
Authors: Angus J. A. , Bobik A. , Korner P. I.
Published: June 2007

1. Hindlimb vascular resistance (HVR) was continuously measured after pharmacological block of the autonomic effectors in unanaesthetized rabbits with previously implanted Doppler ultrasonic flowmeters.

2. Histamine bolus injections caused a dose‐related short lived fall in HVR followed by a more sustained rise. The fall was due to H2‐receptor stimulation (blocked by burimamide or metiamide) and the rise to H1‐receptor stimulation (blocked by mepyramine). At the doses of histamine tested the magnitude of the H1‐mediated vasocoiistriction had a larger peak effect than the H2‐mediated vasodilatation.

3. Histamine infusions up to 200 μg kg−1 min−1 did not alter HVR significantly but both increases and decreases in HVR were observed after giving H2‐ or H1‐antagonists, respectively.

4. From the double reciprocal plots of 1/peak HVR change and 1/dose of histamine the magnitude of the predicted H1‐ and H2‐mediated peak HVR effects at large doses were the same. This suggested that the number of H1‐‐ and H2‐receptors were similar in the hindlimb vascular bed, in agreement with the infusion data.
SERUM DOPAMINE‐β‐HYDROXYLASE ACTIVITY IN FASTING MAN
Authors: Mjøs O. D. , Vik‐Mo H. , Gutteberg T. J. , Strømme J. H.
Published: June 2007

1. Dopamine‐β‐hydroxylase (DβH) activity was measured in sera from ten healthy male students after 2 and 3 days fasting which is associated with increased circulating noradrenaline.

2. Circulating DβH remained essentially unchanged throughout the fasting period, although ‘stress parameters’ like plasma glycerol and free fatty acid concentrations were elevated by a factor of about two from first to second and third day of fasting (P<.0.01).

3. Serum DβH activity is not a sensitive index of increased sympathoadrenal activity in fasting man.
CYCLIC 3′5′‐ADENOSINE MONOPHOSPHATE AND CENTRAL CIRCULATORY CONTROL IN CATS AND DOGS
Authors: Delbarre B. , Senon Danielle , Schmitt H.
Published: June 2007

1. Dibutyryl cyclic AMP (Db CAMP, 75–500 μg/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate.

2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure.

3. A number of drugs are known to activate adenylate cyclase‐induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new β2‐adrenoceptor stimulant, NAB 365.

4. Injection into the lateral ventricle of theophylline or Ro 7/ 2956, both inhibitors of phosphodiesterase, similarly increased blood pressure.

5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1‐ or H2‐receptors.

6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective.

7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
THE EFFECT OF PHENOXYBENZAMINE AND SARALASIN ON THE ALTERED RENAL BLOOD FLOW DISTRIBUTION IN BABOONS WITH OBSTRUCTIVE JAUNDICE
Authors: Bomzon L. , Kew M.C. , Rosendorff C.
Published: June 2007

1. Using the 133xenon (133Xe) washout technique, renal cortical perfusion was measured in fourteen baboons before and 1 and 2 weeks after ligation of the common bile duct.

2. In the 1‐week group (seven animals), ligation of the common bile duct caused no significant changes in cortical perfusion in comparison with preligation values.

3. Intrarenal infusion of the angiotensin II blocking agent, saralasin, at a rate of 0.1 mmol/min caused no change in cortical perfusion in the 1‐week group. However, an infusion of 0.3 mmol/min of the α‐adrenoreceptor blocking agent, phenoxybenzamine, caused significant increases in outer cortical flow over control (P < 0.05) and 1‐week values (P < 0.05).

4. In the 2‐week group (seven animals), ligation of the common bile duct caused a non‐significant decrease in outer cortical flow and a significant decrease in the percentage distribution of radioactivity distributed to the outer cortex (P < 0.001).

5. A 0.1 mmol/min intrarenal infusion of saralasin had no effect on outer cortical flow in the 2 week group, but significantly raised the percentage distribution of flow to the outer cortex (P < 0.001) over the 2‐week value. An intrarenal infusion of 0.3 mmol/min phenoxybenzamine in the 2‐week group significantly increased outer cortical flow levels over the 2‐week (P < 0.001) and control (P < 0.05) values. The percentage distribution to the outer cortex was also significantly raised (P < 0.001) over the 2‐week values.

