bluuebunny/crossref_metadata_2025 huggingface dataset:
HAEMODYNAMIC AND RENAL EFFECTS OF A NOVEL PROSTAGLANDIN ANALOGUE (L644, 122 (+ISOMER)) IN SHEEP
Authors: Tresham Janette J. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. Merino‐cross ewes were given an intravenous injection of a prostaglandin analogue, (+)‐4‐{3‐[3‐[2‐(1 ‐hydroxycyclohexyl)ethyl]‐4‐oxo‐2‐thiazolidinyl]‐propyl} benzoic acid, at doses of 0.01,0.05 and 0.10 mg/kg, on separate days, to determine renal and haemodynamic responses.

2. Peripheral vasodilatory effects, indicated by increases in heart rate and cardiac output, and falls in total peripheral resistance, peaked at 20 min at the two highest doses. By 60 min most values had returned to pre‐injection levels. There were no changes in mean arterial pressure.

3. At the highest dose of 0.10 mg/kg there was a fall in glomerular filtration rate, renal blood flow and effective renal plasma flow within 20 min. Urinary sodium and potassium excretion also fell with all three doses tested.

4. Plasma renin concentration increased at the 0.05 and 0.10 mg/kg doses and was still elevated at 60 min.

5. The results of this study in the sheep contrast with others in the dog, where renal blood flow is increased and the rat, where blood pressure is increased, and indicate a species specificity in regard to the analogue's actions.
THE PATTERN OF ATRIAL NATRIURETIC PEPTIDE RELEASE DURING VENTRICULAR TACHYCARDIA IN MAN
Authors: Crozier Ian G. , Ikram Hamid , Nicholls M. Gary
Published: June 2007

1. Plasma levels of atrial natriuretic peptide (ANP) are high in many patients with tachycardia, but patterns of release with onset and termination of tachycardia and relationships to haemodynamic recordings are not clear. Blood for ANP measurements was therefore drawn from the coronary sinus, femoral artery and femoral vein, and simultaneous haemodynamic recordings were made in five patients before, during and after induction of stable ventricular tachycardia for 30 min.

2. Tachycardia induced increases in ANP to peak levels, 2.6 to 5.7 times higher than baseline values at 20 min or later, whereas maximum haemodynamic changes, including a rise in pulmonary artery diastolic pressure, were achieved within 4 min.

3. Reversion to sinus rhythm resulted in immediate changes in haemodynamic recordings, whereas ANP levels in arterial and venous plasma fell sluggishly with an apparent half‐life of 9.6 and 7 min, respectively.

4. The results support a central role for atrial pressure in determining ANP secretion, but demonstrate a temporal delay between changes in atrial pressure and ANP secretion.
VENOCONSTRICTION CAUSES DIFFERENT EFFECTS IN THE HINDQUARTERS VENOUS COMPARTMENT OF CATS AND DOGS*
Authors: Widdop R. E. , Bentley G. A. , Reynoldson J. A. , Cullen L. K.
Published: June 2007

1. A study was made of venoconstrictor mechanisms in the hindquarters region of cats and dogs by the use of autoperfused hindquarter preparations, together with the measurement of vena cava blood flow (VCBF).

2. Noradrenaline, adrenaline and angiotensin II (AII) were all administered intraarterially and their ability to alter perfusion pressure and VCBF was examined.

3. All three drugs increased perfusion pressure in both cats and dogs as a result of increases in arterial resistance. At the same time, noradrenaline and adrenaline increased VCBF in cats, while AII had a variable effect. In contrast, all three drugs decreased VCBF in dogs.

4. These differences in the venoconstrictor responses obtained in cats and dogs may be explained by an action of the drugs at different loci within the venous compartment of the two species.
PLASMA CATECHOLAMINE CONCENTRATIONS DURING MORPHINE WITHDRAWAL IN CONSCIOUS GUINEA‐PIGS
Authors: Brent P. J. , Johnston P. A. , Chahl Loris A.
Published: June 2007

1. Plasma noradrenaline (NA) and adrenaline (AD) concentrations and locomotor activity were measured in conscious normal and adrenalectomized guinea‐pigs before and after injection of a single dose of morphine (15 mg/kg) and following precipitation of withdrawal with naloxone 2 h later. Arterial blood samples were obtained via carotid catheters inserted 3 days before experiment. Normal guinea‐pigs given saline instead of morphine were used as controls.

2. Increased locomotor activity occurred following naloxone injection in both intact and adrenalectomized morphine‐treated guinea‐pigs.

3. Plasma AD concentration was significantly elevated only during the naloxone‐ precipitated withdrawal period, whereas plasma NA concentration was also elevated during the morphine treatment period. No significant changes occurred in saline‐treated guinea‐pigs given naloxone.

4. In adrenalectomized guinea‐pigs AD did not reach detectable levels in the plasma at any time during the experiments, thus showing that the increased plasma AD level during morphine withdrawal in normal animals reflected adrenal medullary release.

5. It was concluded that measurements of plasma AD concentration and locomotor activity in guinea‐pigs should be useful for the study of the interactions between behavioural and autonomic mechanisms involved in opiate dependence and withdrawal, since the effects of morphine and morphine withdrawal on the autonomic nervous system are clearly different in this species.
INFLUENCE OF BRADYKININ ON BLOOD PRESSURE REGULATION OF SPONTANEOUSLY HYPERTENSIVE RATS MAINTAINED ON DIFFERENT SODIUM INTAKES
Authors: Waeber B. , Aubert J. F. , Nussberger J. , Vavrek R. , Stewart J. M. , Brunner H. R.
Published: June 2007

1. The role of circulating bradykinin in blood pressure regulation was studied in conscious spontaneously hypertensive rats utilizing the competitive antagonist of bradykinin B4162.

2. This antagonist was administered at a bolus dose (400 μg i.v.) known to block the hypotensive effect of exogenous bradykinin for at least 2 min. The rats were maintained for 10 days either on a low or a high sodium intake.

3. The antagonist of bradykinin significantly increased blood pressure only in salt‐ depleted rats. In other rats kept on a low or a high sodium intake, dose‐response curves to exogenous bradykinin were established. Dietary sodium had no influence on the blood pressure‐lowering effect of bradykinin.

