bluuebunny/crossref_metadata_2025 huggingface dataset:
INCREASED PLASMA NORADRENALINE DURING LOW DOSE ADRENALINE INFUSION IN RESTING MAN AND DURING SYMPATHETIC STIMULATION
Authors: Musgrave I. F. , Bachmann A. W. , Jackson R. V. , Gordon R. D.
Published: June 2007

1. Both resting and stimulated (straight‐leg raising and head‐up tilt) levels of arterial and venous plasma noradrenaline were significantly higher during low‐dose adrenaline infusion in five mild hypertensive and four normotensive patients with one adrenal.

2. Repeat adrenaline infusions in the five hypertensive patients while measuring noradrenaline clearance (3H‐noradrenaline constant infusion) achieved similar levels of plasma adrenaline, and similar increases in plasma noradrenaline, within five min of achieving target infusion rate. Increased plasma noradrenaline was not explained by reduced clearance.

3. These results are consistent with the hypothesis that physiological concentrations of adrenaline are capable of facilitating noradrenaline release in man.
A STRUCTURAL ANALYSIS OF HUMAN RENIN
Authors: Morris Brian J. , Guss J. Mitchell , Hunter William N. , Catanzaro Daniel F.
Published: June 2007

1. A three‐dimensional model of human renin has been used to define amino acid residues involved in interaction with substrate.

2. The structure revealed proteolytic cleavage sites on the surface of the molecule that may help explain numerous experimental observations concerning prorenin and its activation and forms of renin differing in size.
ACUTE HAEMODYNAMIC RESPONSES TO UNILATERAL RENAL ARTERY STENOSIS IN CONSCIOUS DOGS
Authors: Anderson Warwick P. , Woods Robyn L. , Kline Robert L. , Korner Paul I.
Published: June 2007

1. The acute responses to renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs.

2. Stenosis of one renal artery produced a rise in arterial pressure and a fall in total peripheral conductance, but no change in cardiac output.

3. The resistance to blood flow of the stenotic kidney 1 h after stenosis was 25% greater than before stenosis. This rise in resistance was due to the resistance of the renal artery stenosis itself.

4. Blood flow to the contralateral kidney fell by 13% (s.e.m. =3) at 1 h and resistance rose by 39% (s.e.m. = 5).

5. Plasma renin activity was elevated approximately 10 fold.

6. Calculations of changes in peripheral conductances following stenosis showed that the stenotic kidney was responsible for 14% of the fall in total peripheral conductance at 1 h, and the contralateral kidney for 18%.

7. Thus acute renal artery stenosis produced a prompt rise in arterial pressure due to reduced peripheral conductance, of which the two kidneys (stenotic and contralateral) were responsible for one‐third.
THE MEDIATORS OF ALLERGIC CONTRACTION OF HUMAN AIRWAY SMOOTH MUSCLE: A COMPARISON OF BRONCHIAL AND LUNG PARENCHYMAL STRIP PREPARATIONS
Authors: Creese B. R. , Temple Diana M.
Published: June 2007

1. Antigen‐induced contractions of passively sensitized preparations of human bronchi and lung parenchymal strips were studied.

2. Mepyramine did not affect the magnitude or time course of the contractile responses of either preparation.

3. Indomethacin potentiated the responses of lung parenchymal strips, but inhibited those of bronchial preparations.

4. Responses of both tissues were inhibited by the leukotriene antagonist FPL 55712, by the lipoxygenase inhibitor BW 755C, and by the anti‐allergic compound disodium cromoglycate

5. Disodium cromoglycate and BW 755C inhibited histamine release from lung parenchymal strips.

6. The results indicate an important role for leukotrienes in allergic contraction of both large and small human airways, while histamine is of little importance. Broncho‐constrictor prostaglandins may also contribute to the response of large airways.
INFLUENCE OF MONENSIN ON FERTILITY IN RATS
Authors: Atef Mohamed , Shalaby Moustafa A. , El‐Sayed Mossad G. A. , El‐Din Salah , Youssef A. H. , El‐Sayed Mohamed A. I.
Published: June 2007

1. Monensin was given orally to female rats at two dose levels (1.75 and 3.50 mg/kg body weight) over the period of 9‐17 days of pregnancy where organogenesis of fetuses occur. The dams were killed on the nineteenth day of gestation and their fetuses were subjected to morphological, visceral and skeletal examination. The small dose of monensin increased the number of resorbed and dead fetuses and induced marked retardation in growth of viable fetuses, but visceral or skeletal defects in these fetuses were not seen. Large doses produced fetal resorption in all dams and no viable fetuses were delivered.

2. Prolonged oral administration of monensin in male rats for 60 successive days at two dose levels, decreased the conception rate in non‐treated females (mated with treated males) to 33.3% and 0% for the small and large doses, respectively. Both doses markedly decreased the weights of testicles, epididymides and seminal vesicles. The small dose of monensin caused oligospermia, whereas the large dose induced azospermia. Both doses decreased the activity of spermatogenic epithelium and caused degeneration in germ cells after histopathological examination of the testicles.

3. It is concluded that monensin given during pregnancy to female rats is fetotoxic and when administered chronically to male rats, causes damage to the reproductive organs. The delayed effects of this drug are especially prominent.
HAEMORRHAGE‐INDUCED SECRETION OF ACTIVE AND INACTIVE RENIN IN CONSCIOUS AND PENTOBARBITONE‐ANAESTHETIZED SHEEP
Authors: Mzail A. H. K. , Noble A. R.
Published: June 2007

1. The response of plasma levels of active and inactive renin to haemorrhage was investigated in sheep with indwelling artery and vein catheters.

2. In conscious animals, loss of 10% of estimated blood volume over a 5 min period increased plasma active renin by a mean of 59%, a surprisingly small change. Plasma inactive renin also increased, but only by 86%. Maximum increases in both forms of renin occurred within 1 h of the haemorrhage.

