bluuebunny/crossref_metadata_2025 huggingface dataset:
INHIBITORY EFFECT OF FRUSEMIDE ON SYMPATHETIC VASOCONSTRICTOR RESPONSES: DEPENDENCE ON A RENAL HORMONE AND THE VASCULAR ENDOTHELIUM
Authors: Gerkens John F.
Published: June 2007

SUMMARY

1. Mesenteric perfusion pressure was measured in the in situ mesentery perfused at a constant rate with blood drawn from the carotid artery of the same anaesthetized rat. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation. These responses were measured before and 30 min after the administration of frusemide (5 mg/kg i.v.) to the rat. Loss of volume due to the frusemide‐induced diuresis was prevented by a urinary bladder‐venous extracorporeal circuit.

2. Responses to stimulation were reduced after frusemide and were not increased by the subsequent administration of indomethacin (2 mg/kg i.v.). This indomethacin treatment rapidly and completely prevented the fall in blood pressure produced by i.v. arachidonic acid.

3. In rats where the renal papilla had been ablated by treatment with bromoethylamine (200 mg/kg i.p.) 5 weeks previously, frusemide administration did not reduce sympathetic responses in the in situ blood‐perfused mesentery.

4. A segment of rat tail artery, cannulated at both ends was mounted in an organ bath and perfused with blood withdrawn from, and returned to, an anaesthetized rat. Increases in perfusion pressure produced by periarterial electrical stimulation of this ex vivo blood perfused tail artery segment were reduced by frusemide administration to the anaesthetized rat.

5. When the endothelium was removed from the tail artery segment, frusemide administration did not lead to any reduction of vasoconstrictor responses.

6. Frusemide may lead to the release of a non‐prostanoid hormone from the renal medulla which results in inhibition of peripheral sympathetic vasoconstrictor responses. The release of the hormone may involve intra‐renal prostaglandins. The final anti‐vasoconstrictor effect requires an intact vascular endothelium.
THE INTERACTION OF NICOTINIC RECEPTOR ANTAGONISTS AT MUSCARINIC RECEPTORS
Authors: Mitchelson F. J.
Published: June 2007

SUMMARY

1. The interaction of some neuromuscular blocking drugs such as gallamine, pancuronium and stercuronium with muscarinic receptors has several features which distinguish these compounds from competitive antagonists in functional and binding studies.

2. They also differentiate between muscarinic receptors and may produce effects on ion channels.
DIETARY SUPPRESSION OF PROSTAGLANDIN SYNTHESIS DOES NOT ACCELERATE DOCA/SALT HYPERTENSION IN RATS
Authors: Codde J. P. , Croft K. D. , Beilin L. J.
Published: June 2007

1. This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in DOCA/salt‐treated rats.

2. After an initial 4 week period on either a 2‐series PG ‘inhibitory’ diet of fish oil (Max EPA), A ‘stimulatory’ diet of safflower oil or a control diet of saturated fat, three groups of rats were placed on a DOCA/salt regimen for a further 4 weeks. Another group on the saturated fat diet continued their diet without DOCA/salt administration.

3. All the DOCA‐treated groups showed a marked increase in blood pressure. However, both polyunsaturated fat (PUFA)‐fed groups had blood pressures significantly lower then the saturated fat control.

4. Rats on the Max EPA showed impaired ability to generate prostanoids in vitro (serum, aorta and kidney) and in vivo (urinary PG excretion). DOCA administration increased urinary PGE2 excretion.

5. Thus, dietary suppression of 2‐series PG is not accompanied by accelerated DOCA/salt hypertension. The reduction in blood pressure observed in both the safflower and Max EPA‐fed groups may be due to PUFA‐induced changes in cell membrane fluidity.
ROLE OF PULMONARY INNERVATION IN CANINE IN SITU LUNG‐PERFUSION PREPARATION: A NEW MODEL OF NEUROGENIC PULMONARY OEDEMA
Authors: Nakamura Jiro , Zhang Shiwei , Ishikawa Naohisa
Published: June 2007

1. In situ canine lungs were perfused in the presence or absence of the nerves which coursed to the heart and lungs (the cardiopulmonary nerves, CPN).

