bluuebunny/crossref_metadata_2025 huggingface dataset:
INTESTINAL BLOOD FLOW IN THE DOG MEASURED BY INDICATOR FRACTIONATION WITHOUT TISSUE SAMPLES
Authors: Eade M. N. , Reid I. R. , Quinn J. P.
Published: June 2007

A modification of Sapirstein's indicator fractionation technique for measurement of intestinal blood flow has been studied and evaluated in the dog.

The concentration of 42K within the intestinal wall was measured simultaneously by a tissue assay procedure and by use of a miniature Geiger‐Müller tube within the intestinal lumen. Both methods gave similar results under a wide variety of conditions.

Isotope measurement by the Geiger‐Müller tube technique obviates the need for tissue samples to be taken and would permit repeat measurements of intestinal blood flow in the same animal.
INCREASED RENAL SENSITIVITY TO ALDOSTERONE IN THE RAT: INDUCTION BY A HIGH POTASSIUM DIET
Authors: Adam William R. , Funder John W.
Published: June 2007

1. The renal response to aldosterone, measured by urinary sodium and potassium excretion, was determined in adrenalectomized rats that had been previously fed either a high potassium diet or a control diet. High K+ rats showed an enhanced response to aldosterone at all doses tested.

2. The induction of this enhanced response to aldosterone could be suppressed by a high sodium intake. It may also require the presence of the adrenal glands during the induction period, although interpretation of adrenalectomy experiments in the present study was made difficult by the effect of maintenance DOC therapy on the renal response to aldosterone.

3. The enhanced response could not be induced by a low sodium diet alone or by the administration of high doses of exogenous aldosterone.

4. No difference between high K+ and control rats could be detected in rat kidney mineralocorticoid receptors, assessed by both in vivo and in vitro binding of tritiated aldosterone.

5. The method of the induction, and the mechanism of the enhanced response remains to be defined.
STUDIES ON NORMAL HUMAN SKELETAL MUSCLE IN RELATION TO THE PATHOPHARMACOLOGY OF MALIGNANT HYPERPYREXIA
Authors: Nelson T. E. , Denborough M. A.
Published: June 2007

1. The effects of dantrolene on pharmacologically‐induced contractures and potentiated isometric twitches in normal human skeletal muscle have been studied in vitro.

2. Dantrolene sodium, at concentrations of 3 μmol/l or less, attenuates basal twitch, inhibits halothane potentiation of basal twitch and inhibits halothane‐potentiated potassium contractures, but has less effect on twitch potentiation by 2 mmol/l caffeine.

3. Caffeine contractures are attenuated by dantrolene concentrations of 12 μmol/l or greater. The effect of dantrolene on caffeine contracture is characterized by decreased contracture tension and by prolonged time to peak contracture.

4. The results indicate that halothane and 2 mmol/l caffeine have agonistic effects on the excitation‐contraction (E‐C) coupling mechanism, and suggest that they may act at separate E‐C coupling sites. The relationships of these findings to the pathopharmacology of malignant hyperpyrexia are discussed.
COMPARATIVE STUDY OF PLASMA DOPAMINE‐β ‐HYDROXYLASE ACTIVITIES IN NORADRENALINE‐SECRETING AND ADRENALINE‐SECRETING PHAEOCHROMOCYTOMAE
Authors: Aunis Dominique , Bouclier Martine
Published: June 2007

1. Circulating dopamine‐β‐hydroxylase activities were measured in two hypertensive patients, with a phaeochromocytoma tumour. Tumours were found to differ by their secretory properties, one secreting noradrenaline, the other adrenaline. After removal of the tumour, the plasma dopamine‐β‐hydroxylase activities in both patients gradually decreased to reach a stable value in correlation with urinary, excreted catecholamine levels. The only difference was the rate of the plasma enzyme activity decrease.

2. Thus, it appeared that some phaeochromocytomae are able to secrete dopamine‐β‐hydroxylase in addition to catecholamines. Therefore, dopamine‐β‐hydroxylase activity measurements may be of interest: (1) in determining secretory properties of phaeochromocytoma tumours, and (2) in following the evolution during the postoperative period.
DISSOCIATION OF INCREASED 5‐HYDROXYINDOLEACETIC ACID LEVELS AND PHYSICAL DEPENDENCE: THE EFFECTS OF NALOXONE
Authors: Laska F. J. , Fennessy M. R.
Published: June 2007

1. A slow release emulsion of naloxone (naloxone SR) was administered sub‐cutaneously to rats in an attempt to induce physical dependence of the morphine type.