3. The effects of an equivalent blood loss were investigated in pentobarbitone‐anaesthetized sheep maintained in an upright posture using padded slings. Anaesthesia per se had no effect on plasma active or inactive renin. In anaesthetized sheep, 3 h after haemorrhage, plasma active renin had increased by 403% and inactive renin by 299% above control values, but a plateau (maximum) response was not reached during this time.

4. In both conscious and anaesthetized animals the haemorrhage‐induced increases in active and inactive renin occurred in parallel.

5. It appears that haemorrhage of this intensity is a comparatively mild stimulus to increase plasma renin concentration in conscious sheep but is much more effective in anaesthetized animals. This may be linked to anaesthetic‐induced increases in prostaglandin synthesis within the kidney.
ALLOGENEIC TRANSFUSION OF MACROPHAGES IN ACUTE URINARY TRACT INFECTION
Authors: AL‐Waili Noori S. , AL‐Ani Miqdad A.
Published: June 2007

1. Three patients with acute urinary tract infections that failed to respond to antibiotics were treated by allogeneic peritoneal macrophage transfusions.

2. No harmful effects were observed following macrophage transfusions and the urinary infections were eradicated in treated patients.

3. It could be concluded that allogeneic macrophage transfusion is feasible between unrelated individuals and can combat severe resistant urinary infections.
THE EFFECT OF NALOXONE ON PRESSOR RESPONSES TO ANGIOTENSIN II IN ANAESTHETIZED GREYHOUNDS
Authors: Wilkinson Dean L. , Scroop Garry C.
Published: June 2007

1. In greyhounds anaesthetized with morphine and chloralose, vertebral artery infusions of angiotensin II resulted in a similar pressor response but smaller tachycardia than in greyhounds anaesthetized with chloralose alone. The pressor responses to intravenous infusions of angiotensin II were significantly larger in the morphine premedicated greyhounds.

2. In greyhounds anaesthetized with morphine and chloralose, pressor responses to vertebral artery angiotensin II were potentiated following the administration of naloxone via either a vertebral artery or intravenously although the effect was more consistent with the former route. No such effect was seen in greyhounds anaesthetized with chloralose alone. Naloxone had no effect on the pressor responses to intravenous angiotensin II or carotid artery occlusion.

3. The heart rate responses to vertebral artery angiotensin II in greyhounds anaesthetized with morphine and chloralose were potentiated by naloxone such that they were not significantly different from the responses obtained in greyhounds anaesthetized with chloralose alone before naloxone. As was observed with the pressor responses, the potentiation was more apparent with the vertebral artery route of administration of naloxone. There was no potentiation of the heart rate responses in the chloralose group of greyhounds.

4. It is suggested that morphine premedication may repress the vagal withdrawal mechanism while potentiating the sympathetic vasomotor mechanism mediating the central cardiovascular actions of angiotensin II.
DEVELOPMENT OF HYPERTENSION AND PROTEINURIA WITH AGE IN FAWN‐HOODED RATS
Authors: Kuijpers Marga H. M. , Provoost Abraham P. , de Jong Wybren
Published: June 2007

Blood pressure and urinary protein excretion were monitored in male fawn hooded rats (FH rats) from 8 until 46 weeks of age. Mild hypertension was already observed at 8 weeks of age. Between the age of 5 and 7 months the blood pressure rose steeply to a plateau of about 200 mmHg. Then it stabilized and the level was different for animals of different litters but similar for littermates. Concomitantly with the increase in blood pressure, proteinuria increased with age. Examination of renal tissue at 6.5 and 9 months of age revealed the presence of focal and segmentai glomerulosclerosis. The renal changes were not accompanied by gross alterations in renal function. In animals with severe hypertension pronounced proteinuria occurred, and they appeared to form a distinct class. In some of the animals intermittent haematuria occurred. Persistent haematuria, however, had a bad prognosis. There was no glucosuria. Water intake of the animals with severe hypertension was increased. Water intake of young FH rats was found to be of value for predicting the severity of the hypertension in these animals at a later age. It is concluded that the FH rat is an example of a non‐inbred rat strain showing spontaneous hypertension. This hypertension may result from an aberrant renal water handling and/or volume regulation.
AUTORADIOGRAPHIC ANALYSIS OF (‐)‐[125I]‐CYP BINDING IN MOUSE KIDNEY
Authors: Lew Robert , Summers Roger J.
Published: June 2007

1. The distribution and binding characteristics of the radioligand (‐)‐[125I]‐cyanopindolol (CYP) have been examined in slide mounted mouse kidney sections, using the technique of in vitro labelling and autoradiography.

2. (‐)‐[125I]‐CYP binding to sections was of high affinity (KD=55.8 pmol/l, s.e.m. = 8. 1, n= 4) to a single population of non‐interacting sites (nH = 0. 95, s.e.m. = 0. 01, Bmax= 0.74 fmol/section, s.e.m. = 0. 12, n= 4) and stereoselective with respect to the (‐)‐ and (+)‐isomers of both propranolol and pindolol.

3. Autoradiographic studies showed that (‐)‐[125I]‐CYP binding was localized to areas in the renal cortex and medulla. Both cortical and medullary binding were abolished by the inclusion of (‐)‐propranolol (1 μmol/l) in the incubation medium, whereas (‐)‐isoprenaline (200 μmol/l) selectively abolished cortical binding.

4. Medullary binding could be prevented by the inclusion of the lipophilic compounds cinanserin (10 μmol/l), haloperidol (10 μmol/l) or phentolamine (10 μmol/l), either alone or together or by washing at 37°C. These results suggest that medullary binding sites are lipid rather than receptor‐related.