6. There was a significant correlation between the changes in outer cortical blood flow induced by phenoxybenzamine at 1 and 2 weeks and the percentage increases in total serum bilirubin (r= 0.802, P < 0.001) and cholesterol (r= 0.668, P < 0.01) plasma levels over baseline values.

7. These results demonstrate that in baboons with experimentally‐induced obstructive jaundice there is increased activity of the renal a‐adrenoreceptors, and when renal cortical vasoconstruction is present, the renin‐angiotensin system may also be activated and contributes to the cortical vasoconstriction.
THE EFFECT OF TRICYCLIC ANTIDEPRESSANT DRUGS ON THE ISOLATED PERFUSED GUINEA‐PIG HEART*
Authors: Dumovic P. , Trethewie E. R. , Burrows G. D.
Published: June 2007

1. The effects of tricyclic antidepressants were studied on the isolated perfused guinea‐pig heart simultaneously recording myocardial contractile force and cardiac electrogram.

2. Tricyclic antidepressants in a concentration 4 × 10−‐5 mol/1 decreased cardiac contractile force and increased cardiac conduction time.

3. Doxepin had significantly greater negative inotropic effect than nortriptyline, protriptyline, desipramine, amitriptyline and imipramine (P < 0.01).

4. There was no significant difference in the increase in P‐R interval (P>0.5) and QRS width (P > 0.95) between the tricyclic antidepressants.

5. The isolated perfused guinea‐pig heart can be used as a toxicological model for testing and treating cardiac arrhythmias induced by tricyclic antidepressants.
SOTERENOL AND RELATED COMPOUNDS:MOLECULAR MODIFICATIONS AND CHANGES IN SELECTIVITY, AFFINITY AND EFFICACY AT β‐ADRENOCEPTORS IN GUINEA‐PIG ATRIA AND TRACHEA
Authors: Malta E. , Raper C.
Published: June 2007

1. Beta‐adrenoreceptor agonistic and antagonistic actions of soterenol and structurally‐related compounds have been assessed in guinea‐pig atrial and tracheal preparations.

2. Changes in the nature and position of the ring substituents affect the type of response obtained (agonistic and/or antagonistic) and the P1/P2‐adrenoceptor selectivity of the compounds.

3. Changes in amine substitution produce little change in pA2 values, but produce marked alterations in pD2 values and in the selectivity of the drugs as agonists at β1‐and β2‐receptors. These results suggest that differences in efficacy rather than affinity determine the nature of the agonistic effects obtained.
AN IMPROVED RADIOIMMUNOASSAY FOR SERUM GENTAMICIN LEVELS USING 125I‐LABELLED GENTAMICIN
Authors: Casley D. J.
Published: June 2007

1. A radioimmunoassay is described for the measurement of gentamicin in serum or plasma.

2. The assay technique uses a tracer labelled with iodine‐125 rather than tritium, and has advantages over previously reported radioimmunoassay methods (Long‐more et al., 1976; Lewis, Nelson & Elder, 1972) with regard to rapidity, precision and simplicity of preparation of labelled gentamicin.

3. The iodination technique is simple and gives tracer in high yield, at high specific activity, and with complete immunological identity to unlabelled gentamicin.

4. There is a significant correlation between results obtained by this technique and by a microbial assay method but the radioimmunoassay is more rapid, specific and accurate.
ANTIARRHYTHMIC PROPERTIES OF 5‐(3‐TERT‐BUTYLAMINO‐2‐HYDROXY)PROPOXY‐3,4‐DIHYDRO‐CARBOSTYRIL HYDROCHLORIDE (OPC‐ 1085), A NEWLY SYNTHESIZED, POTENT β‐ADRENORECEPTOR ANTAGONIST
Authors: Yabuuchi Y. , Hashimoto K. , Yamashita S. , Uno T. , Shintani S. , Nakagiri N.
Published: June 2007

1. The antiarrhythmic properties of 5–(3‐tert‐butylarnino‐2‐hydroxy)propoxy‐3,4‐dihydrocarbostyril hydrochloride (OPC‐1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs.

2. Although OPC‐1085 was the most potent drug to antagonize adrenaline‐induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain‐induced arrhythmia in pentobarbitone sodium anaesthetized animals.

3. When these compounds were administered intravenously to conscious dogs 24 h after two‐stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation‐induced arrhythmia were reduced while regular sinus beats were simultaneously increased.