2. Naltrexone (2.5 mg/kg), injected i. p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h.

3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin.

4. Naloxone SR caused an apparent dose‐related increase in the brain levels of 5‐hydroxyindoleacetic acid.

5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate.

6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine‐like drugs but may be a property of drugs containing the basic opiate molecular structure.
SENSITIVITY CHANGES IN GUINEA‐PIG ATRIA AND ILEUM FOLLOWING SUBACUTE ADMINISTRATION OF DYFLOS
Authors: Mitchelson F. , O'Shea R. A.
Published: June 2007

1. Subacute administration of dyflos to guinea‐pigs (1.2 mg/kg, s. c., daily for 10 days) led to the development of subsensitivity to carbachol in the ileum but not in the electrically stimulated left atrium.

2. Atria from dyflos‐pretreated animals became supersensitive to acetylcholine but the ileum became subsensitive to this agonist despite marked inhibition of cholinesterases. The degree of subsensitivity was less than that for carbachol.

3. Subsensitivity also developed to histamine and was of a similar order to that observed for carbachol supporting the suggestion that subsensitivity is a nonspecific post‐receptor mechanism.

4. Other changes which occurred in the ileum, together with the increase in the EC50 value to agonists were an increase in tissue mass, an increase in the slope of the concentration‐response curve to agonists and an increase in the maximal response to agonists.
EFFECTS OF THIOPENTONE SODIUM, METHOXYFLURANE AND HALOTHANE ON HAEMATOLOGICAL PARAMETERS IN SHEEP DURING PROLONGED ANAESTHESIA
Authors: Edjtehadi M.
Published: June 2007

1. Satisfactory surgical anaesthesia in sheep was achieved by i.v. injection of thiopentone sodium per se (20mg/kg); and also with thiopentone/methoxyfiurane and thiopentone/halothane anaesthetics (2–3% and 1.5–2%, respectively).

2. Cardiac arrhythmias were not observed during thiopentone sodium, thiopentone/methoxyfiurane and thiopentone/halothane anaesthesia. However, during thiopentone anaesthesia, one sheep displayed a high degree of sinus tachycardia followed with ventricular tachycardia.

3. Pneumograms recorded during thiopentone sodium and thiopentone/methoxyfiurane anaesthesia showed no irregularity, but in thiopentone/halothane anaesthesia, 30% of the sheep developed Cheyne‐Stokes periodic respiration.

4. Packed cell volume (PCV) and haemoglobin (Hb) were significantly decreased in thiopentone/methoxyfiurane and thiopentone anaesthetized sheep, but not in animals anaesthetized by thiopentone/halothane.

5. White blood cell count (WBC) was significantly decreased only in thiopentone/methoxyfiurane anaesthetized sheep, but was not remarkable in thiopentone and thiopentone/halothane anaesthetized animals.

6. A significant lymphocytopenia occurred in thiopentone/methoxyfiurane and in thiopentone/halothane anaesthetized sheep, but not in the thiopentone anaesthetized animals. This was accompanied with an increase in neutrophils.

7. Clotting time fell, but the extent and time course was different in thiopentone, thiopentone/methoxyfiurane and thiopentone/halothane anaesthesia.

8. From these data, it is suggested that thiopentone sodium, thiopentone/methoxyfiurane and thiopentone/halothane have different effects on different blood parameters during prolonged anaesthesia, and may be clinically significant.
CONCENTRATION OF GUANIDINES IN NORMAL HUMAN PLASMA
Authors: Lazdins I. , Dawborn J. K.
Published: June 2007

1. The concentration of methylguanidine and guanidinosuccinic acid has been measured in normal human plasma and discrepancies between various published methods for measuring methylguanidine have been resolved. Previous methods have been modified to allow these guanidines, together with guanidinoacetic acid and creatine, to be measured on the same serum sample.

