bluuebunny/crossref_metadata_2025 huggingface dataset:
ACTIVE AND INACTIVE RENIN IN CRITICALLY ILL PATIENTS
Authors: Thatcher Robin , Butty Jill S. , Whitworth Judith A. , Fei David T. W. , Skinner Sandford L.
Published: June 2007

1. The relationship between active (A) and inactive (I) plasma renin concentrations (PRC) was examined in critically ill patients to test for intravascular renin activation in states of shock and tissue damage.

2. Critically ill patients had significantly elevated APRC and lowered IPRC:APRC ratio compared with age and sex matched healthy subjects. IPRC in the critically ill was similar to the control group.

3. During blood donation normal volunteers showed a twofold increase in APRC. The rise in APRC was proportionately greater than for IPRC, with a subsequent fall in IPRCAPRC ratio.

4. In both critically ill patients and blood donors elevated APRC was associated with decreased IPRC:APRC ratio, consistent with either consumption of the inactive renin zymogen or preferential secretion of the active form. Individual critically ill patients displayed markedly depressed ratios but with only moderately elevated APRC, a pattern suggestive of intravascular renin activation. Consistent evidence for intravascular or extravascular activation of renin was not apparent.
INHIBITION OF ACETYLCHOLINESTERASE BY HISTAMINE AGONISTS AND ANTAGONISTS
Authors: Lee H. S. , Cheah L. S. , Gwee M. C. E.
Published: June 2007

1. The histamine H1 and/or H2‐receptor agonists showed weak acetylcholinesterase inhibitory activity. Their dissociation constants (Kis and/or Kii) were 2‐methyl histamine (Kis= 1751 μmol/1, s.e. = 163) < 4‐methyl histamine (Kis= 3551 μmol/1, s.e. = 414) < dimaprit (Kis= 2931 μmol/1, s.e. = 605; Kii= 3668 μmol/1, s.e. = 901) < histamine (Kis= 6480 μmol/1, s.e. = 1360).

2. Both histamine H1 and H2‐receptor antagonists showed stronger acetylcholin‐esterase inhibitory activity. Their dissociation constants were ranitidine (Kii= 1.56 μmol/1, s.e. = 0.14) ≪ oxmetidine (Kis= 14.7 μmol/1, s.e. = 1) < mepyramine (Kis= 178 μmol/1, s.e. = 23; Kii= 440 μmol/1, s.e. = 98) < cimetidine (Kis= 199 μmol/1, s.e. = 12; Kii= 827 μmol/1, s.e. = 126).

3. Using the ROSFIT programs for fitting data to common enzyme kinetic models, the inhibition caused by histamine, 4‐methyl histamine, 2‐methyl histamine, oxmetidine and neostigmine was of the competitive type. Mepyramine, cimetidine and dimaprit appeared to exhibit the modern non‐competitive type of inhibition with their primary action on the enzyme rather than on the enzyme‐substrate complex. Ranitidine seemed to act on the enzyme‐substrate complex rather than the enzyme, conforming to the uncompetitive inhibition model.

4. The clinical implications of acetylcholinesterase inhibition by cimetidine and ranitidine are discussed.
THE EFFECTS OF m‐AMSA ON RAT ISOLATED HEART
Authors: Merkin M. S. , Shinar E. , Shefer A. , Gotsman M.S. , Hasin Y.
Published: June 2007

1. m‐AMSA (4′[9‐acridinylamino]methansulphon‐m‐anisidide) is a new cytoxic agent now under clinical trial.

2. We used the rat isolated perfused heart model in order to investigate the cardiac effects of m‐AMSA.

3. The results of the dose‐response study indicate that m‐AMSA has an acute moderate negative inotropic effect. The 90% effect (25% decrease in developed force compared to the control) was observed at drug concentration of 1.5 μg/ml. The refractory period (as measured by stimuli of twice diastolic threshold intensity) increased progressively as the drug concentration was increased (up to 2.5 μg/ml).

4. Measurements of the strength‐duration and strength‐interval relationship showed that m‐AMSA induced a significant reduction (P < 0.005) in excitability and prolongation of refactoriness.

5. We suggest that m‐AMSA has a membranal cardiotoxic effect in addition to its known intracellular cytotoxic effect.
SODIUM PREFERENCE AND EXCRETION IN SPONTANEOUSLY HYPERTENSIVE RATS ON VARIOUS DIETS
Authors: Wang H. , Ikeda K. , Kihara M. , Nara Y. , Horie R. , Yamori Y.
Published: June 2007

1. Stroke‐prone spontaneously hypertensive rats (SHRSP) and stroke‐resistant SHR (SHRSR) exhibited an increased preference for a 2% NaCl solution, relative to water, in comparison with normotensive Wistar‐Kyoto (WKY), but the preference was lost quickly in SHRSP with unbroken exposure.

2. Neither a high protein diet (50% fish protein) nor a low protein diet (5% protein) changed the salt water preference in SHRSR and the former abolished the preference more quickly in SHRSP.

3. The fish protein diet, however, increased the ratio of urinary sodium excretion to dietary sodium intake in the first three days of exposure to a high salt intake in all groups.

4. Results from this experiment suggest that an increased dietary protein intake can facilitate sodium excretion and may possibly ameliorate the adverse effect of a high sodium diet.
ANGIOTENSIN CONVERTING ENZYME INHIBITION DOES NOT PREVENT DEVELOPMENT OF ACTH‐INDUCED HYPERTENSION IN SHEEP
Authors: Spence Campbell D. , Coghlan John P. , Denton Derek A. , Fei David T. W. , Mills Eric H. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. The role of the renin‐angiotensin system in the onset of ACTH‐induced hypertension was examined in five conscious sheep.

2. Captopril infusion alone (15 μg/kg per day) for 2 days produced a small fall in blood pressure.

3. After 2 days of captopril ACTH was infused (20 μg/kg per day) for 3 days together with captopril. The blood pressure and electrolyte effects of ACTH administration were not modified by captopril pretreatment.