4. OPC‐1085 was very effective on aconitine‐induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol.

5. It is concluded that different potencies among these β‐adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; β‐adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so‐called quinidine‐like effects.
MODIFYING EFFECT OF BRADYKININ ON MOTOR ACTIVITY IN THE GUINEA‐PIG GALL BLADDER
Authors: Stasiewicz J. , Szałaj W. , Gabryełewicz A.
Published: June 2007

1. The interaction of bradykinin and cholecystokinin preparations was investigated on the guinea‐pig isolated gall bladder. Bradykinin (1–100 ng/ml) induced dose‐dependent contractile effects which were considerably smaller than those produced by cholecystokinin octapeptide. Bradykinin in a low concentration (1.0 ng/ml) caused a significant increase of the contraction induced by cholecystokinin octapeptide (P < 0.001) and natural cholecystokinin‐pancreozymin (P < 0.01), and also augmented the effects of acetylcholine on this preparation. Therefore these effects are probably not specific for cholecystokinin.
THE EFFECTS OF SODIUM CHLORIDE, UREA AND MANNITOL ON THE PERMEABILITY IN VITRO OF RAT PAPILLARY COLLECTING DUCTS TO THO, 14C‐UREA AND 22Na
Authors: Morgan T. , Rayson Barbara , Haberle D.
Published: June 2007

1. The diffusional permeabilities of collecting duct membranes to THO, 14C‐urea and 22Na+ have been measured at different concentrations of urea, NaCl and mannitol.

2. In the absence of urea in perfusate and bath or in its presence in low concentrations, the diffusional permeability to urea was 2.0 (s. e. m. = 0.15, n=58) μm s−1, compared with 0.87 (s. e. m. = 0.06, n= 29) μm s−1 when 200 mmol/1 urea was present. The permeability of the collecting ducts to THO or Na+ was not affected by the different urea concentrations.

3. High concentrations of sodium chloride increased the diffusional permeability of collecting ducts to water and urea but did not affect the diffusional permeability of the collecting duct to Na+.

4. Mannitol had effects similar to those of sodium chloride.

5. In all media tested there was an increase in THO and urea permeability when supramaximal amounts of antidiuretic hormone were added. The increases in the various media for each substance were similar, despite widely different starting permeabilities.

6. The results suggest that solutes and water move across collecting duct epithelium by several pathways that respond differently to various stimuli.
EFFECTS OF ACETYLCHOLINE ON THE FREQUENCY‐FORCE RELATIONSHIP OF THE ISOLATED DOG ATRIUM
Authors: Chiba S.
Published: June 2007

1. The effects of acetylcholine on the frequency‐force relationship in isolated atria of the dog were investigated in spontaneously beating and electrically paced preparations, which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized donor dog.

2. The developed tension at low frequencies of stimulation was less suppressed than at higher frequencies by an infusion of a relatively low dose level (1–2 μg/min) of acetylcholine. At higher doses (4–10 μg/min), acetylcholine suppressed the tension development at any given frequency.
INHIBITION OF BOVINE CEREBRAL CORTEX PROSTAGLANDIN SYNTHETASE BY PHENOXYBENZAMINE AND CYPROHEPTADINE IN VITRO
Authors: Kandasamy S. B.
Published: June 2007

1. Bovine cerebral cortex (BCC) microsomes were isolated from fresh brain using standard techniques.

2. Two a‐adrenoceptor antagonists (phenoxybenzamine and phentolamine) and two anti‐serotonin compounds (cyproheptadine and cinanserine) were compared with the anti‐inflammatory drugs indomethacin and keptoprofene for inhibition in vitro of prostaglandin (PG) synthetase.

3. Phenoxybenzanine and cyproheptadine inhibited BCC PG synthetase in vitro, but their potency was 1% that of indomethacin and keptoprofene. Phentolamine and cinanserine did not inhibit PG synthetase in concentrations up to ten times the effective concentrations of the other test drugs.

4. It is suggested that the antipyrogenic effect of phenoxybenzamine and cyproheptadine may be due to their inhibitory effect on prostaglandin synthesis.
EVALUATION OF DRUG‐INDUCED RENO‐RENAL VASOMOTOR REFLEX IN THE DOG
Authors: Robie N. W.
Published: June 2007

1. Renal arterial infusions of endogenous vasoactive compounds were administered, and electromagnetic flow probes were used to measure simultaneous ipsilateral and contralateral renal blood flow.

