bluuebunny/crossref_metadata_2025_split huggingface dataset:
CARDIOVASCULAR AND RESPIRATORY EFFECTS OF CAROTID BODY STIMULATION IN THE MONKEY
Authors: Daly M. de Burgh , Korner P. I. , Angell‐James Jennifer E. , Oliver Judith A. 
Published: June 2007

SUMMARY1. The carotid bodies were stimulated in the anaesthetized pig‐tailed macaque monkey (M. nemestrina) using (i) brief injections of cyanide or CO2‐equilibrated bicarbonate solution into a common carotid artery, and (ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations.2. In spontaneously breathing animals brief stimuli (thirty‐one tests, seven monkeys) consistently increased pulmonary ventilation (by 97 ± 10% of control), slowed the heart rate (the pulse interval increasing by 36 ± 7.5%), and increased femoral vascular resistance (by 44 ± 7%).3. More sustained chemoreceptor stimulation with asphyxial blood (nineteen tests, five monkeys) increased ventilation by 187 ± 23%, but transient bradycardia occurred in only eight of nineteen tests and was followed by tachycardia; in the remaining tests, only tachycardia occurred. After 20–40 s, the pulse interval was 5.8 ± 0.9% below the control level. Femoral vascular resistance either increased (five tests, two animals) or decreased (six tests, two animals).4. Evidence is presented that in the monkey the autonomic effects of chemoreceptor stimulation are influenced by the level of respiratory activity with bradycardia and vasoconstriction occurring when the level is low, and tachycardia and vasodilatation when it is high.5. The interaction of autonomic responses resulting from carotid body stimulation and from mechanisms initiated by the concomitant hyperventilation are qualitatively similar in the monkey and in subprimate species, although there may be quantitative differences such as would account for the species differences to disturbances produced, for instance, by arterial hypoxia.
COMPARATIVE STUDY OF CHRONOTROPIC AND INOTROPIC RESPONSES TO 5‐(1‐HYDROXY‐2‐ISOPROPYLAMINOBUTYL)‐8‐ HYDROXYCARBOSTYRIL HYDROCHLORIDE HEMIHYDRADE (PROCATEROL), SALBUTAMOL, NORADRENALINE AND ISOPRENALINE IN THE DOG HEART
Authors: Chiba S. 
Published: June 2007

SUMMARY1. The cardiac chronotropic and inotropic responses to 5‐(1‐hydroxy‐2‐iso‐propylaminobutyl)‐8‐hydroxycarbostyril hydrochloride hemihydrade (procaterol) and salbutamol have been compared to noradrenaline and isoprenaline in isolated blood‐perfused canine atrial and ventricular preparations.2. All four compounds induced dose‐related positive chronotropic and inotropic effects, but different individual response patterns were observed.3. Procaterol and salbutamol were partial agonists compared to noradrenaline and isoprenaline for causing chronotropic and inotropic responses. The order of efficacy for the adrenoceptors mediating both chronotropic and inotropic responses was isoprenaline, noradrenaline, salbutamol and procaterol. The slopes of the salbutamol dose‐response curves were flatter than those for isoprenaline and noradrenaline; the slopes of the procaterol dose‐response curves were flatter than those for salbutamol.4. Because of these differences, the order of activity depended upon the level of response chosen for the comparison. When doses producing small chronotropic and inotropic responses were compared, the order of activity was isoprenaline, noradrenaline, procaterol and salbutamol; whereas with doses producing large responses the order was isoprenaline, noradrenaline, salbutamol and procaterol.5. Procaterol was longer acting than salbutamol, and salbutamol was longer acting than noradrenaline.
FREE CHOLINE CONCENTRATION AND CEPHALIN‐N‐METHYLTRANSFERASE ACTIVITY IN THE MATERNAL AND FOETAL LIVER AND PLACENTA OF PREGNANT RATS
Authors: Gwee M. C. E. , Sim M. K. 
Published: June 2007