5. In conclusion, in mouse kidney sections, (‐)‐[125I]‐CYP binds to discrete areas in the cortex and medulla. Cortical binding sites have the molecular characteristics of β‐adrenoceptors while medullary binding sites are lipid‐related. Caution should therefore be exercised when defining non‐specific binding of lipophilic radioligands. The autoradiographic technique is useful for discriminating between receptor and non‐receptor binding sites.
ECHOCARDIOGRAPHIC MEASUREMENT OF LEFT VENTRICULAR HYPERTROPHY IN UNTREATED ESSENTIAL HYPERTENSION
Authors: Laufer E. , Jennings G. , Dewar E. , McKenzie A. , Korner P.
Published: June 2007

1. The prevalence of left ventricular hypertrophy (LVH) in human essential hypertension is uncertain. Echocardiography was used to calculate left ventriuclar wall thickness (WT), relative wall thickness (t/r) and left ventricular mass (LVM) in 52 normal subjects, 30 patients with borderline hypertension and 33 untreated patients with essential hypertension.

2. In 52 normal subjects WT was independent of age, sex, BSA, BP or habitual physical activity, but LVM was significantly related to BSA and age.

3. After correction of LVM for age and BSA, 88% of 33 patients with untreated essential hypertension had LVM greater than predicted which identified a larger proportion of hypertensives with LVH than previous studies suggest.

4. Wall thickness measurement alone also indicated that about 80% of newly diagnosed hypertensives have LVH.
CAPTOPRIL ANTAGONIZES THE HYPOTENSIVE ACTION OF ATRIAL NATRIURETIC PEPTIDE IN THE ANAESTHETIZED RAT
Authors: Nicolantonio Robert Di , Stevens Janine , Weaver Debbie , Morgan Trefor O.
Published: June 2007

1. Atrial natriuretic peptide (8‐33; ANP) caused a prolonged hypotensive response following intravenous injection in anaesthetized rats.

2. This response was abolished by captopril treatment and restored by concomitant angiotensin II infusion.

3. These results suggest that ANP exerts its hypotensive action in the anaesthetized rat by the antagonism of the vasoconstrictor action of endogenous angiotensin II.
ENDOTHELIUM‐DEPENDENT VASODILATATION IN BOVINE CORONARY ARTERIES: CALCIUM DEPENDENCE AND INHIBITION BY PROADIFEN
Authors: Macdonald P. S. , Dubbin P. N. , Dusting G. J.
Published: June 2007

1. Vasodilator responses were examined in bovine coronary artery rings pre‐constricted with the thromboxane‐mimetic, U46619.

2. A23187 produced endothelium‐dependent vasodilatation that was abolished in calcium‐free solution. In contrast, endothelium‐dependent vasodilatation produced by arachidonic acid was not altered in calcium‐free solution.

3. In calcium‐free solution, indomethacin (10 μmol/1) did not affect arachidonate‐induced relaxations whereas BW755C (100 μmol/1) reduced relaxations to low concentrations of arachidonate, and proadifen (SKF‐525A, 1 mmol/1) abolished them at all concentrations.

4. Endothelium‐independent relaxations produced by glyceryl trinitrate were not affected by proadifen (1 mmol/1).

5. It is clear that arachidonic acid bypasses a calcium‐dependent step in the release of endothelium‐derived relaxing factor, perhaps acting as an intermediate precursor. The data support the hypothesis that a cytochrome P‐450 mono‐oxygenase may also be involved.
PLASMA LEVELS OF ATRIAL NATRIURETIC PEPTIDE IN MAN IN PRIMARY ALDOSTERONISM, IN GORDON'S SYNDROME AND IN BARTTER'S SYNDROME
Authors: Tunny T. J. , Higgins B. A. , Gordon R. D.
Published: June 2007

1. Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis.

2. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone‐producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid‐suppressible hyperaldosteronism.

3. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition.

4. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.
PRESSOR RESPONSIVENESS IN STEROID‐INDUCED HYPERTENSION IN MAN
Authors: Whitworth Judith A. , Connell J. M. C. , Lever A. F. , Fraser R.
Published: June 2007

1. Pressor responsiveness to angiotensin II (AII) and phenylephrine (PE) was examined before and after 5 days of ACTH (1 mg, i.m., daily) or hydrocortisone (200 mg, orally, daily) in six normotensive men.

2. Pulse pressure was higher prior to PE than AII infusion, presumably due to feeding.

3. Systolic blood pressure (SBP) was increased by both ACTH and hydrocortisone treatment, but more by ACTH.

4. There were no significant changes in AII pressor responsiveness with either ACTH or hydrocortisone.

5. ACTH increased pressor responsiveness to PE at 1.35 and 2 μg/kg per min, and hydrocortisone at 0.6‐2 μg/kg per min, with falls in pulse rate at 0.3‐0.9 μg/kg per min.

6. Changes in pressor responsiveness do not explain ACTH hypertension.
THYROIDAL RESPONSE TO AN INCREASE OR DECREASE OF ENDOGENOUS TSH IN PATIENTS WITH HYPERTHYROIDISM AND ITS CORRELATION WITH TSH BINDING INHIBITING IMMUNOGLOBULIN
Authors: Katakura M. , Koizumi Y. , Aizawa T. , Takasu N. , Yamada T. , Yukimura Y. , Nagata H.
Published: June 2007

1. One hundred and twenty‐one patients with hyperthyroidism of Graves' disease were treated with antithyroid drugs for 3 years and thyroidal response to an increase or decrease of TSH and the serum thyroid stimulating immunoglobulin (TSI) activity were studied in relation to the presence or absence of TSH binding inhibiting immunoglobulin (TBII).

2. TBII activity was positive in 83% of untreated patients but decreased gradually with time during antithyroid drug therapy. Thyroidal radioactive iodine uptake (RAIU) was suppressed by T3 in 86 of 121 treated patients but 16% of suppressible patients had TBII activity. Thyroidal RAIU was not suppressed by T3 in 35 treated patients, and 19 of 35 unsuppressible patients had TBII activity but other 16 patients did not. When suppressible and unsuppressible patients were combined, suppression of serum T4 and thyroidal RAIU by T3 tended to be less in the presence of TBII activity.