4. These experiments establish that angiotensin II is not important in the onset of ACTH‐induced hypertension in sheep.
MIGRATION‐INDUCED CHANGES IN BLOOD PRESSURE: A CONTROLLED LONGITUDINAL STUDY
Authors: Poulter N. R. , Khaw K. T. , Mugambi M. , Peart W. S. , Sever† P. S.
Published: June 2007

1. A longitudinal study of the effects of migration on blood pressure and related factors is being carried out in members of a black Kenyan population who migrate from a traditional rural community to an urban environment.

2. Data on the first 139 migrants (78 male, 61 female) and 204 control non‐migrants (126 male, 78 female) who have been followed up for a period of 6 months are presented.

3. Blood pressure changes rapidly on migration (within the first 2 months); thereafter trends between migrants and controls differ. Significant differences in systolic pressure between migrants and controls are found at all examinations during the 6 month follow‐up in both sexes. Diastolic pressure falls in controls but rises in migrants, the greatest difference being seen at the 6 month examination.

4. Migration is associated with a marked increase in dietary sodium and a fall in potassium demonstrated by measurements of urinary electrolyte excretion in 3 × 12 h or 3 × 24 h urine collections.

5. Analysis of covariance shows that the blood pressure differences between migrants and controls are partly explained by urinary sodium/potassium ratios and in some instances by body weight.
INCREASED SENSITIVITY OF RABBIT EAR ARTERY TO NORADRENALINE FOLLOWING PERIVASCULAR NERVE STIMULATION MAY BE A RESPONSE TO NEUROPEPTIDE Y RELEASED AS COTRANSMITTER
Authors: Glover W. E.
Published: June 2007

1. Neuropeptide Y (NPY 10‐10‐10‐7 mol/l) had little or no effect on the perfusion pressure of rabbit isolated ear arteries but potentiated the brief contractile responses to injections of noradrenaline, histamine or brief periods of electrical stimulation (2–20 Hz for 5 s). This effect was slowly reversible.

2. Similar potentiation was seen following long periods of electrical stimulation (2–40 Hz for 1–5 min) which produced well sustained increases in perfusion pressure.

3. Following even longer periods of electrical stimulation (10–30 min) during which the perfusion pressure was not maintained, responses to noradrenaline and histamine were potentiated but the responses to electrical stimulation for 5 s were greatly reduced.

4. The increase in sensitivity following prolonged electrical stimulation may be due to NPY released as a cotransmitter.
HYPERTENSION CORRECTED AND ALDOSTERONE RESPONSIVENESS TO RENIN‐ANGIOTENSIN RESTORED BY LONG‐TERM DEXAMETHASONE IN GLUCOCORTICOID‐SUPPRESSIBLE HYPERALDOSTERONISM
Authors: Woodland E. , Tunny T. J. , Hamlet S. M. , Gordon R. D.
Published: June 2007

1. Two males with glucocorticoid‐suppressible hyperaldosteronism had hyperaldosteronism, hypertension and hypokalaemia corrected by continuous administration of physiological doses of dexamethasone for more than a year.

2. During long‐term dexamethasone treatment:

(a) Plasma renin activity increased from subnormal to high normal levels, with normal posture‐mediated increases;

(b) Plasma aldosterone became responsive to angiotensin infusion, a new observation;

(c) A fall in plasma aldosterone between 0800 h (recumbent) and 1000 h (upright) was replaced by a rise;

(d) Plasma aldosterone became suppressible with salt loading.

3. These findings are consistent with a shift to more normal control of aldosterone by renin‐angiotensin, once abnormal responsiveness to ACTH has been nullified.
A RANDOMIZED CONTROL TRIAL OF A VEGETARIAN DIET IN THE TREATMENT OF MILD HYPERTENSION
Authors: Margetts B. M. , Beilin L. J. , Armstrong B. K. , Vandongen R.
Published: June 2007

1. The effect of an ovo‐lacto‐vegetarian (OLV) diet on blood pressure was assessed in a randomized, controlled, crossover trial in 58 mild untreated hypertensive subjects recruited from the Perth Centre for the 1983 NHF Risk Factor Prevalence Survey.

2. Subjects were randomly allocated to one of three groups; the first maintained their usual diet throughout 12 weeks; the other two were given an OLV diet for either the first or second 6 weeks of the 12‐week trial.

3. Introduction of an OLV diet was associated with a significant fall in systolic blood pressure, on average of the order of 5 mmHg, which was unrelated to change in urinary sodium, potassium or body weight.

4. It was concluded that a vegetarian diet may have an adjunctive role in control of mild hypertension, but that in view of likely problems with acceptability those dietary components responsible for the blood pressure differences need to be identified.
RETARDED DEVELOPMENT OF HYPERTENSION IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING CHRONIC ALCOHOL CONSUMPTION
Authors: Howe P. R. C. , Rogers P. F. , Smith R. M.
Published: June 2007

1. The influence of chronic alcohol consumption on blood pressure was examined in normotensive Wistar/Kyoto rats (WKY) and in stroke‐prone spontaneously hypertensive rats (SHR‐SP).

2. Ethanol, administered in drinking water from 5 weeks of age to produce moderate blood alcohol levels, substantially retarded the development of hypertension in SHR‐SP and caused a mild reduction of blood pressure in WKY.

3. Alcohol withdrawal caused an acute rise in blood pressure in both strains, followed by a reduction to the subnormal levels previously induced by alcohol treatment.

4. This sustained antihypertensive effect of alcohol was not attributable to reductions of body weight or fluid intake.
EFFECT OF MAGNESIUM ON PASSIVE FLUXES OF LITHIUM IN THE HUMAN ERYTHROCYTE
Authors: Wiley J. S. , Bonacquisto L. , Doyle A. E.
Published: June 2007

1. Extracellular Mg2+ is known to inhibit the passive Na+ and K+ fluxes in the human erythrocyte. In this study the effect of extracellular Mg2+ on Li+ efflux was measured in erythrocytes from 29 normotensive and essential hypertensive subjects.

2. Magnesium produced a variable inhibition of between 0 and 47% in Li+ efflux in different subjects and this effect was unrelated to initial cell Li+, blood pressure or to an action on the co‐ or counter‐transport pathways for this cation.