SUMMARY1. The concentration of free choline and cephalin‐N‐methyltransferase activity of the maternal and foetal liver and placenta of rats in late pregnancy were determined.2. The choline concentration of the liver fell from a mean of 130 nmol/g in adult non‐pregnant rats to 38 nmol/g in late pregnancy.3. The choline concentrations of the foetal liver and placenta had mean values of 135 and 442 nmol/g, respectively.4. There was a significant 24% increase in the cephalin‐N‐methyltransferase activity of the liver during pregnancy. The enzyme activity in the foetal liver was 7% that of the maternal liver, and activity was undetectable in the placenta.5. The results suggest that, during pregnancy, the maternal liver supplies choline to the placenta and foetal organs, like the liver, and that the demand for maternal liver choline far exceeds the supply available.
CARDIAC INTERACTION BETWEEN PARATHYROID HORMONE, β‐ADRENOCEPTOR AGENTS, AND VERAPAMIL IN THE GUINEA‐PIG IN VITRO
Authors: Lhoste F. , Drüeke T. , Larno Suzanne , Boissier J. R. 
Published: June 2007

SUMMARY1. The present study examines the modulation, by parathyroid hormone, of the changes in myocardial contractile force induced by isoprenaline, propranolol isomers, verapamil, and nadolol.2. Cardiac contractile force was estimated by the use of guinea‐pig isolated auricles. Synthetic bovine 1‐34 parathyroid hormone (sPTH) alone did not modify contractile force; conversely, sPTH significantly inhibited the cardiode‐pressant effect of l‐propranolol, d, l‐propranolol, d‐propranolol, and verapamil. These results suggested an action of sPTH independent of β‐adrenoceptors. Against an hypothesis of a single, non‐β‐adrenoceptor mechanism of sPTH action on the heart are the following observations: (i) when β‐adrenoceptors were blocked with nadolol, sPTH no longer inhibited the cardiodepressant effect of propranolol, (ii) sPTH reduced the inotropic effects of isoprenaline. Our conclusion, therefore, is that sPTH probably affects cardiac muscle contraction by at least two mechanisms, one of which involves non‐adrenergic transmembrane calcium flux and the second β‐adrenoceptors.3. When these studies were extended into the clinical pharmacological field, it was found that plasma ultrafiltrates from severely hyperparathyroid patients in chronic renal failure inhibited like sPTH the cardiodepressant action of propranolol. No such effect was seen with ultrafiltrates from parathyroidectomized patients. Accordingly, high PTH levels may inhibit the action of cardiotropic drugs administered to hyperparathyroid patients, and may be one factor in the cardiomyopathy seen in such patients.
FLUID AND SALT INTAKE DURING THE DEVELOPMENT OF RENAL HYPERTENSION IN RATS
Authors: Schömig A. , Szokol M. , Dietz R. , Lüth J. B. , Gross F. 
Published: June 2007

SUMMARY1. In Sprague‐Dawley rats, two‐kidney, one‐clip renal hypertension was induced, and the drinking behaviour as well as total fluid and sodium intake were studied before and for 16 days after the operation.2. When water alone was offered as drinking fluid, the blood pressure reached values that were by about 20 mmHg higher than those in the rats which had free choice of drinking water or 2% saline.3. In those rats which had water and 2% saline to drink, the total sodium and fluid intake rose transiently for three days, as compared with that of the sham‐operated controls, and increased steeply starting from the 7th and 10th day, respectively. When a tighter stenosis of the renal artery was induced, the pressure rose more rapidly, and the total fluid and sodium intake increased continuously after the operation until the end of the experiment.4. A positive correlation was demonstrable between the height of blood pressure and the total daily intake of fluid and sodium, respectively.5. The relation between the total daily fluid and the total daily sodium intake followed a straight regression line.6. The hypertensive rats which had a high total sodium intake responded to the withdrawal of the 2% saline solution, within 2 days, with increased water intake, decreased food intake, and loss of body weight, whereas the blood pressure remained high.7. In the two‐kidney, one‐clip hypertension, no ‘critical level of blood pressure’ can be defined, beyond which the contralateral kidney starts to lose sodium.
HAEMODYNAMIC INTERACTIONS BETWEEN α‐ AND β‐ADRENO‐CEPTOR ANTAGONISTS IN CONSCIOUS OR ANAESTHETIZED RATS
Authors: Oates Helen F. , Stoker Lynette M. 
Published: June 2007