2. A right heart‐bypassed preparation was made first, so that the respiratory and circulatory conditions could be controlled beforehand. It was then switched to a lung‐perfusion preparation, in which the lungs receive all influences of sudden cessation of the brain and systemic circulations solely via the CPN. Hydrostatic mechanisms causing pulmonary oedema were excluded by adjusting the pulmonary arterial pressure under 300 mmH2O (<24 mmHg).

3. Accumulation of extravascular lung water and the rate of reservoir blood loss were significantly lower in the CPN‐severed group than in the CPN‐intact group.

4. After perfusion of 90 min, total loss of reservoir blood was correlated significantly with extravascular water content in lungs. The former was larger than the latter.

5. Elevation of left atrial pressure caused an increase in the rate of reservoir blood loss. When the CPN was severed, the relation between these two parameters was shifted to the right.

6. These findings indicate a CPN‐mediated genesis of permeability pulmonary oedema.
PLATELET MONOAMINE OXIDASE ACTIVITY IN PATIENTS WITH HUNTINGTON'S DISEASE
Authors: Norman Trevor R. , Chiu Edmond , French Margaret A.
Published: June 2007

1. Platelet monoamine oxidase (MAO) activity was investigated in 30 patients with Huntington's disease and compared with the activity in a control group.

2. Significantly elevated activity was found in the patients (P < 0.05; t‐test) when same sex contrasts were carried out to account for the well known influence of sex on MAO activity.

3. The mean MAO activity in male patients was 23.5±6.0 nmol/mg protein per h and female patients was 29.5 ± 8.9 nmol/mg protein per h using tyramine as the substrate.

4. The possible influence of environmental factors on the results is discussed.
EVIDENCE THAT TRACHEAL SMOOTH MUSCLE TONE IN GUINEA‐PIG IS UNAFFECTED BY OVERFLOW OF NORADRENALINE RELEASED BY PERIVASCULAR NERVE FIBRES
Authors: Smith R. V. , Satchell D. G.
Published: June 2007

1. Fluorescence histochemical techniques demonstrated that in the guinea‐pig the cervical common carotid, cranial thyroid and caudal thyroid arteries were surrounded by a rich plexus of adrenergic nerve fibres.

2. The superior cervical ganglia were the source of the perivascular adrenergic fibres of the cranial thyroid arteries and the anterior half of the cervical common carotid arteries. These ganglia may also provide some of the perivascular adrenergic fibres of the caudal thyroid arteries.

3. Perivascular stimulation of the cranial thyroid and caudal thyroid arteries failed to elicit a response from isolated extrathoracic tracheal tube preparations. This suggests that it is unlikely that the guinea‐pig extrathoracic trachealis muscle is innervated by adrenergic fibres arising from these perivascular plexuses or that overflow of noradrenaline from perivascular nerves causes dilatation of the trachealis muscle.
EFFECT OF OPIATE, GENERAL ANAESTHESIA AND SURGERY ON PLASMA ATRIAL NATRIURETIC PEPTIDE LEVELS IN MAN
Authors: Kidd Julie E. , Gilchrist Nigel L. , Utley R. John , Nicholls M. Gary , Espiner Eric A. , Yandle Tim G.
Published: June 2007

1. Animal data suggest that opiates, halothane anaesthesia and activation of the sympathetic system stimulates release of atrial natriuretic peptide (ANP). To examine whether this is so in man, venous ANP levels were measured in five patients undergoing elective cholecystectomy.

2. Plasma levels of cortisol, aldosterone, norepinephrine and epinephrine increased 3–6 fold during the study. Cortisol‐aldosterone relationships were close in all patients (r= 0.73–0.97), whereas plasma renin activity and aldosterone correlations were strong in only two subjects.

3. Baseline plasma ANP concentrations were within the normal range and were not altered by opiate injection, anaesthesia, or surgery.