4. These data therefore suggest that circulating bradykinin may be involved in the blood pressure control of spontaneously hypertensive rats when the renin‐angiotensin system is stimulated by salt depletion.
WHOLE BLOOD PLATELET AGGREGATION IS NOT AFFECTED BY CIGARETTE SMOKING BUT IS SEX‐RELATED
Authors: Taylor R. R. , Sturm M. , Vandongen R. , Strophair J. , Beilin L. J.
Published: June 2007

1. In normal subjects, 18–49 years old, the effects of the smoking habit (>10 cigarettes/day) and the act of smoking two cigarettes over 10 min were studied on whole blood platelet aggregation (in vitro impedance method).

2. Acute smoking (n= 10) did not affect platelet aggregation to ADP, collagen or to platelet activating factor (PAF) nor thromboxane B2 production during aggregation. There was no difference between smokers (n= 13) and non‐smokers (n= 10). However, aggregation to all aggregants was greater in females (n= 11) than males (n= 12) (ADP and collagen, P <0.001; PAF, P <0.01; ANOVA).

3. Although others have obtained diverse results studying platelet‐rich plasma, the absence of an effect of cigarette smoking on whole blood platelet aggregation is consistent with many of those observations. Greater in vitro aggregability in females than males is consistent with the few studies of platelet‐rich plasma. It seems unlikely that the role of cigarette smoking as a risk factor for ischaemic heart disease is related to a direct effect on platelet aggregability.
PERFUSION WITH NON‐OXYGENATED TYRODE SOLUTION CAUSES MAXIMAL CORONARY VASODILATION IN CANINE HEARTS
Authors: Crystal George J. , Downey H. Fred
Published: June 2007

1. Coronary vasodilator effects of non‐ischaemic hypoxia (perfusion with non‐oxygenated Tyrode solution) and ischaemic hypoxia (coronary occlusion) were compared.

2. The left anterior descending coronary artery (LAD) of six in situ canine hearts was perfused selectively at controlled pressure with normal arterial blood or with non‐oxygenated Tyrode solution. LAD flow was measured continuously with an electromagnetic flowmeter. Reactive hyperaemic blood flow responses following 3 min Tyrode perfusion were compared with responses following 3 min complete coronary occlusion.

3. Control LAD blood flow was 26.9 ± 4.6 ml/min. A 3 min period of Tyrode perfusion caused a peak reactive hyperaemic blood flow of 151 ± 31 ml/min, which was not significantly different from that caused by 3 min occlusion, 123 ± 17 ml/min. The duration and total volume of reactive hyperaemia flow following Tyrode perfusion were smaller than values following occlusion.

4. The present findings demonstrate that myocardial hypoxia per se is a sufficient vasodilatory stimulus to account for the peak reactive hyperaemic flow following 3 min occlusion, but that the prolonged reactive hyperaemic response depends on vasodilator metabolites which accumulate in ischaemic myocardium.
THE EFFECT OF THE CAROTID SINUS REFLEX ON LARGE CORONARY ARTERY DIAMETER IN ANAESTHETIZED DOGS
Authors: Woodman Owen L.
Published: June 2007

1. The diameter of, and blood flow in, the left circumflex coronary artery was measured in anaesthetized dogs and the carotid sinus reflex was stimulated by bilateral occlusion of the carotid arteries (BCO) for 2 min.

2. The effect of BCO on coronary artery diameter and late diastolic coronary resistance was examined: (a) after bilateral vagotomy; (b) after vagotomy plus antagonism of β‐adrenoceptors with propranolol (1 mg/kg, i. v.); and (c) after vagotomy, antagonism of β‐adrenoceptors and antagonism of α‐adrenoceptors with phentolamine (0.5 mg/kg, i.v.).

3. After vagotomy BCO increased mean arterial pressure (Δ= 72 ± 7 mmHg), heart rate (16 ± 3 beats/min), coronary blood flow (37 ± 11 ml/min) and coronary artery diameter (0.14 ± 0.04 mm). Late diastolic coronary resistance initially fell (‐0.26 ± 0.13 mmHg min/ml at 30s) but at the end of the 2 min occlusion it had returned to the baseline level (Δ= 0.04 ± 0.08 mmHg min/ml).

4. In the presence of propranolol BCO increased arterial pressure (28 ± 12 mmHg), but did not alter heart rate (0.6 ± 0.4 beats/min) or coronary blood flow (2 ± 2 ml/min). There was a significant decrease in large artery diameter (‐0.24 ± 0.07 mm) and an increase in late diastolic coronary resistance (0.46 ± 0.12 mmHg min/ml). A mechanical increase in afterload did not affect large coronary artery diameter or coronary resistance

5. Antagonism of α‐adrenoceptors abolished the reflex‐induced constriction of the large coronary artery (Δ= ‐0.02 ± 0.02 mm) and the coronary resistance vessels (ΔLDCR = ‐0.02 ± 0.03 mmHg min ml).

6. In conclusion, in the anaesthetized, vagotomized dog BCO induces vasodilatation of the large coronary artery which is reversed to a vasoconstriction by antagonism of β‐adrenoceptors. Antagonism of α‐adrenoceptors abolishes the BCO‐induced constriction of the large coronary artery and the coronary resistance vessels. These findings suggest that the tone of the large coronary arteries, as well as the coronary resistance vessels, may be regulated by neural reflexes.
ALTERATIONS OF β‐ADRENOCEPTORS ON HUMAN LEUKOCYTE SUBSETS INDUCED BY DYNAMIC EXERCISE: EFFECT OF PREDNISONE
Authors: Ratge D. , Wiedemann A. , Kohse K. P. , Wisser H.
Published: June 2007

1. In order to investigate exercise‐induced changes of β2‐adrenoceptors on human leukocyte subsets, β‐adrenoceptor density was determined as specific binding of [125I]‐iodocyanopindolol to granulocytes, monocytes, B and T lymphocytes of six subjects immediately before and after exercise and after 30 min of rest.

2. A 10 min graded bicycle exercise with a workload of 50–250 W caused a transient increase of granulocytes, monocytes, B and T cells of about 32, 43, 120 and 25%, respectively.