SUMMARY1. The α‐adrenoceptor antagonist, phentolamine, was administered intravenously, to conscious or anaesthetized rats, before or after the β‐adrenoceptor antagonist, propranolol.2. The bradycardia which followed the combined administration of propranolol and phentolamine exceeded that induced by propranolol alone, yet the hypotensive effect of phentolamine was attenuated by propranolol.3. The results are compatible with the concept that a significant part of the hypotensive effect of phentolamine is mediated by stimulation of vascular β‐adrenoceptors.
SERUM DOPAMINE β‐HYDROXYLASE (DβH) LEVELS DURING TILTING IN PATIENTS WITH SPINAL CORD INJURIES*
Authors: Ohry A. , Rabinowitz R. , Korczyn A. D. 
Published: June 2007

SUMMARYThe activity of dopamine‐β‐hydroxylase (DβH) in the serum was measured in patients with quadriplegia and in healthy subjects. We assume that the plasma DβH levels reflect sympathetic tone. Quadriplegics had significantly lower DβH levels at rest. After head‐up tilting a significant decrease in DβH levels occurred in patients with spinal cord injury suggesting failure of the sympathetic nervous system. However, a considerable overlap exists between normals and quadriplegics, making this test of limited value in the assessment of autonomic function in individual subjects.
CAPTOPRIL IN MILD AND SEVERE HYPERTENSION
Authors: Walter N. M. A. , Whitworth Judith A. , Kincaid‐Smith Priscilla 
Published: June 2007

SUMMARY1. Ten patients with mild essential hypertension and nine with severe treatment‐resistant hypertension were treated with captopril.2. Supine blood pressure was controlled in 9/10 patients with mild hypertension (four with addition of propranolol).3. There was no correlation between blood pressure fall and initial plasma renin concentration in patients with mild hypertension.4. Captopril (plus diuretic and/or propranolol) controlled only 4/9 patients with severe hypertension.5. Four patients developed reversible dysgeusia and one a skin rash.
AGONIST INTERACTION AND DECENTRALIZATION SUPERSENSITIVITY IN THE NICTITATING MEMBRANE OF THE CAT
Authors: Shavit S. , Korczyn A. D. 
Published: June 2007

SUMMARY1. The responses to individual drugs and to combinations of two drugs were studied in normal and chronically decentralized nictitating membranes (NM) of cats. Noradrenaline (NA), acetylcholine (ACh), serotonin (5HT) and potassium chloride (KC1) and the combinations NA + ACh, NA + 5HT, NA + KC1 and ACh + 5HT were injected intra‐arterially towards the smooth muscle.2. Chronic decentralization resulted in supersensitivity to each of these agonists when injected alone.3. The contraction of the normal NM caused by each drug combination showed potentiation in comparison to the sum of contractions caused by the same drugs given separately. The same drug combinations showed no potentiation in decentralized muscle.4. Decentralization supersensitivity and potentiation due to agonist interactions in normal preparations may share a common mechanism. The involvement of calcium in this phenomenon is discussed.
EFFECTS OF HISTAMINE H1 AND H2‐RECEPTOR ANTAGONISTS IN THE CRANIAL CIRCULATION OF THE MONKEY
Authors: Lord G. D. A. , Mylecharane E. J. , Duckworth J. W. , Lance J. W. 
Published: June 2007