4. Unlike experimental animals, man exhibits little or no ANP response to opiates, halothane, or surgical stimulation of the sympathetic nervous system.
CIRCULATORY CHANGES ASSOCIATED WITH HEAT STROKE: OBSERVATIONS IN AN EXPERIMENTAL ANIMAL MODEL
Authors: Hales J. R. S. , Khogali M. , Fawcett A. A. , Mustafa M. K. Y.
Published: June 2007

1. Although heat stroke is a frequent cause of death in both humans and animals as a result of climatic or exercise‐imposed stress, underlying mechanisms are understood poorly. In order to develop more effective strategies for prevention and treatment of this cause of death and suffering, controlled experiments were conducted on a small number of sheep to examine cardiovascular involvement in the thermoregulatory failure of heat stroke.

2. Sheep were studied in a hot environment at rest and then during exercise until collapse.

3. With exercise, mean arterial pressure (MAP) increased slightly, cardiac output (CO) increased markedly and total peripheral resistance (TPR) decreased slightly. As collapse was imminent, MAP increased but CO and TPR did not change significantly. On collapse, MAP and TPR increased markedly and CO decreased markedly.

4. Radioactive microsphere measurements demonstrated during exercise a redistribution of blood flow (BF) away from abdominal viscera and torso skin, to muscles involved in exercise, respiratory muscles, myocardium, fat, limb skin and nasobuccal tissues. With progressively increasing heat stress and exercise, BF increased in exercise muscles and decreased in limb skin and fat. As collapse was imminent, there were sharp increases in BF in exercise muscles, brain and spinal cord. On collapse, BF decreased markedly in exercise and respiratory muscles and fat.

5. It is concluded that collapse and ultimately heat stroke are not due primarily to cardiovascular ‘failure’ but, rather, to consequences of high body temperatures resulting from thermoregulatory failure attributable to demands for blood pressure regulation dominating requirements for body temperature regulation.
ISOLATION OF OPIATE RECEPTOR LIGANDS IN COFFEE
Authors: Wynne Kenneth N. , Famüari Mary , Boublik Jaroslav H. , Drummer Olaf H. , Rae Ian D. , Funder John W.
Published: June 2007

1. We have reported previously that instant coffee contains ligands for opiate receptors with characteristics similar to those of opiate antagonists.

2. A concentrate of receptor‐active ligands from instant coffee was prepared by serial treatments involving Amberlite XAD‐2, flash chromatography and gel permeation chromatography.

3. Examination of the final concentrate by GC‐MS showed the presence of a number of isomeric (iso)feruloylquinic acid lactones.

4. It is suggested that the synthesis and biological testing of each quinide isomer will establish which is responsible for the opiate receptor activity of instant coffee.
PLASMA AND PITUITARY PROLACTIN AND BLOOD PRESSURE IN BROMOCRIPTINE‐TREATED SPONTANEOUSLY HYPERTENSIVE AND WISTAR‐KYOTO RATS
Authors: Tan B. K. H. , Hutchinson J. S.
Published: June 2007

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar‐Kyoto rats (WKY).

2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine‐treated group compared with the lack of a change in BP observed in the vehicle‐treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine‐treated group than in the vehicle‐treated group.

3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL.

4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY.

5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.
INCREASES IN URINARY KALLIKREIN ACTIVITY AND PROSTANOID SYNTHESIS AFTER DIETARY POTASSIUM SUPPLEMENTATION
Authors: Barden A. , Vandongen R. , Beilin L. J.
Published: June 2007

SUMMARY

1. To determine whether increasing dietary potassium alters kallikrein activity or prostaglandin synthesis, 77 women participated in a 3 week screening to assess their dietary potassium intake. Forty‐four normotensive women whose dietary potassium was less than 60 mmol/day were allocated randomly to one of two groups who took either 80 mmol/day KC1 (Slow‐K, Ciba Geigy) or matching placebo for the first or second of two 4 week periods.

2. Significant increases in urinary kallikrein excretion (P < 0.01), and urinary 6‐keto‐PGF1α (P < 0.01) were observed during potassium supplementation. These changes occurred without alterations in urine volume or sodium excretion.