3. While the number of β2‐adrenoceptors in granulocytes remained unchanged, β‐adrenoceptor densities in B cells, T cells and monocytes increased from pre‐exercise mean values of 2730, 870 and 2400 binding sites/cell to 3500, 1230 and 3220 binding sites/cell, respectively, under physical stress. The rise in receptor numbers was accompanied by an enhanced isoprenaline‐stimulated cyclic AMP formation in unfractionated mononuclear leukocytes (MNL) of about 26% as well as by a 2–3‐fold increase in plasma catecholamine levels. Cell concentrations, β2‐adrenoceptor numbers and adrenergic responsiveness returned to normal after 30 min rest.

4. Administration of 60 mg prednisone 2 h before exercise resulted in granulocytosis and lymphopenia with a preponderant effect on the exercise‐induced rise in B cells and monocytes. Corticosteroids showed no effect on stress‐induced changes of β2‐adrenoceptors and responsiveness.

5. It is concluded that exercise‐induced increases in β2‐adrenoceptor density and adrenergic responsiveness of unfractionated MNL are caused by a release of receptor‐enriched cells into the circulation, particularly of B lymphocytes and monocytes which carry the highest β2‐adrenoceptor density.
A STUDY OF CENTRAL NEUROTRANSMITTER MECHANISMS IN MORPHINE‐INDUCED ‘STRAUB REACTION’ IN MICE: ROLE OF CENTRAL DOPAMINE RECEPTORS
Authors: Gupta M. L. , Nath R. , Gupta T. K. , Gupta G. P.
Published: June 2007

1. The role of putative neurotransmitters was investigated in morphine‐induced Straub reaction (SR) in albino mice.

2. Apomorphine (15 mg/kg) was also effective in inducing SR. However, in a smaller dose (0.2 mg/kg) it blocked SR induced by morphine.

3. Morphine‐induced SR was potentiated by tranylcypromine, reserpine (acute effect), imipramine and l‐dopa and blocked by reserpine (chronic effect), α‐methyldopa, pimozide, chlorpromazine, haloperidol and metoclopramide. Prazosin and clonidine partially blocked morphine SR in high doses.

4. Propranolol, yohimbine, cyproheptadine and atropine were ineffective in blocking morphine SR.

5. The results indicate that morphine SR is mediated through release of DA in the CNS which excites central D2 receptors. Activation of central α1‐adrenoceptors might also play a minor role.
MARKERS OF PHYSICAL INTEGRITY AND METABOLIC VIABILITY OF THE PERFUSED HUMAN PLACENTAL LOBULE
Authors: Cannell G. R. , Kluck R. M. , Hamilton S. E. , Mortimer R. H. , Hooper W. D. , Dickinson R. G.
Published: June 2007

b

1. Peripheral lobules of term placentae obtained from healthy females at Caesarian section were perfused using separate maternal and fetal circulations for 6 h periods under either oxygenated or anoxic conditions.

2. Markers of physical integrity during setting‐up and initial perfusion were establishment of dual perfusion within 25 min of placental delivery, pressure in the fetal capillary network less than 40 mmHg, leakage of perfusate from fetal to maternal compartments ≤ 2 ml/h, and overlap of maternal with fetal perfusion as indicated visually by appropriate blanching and verified by a fetal artery to vein oxygen gradient of ≤ 90 mmHg.

3. Post‐perfusion markers of metabolic viability were most reliably indicated by glucose consumption (oxygenated 7.8 ± 1.5, anoxic 17.7 ± 1.2 mmol/kg per h), lactate production (oxygenated 8.5 ± 1.4, anoxic 33.9 ± 2.5 mmol/kg per h) and human placental lactogen production (oxygenated 41.2 ± 9.8, anoxic 12.2 ± 3.4 mg/kg per h).
INTERACTION BETWEEN PHENYTOIN AND THEOPHYLLINE IN HEALTHY VOLUNTEERS
Authors: Adebayo G. I.
Published: June 2007

SUMMARY

1. The effect of phenytoin, 100 mg thrice daily for 3 weeks, on theophylline disposition was studied in eight healthy volunteers.

2. The anticonvulsant significantly reduced the half‐life of theophylline and this was associated with an increase in the rate of theophylline clearance. The volume of distribution was not significantly altered.

3. There was no correlation between initial theophylline clearance and its percentage increase after phenytoin pretreatment.

4. Coefficients of variation in theophylline clearance before and after phenytoin pretreatment were similar.

5. It is suggested that phenytoin induces theophylline metabolism, that initial theophylline metabolism is not a determinant of the extent of such induction, and that there is a similar potential for induction among healthy volunteers.
EFFECTS OF THROMBOXANE SYNTHETASE INHIBITOR (UK 38,485) AND THROMBOXANE RECEPTOR ANTAGONIST (ICI 185,282) ON DIGOXIN‐INDUCED ARRHYTHMIAS IN ANAESTHETIZED GUINEA‐PIGS
Authors: Kanzik I. , Demiryürek A. T. , Zengil H. , Abacioǧlu N. , Dörtlemez H.
Published: June 2007

1. Increased local thromboxane (Tx) formation has been considered to be a contributing factor in digitalis‐induced arrhythmias.

2. A potent Tx synthetase inhibitor (TxSI), UK 38,485 (0.1, 1.0 or 10.0 mg/kg per h, administered intravenously) and a Tx receptor antagonist (TxRA), ICI 185, 282 (1, 2 or 10 mg/kg bolus and 1, 2 or 10 mg/kg per h, administered intravenously) were tested for their ability to reduce digoxin‐induced arrhythmias in anaesthetized guineapigs.

3. Electrocardiograms, mean blood pressure, heart rate and arrhythmias were recorded, starting 30 min before digoxin administration and continued for 60 min afterwards.

4. ICI 185,282, at the doses used, significantly delayed the time of onset of arrhythmias, and reduced the incidence of ventricular fibrillation, mortality and arrhythmia score. In contrast, UK 38,485 was found to be effective on all measured variables only at the dose rate of 1.0 mg/kg per h, except for time required for the development of arrhythmias. These protective effects of both TxSI and TxRA were not found to be dose‐dependent.