SUMMARY1. The effects of the histamine H2‐receptor antagonists, metiamide and cimetidine, and the Hi‐receptor antagonist, mepyramine, on cranial vasodilator and systemic vasodepressor responses to histamine have been investigated in anaesthetized monkeys.2. In monkeys treated with successively increasing intravenous doses of 0.25, 1 and 5 mg/kg of metiamide, histamine‐induced decreases in external and internal carotid vascular resistances were blocked, but systemic vasodepressor responses were not affected.3. In monkeys treated similarly with 0.25, 1 and 5 mg/kg of cimetidine, external carotid vascular responses to histamine were blocked, but internal carotid vascular and systemic vasodepressor responses to histamine were not affected.4. In monkeys treated similarly with 0.5, 2 and 10 mg/kg of mepyramine, histamine‐induced systemic vasodepressor responses were blocked, but responses in the external and internal carotid circulations were unaffected.5. In those monkeys treated with mepyramine after initial H2‐receptor antagonist treatment, blockade of internal, but not external, carotid vascular responses to histamine appeared to be increased.6. The histamine antagonists did not affect cranial vascular responses to noradrenaline, serotonin, prostaglandin E1 or bradykinin. Metiamide and cimetidine had no appreciable direct effects, but mepyramine produced short‐lasting changes (vasodilatation followed by vasoconstriction).7. These results indicate that H2‐receptors are involved in the external and internal carotid vascular effects of histamine. Hi‐Receptors do not appear to contribute to the external carotid vasodilator response to histamine, but their possible involvement in the internal carotid response cannot be excluded.
A STUDY OF THE THERMOGENIC EFFECT OF ETHANOL IN THE HYPOTHERMIC RAT
Authors: James M. F. M. , van den Berg A. A. , French N. A. , White J. F. 
Published: June 2007

SUMMARY1. The hypothesis that ethanol may exert a thermogenic effect in cold environments was studied by infusing ethanol, dextrose or saline into hypothermic rats and observing the rate of rewarming in each group.2. No difference was found in the rate of heat gain in any of the three groups.
AN ANALYSIS OF THE RESPIRATORY STIMULANT EFFECT OF PHYSOSTIGMINE AND NEOSTIGMINE DM THE CONSCIOUS RABBIT
Authors: Weinstock M. , Roll D. , Zilberman Y. 
Published: June 2007

SUMMARY1. The effects of physostigmine and neostigmine, given by continuous intravenous infusion, were studied on respiration in conscious rabbits.2. Physostigmine (5 μg/kg per min) significantly increased respiration rate, decreased arterial PaCO2 from 25.4 ± 0.9 to 19.8 ± 1.5 mmHg, increased PaCO2 from 100.3 ± 1.9 to 108 ± 3.0 and pH from 7.42 ± 0.01 to 7.46 ± 0.01 within 30 min of its infusion.3. Neostigmine (2.5 μg/kg per min) also decreased PaCO2 and increased PaO2 significantly, but caused a concomitant lactic acidosis, which was associated with the increased muscular activity and fasciculations.4. The respiratory stimulant effect of neostigmine, but not that of physostigmine, was abolished by hexamethonium 2 × (1.5 mg/kg). Atropine methyl nitrate (1 mg/kg) failed to influence the respiratory stimulant effect of physostigmine, but hyoscine (10 mg/kg) blocked it completely.5. It is suggested that augmentation of respiratory activity by neostigmine is mediated via peripheral nicotinic receptors in the carotid and aortic bodies. This may occur either through the accumulation of acetylcholine or of H+ ions from raised blood lactic acid.6. It is further suggested that physostigmine stimulates respiration by raising the concentration of acetylcholine in the central nervous system which, in turn, activates muscarinic receptors.
SOURCES OF CALCIUM FOR CONTRACTION OF GUINEA‐PIG ISOLATED TRACHEAL SMOOTH MUSCLE
Authors: Creese B. R. , Denborough M. A. 
Published: June 2007