3. A positive correlation was observed between the magnitude of the passive Li+ efflux and its inhibition (0 to 47%) by Mg2+ ions. Thus Mg2+ has an inhibitory effect on passive Li+ permeability which is unrelated to essential hypertension.
TOTAL BODY SODIUM IN IMMATURE SPONTANEOUSLY HYPERTENSIVE AND WISTAR KYOTO RATS
Authors: Harrap Stephen B. , Doyle Austin E.
Published: June 2007

1. Total body sodium of male and female spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats was estimated weekly during the first 8 weeks of life by measuring exchangeable sodium (ENa). Blood pressure and sodium intake was measured from weeks 4 to 8.

2. SHR had significantly higher blood pressure and sodium intake than WKY from 4 to 8 weeks of age.

3. ENa was higher in SHR than WKY throughout the first 8 weeks of life.

4. Relative sodium retention was observed in SHR during weeks 5 to 8 despite a significant rise in SHR blood pressure and fall in sodium intake.

5. These findings suggest a change in the renal pressure/natriuresis relationship at this age in the SHR.
IN VITRO CALCIUM DEPENDENCE OF ARTERIAL SMOOTH MUSCLE IN HUMAN HYPERTENSION
Authors: Lipe S. , Moulds R. F. W.
Published: June 2007

1. Digital arteries, removed at autopsy from 12 hypertensives and 11 normotensives, have been compared in vitro for the calcium dependence of contractures produced by potassium chloride and noradrenaline, and the potency of verapamil to antagonize contractures to noradrenaline.

2. No significant differences were found between the vessels from the hypertensives and normotensives for the pD2 values or the maximum response to either potassium chloride or noradrenaline in bathing solutions containing 2.5, 1.0, 0.5 or 0 mmol/l calcium chloride.

3. There were also no significant differences between the vessels, from the hypertensive or normotensives, in the pD2 values for the addition of calcium chloride to arteries exposed to potassium chloride or noradrenaline in a calcium free bathing medium, in the ability of verapamil to shift the pD2 values for noradrenaline, nor in the ability of verapamil to reduce the maximum responses to noradrenaline (except at the two highest concentrations of verapamil tested).

4. It is concluded that it is unlikely to be a primary abnormality of the mechanisms regulating calcium ion entry and release in vascular smooth muscle in human hypertension.
STUDIES ON THE VASODILATOR ACTIONS OF BUCINDOLOL IN THE RAT
Authors: Marwood John F. , Stokes Gordon S.
Published: June 2007

1. Experiments were performed in anaesthetized rats to investigate the vasodilator actions of the β‐adrenoceptor antagonist bucindolol. Bucindolol (3 mg/kg) lowered blood pressure significantly in rats pretreated with (i) prazosin (0.4 mg/kg) (ii) prazosin (0.4 mg/kg) plus propranolol (0.5 mg/kg) or (iii) labetalol (0.5 mg/kg). Thus, a portion of the hypotensive effect of bucindolol was independent of effects on α‐ or β‐adrenoceptors. This was attributed to direct vasodilatation.

2. In reserpinized anaesthetized rats bucindolol increased heart rate and thus had an intrinsic sympathomimetic action (ISA). The ISA was equipotent with that of isoprenaline at the 0.25 nmol/kg dose level, but declined with increasing bucindolol doses, probably due to the onset of β‐adrenoceptor blockade.

3. In isolated perfused rat tail arteries constricted by perfusing with a high‐K+ Krebs solution, bucindolol (10−5 mol/l, 10−4 mol/l) caused a significant reduction in perfusion pressure indicative of vasodilatation. Since the perfusate contained 10−6 mol/l propranolol, the vasodilatation was not due to β‐adrenoceptor stimulation.

4. These results are consistent with a direct vasodilator action of bucindolol. We suggest bucindolol lowers blood pressure by a complex mechanism involving β‐adrenoceptor blockade, α‐adrenoceptor blockade, vasodilatation and perhaps β2‐adrenoceptor stimulation.
DYNAMIC CHANGES IN PLASMA INACTIVE RENIN LEVELS IN BARTTER'S SYNDROME AFTER ADMINISTRATION OF CAPTOPRIL AND ANGIOTENSIN II
Authors: Nagai Hiroyuki , Matsunaga Masato , Ogawa Kazuya , Pak Chun Ho , Kanatsu Kazuro , Hara Akira , Kono Tsuyoshi , Kawai Chuichi
Published: June 2007

1. Changes in plasma active and inactive renin concentration (ARC and IRC) after captopril administration and angiotensin II (AII) infusion were studied in six patients with Bartter's syndrome.

2. A single oral dose of captopril (8‐25 mg) lowered the blood pressure and increased both ARC and IRC. AII infusion elevated blood pressure, suppressed ARC and increased IRC.

3. In this syndrome of high renin levels, infused AII appeared to increase inactive renin secretion by reducing its conversion to active renin. On the other hand, an acute fall in AII levels and/or renal perfusion pressure by captopril increased both active and inactive renin. This indicates that the increase in the secretion of inactive renin, stimulated by captopril, might exceed any increase in its conversion to active renin in patients with Bartter's syndrome, in whom the production of renin is accelerated, and conversion of inactive renin to active renin probably already operates near its maximum.
ACUTE TOLERANCE TO DIAZEPAM IN MICE: PHARMACOKINETIC CONSIDERATIONS
Authors: Yoong Y. L. , Lee H. S. , Gwee M. C. E. , Wong P. T.‐H.
Published: June 2007

1. The tolerance to the hypnotic effect of diazepam developed after a single exposure to diazepam in the presence or absence of cycloheximide, which blocks liver enzyme induction, was studied.

2. At the high dose (30‐35 mg/kg) used in this study, diazepam was found to be metabolized very rapidly in mice, consistent with previous findings using a much smaller dose (5 mg/kg).

3. There was no significant difference in the pharmacokinetics of diazepam in control and tolerant mice as observed by monitoring the plasma and brain concentrations of diazepam and N‐desmethyldiazepam.