2. The expected ipsilateral renal blood flow changes resulting from infusions of acetylcholine, noradrenaline, angiotension II, bradykinin and PGE2 were observed. There were no transient, phasic or sustained contralateral renal blood flow changes.

3. These results suggest that a previously hypothesized reno‐renal vasomotor reflex communication does not exist. The discrepancies between these present studies and previous ones proposing such a reflex may be due to the methods chosen for measurement of renal blood flow.
A COMPARATIVE STUDY OF ANTIPYRINE PHARMACOKINETICS IN SALIVA AND PLASMA USING A COLOURIMETRIC METHOD OF ANTIPYRINE ANALYSIS
Authors: Harman A. W. , Priestly B. G. , Frewin D. B.
Published: June 2007

1. Half‐life, apparent volume of distribution and metabolic clearance rate for antipyrine elimination were reliably estimated from either plasma or saliva samples.

2. Pharmacokmetic analysis of antipyrine from saliva utilizing a simple and sensitive colourimetric technique provided a convenient method for assessing the activity of hepatic microsomal drugmetabolizing enzymes.
AN IN VIVO INVESTIGATION OF THE NEGATIVE CHRONOTROPIC EFFECT OF CHOLIC ACID IN THE RAT
Authors: Joubert P.
Published: June 2007

1. Experimental obstructive jaundice in the Wistar rat causes a significant decrease in heart rate.

2. Intravenous administration of cholic acid in vivo elicits a dose‐dependent negative chronotropic effect.

3. Atropine or vagotomy significantly reduces, but does not abolish, the negative chronotropic effect of cholic acid.

4. Ganglion blockade and decerebration diminishes the negative chronotropic effect of cholic acid, but to a lesser extent than atropine or vagotomy.

5. Sympathetic depletion by reserpine slightly potentiates the response to cholic acid.

6. The effect of cholic acid injected cranially into the common carotid artery is less than when administered into the jugular vein.

7. The haemolysis caused by cholic acid does not appear to be involved in the negative chronotropic effect.

8. It is concluded that cholic acid causes both a direct as well as a vagally mediated negative chronotropic effect in the Wistar rat.
EFFECTS OF MONOSODIUM GLUTAMATE‐INDUCED OBESITY IN MICE ON CARBOHYDRATE METABOLISM IN INSULIN SECRETION
Authors: Cameron D. P. , Cutbush L. , Opat F.
Published: June 2007

1. The syndrome of obesity induced by neonatal injection of monosodium glutamate (MSG) has been further studied in mice. In confirmation of previous studies stunting and decreased pituitary and gonadal weights were observed.

2. After weaning food intake was consistendy less in MSG‐treated than control mice. Body lipid stores were significantly elevated in MSG‐treated mice by 2 weeks of age and increased progressively up to 4 months.

3. Plasma glucose was comparable between MSG‐treated and control mice in the fed state whereas after an overnight fast MSG‐treated mice exhibited relative hypo‐glycaemia.

4. Obese MSG‐treated mice did not exhibit resistance to exogenous insulin and disposed of an intravenous glucose load more rapidly than control mice.

5. Hyperinsulinaemia was present inconsistently in both fed and fasted mice and in response to administered glucose.

6. Neonatal administration of MSG provides a useful additional model for studying the role of the hypothalamus in obesity.
GAS CHROMATOGRAPHIC MEASUREMENT OF PLASMA LEVELS OF SODIUM VALPROATE: TENTATIVE THERAPEUTIC RANGE OF A NEW ANTICONVULSANT IN THE TREATMENT OF REFRACTORY EPILEPTICS
Authors: Vajda F. J. E. , Drummer O. H. , Morris P. M. , McNeil J. J. , Bladin P. F.
Published: June 2007

1. A precise and rapid gas chromatographic method for the measurement of plasma sodium valproate concentrations is presented.

2. The extraction is a single step procedure, and is reproducible and linear throughout the concentration range encountered.

3. Clinical evaluation of the drug is presented in eighteen epileptics on the basis of the percentage of days on which subjects had seizures before and after sodium valproate therapy.