3. TSI activity was detected in the sera of untreated patients but did not correlate with TBII activity. TSI activity was undetectable after treatment for 3 years irrespective of presence or absence of TBII activity and T3‐suppressibility.

4. TSH, T4 and T3 elevation in response to 500 μg thyrotropin releasing hormone (TRH) was normal in all treated patients irrespective of presence or absence of TBII activity and T3‐suppressibility.

5. It is suggested that in vivo thyroidal responsiveness to an increase or decrease of endogenous TSH did not correlate with the presence or absence of TBII activity after long‐term therapy with antithyroid drugs.
PLASMA NEUROPEPTIDE Y LEVELS RISE IN PATIENTS UNDERGOING EXERCISE TESTS FOR THE INVESTIGATION OF CHEST PAIN
Authors: Morris M. J. , Elliott J. M. , Cain M. D. , Kapoor V. , West M. J. , Chalmers J. P.
Published: June 2007

1. Neuropeptide Y (NPY) is colocalised with noradrenaline in post‐ganglionic sympathetic neurons. In order to examine the possibility that activation of the sympathetic nervous system might cause release of NPY into the plasma NPY levels were measured in 16 patients undergoing exercise tests for investigation of chest pain.

2. Plasma NPY concentrations rose in 14 out of the 16 patients, and the mean level of plasma NPY increased from 335 (s.e.m. = 37) to 455 (s.e.m. = 41) pg/ml.

3. Plasma noradrenaline and adrenaline levels increased four‐ and two‐fold respectively.

4. The increase in NPY correlated with the increase in noradrenaline, suggesting that NPY may be released with noradrenaline when sympathetic noradrenergic nerves are activated.
FRUSEMIDE INHIBITION OF SYMPATHETIC VASOCONSTRICTION IN THE RAT IN SITU BLOOD PERFUSED MESENTERY
Authors: Armsworth Stuart J. , Gerkens John F. , Smith Anthony J.
Published: June 2007

1. Mesenteric perfusion pressure was measured in the in situ blood‐perfused mesentery of anaesthetized rats. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation at 3, 6 and 10 Hz before and after the administration of frusemide 5 mg/kg intravenously (i.v.) or vehicle. Loss of volume due to diuresis was prevented by replacement with intravenous saline.

2. Frusemide did not cause any changes in blood pressure or baseline perfusion pressure. Responses to electrical stimulation were inhibited by frusemide (P < 0.05) but unchanged by vehicle administration.

3. Acute bilateral nephrectomy or treatment with indomethacin (2 mg/kg i.v.) prevented the inhibitory effect of frusemide on responses to sympathetic nerve stimulation.

4. Responses to sympathetic nerve stimulation were potentiated by an infusion of angiotensin II (12 ng/min) into the mesenteric artery. This infusion did not alter either blood pressure or baseline perfusion pressure. Administration of frusemide 5 mg/kg i.v. attenuated the potentiating effect of angiotensin II on vasoconstrictor responses to electrical nerve stimulation.

5. Frusemide may lead to the release of a prostanoid or prostanoid precursor which inhibits vascular constrictor responses.
TEMPORAL PROFILE OF TISSUE LEVELS OF DOPAMINE AND ITS METABOLITES, HVA AND DOPAC FOLLOWING FOCAL CEREBRAL ISCHAEMIA IN ANAESTHETIZED PRIMATES
Authors: Kuruvilla A. , Cherian R. , Theodore D. R. , Abraham J.
Published: June 2007

1. Occlusion of the middle cerebral artery produced ischaemia and consequent changes in basal ganglia in the primate model of stroke within 0.5 h.

2. Dopamine content was decreased in the right basal ganglia from 0.5 h up to 12 h after occlusion.

3. Homovanillic acid content of the right basal ganglia increased initially at 0.5 h but, was decreased at 12 h.

4. The DOPAC content was increased at 2 h after occlusion in the right basal ganglia, but was decreased significantly at 12 h.

5. In the substantia nigra, there was a significant reduction in the DA content in the right side at 12 h.

6. Minimal changes were observed in the DOPAC and HVA content in the right substantia nigra at 2 h and 4 h, respectively. At other time periods there was no significant change in the content of HVA and DOPAC in substantia nigra.
EFFECT OF ACUTE ADMINISTRATION OF PRAZOSIN ON BLOOD PRESSURE, HEART RATE AND PLASMA RENIN LEVEL IN THE CONSCIOUS NORMOTENSIVE RAT
Authors: Atkinson J. , Luthi P. , Sonnay M. , Boillat N.
Published: June 2007

1. This study investigated whether the specific α‐antagonist, prazosin, stimulated basal plasma renin levels and heart rate. Furthermore the β‐adrenergic nervous system was also investigated to ascertain whether it was involved in this effect.

2. Prazosin (0.1 or 1 mg/kg) was injected subcutaneously (s.c.) to conscious normotensive rats, either alone or in combination with the β‐adrenoceptor antagonist, dl‐propranolol (1 or 3 mg/kg). Rats bore chronically implanted dorsal aorta cannula for measurement of blood pressure and heart rate and blood sampling for renin determinations.

3. Acute administration of prazosin (1 mg/kg, s.c.) produced a fall in mean arterial pressure accompanied by renin release and tachycardia. A tenfold lower dose of prazosin did not alter blood pressure or heart rate but did stimulate renin release.

4. Acute administration of dl‐propranolol, (1 or 3 mg/kg, s.c.) produced falls in blood pressure and heart rate but did not affect plasma renin level.

5. Combinations of prazosin with propranolol gave falls in blood pressure similar to those predicted on the basis of a simple addition of the effects of the two drugs given separately. Prazosin‐induced tachycardia and renin release were attenuated by propranolol.