5. Arterial blood pressure and heart rate changes caused by either UK 38,485 or ICI 185,282 infusions did not have any marked effects on digoxin‐induced arrhythmias.

6. These data suggest that endogenously released TxA2 and prostaglandin endoperoxides may play an important role in digoxin‐induced arrhythmias in guinea‐pigs.
ANGIOTENSINS II AND III PREVENT CAPTOPRIL‐INDUCED RENIN RELEASE IN THE RAT
Authors: Moldenhauer G. K. , Smith M. D. , Nicolantonio R. Di , Doyle A. E. , Morgan T. O.
Published: June 2007

1. The effects of exogenous angiotensins II and III (50 pmol/min i.v.) on plasma renin release following captopril injection (5 mg/kg, i.v.) were studied in anaesthetized Sprague‐Dawley rats, to determine whether angiotensin II blockade is the major mechanism by which captopril induces renin release.

2. Captopril produced a 12‐fold increase in plasma renin concentration compared with saline‐injected controls. This was completely reversed by pre‐infusion of angiotensin II or III.

3. The fall in blood pressure following captopril treatment was also abolished by angiotensins II and III pre‐infusion. Noradrenaline pre‐infusion (200–800 ng/min, i.v.) also prevented the captopril‐induced hypotension but did not alter the rise in plasma renin.

4. Ureteric ligation did not significantly reduce captopril‐induced renin release suggesting that acute changes in sodium excretion or delivery of electrolyte to the macula densa were not involved in renin release.

5. These findings suggest that captopril induces renin release by inhibiting angiotensin II feedback control of renin secretion and that angiotensin III may also modulate renin release.
RISK‐BENEFITS OF ANTIHYPERTENSIVE DRUGS ‐ β‐BLOCKERS
Authors: Prichard B. N. C.
Published: June 2007

1. β‐Blockers are of similar efficacy in the treatment of hypertension to other antihypertensive drugs of first choice; they have a wide spectrum of activity both alone and in combination.

2. Although β‐blockers first appear to worsen the haemodynamic changes of hypertension, subsequently peripheral resistance falls. The cardiovascular reflexes responsible for the responses of posture or other responses requiring normal functioning of α‐mediated tone are not inhibited.

3. Important contra‐indications are asthma and heart failure in susceptible subjects. Lipid soluble drugs have somewhat greater CNS side effects.

4. Triglyceride levels, notably an increase in VLDL and a fall in HDL occur from non‐selective agents (less so from Pi‐selective agents) and there is a marginal effect from drugs with relatively high ISA.

5. In contrast to other antihypertensive drugs β‐blockers reduce the myocardial infarction rate in high risk patients (i.e. post‐myocardial infarct). Results in primary prevention of mild hypertension have been less promising.

6. Those drugs which are lipid soluble and liver metabolized result in greater variation of plasma concentration after oral administration and some pharmacokinetic drug interactions. Once daily administration is possible with many β‐blockers.

7. β‐Blocking drugs have an established and proven place in the treatment of hypertension.
NON‐PHARMACOLOGICAL CONTROL OF BLOOD PRESSURE
Authors: Beilin L. J.
Published: June 2007

1. Essential hypertension is a disorder caused by environmental factors operating against a background of genetic susceptibility.

2. Weight control, sodium restriction, increased potassium intake and reduced alcohol consumption can all cause a fall in blood pressure in hypertensive people.

3. A vegetarian diet causes a fall in blood pressure but it is not clear which dietary components are responsible for these effects.

4. The role of calcium, magnesium, dietary fish and fish oils in lowering blood pressure is uncertain.

5. Physical activity lowers blood pressure.

6. Psychological techniques appear to lower blood pressure but their role in management of hypertensive patients is not clear.

7. Most non‐pharmacological measures have not been evaluated over a long time period.

8. Recent studies suggest that hypertensives who have been controlled with drugs may then be able to be controlled by non‐pharmacological measures.
POINT OF VIEW: WHY HYPERTENSION IS OVERDIAGNOSED AND OVERTREATED IN 1987
Authors: Gordon Richard D.
Published: June 2007

1. The decision whether arterial blood pressure (BP) is elevated or normal is usually based on inadequate data: few readings in the presence of great variability of BP; levels higher in the presence of the doctor; and diastolic BP often higher sitting and standing than lying.

2. Assessments of response and of the need for increases in drug dosage are also based on insufficient data.

3. Increased morbidity and mortality from stroke and heart attack, and incomplete correction with treatment have been interpreted as suggesting further benefit from aggressive reduction of BP to ‘normal’ in all patients.

4. The emergence of powerful drugs with few side‐effects, and the promise of lowering office BP to ‘normal’ as monotherapy, has removed the hesitation to treat ‘mild’ hypertension.

5. Attempts to lower sitting office diastolic BP to ‘normal’ have led to increasing drug dosage, dose‐related, drug‐specific side‐effects, and lethargy due to hypotension.

6. Newer self‐measurement BP units can be used easily by most patients, cost less than five visits to the doctor and provide a cheap method of obtaining sufficient data on which to base informed management decisions. Supported by normal echocardio‐graphic left ventricular mass, normal ‘home BP’ (including lying diastolic) permits many mild hypertensives to remain off medications.

7. Non‐drug therapy avoids or reduces long‐term drug therapy, with its side‐effects.
RED BLOOD CELL IONIZED CALCIUM CONCENTRATION IN SPONTANEOUS HYPERTENSION: MODULATION IN VIVO BY THE CALCIUM ANTAGONIST PN 200.110
Authors: Morris M. J. , David‐Dufilho M. , Devynck M. A.
Published: June 2007

1. Altered calcium regulation has been observed in experimental and human hypertension. In this study erythrocyte (RBC) intracellular calcium concentration ([Ca2+]i) was compared in conscious spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) at rest and after injection of the dihydropyridine calcium antagonist PN 200.110.

2. Resting [Ca2+]i was similar in SHR and WKY.

3. PN 200.110 administration induced a rapid decrease in blood pressure in SHR and WKY. Five minutes after the injection no change in [Ca2+]i was observed; at 1 h [Ca2+]i was significantly decreased in SHR, but not in WKY.