4. A tentative therapeutic range for sodium valproate is presented on the basis of plasma levels and therapeutic effect.
INTERACTIONS BETWEEN PRAZOSIN, CLONIDINE AND DIRECT VASODILATORS IN THE ANAESTHETIZED RAT
Authors: Oates H. F. , Stoker L. M. , Stokes G. S.
Published: June 2007

1. Prazosin, clonidine, hydrallazine and diazoxide were administered intravenously, alone or in various combinations, to anaesthetized rats.

2. Prazosin and clonidine were equipotent. Their combined hypotensive effects in no instance exceeded the maximum effect attainable with either agent alone. The hypotensive effects of hydrallazine or diazoxide were, in contrast, additive to those of either prazosin or clonidine.

3. Pressor responses to clonidine were antagonized by prazosin. Prazosin may prove useful in hypertensive crises provoked by clonidine.
MODIFICATION OF BRAIN BIOGENIC AMINES BY METS‐ENKEPHALIN AMIDE IN THE RAT
Authors: Laska F. J. , Fennessy M. R.
Published: June 2007

1.Gross changes in behaviour and whole brain levels of noradrenaline, dopamine, serotonin and 5‐hydroxyindoleacetic acid were examined in rats for 3 min following intracerebral injections of met5‐enkephalin amide or morphine.

2. Both the enkephalin and morphine depressed respiration and induced a cataleptic‐like state, but only the enkephalin produced wet‐shake responses.

3. All doses of met5 enkephalin amide (150, 200 and 600μg) and morphine (134 and 200 /Kg) increased the brain levels of 5‐hydroxyindoleacetic acid, whereas only the large doses modified the levels of noradrenaline and serotonin.

4. The similarity of the effects of these two compounds indicates that morphine may act through an enkephalin‐like mechanism.
A STUDY OF THE INTERACTION OF PRACTOLOL WITH ACETYLCHOLINE, HISTAMINE, SEROTONIN AND BRADYKININ IN THE GUINEA‐PIG, AND WITH BEAN‐SPROUT JUICE IN THE MOUSE
Authors: Chang L. C. T. , Wong J. C. Y. , Roberts M. B.
Published: June 2007

1. The interactions of practolol with acetylcholine, histamine, serotonin and bradykinin were studied on the trachea and lung of the guinea‐pig, an animal whose sensitivity to bronchoactive endogens is known to be similar to that of human asthmatic bronchi.

2. Practolol, like propranolol, potentiated the action of the first three agonists mentioned above, but, unlike propranolol, it did not potentiate the bronchospastic effect of bradykinin.

3. Practolol, in fact, antagonized the action of bradykinin, but this effect was unlike that produced by nonsteroidal anti‐inflammatory drugs.

4. The possibility that β‐adrenoreceptor antagonists might show adverse interactions with certain foodstuffs was investigated, and is discussed.

5. It is suggested that the feasibility of the continued use of practolol (or the newer cardioselective β‐blockers) in asthmatics necessarily depends on the type of allergic reaction involved, and so it is not possible to generalize. Any drug or food that might cause a bronchospastic effect synergistically in the presence of a β‐adrenoreceptor antagonist, even a cardioselective one, should be regarded with suspicion.
ASSESSMENT OF THE CORONARY VASODILATOR ACTION OF SK&F 24260 IN THE DOG
Authors: Narimatsu A. , Satoh K. , Taira N.
Published: June 2007

1. The effects of SK&F 24260 administered intravenously or intraduodenally on the coronary sinus outflow, coronary arteriovenous oxygen difference (A‐V O2), myocardial oxygen consumption (MVO2), systemic blood pressure, heart rate and atrioventricular (AV) conduction time were examined in open‐chest dogs.

2. SK&F 24260 in doses of 0.3–10 μg/kg, i.v., caused a dose‐dependent increase in coronary sinus outflow, but the increase was smaller with 30 μg/kg, i.v., than with 10μg/kg, i.v.

3. SK&F 24260 (0.3–30μg/kg, i.v.) decreased A‐V O2 and MVO2 in a dose‐dependent manner.

4. SK& F 24260 (0.3–30μg/kg, i.v.) decreased systemic blood pressure and heart rate, and increased AV conduction time.

5. Intraduodenal administration of SK&F 24260 (1 mg/kg) produced almost the same effects on coronary sinus outflow, A‐V O2, MVO2, systemic blood pressure, heart rate and AV conduction time as did the intravenous administration of the compound (10μg/kg).