6. It appears that prazosin produces renin release and tachycardia via stimulation of the β‐adrenergic adrenoceptor.
FREE AND CONJUGATED CATECHOLAMINES IN HUMAN PLASMA DURING PHYSICAL EXERCISE
Authors: Ratge D. , Gehrke A. , Melzner I. , Wisser H.
Published: June 2007

1. To investigate changes of free and sulfoconjugated catecholamines in response to alterations in sympatho‐adrenal activity, free and conjugated noradrenaline, adrenaline and dopamine were determined radioenzymatically in plasma of 49 subjects.

2. During brief vigorous bicycle exercise (8 min, maximal heart rate: 177 beats/min) mean free noradrenaline and adrenaline values of 2.0 and 0.51 nmol/1 at rest, increased to 6.7 and 2 nmol/1 (P<0.001) respectively, at the maximal workload of 200 watt, whereas conjugated noradrenaline and adrenaline decreased from 3.4 and 0.8 nmol/1 to 2.1 and 0.4 nmol/1 (P<0.001) respectively. In the tenth min of the recovery period basal free and conjugated noradrenaline and adrenaline levels were measured.

3. The moderate stress of a steam bath (20 min, maximal heart rate: 131 beats/min) doubled free noradrenaline and adrenaline levels. However, conjugated noradrenaline and adrenaline concentrations remained unchanged.

4. The increase in free catecholamine values during an exhausting cross‐country march over 20 km was associated with an accumulation of sulfated catecholamines. After a rest of 30 min free noradrenaline and adrenaline reached basal values, whereas conjugated noradrenaline and adrenaline remained elevated by 64 and 70% respectively, compared to pre‐exercise concentrations.

5. It was concluded that conjugated noradrenaline and adrenaline may be used as pools for free noradrenaline and adrenaline during brief vigorous exercise. In addition, they may also be indicators of chronic activation of the sympatho‐adrenal system.
THE CARDIOVASCULAR EFFECTS OF TRIMAZOSIN AND PRAZOSIN IN THE RABBIT
Authors: Vincent J. , Hamilton C. A. , Reid J. L.
Published: June 2007

1. The cardiovascular effects of trimazosin, a quinazoline derivative similar in structure to prazosin, were investigated and compared with prazosin in the rabbit.

2. Radioligand binding to cerebral membranes showed that trimazosin has roughly 100‐fold less affinity for the α1‐adrenoceptor. This was further supported by its lower pA2 derived from phenylephrine contractile responses in isolated thoracic aorta preparations.

3. Trimazosin is less extensively distributed and has a lower clearance from whole blood than prazosin although their whole blood elimination half‐lives are comparable. In addition, although it is a less potent α1‐adrenoceptor antagonist in vivo, its peripheral vascular depressor effect tends to be greater than prazosin.

4. Trimazosin at the dose used and under the conditions of study did not reverse the peripheral pressor effect of angiotensin II or B‐HT920 but at higher concentrations, unlike prazosin, it relaxed the K+ contracted thoracic aorta. In addition, following pharmacological autonomie blockade and treatment with prazosin in vivo, trimazosin caused a further depressor response. A similar though shorter lasting non‐α1‐receptor mediated action was also observed with prazosin.

5. 1‐Hydroxytrimazosin (CP23445), the major metabolite of trimazosin in man, showed little affinity for either the α1‐ or α2‐adrenoceptor from radioligand binding studies.

6. In addition to α1‐adrenoceptor antagonism, trimazosin may exert an additional direct vasodilator effect in rabbits.
PERSISTENT EFFECTS ON BLOOD PRESSURE AND RENAL HAEMODYNAMICS FOLLOWING CHRONIC ANGIOTENSIN CONVERTING ENZYME INHIBITION WITH PERINDOPRIL
Authors: Harrap Stephen B. , Nicolaci Joseph A. , Doyle Austin E.
Published: June 2007

1. Spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats aged 4 and 16 weeks were given an acute oral dose of either Perindopril (3 mg/kg) or vehicle. Direct blood pressure (BP), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, and renal vascular resistance (RVR) calculated. GFR and RBF were lower in vehicle‐treated SHR than WKY at 4 weeks of age, but were not different at 16 weeks. Acute Perindopril increased GFR and RBF and reduced RVR in both strains at both 4 and 16 weeks.

2. Total body sodium, sodium intake and blood pressure were measured in SHR and WKY from 1 to 28 weeks of age. Rats of both strains were treated daily between 4 and 16 weeks of age with either Perindopril (3 mg/kg per day) or vehicle. Chronic Perindopril treatment prevented the development of hypertension in the SHR. From 16 to 28 weeks of age, after stopping Perindopril, BP rose slowly in SHR, but remained lower than vehicle‐treated SHR. No changes in total body sodium occurred during Perindopril treatment.

3. GFR and RBF were measured in SHR and WKY chronically treated with either Perindopril or vehicle, 3 days or 12 weeks after stopping treatment. In WKY, GFR and RBF were not different between Perindopril‐treated and untreated rats at either measurement. In SHR, GFR and RBF remained significantly higher in rats previously treated with Perindopril at both ages.

4. These findings suggest that renal haemodynamic abnormalities may be important in the initiation of hypertension in the SHR. These renal circulatory abnormalities and the hypertension of the SHR depend, at least in part, on intact converting enzyme activity, yet appear to be independent of abnormalities of total body sodium. At a later age, hypertension seems to develop independently of renal vascular abnormalities.
INFLUENCE OF ETHANOL TREATMENT ON THE PLASMA CONCENTRATIONS OF PROLACTIN AND LEUTINIZING HORMONE IN TURKEYS (MELEAGRIS GALLOPAVO)
Authors: Ali B. H. , Czarnecki Caroline M. , EL Halawani M. E.
Published: June 2007

1. The effect of ethanol consumption on the plasma concentrations of prolactin (PRL) and leutinizing hormone (LH) was investigated in turkey poults.

2. Ethanol (4–5% v/v in drinking water for 42 days) significantly increased the concentration of PRL, and tended to decrease that of LH.