4. These results suggest that the mutual adaptation of the rate of calcium influx through calcium channels and the activity of the calcium extruding pump differ between WKY and SHR.
TIME COURSE OF CHANGES IN BARORECEPTOR REFLEX CONTROL OF HEART RATE IN CONSCIOUS SHR AND WKY: CONTRIBUTION OF THE CARDIAC VAGUS AND SYMPATHETIC NERVES
Authors: Head Geoffrey A. , Adams Michael A.
Published: June 2007

1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine‐ and nitroprusside‐induced steady‐state changes in blood pressure.

2. MAP increased with age in both strains but was 17–23% higher in SHR.

3. By contrast baroreflex parameters (HR range: difference between upper and lower HR plateaus, and gain: average slope between inflection points of the logistic MAP‐HR relationship) decreased with age in SHR but increased in WKY.

4. After methylatropine, no differences in the cardiac sympathetic baroreflex range or gain parameters were observed between strains or ages.

5. It was concluded that older SHR have normal sympathetic but reduced vagal capacity to control HR in response to changes in MAP, but that this deficit was not dependent on the absolute level of blood pressure.

6. Because the differences were confined to one effector, SHR may have different central rather than arterial baroreceptor afferent mechanisms.
EFFECTS OF VOLUME EXPANSION AND CONTRACTION ON PLASMA LEVELS OF ATRIAL NATRIURETIC PEPTIDE IN MAN
Authors: Finn Wendy L. , Gordon Richard D. , Tunny Terry J. , Klemm Shelley A. , Hamlet Stephen M.
Published: June 2007

1. Effects of saline infusion and blood removal on atrial natriuretic peptide (ANP) in normal subjects were examined in order to better define the magnitude of acute central volume regulatory influences on ANP.

2. Plasma ANP levels increased progressively during volume expansion with saline infusion, increasing by 18% after 30 min and by 93% after 120 min, and did not change during recumbency alone.

3. Plasma ANP levels immediately after a standard blood donation performed semirecumbent were significantly lower than before blood donation; they fell by 18%.

4. The magnitude of the fall in ANP induced by blood donation correlated significantly with basal plasma ANP.

5. In man, ANP responds to both increases and decreases in central blood volume, consistent with a role for ANP in blood volume homeostasis.
EFFECT OF GLYCAEMIC CONTROL ON GLOMERULAR FILTRATION RATE IN THE STREPTOZOTOCIN DIABETIC RAT
Authors: Jackson B. , Franze L. , Allen T. J. , O'Brien R. , Cooper M. , Hodsman G. P. , Jerums G.
Published: June 2007

1. Diabetes was induced in 32 adult Wistar‐Kyoto rats with streptozotocin (60 mg/kg). Fourteen rats remained untreated, 10 received insulin three times per week, and eight received insulin daily. Fourteen non‐diabetic rats served as controls.

2. Exchangeable sodium and plasma volume were elevated in the untreated diabetic rats. Treatment normalized these parameters,

3. Glomerular filtration rate (GFR) was elevated in the untreated diabetic group and the group receiving insulin three times per week compared with the control group. Daily insulin treatment restored GFR towards control values.

4. Plasma atrial natriuretic factor was similar in untreated diabetic rats and non‐diabetic rats.
PRE‐AND POSTJUNCTIONAL EFFECTS OF NEUROPEPTIDE Y ON THE RABBIT ISOLATED EAR ARTERY
Authors: Wong‐Dusting H. K. , Rand M. J.
Published: June 2007

b

1. In the isolated perfused and superfused rabbit ear artery, neuropeptide Y (NPY, 0.3–100 nmol/l) had no direct vasoconstrictor action, but produced a concentration‐dependent and reversible enhancement of vasoconstrictor responses to both sympathetic nerve stimulation and exogenous noradrenaline.

2. In arteries in which the noradrenergic transmitter stores had been radiolabelled with [3H]‐noradrenaline, 100 nmol/l NPY inhibited the stimulation‐induced (1 Hz for 30 s) release of radioactivity, but the lower concentrations tested (10 and 30 nmol/l) had no effect. NPY (10, 30 and 100 nmol/l) had no effect on the resting release of radioactivity.

3. Thus, NPY in low concentrations enhances vasoconstrictor responses in the rabbit ear artery by a postjunctional action; prejunctionally, NPY inhibits stimulation‐induced transmitter release when it is present in high concentrations.
EFFECTS OF TUBOCURARINE ON END‐PLATE CURRENT RUNDOWN AND QUANTAL CONTENT DURING RAPID NERVE STIMULATION IN THE SNAKE
Authors: Harborne A. J. , Bowman W. C. , Marshall I. G.
Published: June 2007

1. The effects of tubocurarine, pancuronium, vecuronium and trimethyl‐tubocurarine were examined on the amplitudes of end‐plate currents (EPC) produced by repetitive nerve stimulation in cut voltage‐clamped fibres of the costocutaneous muscle of the garter snake. The effects of tubocurarine were further studied on the amplitudes of miniature end‐plate currents (MEPC) recorded immediately before the trains of nerve stimulation, thus allowing estimates to be made of EPC quantal content.

2. All four compounds increased the decline of EPC amplitude with successive impulses (rundown), compared with that observed in control end‐plates. There was little effect on the decay time constants of EPC and the effects on rundown were not dependent on membrane potential, indicating that end‐plate ion channel blockade was not a major effect in producing rundown.

3. In the presence of tubocurarine the quantal content of the EPC in the plateau phase of the trains was reduced when compared with control, indicating a reduction of transmitter mobilization. However tubocurarine had no significant effect on the quantal content of the first EPC of the trains, indicating that the decreased mobilization is not due to an initial effect on transmitter release.