2. Mean values in six normal subjects were as follows: methylguanidine 1.62 μmol/1 (s.d. = 1.3); guanidinosuccinic acid 0.66 μmol/1 (s.d. = 0.22); guanidinoacetic acid 7.06μmol/l (s.d. = 1.29); creatine 80.9μmol/l (s.d. = 37.9).
COMPARATIVE HAEMODYNAMIC EFFECTS OF CLONIDINE ADMINISTERED INTRAMUSCULARLY OR INTRAVENOUSLY TO ANAESTHETIZED RATS
Authors: Oates H. F. , Stoker L. M. , Throupe P. , Stokes G. S.
Published: June 2007

1. The acute haemodynamic effects of clonidine, 0.001–1.0 mg/kg, administered intramuscularly or intravenously, were studied in anaesthetized rats.

2. The direct pressor potency of clonidine was 100‐fold greater following intravenous administration than after intramuscular injection, but hypotensive efficacy was equal by either route.
SEPARATION OF TWO CONJUGATES OF CLOFJBRIC ACID (CPIB) FOUND IN THE URINE OF SUBJECTS TAKING CLOFIBRATE
Authors: Faed Ellen M. , McQueen E. G.
Published: June 2007

1. Two main conjugates of CPIB (2‐[chlorophenoxy]‐2‐methylpropionic acid) are present in the urine of subjects taking clofibrate. The metabolites can be separated by thin‐layer chromatography (TLC).

2. Both conjugates are hydrolysed by dilute alkali, but only one is hydrolysed by the enzyme β‐glucuronidase. In eighty‐five urine specimens this conjugate accounted for an average of 54.5% (range 25–70%) of the total CPIB, while 2.6–12.45% (mean 5.1%) was present as free CPIB.
THE EFFECT OF SPONTANEOUS DIABETES MELLITUS ON FATTY ACID OXIDATION, 0‐HYDROXYBUTYRATE DEHYDROGENASE ACTIVITY AND RESPIRATORY COUPLING OF HEPATIC MITOCHONDRIA IN THE GUINEA‐PIG (CAVIA PORCELLUS)
Authors: Nevalainen T. O. , White W. J. , Lang C. M. , Munger B. L.
Published: June 2007

1. The purpose of this study was to determine whether hepatic mitochondria of guinea‐pigs with spontaneous diabetes mellitus differ from those of non‐diabetic guinea‐pigs in the oxidation of fatty acids, the activity of β‐hydroxybutyrate dehydrogenase, or respiration‐linked oxidative phosphorylation. During the course of the study, a third group of animals (referred to as the unclassified group) was discovered which, on the basis of the clinical chemistry and histological changes in the pancreas, appeared to be in a pre‐diabetic or post‐diabetic state.

2. No differences in the respiratory control ratios were found between any of the three groups. Fatty‐acid oxidation in hepatic mitochondria was greater in both the unclassified and diabetic groups than in the non‐diabetic group. /3‐Hydroxy‐butyrate dehydrogenase activity, however, was increased only in the diabetic group. These findings suggest that increased fatty acid oxidation is probably an intermediate change in the development of or the recovery from diabetes mellitus, whereas the activity of β‐hydroxybutyrate dehydrogenase is affected only in more advanced stages.
THE EFFECTS OF INTRACISTERNAL ADMINISTRATION OF α‐ADRENORECEPTOR AGONISTS ON THE SYSTEMIC BLOOD PRESSURE AND ITS RESPONSE TO HEAD‐UP TILTING IN ANAESTHETIZED CATS
Authors: Nolan P. L. , Bentley G. A.
Published: June 2007

1. The effects of intracisternal injections of the α‐adrenoreceptor agonists clonidine (0.2, 0.63 and 2.0μg/kg), xylazine (0.5, 8.0 and 50μg/kg), oxymetazoline (2.0 and 8.0μg/kg), noradrenaline (12.5, 50 and 100μg/kg) and α‐methylnoradrenaline (5.0 and 25;μ/kg) on mean arterial pressure and the reflex pressure responses to bilateral carotid occlusion and 45° vertical head‐up tilting have been investigated in chloralose‐urethane‐anaesthetized cats.