SUMMARY1. Contractile responses of guinea‐pig tracheal smooth muscle to KC1, histamine, acetylcholine and prostaglandins were reduced after the removal of extracellular Ca2+ from the bathing medium.2. KCl‐induced contractures were more dependent on extracellular Ca2+ than acetylcholine‐induced responses, but less so than histamine‐induced contractures.3. Responses to high concentrations of contractile agents were less dependent on extracellular Ca2+ than those to low concentrations.4. Repeated additions of histamine or acetylcholine in the absence of extracellular Ca2+ resulted in progressively smaller contractile responses.5. Treatment of tracheal muscle with EGTA considerably inhibited drug‐induced contractures and abolished the response to KCl.6. It is concluded that contractile responses of guinea‐pig tracheal smooth muscle involve both the influx of Ca2+ from the extracellular space and release of Ca2+ from intracellular sites. The relative contributions of these two Ca2+ sources depend on both the contractile agent and its concentration. Intracellular Ca2+ stores may be depleted by treatment with EGTA, or by repeated drug additions in the absence of extracellular calcium.
EFFECT OF CAPTOPRIL ON BLOOD PRESSURE AND BRADYKININ VASODEPRESSOR RESPONSES AFTER NEPHRECTOMY AND SUPPRESSION OF PROSTAGLANDIN SYNTHESIS IN ANAESTHETIZED RATS
Authors: Vandongen R. , Barden A. , Tunney A. , Mahoney D. 
Published: June 2007

SUMMARY1. Captopril markedly potentiated the vasodepressor responses to bradykinin. Neither the magnitude nor duration of the blood pressure fall were altered by bilateral nephrectomy or treatment with indomethacin which suppressed urinary excretion of the prostacyclin metabolite 6‐Keto PGF1a.2. It is concluded that in the anaesthetized rat augmentation of the bradykinin depressor responses by captopril occurs independently of endogenous prostaglandin synthesis.
PRODUCTION OF ANGIOTENSIN CONVERTING ENZYME BY CULTURED BOVINE ENDOTHELIAL CELLS
Authors: Mendelsohn F. A. O. , Kachel C. 
Published: June 2007

SUMMARY1. Endothelial cells from bovine aortae were grown to confluence in tissue culture. The cells were subcultured and angiotensin converting enzyme (ACE) production was measured while the cells were maintained in serum‐free medium for 4 days.2. During this period, there was a ten‐fold increase in ACE concentration in the medium whereas the cellular content of the enzyme remained constant at approximately 23% of the total enzyme produced. Cycloheximide (1 μmol/1) blocked production of ACE.3. The enzyme liberated into the medium closely resembled ACE in the following respects: it cleaved the dipeptide histidyl‐leucine from a synthetic tripeptide substrate, was markedly Cl‐ activated and inhibited by EDTA(1 mmol/l), SQ 14225 (1 μmol/1) or SQ 20881 (1 μmol/1).4. Cells maintained in culture for up to ten passages have maintained morphology typical of endothelial cells and continue to produce ACE.
THE CARDIOVASCULAR ACTIONS OF 1‐METHYLISOGUANOSINE
Authors: Marwood John F. 
Published: June 2007

SUMMARY1. 1‐Methylisoguanosine was found to cause a potent long‐lasting decrease in both blood pressure and heart rate after oral administration to conscious hypertensive rats. Dose‐response curves to intravenously administered 1‐methyliso‐guanosine and adenosine in anaesthetized rats demonstrated qualitatively similar decreases in blood pressure and heart rate, with 1‐methylisoguanosine being two to three times more potent than adenosine.2. In guinea‐pig isolated atria, 1‐methylisoguanosine exhibited a negative inotropic and a negative chronotropic effect with a greater potency than adenosine.3. In halothane‐anaesthetized cats, 1‐methylisoguanosine produced a biphasic response on cardiac output: a rapid initial decrease followed by a slow increase.4. 1‐Methylisoguanosine had no effect on the response to intralumenally administered noradrenaline in isolated perfused rat tail arteries but reduced the response to electrical stimulation. In these effects, 1‐methylisoguanosine was similar to adenosine.
METABOLIC ACTIVATION AS A BASIS FOR ORGAN‐SELECTIVE TOXICITY
Authors: Boyd Michael R. , Grygiel John J. , Minchin Rodney F. 
Published: June 2007