3. It is suggested that potassium‐induced changes in urinary 6‐keto‐PGF1α may reflect increased renal and possibly vascular synthesis of prostacyclin. These increases may be mediated by increased plasma potassium stimulating kallikrein synthesis, leading to bradykinin‐induced activation of phospholipase A2. Enhanced kallikrein/kinin and prostacyclin formation could contribute to the blood pressure lowering effect of potassium reported in hypertensive subjects.
(±)‐PINDOLOL HAS β2‐ADRENOCEPTOR ANTAGONIST BUT NOT AGONIST ACTION ON THE COSTO‐UTERINE MUSCLE OF THE RAT
Authors: Pennefather Jocelyn N. , Hartley Margaret L. , Leedham Judith A.
Published: June 2007

1. The effects of isoprenaline and (±)‐pindolol on rat isolated costo‐uterine muscle have been compared.

2. Isoprenaline produced reproducible concentration‐dependent inhibition of contractions, and maximal doses (< 0.1 μmol/l) produced mean inhibition of 87, 94 and 97% of field, carbachol and potassium‐stimulated preparations, respectively.

3. (±)‐Pindolol, when effective, produced inhibition only in concentrations greater than its pA2 value (9.87) as an antagonist of isoprenaline; mean maximal effects were < 60% of those produced by isoprenaline.

4. It is concluded that (±)‐pindolol is a potent antagonist, but has only variable agonist action, at the β2‐adrenoceptors of the rat costo‐uterine muscle.
EFFECTS OF INTRAHIPPOCAMPAL INJECTIONS OF THE CHOLINERGIC NEUROTOXIN AF64A ON PRESYNAPTIC CHOLINERGIC MARKERS AND ON PASSIVE AVOIDANCE RESPONSE IN THE RAT
Authors: Tateishi Narito , Takano Vukio , Honda Kenji , Yamada Katsushi , Kamiya Yoshiko , Kamiya Hiro‐o
Published: June 2007

1. The effects of the intrahippocampal injection of ethylcholine mustard aziridinium ion (AF64A) on the following cholinergic markers were examined.

2. Bilateral injection of 10 nmol of AF64A into the dorsal hippocampus caused a loss of choline acetyltransferase (CAT) activity in the dorsal hippocampus, ventral hippocampus, cortex and striatum.

3. This treatment caused significant decreases in ACh contents in the dorsal hippocampus, ventral hippocampus and cortex, but not in the striatum.

4. The step‐down latencies during the test trials of both 10 and 50 nmol AF64A‐treated groups were significantly shorter than those of vehicle‐treated groups.

5. None of the control animals stepped down to the large box where they had previously received a foot shock, but 40% of the 10 nmol and 60% of the 50 nmol AF64A‐treated animals stepped down to the large box within 600 s.

6. These results indicate that AF64A treatment produces biochemical and functional deficits in the cholinergic neurons in the CNS.
THE EFFECT OF TWO NEW α‐GLUCOSIDASE INHIBITORS ON METABOLIC RESPONSES TO A MIXED MEAL IN NORMAL VOLUNTEERS
Authors: Kennedy Frank P. , Miles John M. , Heiling Valarie , Gerich John E.
Published: June 2007

1. α‐Glucosidase inhibitors delay carbohydrate absorption and have been proposed as adjunctive therapy for diabetes mellitus.

2. To determine the effects of two new α‐glucosidase inhibitors, Bay‐m‐1099 and Bay‐o‐1248, on meal carbohydrate and lipid tolerance, plasma glucose, insulin and triglyceride levels were measured at 15–60 min intervals over 12 h after ingestion of a standard breakfast, lunch and dinner of identical composition in 31 normal volunteers.

3. The volunteers were randomized to receive either Bay‐m‐1099 (50 or 25 mg) or placebo prior to each meal, or the single administration of Bay‐o‐1248 (20 or 10 mg) or placebo prior to breakfast.

4. Only Bay‐m‐1099 at the 50 mg dose reduced significantly the postprandial increase in plasma insulin levels after each meal when compared with placebo (25, 36, 54% at breakfast, lunch, and dinner, respectively; P<0.05). Both drugs were well tolerated, with side effects limited to complaints of flatulence.

5. Thus, with the dosage schedule employed, Bay‐m‐1099, but not Bay‐o‐1248, significantly reduced postprandial increments in plasma insulin.
EFFECTS OF FIVE NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS ON THE RENAL AND SYSTEMIC RESPONSES TO ARACHIDONATE IN CONSCIOUS DOGS
Authors: Anderson W. P. , Bobik A.
Published: June 2007

1. The effects of five different non‐steroidal anti‐inflammatory drugs (NSAID) on the renal blood now responses to arachidonate were compared.