2. All the a‐adrenoreceptor agonists tested caused dose‐dependent reductions in mean arterial pressure (P<0.05, Anova, d.f. = 1,58) and the reflex pressor response to bilateral carotid occlusion (P < 0.05, Anova, d.f. = 1,58).

3. Only xylazine (50μg/kg) and noradrenaline (100μg/kg) produced a significant depression of the magnitude of the pressure compensatory response to tilting (P<0.05, Anova, d.f. = 1, 58) whilst all the agonists tested caused an increase in the period required for pressure compensation to occur (P<0.05, Anova, d.f. = 1,58).

The action of the a‐adrenoreceptor agonists to depress mean arterial pressure and the reflex responses to bilateral carotid occlusion and tilting could be reversed by the subsequent intracisternal injection of the a‐adrenoreceptor antagonist piperoxane (50 or 100μg/kg).

5.Clonidine (0.63 μg/kg) decreased the perfusion pressure of the vascularly isolated autoperfused hindquarters (P<0.05, Anova, d.f. = 1,19), but had no significant effect on the reflex rises in perfusion pressure evoked by bilateral carotid occlusion or tilting. Noradrenaline (50 jug/kg) significantly reduced the reflex response to tilting (P<0.05, Anova, d.f. = 1,19), but had no effect on the other hindquarter parameters. Oxymetazoline (8.0 μg/kg) caused no significant change in any of these parameters.

6. It is concluded that intracisternally administered a‐adrenoreceptor agonists may cause some depression of orthostatic cardiovascular reflexes via a central interaction with adrenergic mechanisms.
THE CONTRACTION INDUCED BY ETHYLENEDIAMINETETRACETIC ACID‐4 SODIUM (EDTA‐4Na) IN GUINEA‐PIG ISOLATED VAS DEFERENS KEPT IN ISOTONIC SUCROSE MEDIUM
Authors: Sugimoto J. , Furumichi A. , Murakami M. , Morita M.
Published: June 2007

1. Ethylenediaminetetracetic acid‐4 sodium (EDTA–4Na) induced a contraction in guinea‐pig isolated vas deferens kept in isotonic sucrose medium containing 0.07%NaHCO3 and 0.1% glucose after preincubation in Locke's solution. The maximum contraction was 82.1 ± 6.7% of that induced by added KCl.

2. EDTA‐Ca‐2Na (10‐7 to 10‐3 g/ml) induced no contraction in preparations. kept in the sucrose medium.

3. The EDTA‐4Na‐induced contraction was also obtained when sucrose in the sucrose medium was replaced by glucose but not when the preparation was kept in Locke's solution.

4. The EDTA‐4Na‐induced contraction was decreased by reduction of the CaCl2 or KC1 concentration of the Locke's solution in which the preparation had been preincubated before placing in the sucrose medium.

5. The EDTA‐4Na‐induced contraction was suppressed with increasing concentrations of NaCl used to partially replace sucrose in the sucrose medium.

6. When the preparation was kept in EDTA‐free sucrose medium after pretreat‐ment with 10‐4 g/ml of EDTA‐4Na in the sucrose medium for 20 min, a contraction was induced by added CaCl2. The maximum contraction induced by CaCl2 was 30.1 ± 11.8% of that of the EDTA‐4Na‐induced contraction, when CaCl2 was added at 20 min after the exchange of medium.
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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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

The 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

1. 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

1. 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

1. 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

1. 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

1. 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

1. 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.
BOOK REVIEW
Authors: Prinsley D. M.
Published: June 2007

The Biology of Senescence. Third Edition. By Alex Comfort.
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

1. 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

1. 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

1. 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

Historically, 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.

To 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

1. 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

1. 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.
DIFFERENTIATION OF NORADRENERGIC AND DOPAMINERGIC NERVES IN THE RAT KIDNEY: EVIDENCE AGAINST SIGNIFICANT DOPAMINERGIC INNERVATION
Authors: McGrath B. P. , Lim A. E. , Bode K. , Willis G. L. , Smith G. C.
Published: June 2007

1. In the rat kidney catecholaminergic nerve elements were identified by fluorescence histochemistry in perivascular plexuses around corticula arteries and juxtaglomerular arterioles and in medullary vascular bundles. Fluorescence was abolished in all areas 24 h after treatment with 6‐hydroxydopamine (6‐OHDA; 150 mg/kg i.v.). Protection of noradrenergic endings from destruction by 6‐OHDA was afforded by pretreatment with desipramine (DMI; 25 mg/kg i.p.) which restored fluorescence towards control levels. By semiquantitative analysis fluorescence was identical in juxtaglomerular regions but slightly reduced around larger vessels in (DMI + 6‐OHDA)‐treated rats when compared to controls.