3. It is suggested that the hyperprolactinaemia produced by ethanol might be due to its stressor action on the birds.
NALOXONE ATTENUATES AUGMENTATION OF cAMP LEVELS AND ARRHYTHMIAS FOLLOWING MYOCARDIAL ISCHAEMIA AND REPERFUSION IN THE ISOLATED PERFUSED RAT HEART
Authors: Lee A. Y. S. , Wong T. M.
Published: June 2007

1. The effects of myocardial ischaemia and reperfusion on arrhythmias and cAMP levels were studied using the Langendoff isolated perfused rat heart preparation.

2. Myocardial ischaemia and reperfusion caused arrhythmias and augmentation of cAMP levels concurrently, supporting the suggestion that myocardial cAMP is related to arrhythmias.

3. Pretreatment with naloxone attenuated both arrhythmias and augmentation of cAMP levels to a similar extent. The results suggest that the anti‐arrhythmic effect of naloxone may involve myocardial cAMP.
THE EFFECTS OF 4‐METHYL‐2‐THIOURACIL ON FIBRE TYPE AND CROSS‐SECTIONAL AREA IN THE SOLEUS MUSCLE OF THE RAT
Authors: Rajikin Mohd Hamim , Merican Zainuddin , Morat Paden
Published: June 2007

1. The effects of 4‐methyl‐2‐thiouracil (MTU, 0.1% in drinking water) on the composition and cross‐sectional area of muscle fibres of the rat soleus muscle were studied.

2. The percentage of fast twitch‐oxidative‐glycolytic (FOG) fibres fell after 2 weeks of treatment with MTU to zero at 8 weeks. In contrast the percentage of FOG fibres in untreated animals fell to 19.2±2.1% during this period.

3. The mean cross‐sectional area of FOG and slow twitch‐oxidative (SO) fibres were respectively 39.9% and 23.8% smaller than those of their respective controls 6 weeks after treatment. At 8 weeks the percentage reduction of SO fibre area was 26.8% of the control value.

4. This study indicates that MTU treatment causes atrophy and redistribution of fibre type in the soleus muscle.
BLOCKADE OF ANGIOTENSIN CONVERTING ENZYME IN CIRCUMVENTRICULAR ORGANS OF THE BRAIN AFTER ORAL LISINOPRIL ADMINISTRATION DEMONSTRATED BY QUANTITATIVE IN VITRO AUTORADIOGRAPHY
Authors: Sakaguchi Keiji , Chai Siew Yeen , Jackson Bruce , Johnston Colin I. , Mendelsohn Frederick A. O.
Published: June 2007

1. To elucidate the central effect of lisinopril, a new angiotensin converting enzyme (ACE) inhibitor, ACE localization and levels were followed in the brain of Sprague‐Dawley rats by quantitative in vitro autoradiography after administration of the drug.

2. Following acute lisinopril (10 mg/kg p.o.) treatment, serum ACE activity was acutely reduced, but returned to normal by 24 h.

3. Levels of ACE in most parts of the brain, including the basal ganglia and choroid plexus of all ventricles were not affected by lisinopril. Lisinopril inhibited brain ACE in the subfornical organ and organum vasculosum of the lamina terminalis, circumventricular organs, where the blood brain barrier is deficient. These regions are rich in ACE and angiotensin II receptors, and are known targets for angiotensin II‐induced effects on fluid, electrolyte and blood pressure homeostasis.

4. These observations indicate that quantitative in vitro autoradiography is a powerful method to study the access of drugs to the central nervous system.

5. This study shows that blood brain barrier plays an important role in limiting the penetration of lisinopril into the central nervous system. The circumventricular organs may be important targets for ACE inhibitors.
EFFECT OF GRADED LOW‐DOSE NORADRENALINE INFUSIONS ON NORADRENALINE CLEARANCE IN NORMALS AND ESSENTIAL HYPERTENSIVES
Authors: Gordon Richard D. , Bachmann Anthony W. , Gueizelar Brenda , Dai Yung
Published: June 2007

1. In normal subjects and essential hypertensives, plasma noradrenaline (NA) levels, and NA clearance (3H‐NA constant infusion), were measured during graded infusion of NA.

2. Plasma levels of NA were similar in both groups, with parallel increases to levels approximately three times basal, but still in the upper normal range.

3. Clearance did not increase in either group with increasing plasma NA levels. There was no correlation between plasma NA achieved and NA clearance, which was similar in hypertensives and normotensives.

5. Insofar as plasma clearance reflects tissue clearance, these studies provide no support for the contention that altered NA metabolism might predispose to elevated NA levels in essential hypertension.
EFFECT OF ATRIAL NATRIURETIC PEPTIDE ON COLLECTING DUCT FUNCTION EVALUATED BY STOP‐FLOW IN RABBITS
Authors: Fitzgibbon Wayne , Morgan Trefor
Published: June 2007

1. The effect of a low dose of a synthetic atrial natriuretic peptide (ANP), rat atriopeptin II (23 amino acids), on stop‐flow sodium concentrations was examined in rabbits in water diuresis.

2. Atrial natriuretic peptide (2 μg/kg body weight) was injected intravenously as a bolus either before or after the commencement of stop‐flow.

3. Atrial natriuretic peptide induced a significant natriuresis within 2 min of injection. This natriuresis was associated with smaller increases in urine volume and potassium excretion. Atrial natriuretic peptide did not alter blood pressure.

4. Atrial natriuretic peptide did not significantly alter stop‐flow sodium concentrations.

5. These findings indicate that ANP does not directly alter sodium transport across medullary collecting ducts.

6. It is proposed that ANP acts via a mediator to alter sodium movement across terminal segments of the nephron.
ALDOSTERONE‐PRODUCING ADENOMAS RESPONSIVE TO ANGIOTENSIN POSE PROBLEMS IN DIAGNOSIS
Authors: Gordon R. D. , Hamlet S. M. , Tunny T. J. , Klemm S. A.
Published: June 2007

1. A subgroup of patients with aldosterone‐producing adenoma (APA) have been identified who lack many of the biochemical features regarded as characteristic of APA and used to distinguish APA from bilateral adrenal hyperplasia.