4. It is suggested that the prejunctional effect of tubocurarine which results in increased EPC train rundown is primarily on transmitter mobilization. It is also suggested that the actions of tubocurarine and the other neuromuscular blockers tested are mediated through a prejunctional nicotinic receptor which may act as a positive feedback mechanism modulating transmitter mobilization.
EFFECTS OF ORPANOXIN ON ARACHIDONIC ACID METABOLISM OF HUMAN POLYMORPHONUCLEAR LEUCOCYTES AND PLATELETS IN VITRO
Authors: Doerr Iris L. , Kaufman Jeffrey , Brooks Robert R.
Published: June 2007

1. The effect of orpanoxin, a nonsteroidal anti‐inflammatory drug, on cyclooxygenase and lipoxygenase activity in human polymorphonuclear leucocytes (PMNL) and platelets was studied ex vivo to see if lipoxygenase inhibition contributed to orpanoxin's mechanism of action.

2. In PMNL, orpanoxin (50, 100, and 200 μmol/l), like indomethacin (100 μmol/l), had little effect on synthesis of leukotriene B4 or 5S‐hydroxy‐6‐trans,8,11,14‐cis‐eicosatetraenoic acid. BW755c at 100 μmol/l inhibited synthesis of both.

3. In PLT, orpanoxin (100 μmol/l) inhibited formation of cyclooxygenase products (thromboxanes, prostaglandins, and 12‐l‐hydroxy‐5,8,10‐heptadecatrienoic acid) and increased synthesis of the lipoxygenase product, 12S‐hydroxy‐5,8‐cis, 10‐trans,14‐cis‐eicosatetraenoic acid. Effects of indomethacin (100 μmol/l) and benoxaprofen (100 μmol/l) in platelets were qualitatively similar to those of orpanoxin.

4. These results indicate that the discrepancy between the low potency of orpanoxin in inhibiting bovine seminal vesicle cyclooxygenase in vitro and its high potency as an anti‐inflammatory agent in vivo is not explained by its having an additional lipoxygenase inhibitory mechanism.
MODULATION OF ADRENAL CATECHOLAMINE RELEASE BY DA2 DOPAMINE RECEPTORS IN THE ANAESTHETIZED DOG
Authors: Foucart S. , Lacaille‐Belanger P. , Kimura T. , Nadeau R. , de Champlain J.
Published: June 2007

SUMMARY

1. The effects of DA2 agonist, quinpirole (50 μg/kg, i.v.) and a DA2 antagonist, domperidone (50 μg/kg, i.v.) on the release of adrenal catecholamines were evaluated in the anaesthetized and vagotomized dog.

2. Stimulations (5 V pulses of 2 ms duration for 3 min) of the splanchnic nerve at frequencies of 1, 3 and 5 Hz were applied randomly before and after injection of the drug.

3. The results show that quinpirole reduces significantly the release of adrenaline at 1 and 3 Hz but not at 5 Hz, while the release of noradrenaline is reduced at 1 Hz but not at 3 and 5 Hz. Inversely, domperidone potentiates significantly the release of both catecholamines at 3 and 5 Hz, but not at 1 Hz.

4. There was no change in basal release of adrenal catecholamines, adrenal blood flow or heart rate after both drug treatments.

5. The mean arterial pressure was not affected by domperidone treatment but there was a significant reduction in basal mean arterial pressure after the injection of quinpirole.

6. There was no change in any of these parameters during electrical stimulation.

7. Therefore, these results strongly suggest that DA2 dopamine receptors are present at the level of the adrenal medulla and that their activation could mediate an inhibitory modulation on the adrenal catecholamines release within a certain range of electrical stimulation.
POTASSIUM EXCRETION IN RENAL FAILURE IN THE RAT: THE ROLE OF DISTAL TUBULE FLOW AND ALDOSTERONE
Authors: Adam William R. , Adams Beverlie A. , Ellis Andrew G.
Published: June 2007

SUMMARY

1. This study examines the contribution of an increased distal tubule flow and of aldosterone to the handling of a potassium load in conscious rats with renal failure induced by subtotal nephrectomy or by gentamicin on a control or high K+ diet.

2. Glomerular filtration rate was reduced by subtotal nephrectomy to 40% and by gentamicin treatment to 60% of control. Subtotal nephrectomy induced significant hypertrophy of glomeruli and proximal and distal tubules, but gentamicin did not. Both experimental groups had a normal iothalamate space and plasma potassium after a 20 h fast.

3. Two hours after an acute KCl load rats with renal failure excreted less potassium than control rats. There was also a lesser natriuretic effect of KCl in the renal failure groups.

4. A high K+ diet, given for 5–7 days, increased excretion of an acute KCl load in control rats and rats with renal failure.

5. (UNaV + UKV) was used as an estimate of distal tubule flow. Potassium excretion, related to distal tubule flow, was similar in the renal failure and control rats when on the same diet. This is consistent with potassium excretion being strongly, but not necessarily solely, dependent on distal flow.

6. Adrenalectomy reduced, and aldosterone restored, potassium excretion in the renal failure and control groups. This suggests a role for aldosterone in excretion of an acute potassium load with this degree of renal failure.
HUMAN PLACENTAL ACETYLCHOLINE CONTENT AND RELEASE AT PARTURITION
Authors: Brennecke S. P. , Chen S. , King R. G. , Boura A. L. A.
Published: June 2007

1. Measurements were made of human placental acetylcholine (ACh) content and release into maternal and fetal circulations from placenta obtained before, during and after labours of both spontaneous and induced onsets. ACh content was determined in ex vivo placental biopsies using a radio‐enzymatic assay. ACh release was determined by bioassay of the effluent from placental lobules perfused with amniotic fluid‐like Kreb's containing physostigmine (2.4 μmol/1).

2. ACh content of placentae obtained after labour (spontaneous onset of labour, normal vaginal delivery) and during labour (spontaneous onset of labour, Caesarean section delivery) was significantly less than before labour (no labour onset, Caesarean section delivery).

3. Mean ACh output into maternal vessels 1.5–4.0 h after commencement of perfusion of placentae obtained after labour (spontaneous onset of labour, normal vaginal delivery) was significantly less than from those obtained before labour (no labour onset, Caesarean section delivery). No differences were found in ACh output into fetal vessels of placentae obtained before, during or after labour.