2. Changes in tissue noradrenaline content, but not dopamine content, paralleled the changes in nerve fluorescence. Noradrenaline content was 4.10 pmol/mg protein (s.e.m. =0.22, n= 32) in controls and was reduced by 90% to 0.40 pmol/mg (s.e.m. =0.05, n= 23) in 6‐OHDA‐treated and by 26% to 3.01 pmol/mg (s.e.m. = 0.21, n= 23) in (DMI + 6‐OHDA)‐treated rats. Kidney dopamine content was 0.38 pmol/mg protein (s.e.m. =0.05, n= 32) in controls and was reduced by 55% to 0.18 pmol/mg (s.e.m. =0.02, n=17) in 6‐OHDA‐treated and by 53% to 0.17 pmol/mg (s.e.m. =0.02, n= 23) in (DMI +6‐OHDA)‐treated rats.

3. The renin response to haemorrhage was examined in pentobarbitone sodium‐anaesthetized rats as a test of functional integrity of renal nerves in the three groups. Progressive 1 ml haemorrhages (to total blood loss of 4 ml, 1.3% body weight) resulted in similar increases in plasma renin activity in controls and (DMI + 6‐OHDA)‐treated animals but the response was significantly attenuated in 6‐OHDA‐treated rats.

4. Renal catecholaminergic nerves appear to be predominantly noradrenergic. It is doubtful if a significant intrarenal dopaminergic system exists in the rat.
INFLUENCE OF NICORANDIL, AN ANTIANGINAL AGENT, ON THE THERAPEUTIC AND TOXIC CARDIOVASCULAR ACTIONS OF OUABAIN IN THE ANAESTHETIZED DOG
Authors: Nakamura Yasuyuki , Akima Michitaka , Sakai Kazushige
Published: June 2007

1. The effects of nicorandil were investigated on ouabain‐induced cardiovascular actions in pentobarbitone‐anaesthetized dogs. Nicorandil (500 μg/kg per h) and ouabain (100 μg/kg per h), alone and in combination, were infused intravenously to three groups of dogs.

2. Nicorandil gradually decreased systemic blood pressure, pressure‐rate product, left ventricular systolic pressure, and coronary vascular resistance, but did not significantly affect heart rate, left ventricular dP/dt max, coronary blood flow, plasma electrolyte concentrations and ECG patterns.

3. The lethal dose of ouabain was 122 μg/kg (s.e.m. = 3, n= 6) and the dose required to elicit ventricular premature beats was 63 μg/kg (s.e.m. = 3, n= 6).

4. When nicorandil and ouabain were simultaneously infused intravenously, nicorandil did not affect either the lethal dose of ouabain or the dose required to produce ventricular premature beats, but it significantly inhibited the marked increases in coronary vascular resistance and systemic blood pressure induced by ouabain alone. Even in combination with nicorandil, ouabain maintained its own positive inotropic effect.

5. The results indicate that the combination of ouabain with nicorandil may be beneficial in some conditions of angina pectoris.
STRUCTURE OF HUMAN RENIN AND EXPRESSION OF THE RENIN GENE
Authors: Morris Brian J. , Catanzaro Daniel F. , Hardman Judy , Mesterovic Nikola , Tellam Judy , Hort Yvonne , Bennetts Bruce H. , Shine John
Published: June 2007

1. The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques.

2. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique Leu10‐Val11 bond of human angiotensinogen revealed features peculiar to this highly specialized aspartyl protease.