6. The property of SK&F 24260 to increase the coronary blood flow and to moderately decrease MVO2, systemic blood pressure and heart rate indicates that this agent is a potential antianginal drug.
WARFARIN SODIUM: STEADY‐STATE PLASMA LEVELS AND PATIENT AGE
Authors: Hotraphinyo Kanda , Triggs E. J. , Maybloom B. , Maclaine‐Cross A.
Published: June 2007

1. Steady‐state plasma levels of warfarin were measured in thirty‐nine ambulatory patients attending a haematology clinic.

2. Plasma concentrations, plasma clearance, and prothrombin ratio showed no significant differences when patients below 65 years of age were compared with those above 65 years. The mean daily maintenance dose of warfarin required was marginally greater for the younger patients but the difference was not statistically significant (P= 0.10).

3. A significant relationship was found between the daily maintenance dose of warfarin required by all patients and their mean steady‐state plasma level (r = 0.5667, P< 0.001).

4. For one elderly hospitalized patient it was apparent that there was a marked depression of the vitamin K‐dependent clotting factor synthesis by warfarin which was associated with a hypoprothrombinaemic response.
STUDY OF THE IN VITRO PHARMACOLOGICAL EFFECTS OF GRAM‐NEGATIVE ENDOTOXINS IN PARALLEL WITH TOXICITY TESTING IN NORMAL ADULT GUINEA‐PIGS
Authors: McLean A.J.
Published: June 2007

1. Lipopolysaccharide extracts (endotoxins), obtained from E. coli organisms by heat, trichloracetic or phenol‐water extraction, were shown to be toxic to normal adult guinea‐pigs.

2. These agents did not produce any detectable changes in the contractile properties of a range of standard guinea‐pig smooth muscle‐containing tissues; however, the heat‐extract of E. coli cells caused relaxation of isolated preparations of guinea‐pig ileum. This effect was not demonstrated by the trichloracetic acid or phenol‐water extracts.

3. These agents did not produce any changes in the electrical properties of the smooth muscle membranes of guinea‐pig vas deferens studied by microelectrode techniques, or in the properties of rabbit and sheep mesenteric portal veins studied using sucrose gap techniques.

4. There were no effects observed when isolated preparations of guinea‐pig atrium were exposed to endotoxins.

5. No effects of endotoxin were detected on sympathetic adrenergic neuromuscular transmission in guinea‐pig vas deferens and portal vein, and there was no change in the responsiveness of the portal veins to noradrenaline.

6. Endotoxin did not produce any changes in the responses of isolated preparations of ileum and atrium to histamine.

7. It is concluded that the toxic effects of endotoxin in guinea‐pigs are likely to be independent of direct pharmacological effects on smooth and cardiac muscle or neuromuscular transmission. It is suggested that the toxic effects do not involve interactions with receptor mechanisms for a‐adrenoceptor agonists or histamine in this species.
THE EFFECT OF HEART RATE ON MYOCARDIAL OUABAIN UPTAKE AND ON THE SUSCEPTIBILITY TO OUABAIN CARDIOTOXICITY IN THE DOG
Authors: Lloyd Brian L. , Taylor Roger R.
Published: June 2007

1. Tissue ouabain concentrations were estimated 30 min after intravenous 3H‐ouabain administration to sedated dogs, the heart rates of which were adjusted to range between 50 and 200 beats/min. Significant correlations were present between heart rate and ouabain content in left ventricle (r=0.93, P< 0.001), in right ventricle and left atrium. In contrast, no significant correlations were present between heart rate and ouabain content in liver, in renal cortex, skeletal muscle or plasma.

2. To determine the functional effect of the greater myocardial ouabain uptake associated with higher heart rate, anaesthetized open‐chest dogs were studied. The heart rates of two groups were controlled at 199 ± 9 (s.d.) beats/min and 90 ± 14 beats/min during ouabain administration, and 30 min later, at a common heart rate, acetyl strophanthidin tolerance tests were performed.

3. Acetyl strophanthidin infusion induced ventricular tachycardia significantly earlier, after a correspondingly lower dose in the fast heart rate group (P<0.01). Significant inverse correlations were present between the concentrations of ouabain in both left and right ventricular muscle and the duration of acetyl strophanthidin infusion.