2. Arachidonate (5–200 μg/kg) injected into the renal arteries of conscious dogs caused dose‐related renal vasodilatation with no systemic effects.

3. Aspirin (35 mg/kg), phenylbutazone (12 mg/kg) and ibuprofen (25 mg/kg) all markedly reduced arachidonate‐induced renal vasodilatation.

4. In contrast, neither indomethacin (3 mg/kg) or its related drug sulindac sulphide (6 mg/kg) significantly reduced arachidonate‐induced renal vasodilatation.

5. All NSAID abolished the hypotensive response to intravenous injection of arachidonate (10 mg).

6. Thus, indomethacin and sulindac did not block the effects of renal artery injections of arachidonate but did abolish the systemic effects. Aspirin, phenylbutazone and ibuprofen greatly reduced responses to both renal artery and intravenous arachidonate.

7. Indomethacin and aspirin both reduced the production of prostaglandin E2 and 6‐keto‐PGF1α by dog renal cortical microsomes in vitro.

8. Thus, indomethacin and sulindac had different effects to other NSAID on arachidonate‐induced renal vasodilatation. The results are compatible with the hypothesis that some sites of prostaglandin production in the kidneys of conscious dogs may be relatively resistant to inhibition by indomethacin and sulindac.
EFFECTS OF POMC‐DERIVED PEPTIDES ON ALDOSTERONE SECRETION IN VIVO
Authors: McDougall John G. , Murphy Gregory J. , Coghlan John P. , Denton Derek A. , Hardy Kenneth J. , Johnson Elizabeth I. M. , Scoggins Bruce A. , Wright R. Douglas
Published: June 2007

1. To investigate a role for peptides derived from the precursor molecule pro‐ opiomelanocortin (POMC) on the control of aldosterone secretion (ASR), α‐, β‐, γ1, and γ2‐melanocyte stimulating hormone (MSH), corticotropin‐like intermediate lobe peptide (CLIP) or β‐endorphin were infused into the adrenal arterial supply of sheep with an adrenal cervical autotransplant.

2. None of the peptides had any significant effect on aldosterone secretion rate in Na replete, unstressed, conscious animals. In contrast, ACTH‐stimulated ASR approximately twofold.

3. POMC‐derived peptides other than ACTH appear to have little or no effect on the short‐term control of aldosterone secretion in vivo, although a role in control and modulation of adrenal function over the longer term cannot be discounted.
ATRIAL NATRIURETIC PEPTIDE RELEASE IN THE RABBIT IS INDEPENDENT OF CARDIAC NERVE ACTIVITY
Authors: McGrath Barry P. , Blake Duncan , Jover Bernard , Arnolda Leonard , Ogawa Kazuya , Hodsman G. Peter , Johnston Colin I.
Published: June 2007

1. Changes in plasma atrial natriuretic peptide (ANP) were examined in conscious rabbits in response to a 33% blood volume expansion in intact animals and after blockade of cardiac nerve activity.

2. Blood volume expansion by one‐third markedly increased right atrial pressure and resulted in a four‐fold increase in plasma ANP.

3. Cardiac nerve blockade with intrapericardial procaine had no effect on resting plasma ANP levels. The ANP responses to volume expansion in the presence of cardiac nerve blockade were similar to those seen in intact animals.

4. Release of ANP from its cardiac stores in response to volume expansion is not influenced by cardiac nerve activity.
SALIVARY PARACETAMOL ELIMINATION IN PATIENTS WITH CONGESTIVE CARDIAC FAILURE
Authors: Kumar N. Pradeep , Sethuraman K. R. , Chandrasekar S. , Ray K. , Adithan C. , Shashindran C. H.
Published: June 2007

1. Salivary paracetamol elimination was studied in nine patients with congestive cardiac failure (CCF). Six healthy volunteers served as the control group.

2. Paracetamol elimination t1/2 and apparent volume of distribution were significantly higher in patients with CCF compared with controls. There was no significant change in the clearance rate.