4. It is concluded that acute tolerance to diazepam in mice may not be attributed to changes in pharmacokinetic factors.
INHIBITION OF ACETYLCHOLINESTERASE BY VARIOUS OPIOIDS
Authors: Sim M. K. , Chua M. E.
Published: June 2007

1. The anti‐acetylcholinesterase (AChEase) activity of 15 opioids, namely morphine, nalorphine, oxymorphone, naloxone, naltrexone, N‐methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo‐methadone, dextro‐methadone, pethidine, leu‐enkephalin and U‐50,488H was investigated.

2. Among the opioids, the morphinans (in terms of their dissociation constants) are the strongest inhibitors of the enzyme. These are followed by the phenanthrenes and the morphones, though two members of the latter group are non‐inhibitors. Levo‐methadone, dextro‐methadone, pethidine and leu‐enkephalin are also non‐inhibitors of the enzyme.

3. The present results, together with our previous findings, support the suggestion that opioids which are poor or non‐inhibitors of AChEase are strong inhibitors of the ACh‐induced contraction of the toad rectus, whereas the reverse is true for inhibitors of AChEase.
VERAPAMIL‐INDUCED SECRETION OF ACTIVE AND INACTIVE RENIN IN CONSCIOUS SHEEP
Authors: Mzail A. H. K. , Noble A. R.
Published: June 2007

1. Regulation of plasma active and inactive renin was investigated using conscious sheep with indwelling artery, vein and bladder catheters. Control and experimental studies were carried out in the same animals on different days.

2. The calcium antagonist drug verapamil was given as an initial bolus injection (0.5 mg/kg) followed by a continuous infusion (0.1 mg/kg per h) over a 2.5 h period.

3. Plasma active and inactive renin changed in parallel. Both were significantly increased within 15 min of the initial drug dose and both attained a peak increase after 45 min. Thereafter, the two forms of renin returned to basal levels despite continued infusion of the drug.

4. Effective renal plasma flow (CPAH) was also transiently increased by verapamil and followed a similar time course to changes in plasma active and inactive renin concentration. Arterial blood pressure, however, remained suppressed by verapamil for the duration of the study.

5. Verapamil did not alter urine flow or sodium and potassium excretion rates.

6. These results are discussed in relation to the possible link between intrarenal haemodynamics and renin secretion in conscious and in anaesthetized animals and also in relation to the concept that variation in the relative amounts of active and inactive renin secreted in differing physiological situations represents a mechanism for regulating the renin‐angiotensin system.
ADRENALINE AND STRESS‐INDUCED INCREASES IN BLOOD PRESSURE IN RATS
Authors: Majewski H. , Alade P. I. , Rand M. J.
Published: June 2007

1. Stress was induced by immobilizing the hind limbs of rats for 12 days and housing the rats in individual cages. Control rats were housed in groups without immobilization. Blood pressure and heart rate were measured through an indwelling carotid cannula.

2. After 10 and 12 days of immobilization and isolation, the stressed rats had significantly higher blood pressures (ca. 10 mmHg) and higher cardiac adrenaline levels (ca. 90%). After adrenal medullectomy cardiac adrenaline levels were markedly reduced in both stressed and control rats. Furthermore, the stressing procedure did not cause a rise in blood pressure in adrenal‐medullectomized rats.

3. Desipramine HCl (2 mg/kg per day), administered orally to block the neuronal uptake of adrenaline, prevented the elevation in blood pressures and cardiac adrenaline levels. Propranolol HCl (2.8 mg/kg per day), orally, also prevented the rise in blood pressure.

4. The results are consistent with the hypothesis that activation of facilitatory prejunctional β‐adrenoceptors on sympathetic nerves by neuronally‐released adrenaline may be responsible for the raised blood pressure.
ENDOTHELIUM‐DEPENDENT RELAXATION IS UNALTERED BY HYPERTENSION, CHOLESTEROL OR INTIMAL THICKENING
Authors: Angus J. A. , Wright C. E. , Cocks T. M. , Satoh K. , Campbell G.
Published: June 2007

1. The effect of cellophane wrap hypertension (WRAP) and hypercholesterolemia (1% cholesterol diet, CHOL) for 4 weeks was assessed on the endothelium‐dependent vasodilator response to acetylcholine in conscious rabbits after pharmacological autonomic blockade.

2. Dose‐response curves for the hindlimb vascular resistance (ear artery pressure/lower aortic blood flow; Doppler flowmeter) and acetylcholine infusion (i.v.) doses were unaltered in sensitivity (ED50) for any of the treatment groups. The range and slope of the curves were significantly altered by WRAP, CHOL or WRAP plus CHOL for acetylcholine and adenosine infusions consistent with medial hypertrophy in resistance vessels and raised serum viscosity.

3. The effect of intimai thickening on the response to endothelium derived relaxing factor (EDRF) was tested in dog carotid artery ring segments in vitro 4 weeks after endothelium removal.

4. The relaxation responses to acetylcholine (EDRF‐dependent) and adenosine or nitroglycerin were not significantly altered by the neo‐intima.

5. Therefore the response to EDRF released by acetylcholine in resistance vessels was unaltered by hypertension, hypercholesterolemia or both together. Neo‐intimal thickening in response to initial endothelium loss does not appear to alter EDRF responses in the carotid artery.
EFFECT OF SALT LOADING ON BLOOD PRESSURE AND EICOSANOID METABOLISM OF SPONTANEOUSLY HYPERTENSIVE RATS FED A FISH OIL ENRICHED DIET
Authors: Codde J. P. , Croft K. D. , Beilin L. J.
Published: June 2007

1. This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats under conditions of normal and elevated salt intake.

2. After an initial period of 4 weeks on either a 2‐series PG ‘inhibitory’ diet offish oil (maxEPA) or a control diet of saturated fat, half of each group received 1.5% saline for 1 week.

3. Blood pressures were unaffected by diet during the period of normal salt intake, but following salt loading, the maxEPA‐fed SHR showed a blood pressure increase (mean = 21 mmHg) relative to the EPA‐fed rats on water.