4. The results indicate that higher heart rate is associated with greater myocardial ouabain uptake and that this ouabain is functionally active.
RENOVASCULAR HYPERSENSITIVITY TO NORADRENALINE IN DIETARY‐INDUCED HYPERCHOLESTEROLAEMIA IN BABOONS
Authors: Bomzon L. , Kew M. C. , Rosendorff C.
Published: June 2007

1. Using the xenon‐133 washout technique, the renovascular response to intra‐renal infusions of 3 and 30 μ/min noradrenaline in four baboons with dietary‐induced hypercholesterolaemia was measured.

2. The degree of reduction in cortical blood flow rate during an intrarenal infusion of 3μmol/min. noradrenaline in the four hypercholesterolaemic baboons was not significantly different from that in normocholesterolaemic baboons. However, a significant difference in the degree of reduction in cortical blood flow rate was found with the 30μmol/min noradrenaline infusion (P < 0.05).

3. The mean arterial blood pressure of the four animals was significantly higher (P< 0.001) than the mean blood pressure in baboons used in this laboratory for other experiments.

4. These results have shown that baboons with dietary‐induced hypercholesterolaemia have an enhanced renovascular sensitivity to exogenous noradrenaline. However, the possibility that this enhanced sensitivity was due to the associated hypertension cannot be excluded.
CLINICAL DOSE‐RESPONSE STUDIES WITH GUANFACINE (BS 100‐141), A NEW ANTIHYPERTENSIVE AGENT
Authors: MacCarthy P. , Isaac P. , Frost G. , Freeman A. , Stokes G.
Published: June 2007

1. Blood pressure, pulse rate, salivary flow and the degree of sedation were recorded at intervals following oral administration of single doses of guanfacine, a clonidine‐like agent, to hypertensive patients.

2. Between 2 and 10 h after administration of guanfacine (3 mg or S mg), there were dose‐related decreases in lying and standing blood pressure, together with significant reductions in pulse rate and salivary flow.

3. It is concluded that guanfacine lowers blood pressure in hypertensive patients and is probably suitable for twice daily administration, but produces xerostomia and sedation.
THE EFFECTS OF ADRENALECTOMY ON THE CARDIOVASCULAR RESPONSES TO A'‐TETRAHYDROCANNABINOL IN RATS
Authors: Li D. M. F. , Chung J. P. C.
Published: June 2007

1. In urethane anaesthetized sham‐operated rats, intravenous administration of Δ1‐THC (1 mg/kg) caused an immediate and prolonged fall in blood pressure, with a concomitant reduction in pulse rate.

2. In rats which had been adrenalectomized 24 h previously, Δ1‐THC (1 mg/kg, i.v.) also caused a depressor response, but it was significantly shorter in duration than that observed in sham‐operated animals. The durations of the cardiac slowing effect were similar in both groups of rats.

3. Hydrocortisone pretreatment (25 μg/kg> i‐v), given 45 min before Δ1‐THC, restored the duration of the depressor response to Δ1‐THC in adrenalectomized rats, but it did not have any effect on the bradycardia induced by Δ‐THC.

4. Hydrocortisone did not produce any significant effect on the hypotensive action of Δ1‐THC in sham‐operated rats, but the cardiac slowing effect was markedly potentiated.

5. These results suggest a lack of correlation between the hypotensive and cardiac slowing actions of the drug and that a certein level of adrenal steroids is necessary for the maintenance of the depressor response to Δ1‐THC.
THE EFFECT OF VARIOUS DRUGS ON ADENOSINE TRIPHOSPHATE CONTENT AND HISTAMINE RELEASE FROM RAT PERITONEAL CELL SUSPENSIONS RICH IN MAST CELLS
Authors: Day R. O. , Wade D.N.
Published: June 2007

1. Iopanoic acid and iophenoxic acid were potent inhibitors of compound 48/80‐induced histamine release from rat peritoneal cell suspensions rich in mast cells and caused a parallel dose‐related reduction in ATP content of these cells.

2. Lignocaine was less potent and ouabain and probenecid were ineffective in inhibiting histamine release and reducing cellular ATP content.