3. The expression of the renin gene was examined with a hybridization probe for renin mRNA in sections and extracts of tissues. In the submandibular gland of mice renin mRNA, like renin, increased during development and in response to testosterone in females; sodium depletion increased renin mRNA in kidney.
DIFFERENTIAL BLOCKING EFFECTS OF PRAZOSIN AND YOHIMBINE ON PRESSOR RESPONSES TO NEURONALLY RELEASED AND EXOGENOUSLY ADMINISTERED NORADRENALINE IN THE PITHED RAT
Authors: Kimura T. , Suzuki S. , Satoh S.
Published: June 2007

1. The effects of prazosin and yohimbine on pressor responses to sympathetic nerve stimulation and intravenous injections of noradrenaline, phenylephrine and clonidine were examined in pithed rats to determine the postjunctional location of α2‐adrenoceptors in the vascular smooth muscle.

2. Prazosin antagonized the pressor responses to phenylephrine and to sympathetic nerve stimulation more effectively than the responses to noradrenaline and to clonidine.

3. Yohimbine antagonized the pressor responses to noradrenaline and to clonidine more effectively than the responses to sympathetic nerve stimulation and to phenylephrine.

4. These results suggest that α2‐adrenoceptors as well as α1‐adrenoceptors produce vasoconstriction in the rat vasculature and support the hypothesis that α1‐adrenoceptors are predominantly located within the neuroeffector junction in contrast to an extrajunctional location of α2‐adrenoceptors.
THE POSSIBLE INVOLVEMENT OF ADRENOCEPTORS IN THE INTESTINAL EFFECT OF MORPHINE IN MICE
Authors: Wong Chak‐Lam
Published: June 2007

1. The inhibitory effect of morphine on intestine was observed by following the intestinal transit of a charcoal meal. This inhibitory effect of morphine was antagonized by naloxone.

2. In addition, the inhibitory effect of morphine was also suppressed by prior administration of yohimbine and phentolamine. However, prazosin, a selective α1‐adrenoceptor antagonist, had no effect on the inhibitory effect of morphine on intestinal transit.

3. Furthermore, prior administration of propranolol did not alter this effect of morphine.

4. These adrenoceptor antagonists by themselves, at the doses used, had no effect on the rate of intestinal transit of a charcoal meal in mice.

5. These results suggest that α2‐adrenoceptors may be involved in the intestinal effect of morphine while α1‐ and β‐adrenoceptors do not appear to play any significant role in this aspect of morphine action.
EFFECTS OF PHENOXYBENZAMINE ON RESPONSES TO SOME RECEPTOR AGONISTS AND CALCIUM IN VITRO
Authors: McPherson Grant A. , Krstew Elena , Malta Errol
Published: June 2007

1. Noradrenaline‐induced contractions of the rabbit and rat isolated aorta and guinea‐pig spleen strips were inhibited by concentrations of phenoxybenzamine which did not affect responses to calcium. This may suggest a specific action on α‐adrenoceptors. However, analysis of noradrenaline concentration‐effect curves in guinea‐pig spleen indicated that 1 μmol/1 phenoxybenzamine should have reduced the available receptor population to 6% of control, but data from radioligand binding experiments on the same tissues using [3H]‐prazosin indicated a reduction of the receptor population to only 82% of control. The reduced responsiveness observed in the organ bath study after phenoxybenzamine pretreatment, whilst not apparently related to effects on voltage‐dependent calcium channels, could be due to the actions of phenoxybenzamine on other (non‐receptor) processes such as receptor‐operated calcium channels.

2. Maximal contractile responses to histamine in rabbit isolated aorta but not those in guinea‐pig isolated ileal preparations, were depressed by concentrations of phenoxybenzamine which depressed responses to calcium. Phenoxybenzamine produced parallel rightward shifts of curves to carbachol in guinea‐pig ileal preparations but only depressed maximal responses to the agonist in higher concentrations which reduced responses to calcium.

3. On the basis of the results obtained with calcium it is possible that the effects of phenoxybenzamine on receptor‐mediated responses could be produced through the actions of this antagonist at less specific sites such as voltage‐dependent calcium channels for histamine in rabbit aorta and carbachol in guinea‐pig ileum. For α‐receptor mediated responses in aortic and splenic strip preparations and for histamine‐mediated responses in guinea‐pig ileum, the actions of phenoxybenzamine may reflect an interaction of the antagonist with receptor‐operated calcium channels.