4. Rats on maxEPA showed impaired ability to generate serum thromboxane and diminished excretion of urinary 6‐keto‐PGF1α and PGE2. SHR on water showed greater serum TXB2 generating capacity than WKY, but diminished urinary PGE2 excretion.

5. Thus, the increased blood pressure observed in the salt‐loaded SHR on the maxEPA diet may be explained by reduced renal PG synthesis resulting in either mild sodium retention and/or increased vascular reactivity.
NATRIURETIC EFFECT OF CHRONICALLY ADMINISTERED α‐HUMAN ATRIAL NATRIURETIC POLYPEPTIDE IN SODIUM DEPLETED OR REPLETED CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kondo K. , Kida O. , Sasaki A. , Kato J. , Tanaka K.
Published: June 2007

1. Hypotensive and natriuretic effects of chronically administered α‐human atrial natriuretic polypeptide (α‐hANP) were investigated in conscious spontaneously hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY) in both sodium depletion and repletion.

2. Systolic blood pressure was significantly reduced in SHR and WKY in both sodium deplete and replete states.

3. Urinary sodium excretion was significantly increased in SHR and tended to be increased in WKY on sodium repletion, but remained unchanged on sodium depletion.

4. It is suggested that extracellular fluid volume may be an important determinant factor of the natriuretic action of ANP but may not affect the hypotensive effect.
A COMPARISON OF THE EFFECTS OF END‐TO‐SIDE PORTACAVAL SHUNTING AND SIDE‐TO‐SIDE MESOCAVAL SHUNTING ON HEPATIC HAEMODYNAMICS IN THE DOG
Authors: Jenkins S. A. , Taylor A. , Johnson J. , Shimlrty S. K. , Baxter J. N. , Shields R.
Published: June 2007

1. Functional liver blood flow and hepatic artery flow were measured before and after either end‐to‐side portacaval or side‐to‐side mesocaval shunting in dogs.

2. Functional liver blood fell by approximately 50% following both portacaval and mesocaval shunting.

3. The hepatic artery response was variable after both portacaval and mesocaval shunts.

4. It is concluded that side‐to‐side mesocaval shunts do not preserve hepatic blood flow or produce a greater compensatory increase in hepatic artery flow than conventional portacaval shunts.
ACTION OF ALMITRINE BISMESYLATE ON VENTILATION‐PERFUSION MATCHING IN CATS AND DOGS WITH PART OF THE LUNG HYPOVENTILATED
Authors: Wach R. A. , Gill G. W. , Suggett A. J. , Bee D. , Barer G.
Published: June 2007

1. Ventilation to one lobe of lung was reduced in anaesthetized open‐chest cats and dogs to simulate the ventilation/perfusion (V̇/Q̇) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V̇/Q̇ diminished.

2. In seven cats almitrine (0.5 mg/kg + 10 μg/kg per min, i.v.) caused a rise in pulmonary artery pressure (PPA), increased flow through the hypoventilated lobe in six out of seven cats and both increased or decreased lobar vascular resistance (PVR); the lobar V̇/Q̇ ratio therefore fell. Arterial and lobar venous oxygen tension (Po2) fell.

3. In five dogs almitrine caused a rise in PPA and PVR but lobar flow changes were variable. Arterial and lobar venous Po2 fell.

4. With fixed ventilation, almitrine failed to improve V̇/Q̇ matching; there was no improvement in gas exchange in the hypoventilated lobe.

5. In eight dogs the hypoventilated lobe was perfused at constant flow with right atrial blood (i.e. while V̇/Q̇ was held constant). Almitrine caused a rise in perfusion pressure, vasoconstriction, followed, in five out of eight dogs, by vasodilatation.

6. In six similar cat preparations, vasoconstriction but not vasodilatation was clearly shown. In two cats dilatation after almitrine was demonstrated during ventilation with Nitrogen.

7. In all experiments there was no significant effect of the solvent.

8. Thus the dual action of almitrine seen in other species was seen in a proportion of cats and dogs.

9. Results do not support the view that improved arterial gas tensions in patients after almitrine are attributable to diversion of blood flow away from hypoxic lung. Alternative mechanisms are discussed.
ACUTE AND CHRONIC PHARMACOKINETIC STUDIES OF SLOW RELEASE KETOPROFEN (ORUVAIL) IN RHEUMATOID ARTHRITIS
Authors: Christophidis N. , Rotstein A. , Louis W. J.
Published: June 2007

1. Slow release preparations of non‐steroidal anti‐inflammatory drugs are used to simplify dose regimes in the treatment of rheumatoid arthritis with the aim of improving patients compliance. This study examines the acute and chronic pharmacokinetics of slow release ketoprofen in 13 rheumatoid patients with a mean age of 59.8 years.

2. Pharmacokinetic parameters following the first dose including Tmax which was 6.92 h (s.e.m. = 0.80), Cmax 3.87 μg/ml (s.e.m. = 0.54), apparent half‐life 8.8 h (s.e.m. = 1.0) and AUC 41.92 μg.h/ml (s.e.m. = 4.02) were not significantly different from those following the last dose after 3 months of chronic treatment, when these were Tmax 6.38 h (s.e.m. = 0.84) Cmax 3.57 μg/ml (s.e.m. = 0.33) apparent half‐life 8.8 h (s.e.m. = 1.1) and AUC 43.18 μg.h/ml (s.e.m. = 5.34) respectively. These results show that no accumulation of ketoprofen occurred with chronic treatment.

3. Clinical assessments were performed in an open design and showed significant improvement in pain, articular index, grip strength and duration of morning stiffness when these parameters were compared to treatment with paracetamol during an initial washout. The drug was well tolerated although there was a trend for the haemoglobin to fall and this parameter should be monitored during therapy with ketoprofen.
TREATMENT OF DIABETES MELLITUS BY ARTEMISIA HERBA‐ALBA EXTRACT: PRELIMINARY STUDY
Authors: Al‐Waili Noori S. Dawood
Published: June 2007

1. Fifteen patients with diabetes mellitus were treated with Artemisia herba‐alba Asso. extract (AHE).

2. Results showed that AHE caused considerable lowering of elevated blood sugar and 14 out of 15 patients had good remission of diabetic symptoms with use of AHE.