2. In these patients, aldosterone is responsive to infused angiotensin II (angiotensin‐responsive APA), which explains their uncharacteristic responses to upright posture, saline infusion and fludrocortisone acetate administration.

3. The angiotensin‐responsiveness of these patients may derive from the contra‐lateral adrenal gland, since renin levels are less completely suppressed in angiotensin‐responsive APA than in angiotensin‐unresponsive APA.

4. However, while the excretion of 18‐oxo‐cortisol was consistently increased in angiotensin‐unresponsive APA, it was normal in angiotensin‐responsive APA, consistent with biochemical and biosynthetic distinctiveness residing in the tumours.

5. Angiotensin‐responsive APA should always be considered as an alternative diagnosis to bilateral hyperplasia causing primary aldosteronism.
INTERACTION OF VASOPRESSIN, ANGIOTENSIN AND α‐ADRENERGIC SYSTEM IN SODIUM DEPLETION IN THE RAT
Authors: Jover Bernard F. , McGrath Barry P.
Published: June 2007

1. The role of vasopressin in cardiovascular adaptation to sodium depletion was examined in rats after 6 days on a low sodium diet. Studies were performed after selective or combined blockade with d(CH2)5 Tyr(Me)AVP (AVPA), enalaprilat (CEI) and phentolamine (PHENTOL). AVPA alone had no effect on systemic haemodynamics or regional blood flow distribution. After CEI or PHENTOL pretreatment, AVPA led to significant falls in peripheral resistance and increases in cardiac output and renal blood flow. In sodium depletion, endogenous vasopressin acts as a vasoconstrictor hormone, particularly in the kidney, when either the renin‐angiotensin or α‐adrenergic system is inhibited.
REGULATION OF SODIUM INFLUX AND SODIUM, POTASSIUM PUMP ACTIVITY BY A SODIUM‐HYDROGEN ANTIPORT IN RAT VASCULAR SMOOTH MUSCLE
Authors: Bobik Alex , Weissberg Peter L. , Little Peter J.
Published: June 2007

1. The effects of Na‐H antiport inhibitors on sodium influx, intracellular pH and Na, K‐pump activity were examined in vascular smooth muscle from rats.

2. Amiloride and 5‐(N‐ethyl‐N‐isopropyl)amiloride inhibited Na accumulation following inhibition of the Na, K‐pump.

3. Inhibition of Na influx was associated with a reduction in basal Na, K‐pump activity and intracellular pH.

4. It is concluded that a Na‐H antiport system in vascular smooth muscle regulates Na influx rate, contributes to intracellular pH regulation and influences basal levels of Na, K‐pump activity.
ADRENALINE INFUSION AND ADRENOCORTICOTROPHIN (ACTH) AND CORTISOL RELEASE IN NORMOTENSIVE AND HYPERTENSIVE MAN
Authors: Jackson R. V. , Jackson A. J. , Grice J. E. , Penfold P. J. , Armour M. B. , Bachmann A. W.
Published: June 2007

1. Adrenaline causes ACTH release from cultured rat pituitary corticotrophs (Vale et al. 1983) and there is evidence that it causes ACTH release in rats in vivo (Plotsky et al. 1985).

2. The present study examined the effects of intravenous adrenaline infusion with and without simultaneous administration of the known ACTH secretagog, arginine vasopressin, in normotensive and mild essential hypertensive men on their plasma ACTH and cortisol levels.

3. Low dose adrenaline infusion (0.013 μg/kg per min) does not cause ACTH or cortisol release, but appears to blunt the ACTH and cortisol rise caused by arginine vasopressin (0.14 pressor units/kg, i.m.).
EFFECTS OF ANGIOTENSIN AND NORADRENALINE ON ATRIAL NATRIURETIC PEPTIDE LEVELS IN MAN
Authors: Tunny T. J. , Klemm S. A. , Gordon R. D.
Published: June 2007

1. A significant positive correlation was found between changes in circulating noradrenaline (NA) levels and changes in atrial natriuretic peptide (ANP) levels during NA infusion and clonidine administration.

2. A significant positive correlation was also found between changes in arterial blood pressure and changes in ANP level during infusion of angiotensin II and of NA.

3. Two patients with very high circulating NA levels due to phaeochromocytoma, but receiving α‐and β‐blockade, did not have clearly elevated ANP. A third not receiving medications and aged 73 years had elevated levels.

4. Atrial natriuretic peptide response to NA and angiotensin II may be mediated by changes in blood pressure levels or increased noradrenergic and angiotensinergic receptor activity in the atria or both. Atrial natriuretic peptide may have a role in blood pressure regulation in both normotensive and hypertensive man.
RENIN SECRETION FROM MALIGNANT PULMONARY METASTATIC TUMOUR CELLS OF VASCULAR ORIGIN
Authors: Morris B. J. , Pinet F. , Michel J.‐B. , Soubrier F. , Corvol P.
Published: June 2007

1. A pulmonary chemodectoma/glomangiosarcoma that had metastasized from the thigh was studied after removal from a 22 year old Algerian patient with hypertension, high plasma prorenin and signs of secondary aldosteronism.

2. Renin and renin mRNA were localized in sections of the tumour tissue using monoclonal anti‐human renin antibody and human renin cDNA probe, respectively.

3. The cells grew prolifically in culture, but, even though their renin content was similar to that of transfected human juxtaglomerular cell tumour cells (∼1 pg/μg DNA), their rate of secretion of renin was much lower (0.05–0.15 cf. 0.5–1.5 pg/h per μg DNA).

4. Forskolin (10 μmol/l for 24 h) increased secretion of renin from 1.9 ± 0.36 to 4.1 ± 0.64 pg/ml per h of culture (P< 0.001, n= 11), consistent with cAMP being a second messenger in the secretory mechanism.