ABSTRACTHistorically, the concept of metabolic activation was first forwarded to explain the in vivo activity of certain carcinogenic chemicals that without prior metabolism were chemically inert and biologically inactive. Subsequently, the concept has been extended to explain the effects of many different classes of chemicals causing diverse toxicities. Because of its major role in drug metabolism, the liver is a prominent site for toxic injury by agents requiring metabolic activation. The liver can also be the source of reactive metabolites that damage extrahepatic organs. But, organ selective toxicity can also result from the in situ metabolic activation of foreign chemicals in extrahepatic target tissues such as the lungs and the kidneys. Moreover, extrahepatic tissues generally are much more heterogeneous in cellular composition compared to the liver, and the localization of drug metabolizing enzymes in certain cell populations may result in highly cell selective toxic injury. The significance of metabolic activation and toxicity–and the importance of the particular chemical structure of individual compounds, as well as host factors such as species, age, sex, and pretreatment effects –on target‐organ‐selective toxicity by reactive metabolites are illustrated by studies with various furan derivatives, an important class of environmental chemicals.SUMMARYTo conclude this paper, we should simply like to restate the major points we have attempted to illustrate herein: (a) some general concepts concerning the relationships between metabolic activation, reactive intermediates, and toxicity; (b) the potential involvement of metabolic activation both in hepatic and in extrahepatic toxicities; (c) a consideration of chemical/structural factors and host factors (e.g. species, strain, sex, age, pretreatments) affecting target organ selectivity, exemplified by furan compounds; and (d) the importance of cellular specificity for metabolism and toxicity in extrahepatic tissues, as exemplified for pulmonary Clara cells with the pulmonary toxin 4‐ipomeanol.
FAILURE OF CAPTOPRIL TO LOWER BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS OFFERED WATER AND SALINE TO DRINK
Authors: DiNicolantonio R. 
Published: June 2007

SUMMARY1. The hypotensive action of chronic oral captopril treatment (50 mg/kg per day) was examined in two groups of male spontaneously hypertensive rats (SHR) of the Okamoto strain, one group offered a choice of water and 0.9% saline as drinking fluid, the other offered water alone, a third group of SHR, offered a choice of water and 0.9% saline, were treated with vehicle (0.9% saline, 2 ml/kg per day).2. Captopril treatment, over ten days, significantly lowered blood pressure in the group drinking water only but failed to significantly alter the blood pressure of SHR drinking a choice of water and 0.9% saline. Vehicle treatment did not alter the blood pressure of SHR drinking a choice of saline and water.3. In an identical experiment using male, genetically hypertensive rats (GHR) of the Smirk strain, captopril lowered blood pressure to the same extent in GHR drinking either a choice of water and 0.9% saline or water alone.4. In conclusion, the reported exaggerated saline preference of the spontaneously hypertensive rat appears to antagonize the hypotensive action of captopril.
THE INFLUENCE OF A HIGH K INTAKE ON THE HYPERTENSIVE EFFECT OF ACTH AND DOC IN SHEEP
Authors: Mills E. H. , Coghlan J. P. , Denton D. A. , Scoggins B. A. , Spence C. D. , Whitworth J. A. 
Published: June 2007

SUMMARY1. The effect of 5 days administration of ACTH or DOC, was examined before and after chronic potassium (K) loading in sheep.2. K loading raised plasma [K], urine volume and K excretion but had no effect on mean arterial pressure (MAP).3. On a normal K intake DOC (5 mg/day i.v.) increased MAP and plasma sodium [Na]. Plasma [K], urinary Na (day 1) and K (day 1) excretion were decreased. On a high K intake (≃800 mmol K/day), DOC lowered plasma [K] but had no effect on MAP or Na excretion.4. The hypertensive effects of ACTH were not affected by K intake.