4. These results suggest a role for placental ACh in the events of human labour. The decrease in ACh content and maternal vascular release in placenta obtained after labour is consistent with a depletion of placental ACh during labour which may indicate ACh release at this time. The lack of any significant change in fetal vascular release of ACh in placenta obtained before, during or after labour, raises the possibility of different roles for ACh released into fetal and maternal vasculature.
CARDIOVASCULAR EFFECTS OF RILMENIDINE, A NEW α2‐ADRENOCEPTOR AGONIST, AND CLONIDINE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Sannajust F. , Julien C. , Barrès C. , Cerutti C. , Koenig‐Bérardd̊ E. , Sassard J.
Published: June 2007

1. The acute and chronic effects of rilmenidine, a partial agonist of α1‐ and α2‐adrenoceptors with antihypertensive properties, were compared to those of clonidine on blood pressure (BP), heart rate (HR) and the urinary excretion of catecholamines, which was used as an index of sympathetic activity.

2. As these drugs are known to interfere centrally and peripherally with the sympathetic nervous system, long‐term arterial blood pressure recordings in freely moving unstressed adult spontaneously hypertensive rats (SHR) were used.

3. Acute i.v. administrations of rilmenidine (0.3 mg/kg at 1200 h, 1.2 mg/kg at 1700 and 2200 h) and clonidine (12 μg/kg at 1200 h, 50 μg/kg at 1700 and 2200 h) induced short‐lasting increases in BP associated with a decrease in HR, which were followed by prolonged, dose‐dependent decreases in BP without bradycardia. The pressor effect was less marked and the associated bradycardia was more marked in active SHR with physiologically high sympathetic activity than in resting SHR.

4. A 12‐day oral treatment with rilmenidine (6.0 mg/kg daily) or clonidine (150 μg/kg daily) induced moderate decreases in BP without change in HR. Rilmenidine but not clonidine decreased normetanephrine (NMN) excretion in active but not in resting SHR.

5. Finally, during the 24 h following the cessation of the treatments, BP returned to normal, without significantly exceeding that of untreated controls. However, upswings in BP or HR were observed, more markedly and frequently after clonidine than after rilmenidine.

6. In conclusion the effects of α2‐adrenoceptor agonists appear to be influenced by the pre‐existing sympathetic tone. The general agreement between these data and those observed in patients demonstrates that the use of conscious unstressed animals is of value to determine the cardiovascular effects of drugs which act on the sympathetic nervous system.
CHANGES IN MET‐ENKEPHALIN AND β‐ENDORPHIN CONTENTS IN THE HYPOTHALAMUS AND THE PITUITARY IN DIABETIC RATS: EFFECTS OF INSULIN THERAPY
Authors: Tang Fai
Published: June 2007

1. Immunoreactive (IR)‐met‐enkephalin and β‐endorphin contents in the hypothalamrus and the pituitary were measured in alloxan‐diabetic rats with or without insulin treatment.

2. Both IR‐met‐enkephalin and IR‐β‐endorphin in the pituitary were substantially reduced in alloxan‐diabetic rats 1 month after treatment.

3. Hypothalamic IR‐β‐endorphin content was also significantly lower.

4. Gel‐filtration chromatography showed that the peaks co‐eluting with met‐enkephalin precursor, met‐enkephalin and β‐endorphin were lower in the pituitaries from the diabetic rats, whereas the peaks co‐eluting with β‐endorphin precursor and β‐lipotropin were not.

5. In another experiment, the IR‐β‐endorphin contents of the neuro‐intermediate lobe and hypothalamus, but not the anterior lobe were significantly lowered in diabetic rats, whereas IR‐met‐enkephalin contents were significantly reduced in both the anterior and neuro‐intermediate lobe.

6. All these changes were reversed by insulin treatment.

7. As a decrease in general protein synthesis could not explain the recorded changes, these results suggest a possible direct role of insulin in regulating the opioid peptide content of the hypothalamus and pituitary.
PLASMA, CARDIAC TISSUE AND BRAIN MORPHINE CONCENTRATIONS IN ACUTE AND CHRONIC MORPHINE‐TREATED RATS
Authors: Ko Wendy W‐W. , Dai Soter
Published: June 2007

1. The plasma, cardiac tissues and brain morphine concentrations in rats after acute or chronic morphine treatment were measured by high‐performance liquid chromatography.

2. Morphine concentrations in plasma and cardiac tissues were found to be significantly higher than those in brain after acute morphine injection. However, after chronic oral administration, morphine concentrations in plasma, cardiac tissues and brain were similar.

3. Brain concentrations of morphine following chronic administration were higher than those obtained after acute administration although concentrations in plasma and cardiac tissues were lower.
IMMUNOCHEMICAL AND CATALYTICAL CHARACTERIZATION OF THE HUMAN LIVER NADPH‐CYTOCHROME P450 REDUCTASE
Authors: McManus Michael E. , Huggett Anthony , Burgess Wendy , Robson Richard , Birkett Donald J.
Published: June 2007

1. The NADPH‐cytochrome P450 reductases (EC 1.6.2.4) from human and rabbit liver have been purified to electrophoretic homogeneity. The human reductase had an apparent monomeric molecular weight of 77 500 and the rabbit enzyme of 76 500.

2. Both flavoproteins exhibited typical flavoprotein spectra and contained equimolar quantities of FAD and FMN. The two reductases were catalytically active in reducing cytochrome c, ferricyanide and dichlorophenolindophenol, and in supporting rabbit liver cytochrome P450 Form 4 metabolism of 2‐acetylamino‐fluorene.

3. An antibody raised in the goat against the human enzyme formed a precipitin line with the human reductase in a double‐diffusion assay, but did not react with the rabbit reductase. Similarly, an antibody raised in the goat against the rabbit reductase formed a precipitin line with the rabbit enzyme, but did not cross‐react with the human reductase.

4. Both antibodies inhibited cytochrome c reduction by the two reductases suggesting some immunochemical recognition.

5. Immunochemical cross‐reactivity was confirmed when both reductases were subjected to the more sensitive immunoblot technique using either anti‐human or anti‐rabbit reductase IgG.