3. It is concluded that AHE contains material capable of reducing raised blood sugar in diabetes mellitus.

4. No side effects were recorded during or after treatment with AHE.
ARTERIAL PRESSURE AND HEART PERIOD IN THE CONSCIOUS RABBIT: DIURNAL RHYTHM AND INFLUENCE OF ACTIVITY
Authors: Eijzenbach V. , Sneek J. H. J. , Borst C.
Published: June 2007

1. Mean‐arterial pressure (MAP), heart period (HP) and the level of physical activity were measured in conscious rabbits and averaged over one‐hour periods during 14 consecutive days. Serial autocorrelation coefficients and serial crosscorrelation coefficients were computed, to analyse periodicity.

2. Measurements were started immediately after implantation of the cannula (group A, n= 11) or 10–46 days after implantation of the cannula (group B, n= 6).

3. In the course of 14 days, in group A, MAP decreased 9 mmHg and HP increased 21 ms (P <0.05). In group B, MAP decreased and HP increased in a similar way. Percentage activity did not show a trend.

4. Significant diurnal rhythms were found. MAP and percentage activity reached the lowest values at noon, and the highest late in the evening. HP reached the highest values at noon and the lowest late in the evening. MAP and HP fluctuated exactly in antiphase. This suggests a common origin for both rhythms.

5. During physical activity MAP was 10–15 mmHg higher and HP was 35–40 ms shorter than during rest. These differences did not show a trend or a diurnal variation.

6. In individual animals MAP and HP varied greatly from hour to hour.

7. These biological variations in MAP and HP as well as the influence of activity should be taken into account when conclusions are drawn from short‐term measurements.
EFFECT OF L‐THYROXINE ON SERUM ANGIOTENSIN CONVERTING ENZYME ACTIVITY IN SHEEP*
Authors: Verma P. , Noble S. , Miller R.
Published: June 2007

1. The effect of l‐thyroxine on serum angiotensin converting enzyme activity using a sheep model was examined.

2. Following two weeks of l‐thyroxine treatment, the activity of serum angiotensin converting enzyme was increased from 6.92 U/ml to 8.65 U/ml (s.e.m. = 0.40, n= 13, P<0.01).

3. Discontinuation of l‐thyroxine treatment resulted in lowering the activity of serum angiotensin converting enzyme within three weeks to values close to those observed during the control period.

4. It was concluded that l‐thyroxine modulates serum angiotensin converting enzyme activity. The sheep is an appropriate animal model for the study of the factors that control serum angiotensin converting enzyme activity.
CARDIOVASCULAR EFFECTS OF ISOSORBIDE DINITRATE INFUSED INTRAVENOUSLY INTO ANAESTHETIZED DOGS
Authors: Kuromaru Osamu , Sakai Kazushige
Published: June 2007

1. The cardiohaemodynamic response and the development of tolerance to isosorbide dinitrate (ISDN) were examined in anaesthetized, open‐chest dogs.

2. ISDN, infused intravenously (i.v.) for 2 h at a rate of 10 or 30 μg/kg per min, decreased systemic blood pressure (systolic, mean and diastolic; SBP), left ventricular (LV) systolic and end‐diastolic pressure, LVdP/dt max, pressure‐rate product and coronary blood flow. No significant changes in heart rate (HR) and coronary vascular resistance were observed.

3. Intravenous ISDN significantly attenuated the vasodilator effect of bolus intra‐coronary (i.a.) glyceryl trinitrate (GTN, 1 μg), and ISDN (30 μg), whereas that of bolus i.a. nicorandil (mononitrate, 20 μg) remained unaffected.

4. Just after acute tolerance towards i.a. ISDN was provoked 1 h after starting ISDN infusion (30 μg/kg per min, i.v.), the combined infusion of ISDN (i.v.) and nicorandil (30 μg/kg per min) was instigated for a further hour. Also, 1 h after the onset of vehicle infusion (i.v.), the combined infusion of vehicle and nicorandil (30 μg/kg per min, i.v.) was started.

5. There were essentially no significant differences between the corresponding values concerning the coronary vascular responses obtained from the two combined infusion groups.
COMPARISON OF NORADRENALINE AND ISOPRENALINE REMOVAL IN THE CANINE HINDLIMB AND KIDNEY
Authors: Zimlichman Reuven , Goldstein David S. , Eisenhofer Graeme , Stull Robin , Keiser Harry R.
Published: June 2007

1. Because isoprenaline is not a substrate for neuronal uptake (Uptake‐1, U‐1), the difference in regional removal of isoprenaline from regional removal of the sympathetic neurotransmitter noradrenaline has been proposed as an index of regional U‐1 activity.

2. U‐1 activity has not been assessed in the kidney, where decreased U‐1 may account for increased renal spillover of noradrenaline into plasma in disorders such as essential hypertension.

3. Tracer‐labelled noradrenaline and isoprenaline were simultaneously infused intravenously into anaesthetized dogs, and the regional removal of noradrenaline and isoprenaline was measured in the hindlimb and kidney after administration of the U‐1 blocker desipramine, hydrocortisone, which inhibits extra‐neuronal uptake of noradrenaline (Uptake‐2, U‐2), or no drug.

4. Hindlimb removal of noradrenaline (51%) exceeded that of isoprenaline (36%). Desipramine abolished this difference by decreasing removal of noradrenaline without affecting removal of isoprenaline. Renal removal of isoprenaline exceeded that of noradrenaline (74% vs 54%) even after U‐1 blockade. Hydrocortisone did not affect removal of noradrenaline or isoprenaline in either bed.

5. The results suggest that differences in removal of noradrenaline and isoprenaline reflect U‐1 activity in the hindlimb but not in the kidney; U‐1 is much more important than U‐2 in the regional removal of noradrenaline; and one mechanism of noradrenaline removal in the kidney is by neuronal uptake.
ERYTHROCYTE WATER CONTENT IN SPONTANEOUSLY HYPERTENSIVE RATS AND DOCA‐SALT HYPERTENSIVE RATS
Authors: Kawarabayashi T. , Yasunari K. , Kanayama Y. , Takeuchi K. , Takeda T.
Published: June 2007

1. Intra‐erythrocyte water, sodium and potassium contents were measured in spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)‐salt rats.