3. Various drugs can inhibit 48/80‐induced histamine release from rat peritoneal cells and this activity may result from depletion of cellular ATP. It is apparent that little structural specificity is required for activity in this cell system.
PERIPHERAL MUSCLE EFFECTS OF LEVODOPA IN THE ANAESTHETIZED CAT
Authors: Bowman W. C. , Nott M. W.
Published: June 2007

1. Levodopa, dopamine, noradrenaline and adrenaline (in increasing order of potency) depressed the tension and degree of fusion of incomplete tetanic contractions of the slow‐contracting soleus muscle in chloralose‐anaesthetized cats.

2. The effects of all compounds were antagonized by propranolol (50‐20 μg/kg), but not practolol (1.0‐5.0 mg/kg). This indicates that effects are mediated by β2‐adrenoceptor stimulation.

3. The effect of levodopa, but not of the catecholamines, was antagonized by prior administration of the dopa decarboxylase inhibitor benserazide. This indicates that levodopa itself is inactive, whereas its decarboxylated metabolites are active.

4. The depressant action of β‐adrenoceptor agonists on incomplete tetanic contractions of the cat soleus muscle, which are exerted directly on the muscle fibres, is a model for effects exerted on slow‐contracting units of human muscles; the latter effects probably underlie the tremor observed after β‐adrenoceptor agonist administration.

5. These results therefore suggest that levodopa, via its decarboxylated metabolites, dopamine, noradrenaline and adrenaline, may produce or exacerbate tremor in man. Thus in Parkinsonian patients, any centrally induced relief of tremor that levodopa may produce may be masked by tremorogenic effects of such metabolites exerted in the periphery.
ACTION OF OCTOPAMINE AGONISTS AND STEREO ISOMERS AT A SPECIFIC OCTOPAMINE RECEPTOR
Authors: Dougan D. F. H. , Wade D. N.
Published: June 2007

1. (±)‐Octopamine, (±)‐N‐methyl octopamine and (‐)‐α‐methyl octopamine increase the amplitude of contraction of the spontaneously beating ventricle of the mollusc Tapes watlingi through action on a specific octopamine receptor.

2. Unlike the excitatory responses to dopamine, noradrenaline or serotonin, the excitatory response of the ventricle to agonists at the octopamine receptor is attenuated by metoclopramide.

3. Compounds with potent agonist activity at the octopamine receptor all have a single phenolic hydroxyl in the para position of the benzene ring and a β‐hydroxyl group in the phenethylamine side chain. O‐Methylation of the para phenolic group or removal of the /3‐hydroxyl group results in complete loss of agonist activity. Bulky substituents but not a single methyl group on the amino groups impair agonist activity.

4. The octopamine receptor is stereo‐selective, (‐)‐octopamine is more than twenty times more active than (+)‐octopamine.

5. The weak octopamine‐like activity of (‐)‐N‐methyl and a‐methyl meta octopamine indicates that the stereo‐selective receptor has a relative rather than an absolute requirement for a single phenolic hydroxyl in the para position of the benzene ring.

6. These data indicate the presence of a specific, stereo‐selective receptor for octopamine in the ventricle of the mollusc Tapes watlingi.

7. The stereo‐selectivity and structural specificity of the octopamine receptor differentiates it from receptors for dopamine and serotonin also present in the ventricle.
BRAIN BIOGENIC AMINES AND INTRAVENOUS SELF‐ADMINSTRATION OF COCAINE IN RATS
Authors: Ross J. W. , Laska F. J. , Fennessy M. R.
Published: June 2007

1. The possible involvement of noradrenaline, dopamine, serotonin and 5‐hydroxyindoleacetic acid in the behavioural reinforcement produced by intravenous cocaine has been investigated.

2. Rats, in Skinner boxes, were allowed to self‐administer cocaine through a chronically implanted jugular vein cannula. A consistent response rate in the order of one self‐administration every 10 min was observed with a dose of 3.0 mg/kg cocaine hydrochloride per response.

3. Another group of rats was cannulated and injected with a range of one to six such doses of cocaine at 10 min intervals on the basis of the responding rate, established by rats in the Skinner box. At times of 2, 5 and 8 min after each dose of cocaine, the rats were decapitated and brain concentrations of noradrenaline, dopamine, serotonin and 5‐hydroxyindoleacetic acid were determined.

4. The brain levels of noradrenaline exhibited a cyclic pattern of rise and fall after each dose of cocaine, which corresponded in its time base with the time interval between responses established by the rats in the Skinner box.