5. The cells should provide valuable information about intracellular mechanisms for the regulation of renin synthesis and secretion.
ACTIVATION BY PUFF ADDER VENOM OF INACTIVE RENIN IN NORMAL AND HYPERTENSIVE RAT PLASMA
Authors: Morris Brian J. , Taylor Jane E.
Published: June 2007

1. Inactive renin has been studied extensively in human plasma, but in animal plasma its accurate quantification has proved more difficult, due partly to higher activity of plasma protease inhibitors. Such activity in human plasma can be conveniently destroyed by a metalloprotease in Bitis arietans venom, with concommitant release of endogenous enzyme activities, such as plasma kallikrein, that then activate inactive renin. It was therefore of interest to look for inactive renin in rat and rabbit plasma using this approach, so providing, in addition, a comparison for the disparate data of other groups who have used trypsin or acid for activation.

2. In both rat and rabbit plasma the proportion of inactive renin was 62% of total renin, whereas human plasma contained more inactive renin and a higher proportion, 82%. A higher concentration of venom was required for rat (33 ug venom/ml plasma) and rabbit (4 μg/ml) than needed for activation, at a similar rate, in human plasma (1 μg/ml).

3. When applied to studies of rats made hypertensive and hyper‐reninaemic by aortic ligation for 5 days, higher total (active + inactive) renin was observed. The proportion of inactive renin, as a percentage of total renin in plasma collected at this time, was, however, found to diminish significantly.

4. In conclusion, puff adder venom activates inactive renin in rat and rabbit plasma and can be used to study physiological changes in inactive renin in such animal plasma.
VINBLASTINE BUT NOT OTHER MICROTUBULE INHIBITORS BLOCK TRANSFERRIN ENDOCYTOSIS AND IRON UPTAKE BY RETICULOCYTES
Authors: Morgan Evan H. , Iacopetta Barry J.
Published: June 2007

SUMMARY

1. The antimicrotubule reagents, colchicine, griseofulvin, nocodazole, podophyl‐lotoxin and taxol had no effect on transferrin endocytosis or iron uptake by rabbit or rat reticulocytes but were inhibitory when used at high concentrations with rat fetal liver erythroid cells. The results imply that microtubules do not have a role in endocytosis and iron uptake by reticulocytes but may have a permissive role in the fetal cells.

2. The only reagent found to inhibit iron uptake by reticulocytes was vinblastine. It was shown to act by inhibiting the endocytosis of transferrin.

3. It is concluded that this effect is not the result of an interaction with microtubules, but may result from a non‐specific action on the cell membrane or a more specific effect, such as inhibition of calmodulin.
COMPLEMENTARY CHANGES IN PLASMA ATRIAL NATRIURETIC PEPTIDE AND ANTIDIURETIC HORMONE CONCENTRATIONS IN RESPONSE TO VOLUME EXPANSION AND HAEMORRHAGE: STUDIES IN CONSCIOUS NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Morris Margaret , Cain Michael , Chalmers John
Published: June 2007

SUMMARY

1. Plasma concentrations of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured in conscious stroke‐prone spontaneously hypertensive (SPR), spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) rats before and after acute volume expansion or haemorrhage.

2. Plasma ANP concentration was reduced to one‐third of resting values 30 min after a 1.5% haemorrhage (1.5 ml of blood per 100 g bodyweight). Plasma ADH concentration rose immediately 50‐fold on haemorrhage and remained elevated at 30 min.

3. Plasma ANP concentration increased 2.5‐fold relative to resting values 1 min after infusion of 2.0 ml per 100 g 5% dextrose; after 10 min plasma ANP remained elevated. Plasma ADH concentration tended to fall on volume expansion although no significant decrease was observed.

4. There was no difference in the basal levels of ANP and ADH, or in the changes produced by alterations in blood volume, in hypertensive SPR and SHR compared with normotensive WKY.

5. Thus, plasma ANP concentrations moved in opposite directions in response to two physiological stimuli: volume expansion and haemorrhage. Reciprocal changes were observed in plasma ADH.
BLASTOCYSTIS HOMINIS: EVIDENCE FOR HUMAN PATHOGENICITY AND EFFECTIVENESS OF METRONIDAZOLE THERAPY
Authors: Guirges Sami Y. , Al‐Waili Noori S.
Published: June 2007

1. Clinical symptoms and oral treatment with metronidazole were studied in 103 patients with pure infections by Blastocystis hominis.

2. The results showed that excessive flatulence is the chief gastrointestinal symptom associated occasionally with diarrhoea and abdominal cramps. All the patients showed good responses with treatment of metronidazole and 74 patients whose stools were reexamined 1–2 months after the treatment demonstrated no signs of infections.

3. It is concluded that B. hominis is a pathogenic intestinal parasite and the infection could be eradicated successfully by oral metronidazole.
PHARMACOKINETICS OF ANGIOTENSIN CONVERTING ENZYME INHIBITION IN TISSUES FOLLOWING ORAL LISINOPRIL: STUDIES IN THE RAT USING QUANTITATIVE RADIOINHIBITOR BINDING
Authors: Jackson B. , Cubela R. , Sakaguchi K. , Johnston C I.
Published: June 2007

1. The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in plasma and tissues were measured in the rat following 10 mg/kg lisinopril given by oral gavage.

2. Specific binding of 125I‐351A to ACE was measured in plasma, and homogenates of lung, aorta, kidney, testis, epididymis and brain, and used as an index of ACE activity.

3. Plasma ACE binding of 125I‐351A was reduced to 5% of that in untreated rats 2 h after treatment, and returned to normal by 48 h. Kidney ACE showed a similar time course. Angiotensin converting enzyme from lung, aorta and brain was inhibited at a slower rate, and to a lesser degree. No significant inhibition of ACE was detected in epididymis or testis.

4. Individual tissues in the rat had differences in time course and degree of ACE inhibition after a single dose of lisinopril.