2. In 12 week old SHR, the intra‐erythrocyte water content was slightly but significantly lower than that in age‐matched Wistar‐Kyoto (WKY) rats. SHR also exhibited a significantly lower intra‐erythrocyte potassium content, but sodium content tended to be elevated.

3. Although sodium content was not correlated with the water content, potassium content was.

4. In DOCA‐salt hypertensive rats, the intra‐erythrocyte sodium content was higher than that in age‐matched normotensive Sprague‐Dawley rats by about 33%, but the water and potassium contents were similar. There were no significant correlations between these parameters.

5. These findings provide no evidence of water retention in erythrocytes from DOCA‐salt rat or SHR even though intra‐erythrocyte sodium content was increased.
EFFECT OF CALCIUM WITHDRAWAL AND AGENTS AFFECTING CALCIUM TRANSLOCATION ON AGONIST‐INDUCED CONTRACTIONS OF THE RABBIT OVARIAN ARTERY
Authors: Oriowo M. A. , Bevan J. A.
Published: June 2007

1. The effect of extracellular calcium ion (Ca2+) depletion, diltiazem, D‐600 and TMB‐8 on potassium (K+), norepinephrine‐(NE) and histamine‐induced contractions of the rabbit isolated ovarian artery was studied.

2. K+‐induced contractions, which were biphasic, were rapidly lost (∼ 5 min) when calcium was removed from the physiological saline solution (O‐Ca2+ PSS). NE and histamine‐induced contractions also declined rapidly under nominal O‐Ca2+ conditions without any evidence of a depletion resistant component. However, after 1 h under these conditions there was a partial restoration of their responses.

3. EGTA (10‐3 mol/l) abolished these contractions to NE and histamine but not those in normal PSS.

4. Diltiazem and D‐600 were more effective against K+‐induced than NE‐ and histamine‐induced contractions while the intracellular Ca2+ antagonist TMB‐8 was equally effective against all three responses.

5. Histamine could still evoke contraction of the K+‐contracted ovarian artery after this had been completely abolished with diltiazem or D‐600 but not TMB‐8.

6. These results are interpreted to suggest that K+, NE and histamine probably release intracellular Ca2+ to evoke contractions of the ovarian artery. They differ, however, in the mechanisms they employ to facilitate entry of extracellular calcium, which in turn leads to intracellular calcium release.
EFFECTS OF TOTAL AND SELECTIVE PORTASYSTEMIC SHUNTING ON HEPATIC HAEMODYNAMICS AND SOME ASPECTS OF LIVER FUNCTION IN THE CIRRHOTIC RAT
Authors: Jenkins S. A. , Baxter J. N. , Devitt P. , Shields R.
Published: June 2007

1. The effects of total and selective portasystemic shunting on hepatic haemodynamics and some aspects of liver function were studied in rats with dimethylnitro‐samine‐induced cirrhosis.

2. Immediately following end‐to‐side portacaval shunting there were significant reductions in wedged hepatic venous pressure (WHVP) and liver blood flow. After side‐to‐side mesocaval shunting liver blood flow and wedged hepatic venous flow fell by approximately the same magnitude.

3. Selective shunting (mesocaval ‘H’‐grafts and splenopancreaticocaval) preserved liver blood flow to a greater extent than total portasystemic shunting but had a less marked effect on WHVP.

4. Furthermore, selective portasystemic shunting prevented liver atrophy and deterioration in liver function which was observed in rats following total portasystemic shunting.

5. These results suggest that in the cirrhotic rat, selective portasystemic shunts which preserve functional liver blood flow and prevent liver atrophy and a deterioration in liver function do not produce such a marked decrease in WHVP as total shunts. Further studies in man are required to evaluate the relative advantages of total and selective portasystemic shunts.
STUDIES ON THE CYTOTOXICITY OF PENICILLAMINE IN A RAT OSTEOGENIC SARCOMA
Authors: Cosolo W. , Christophidis N. , Drummer O. H. , Findlay D. M.
Published: June 2007

1. The effect of penicillamine on the growth rate of an osteogenic sarcoma of rats was investigated and compared with cyclophosphamide.

2. Rats were inoculated with a readily transplantable osteogenic sarcoma subcutaneously into the left thigh and treated with penicillamine and cyclophosphamide alone or in combination.

3. Cyclophosphamide inhibited tumour growth.

4. Penicillamine did not delay the appearance or the growth rate of the tumour. Tumour sizes tended to be larger in the penicillamine‐treated rats, but there was no evidence that penicillamine interfered with the antitumour effect of cyclophosphamide given in large doses (100 mg/kg).
ALDOSTERONE REGULATION DURING SALINE INFUSION: USEFULNESS OF ALDOSTERONE/CORTISOL RATIO IN THE DIAGNOSIS OF ALDOSTERONE‐PRODUCING ADENOMA
Authors: Hamlet S. M. , Tunny T. J. , Klemm S. A. , Gordon R. D.
Published: June 2007

1. Saline infusion was performed in normal subjects, in essential hypertensives and in patients with aldosterone‐producing adenoma (APA), with serial measurements of plasma aldosterone, cortisol and atrial natriuretic peptide (ANP). The effect of recumbency alone was also observed in the normal subjects.

2. Plasma aldosterone after saline infusion was less than 7 ng per 100 ml in the essential hypertensives and normal subjects, but greater than 9 ng per 100 ml in the patients with APA.

3. The aldosterone/cortisol ratio in normal subjects and in essential hypertensives was unchanged or fell during saline infusion, but rose in five of eight patients with APA.