6. The human and rabbit reductases are essentially similar in amino acid composition, except that the former has larger amounts of serine and glycine.
RAT AORTIC ENDOTHELIUM ANTAGONIZES NITROPRUSSIDE‐INDUCED RELAXATION BY RELEASE OF THE PEPTIDE ENDOTHELIN
Authors: Macdonald P. S. , Kudo K. , Dubbin P. N. , Dusting G. J.
Published: June 2007

1. The effects of porcine endothelin were examined in rat thoracic aortic rings.

2. Endothelin was a potent contractile agonist (EC50 4.0 ± 0.6 nmol/L).

3. Endothelin (1 nmol/L) did not affect contractile responses to cumulative concentrations of the thromboxane analogue, U46619.

4. In the presence of U46619, but not phenylephrine, endothelin (1 nmol/L) and endothelium abrogated the vasodilator response to cumulative concentrations of sodium nitroprusside.

5. The inhibitory effect of endothelin on vasodilator responses to nitroprusside in the presence of U46619 was abolished by nifedipine (0.1 μmol/L) but unaffected by indomethacin (3 μmol/L) or haemoglobin (10 μmol/L).

6. These data suggest that endothelin generated by native endothelium exerts a physiological antagonism of sodium nitroprusside in the presence of thromboxane.
PARADOXICAL EFFECTS OF ENDOTHELIN ON CARDIOVASCULAR NORADRENERGIC NEUROTRANSMISSION
Authors: Wong‐Dusting H. K. , Reid J. J. , Rand M. J.
Published: June 2007

1. Pre‐ and postjunctional effects of endothelin (1–10 nmol/L) have been studied in the rabbit isolated ear artery and in rat isolated atria.

2. Endothelin produced concentration‐dependent increases in arterial perfusion pressure, and had positive chronotropic and inotropic effects in rat atria.

3. Vasoconstrictor responses of the arteries to sympathetic nerve stimulation were reduced by 1 nmol/L endothelin and abolished by 10 nmol/L endothelin. In rat atria, the chronotropic responses to nerve stimulation were markedly reduced by 10 nmol/L endothelin.

4. In rabbit ear artery, vasoconstrictor responses to noradrenaline were enhanced by 1 nmol/L endothelin, but were reduced by 10 nmol/L endothelin. In rat atria, endothelin reduced the chronotropic response to isoprenaline.

5. Endothelin (10 nmol/L) increased the stimulation‐induced release of radioactivity in arteries and atria labelled with [3H]‐noradrenaline by 91% and 23%, respectively.

6. The p‐ and postjunctional effects of endothelin persisted in both arterial and atrial preparations for at least 30 min after its removal.
BIOCHEMICAL AND HORMONAL CHANGES DURING A 1000 km ULTRAMARATHON
Authors: Pestell Richard G. , Hurley David M. , Vandongen Robert
Published: June 2007

1. To examine individual hormonal responses to extreme physical stress, blood samples were taken from eight highly trained athletes 1 day before and within 15 min of finishing the 1986 1000 km Sydney to Melbourne Ultramarathon foot race.

2. The baseline hormonal state of these highly trained athletes was quite different from normal. Resting serum conjugated catecholamines — epinephrine (E), nor‐epinephrine (NE), dopamine (D), free E and free D — were significantly elevated above the normal mean (P < 0.01). ACTH levels were significantly elevated above the normal range. Immunoreactive β‐endorphin (IR‐βEP), growth hormone (GH), prolactin (PRL), testosterone, cortisol and cortisol‐binding globulin (CBG) were within the normal range.

3. The effect of the race on serum catecholamine levels was to elevate further free and conjugated NE (P < 0.01). Other catecholamines, free and conjugated, remained significantly elevated above the normal mean (P < 0.01). Adrenocorticotrophic hormone (ACTH) remained elevated, and IR‐βEP within the normal range, without significant change. A significant increase in GH (P < 0.05), PRL (P < 0.01), and cortisol (P < 0.01) was seen, with no change in CBG.

4. As a model of chronic physical stress, the ultramarathon runner demonstrates a significantly altered baseline hormonal state as reflected in the primary mediators of the stress response, the catecholamines and the hypothalamic‐pituitary‐adrenal axis. Their response to severe exercise is distinct from that of untrained individuals in whom conjugated catecholamines decrease and ACTH increase. This may represent hormonal adaptation to prolonged stress.
HYPOTHERMIA ENHANCES THE EFFECTS OF MORPHINE ON HORMONAL AND HISTAMINE RELEASE
Authors: Alcaraz Cristina , Bansinath Mylarrao , Turndorf Herman , Puig Margarita M.
Published: June 2007

1. The effects of intravenous (i.v.) morphine on adrenocorticotrophic hormone (ACTH), β‐endorphin (β‐END), total catecholamines (CA) and histamine (HIS) plasma concentrations, were determined in anaesthetized dogs at 30°C and 37°C.

2. Hypothermia initially increased CA levels by 29%, but the values returned to baseline after 2 h. Morphine (1 mg/kg, i.v.) produced a significant decrease in CA both at 37°C and 30°C (34% and 54%, respectively). Subsequent administration of naloxone (1 mg/kg, i.v.) significantly increased CA levels in both groups.

3. Hypothermia per se had no effect on ACTH, β‐END, and HIS concentrations. Morphine produced a significant increase in pituitary hormones and HIS, in hypo‐ thermic but not in normothermic animals. Morphine concentrations were significantly higher at 30°C during the first 45 min.

4. The results suggest that the effects of morphine on hormonal and histamine release observed at 30°C are concentration‐dependent and related to changes in morphine pharmacokinetics.
PROCONVULSANT EFFECT OF PAPAVERINE ON THEOPHYLLINE‐INDUCED SEIZURES IN RATS
Authors: Ramzan Iqbal
Published: June 2007

1. The effects of papaverine, an adenosine uptake inhibitor, were tested against theophylline‐induced seizures.

2. Rats were infused with a constant intravenous infusion of theophylline at 10.3 mg/min immediately following intraperitoneal pretreatment with either papaverine 35 mg/kg or saline vehicle.

3. Papaverine produced a potent proconvulsant effect towards theophylline seizures, reducing the onset time and cumulative dose to seizure and theophylline concentrations in arterial serum, cerebrospinal fluid and brain, respectively, at onset of maximal seizures.