bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inhibition of renin secretion in the isolated rat kidney by clonidine hydrochloride (Catapres)
Authors: Vandongen R. , Greenwood Dianne M. 
Published: June 2007

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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

SUMMARY1. 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.