4. Thus, an increase in aldosterone/cortisol ratio after saline infusion appears to be diagnostic of APA, but its absence does not exclude it.
PRENATAL HIGH SALT DIET INCREASES BLOOD PRESSURE AND SALT RETENTION IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Nicolantonio R. Di , Spargo S. , Morgan T. O.
Published: June 2007

1. An examination was made of the effect of prenatal, high salt (5% w/w) and low salt (0.1% w/w) diet on the blood pressure and ability to excrete a salt load of mature spontaneously hypertensive rats (SHR) of the Okamoto strain maintained on normal salt (0.8% w/w) diet after weaning.

2. Prenatal high salt diet resulted in a significant exacerbation of the hypertension of 4 month old SHR when compared with animals given prenatal low salt diet.

3. Three month old SHR given prenatal, high salt diet exhibited a significantly reduced Na+ excretion following a single, oral salt load (150 mmol/l, 1% bodyweight) when compared with the low salt group.

4. Thus, prenatal, high salt diet may influence body fluid homeostasis in genetically susceptible individuals later in life.
THE URIDINE NUCLEOTIDES CONSTITUTE A NATRIURETIC PRESSOR SYSTEM
Authors: Macdonald Graham , Assef Rhonda , Watkins Stan , Burrell Judith
Published: June 2007

1. Uridine monophosphate was tested in the conscious rat for natriuretic properties and an immunoperoxidase technique was used to localize uridine‐containing compounds in the rat kidney.

2. Uridine monophosphate, infused in a moderate pressor dose, caused a significant natriuresis compared to the effect of control infusions of solvent vehicle.

3. Uridine‐containing compounds were found in most tubular elements with particularly dense staining in the distal and collecting tubules.

4. While the increased sodium excretion may have been due to increased renal perfusion pressure, the high density of uridine staining in distal nephrons suggests that the uridine nucleotides have a specific nephron function, possibly relating to sodium transport.
THE EFFECT OF DOCA AND 9α‐FLUDROCORTISONE ON RENAL RENIN CONTENT AND PRODUCTION
Authors: Menting J. , Morgan T. , Barrett G. , Nicolantonio R. Di
Published: June 2007

1. DOCA and 9α‐fludrocortisone were given to rats.

2. Plasma renin fell rapidly with both treatments.

3. Renal renin fell slowly to a low level.

4. Renal renin fell to a lower level with DOCA than with 9α‐fludrocortisone.

5. When DOCA and 9α‐fludrocortisone were stopped plasma renin levels rose rapidly and the renal renin levels increased.

6. The data suggest that synthesis is altered rapidly but it takes a prolonged time for the kidney to become depleted of renin due to the high tissue stores and the associated inhibition of release.
DOSE‐RESPONSE RELATIONSHIPS FOR ADRENOCORTICOTROPHIN‐INDUCED HYPERTENSION IN MAN
Authors: Whitworth Judith A. , Gordon Deanna , Scoggins Bruce A.
Published: June 2007

1. Adrenocorticotrophin (ACTH), given as long‐acting Synacthen depot (Ciba‐Geigy), at 1000 μg/day, in divided doses 12 hourly, is known to increase blood pressure in man.

2. Fifty μg/day of short‐acting Synacthen given intravenously produced a rise in blood pressure and may be a threshold dose.

3. Twelve hourly intramuscular injections of short‐acting Synacthen over the dose range 100–400 μg/day was not sufficient to raise blood pressure.
PLASMA ATRIAL NATRIURETIC PEPTIDE: CONCENTRATIONS AND CIRCULATING FORMS IN NORMAL MAN AND PATIENTS WITH CHRONIC RENAL FAILURE
Authors: Ogawa Kazuya , Smith A. Ian , Hodsman G. Peter , Jackson Bruce , Woodcock Elizabeth A. , Johnston Colin I.
Published: June 2007

SUMMARY

1. A specific and sensitive radioimmunoassay has been developed and used to measure circulating atrial natriuretic peptide (ANP) in normal man and in patients with chronic renal failure.

2. Circulating ANP levels rose with head‐down tilt and exercise, and were raised in patients with chronic renal failure in proportion to volume status. This suggests that ANP release is mediated via increased atrial stretch, although other release mechanisms cannot be excluded.

3. Extracts of normal human plasma subjected to reverse phase HPLC showed one major peak of immunoreactivity co‐migrating with α‐human ANP. However, when plasma extracts from patients with renal failure were chromatographed on a similar system, a second later eluting peak of ANP immunoreactivity was observed. This may represent circulating ANP precursors or degradation molecules.

4. Significant arteriovenous differences in plasma ANP concentration were observed in patients with chronic renal failure. Arterial and venous plasma ANP levels decreased slightly after haemodialysis. Plasma ANP concentrations were inversely correlated with haematocrit in these patients.
ACUTE HAEMODYNAMIC AND HORMONAL EFFECTS OF ORAL DOXAZOSIN IN NORMAL SUBJECTS
Authors: Whitworth Judith A. , Butty Jill , Gordon Deanna
Published: June 2007

SUMMARY

1. Haemodynamic and hormonal effects of doxazosin, a long‐acting α1‐adrenoceptor antagonist (2 mg) were compared with placebo in six normal men.

2. Doxazosin at 2 mg produced lower supine systolic blood pressure and plasma cortisol concentration than control at 4 h only, but these changes were not sustained. Both supine and standing pulse rate were increased by active drug after 6 h.

3. In this acute study doxazosin did not affect plasma renin or aldosterone concentrations.
THE EFFECT OF ENDOGENOUS OPIOIDS ON BLOOD PRESSURE DURING STRESS
Authors: Nordin M. , Moral P. , Zainora M.
Published: June 2007

1. A series of experiments were conducted to investigate the effect of endogenous opioids on blood pressure of laboratory rats during stress.

2. Rats subjected to 120 min immobilization showed a significant drop in systolic pressure which could be prevented by pretreatment injections of naloxone.

3. Adrenalectomized rats subjected to the same kind of stress showed a drop in systolic pressure equivalent to only 30% of the systolic pressure drop in the intact animals. This decrease in systolic pressure could also be prevented by pretreatment injections of naloxone.

4. It was concluded that the decrease in systolic pressure in intact rats during immobilization was mostly due to endogenous opioids released from the adrenal glands, whereas opioids of other origins such as the pituitary gland, were also important.