3. Drug therapy of failure for a period of 15 days returned the t1/2 and V values to normality.
EFFECT OF ALMITRINE BISMESYLATE ON BREATHING PATTERN DURING HYPOXIA/HYPERCAPNIA IN RATS AND FERRETS
Authors: Austin C. A. , Wach R. A. , Bee D. , Finlay M. , Emery C. J. , Suggett A. J. , Barer G. R.
Published: June 2007

1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead‐space. Some chronically hypoxic rats, which have muscularized pulmonary arterioles similar to COAD patients, were also studied.

2. In 18 chronically hypoxic (CH) rats and 17 littermate control rats (C), breathing air, doses of almitrine bismesylate caused greater increases in ventilation (VE) in C than in CH rats. FRC, which was initially greater in CH rats, increased significantly in both groups after almitrine.

3. In C rats, breathing hypoxic or hypoxic/hypercapnic gas mixtures caused large increases in VE. Slow infusions of almitrine caused a further increase in VE usually via an increase in tidal volume (VT) but not frequency (f).

4. In two series of rats (n= 9; n= 6) severe and moderate degrees of tracheal obstruction caused a fall in PaO2 and a rise in PaCO2, a fall in VE due to both VT and f and large changes in oesophageal pressure (Poes), which often became positive on expiration. Almitrine infusions usually caused a rise in PaO2, a rise in VT and no change in f; with moderate obstruction, Poes also rose. The results were thought to depend on the balance between improved ventilation and increased O2 demand of the respiratory muscles.

5. Eleven ferrets were made hypoxic and hypercapnic by adding a large dead‐space to the trachea. A slow infusion of almitrine caused a significant rise in PaO2 before any significant change in VE was detected; PaCO2 fell at some time during the infusion, but not significantly. The initial significant rise in PaO2, at 2.5 min, was not associated with significant changes in TI (time of inspiration) and VT/TI. At 5 min VT/TI, TI and PaO2 were all significantly altered.

6. Infusions of almitrine into hypoxic and hypercapnic animals caused improvements in the arterial oxygen tension which were associated with subtle changes in the breathing pattern; inspiratory time and inspiratory flow rate changed in the absence of an increase in total VE. Possible conclusions with respect to the action of almitrine in patients with COAD are discussed.
HIGH AFFINITY ALDOSTERONE BINDING SITES (TYPE I RECEPTORS) IN RAT HEART
Authors: Pearce Paul , Funder John W.
Published: June 2007

1. The use of the receptor stabilizing agent sodium molybdate, and of RU26988 to exclude [3H]‐aldosterone binding from Type II glucocorticoid receptors, has enabled the characterization of high affinity Type I aldosterone binding sites in rat atrial and ventricular cytosols.

2. In adult male and female rats the affinity of binding (Kd 4°C) is ∼ 1–2 nmol/l for both atria and ventricles; specificity of binding is similar to that for Type I sites in classical aldosterone target tissues (aldosterone = corticosterone≫dexamethasone).

3. Levels of atrial Type I sites are higher than the corresponding levels in ventricle in both males and females, whereas for Type II (classical glucocorticoid) receptors the reverse is the case; levels of both Type I and Type II sites fall over the age range examined (40 days‐6 months).

4. The physiological function(s) of cardiac Type I sites, and their in vivo mineralo‐corticoid or glucocorticoid selectivity, remain to be explored.
EFFECT OF 3 DAY INFUSION OF ACTH OR CRF ON THE PITUITARY‐ADRENAL AXIS
Authors: Silberberg Suzanne , Funder John W.
Published: June 2007

1. The effects of 72 h subcutaneous infusion of graded doses of rat CRF and ACTH(1–24) were studied in rats of initial weight 150–170 g. Rat CRF was infused at 30, 100 or 300 ng/h, and ACTH(1–24) at 125, 250 or 500 ng/h.

2. There was a progressive though modest increase in adrenal weight for all CRF doses, and an associated reduction of thymus weight. Circulating ir‐ACTH, ir‐β‐endorphin and corticosterone levels, and adrenal DN A content, were not increased after 3 days. Adrenal RNA and protein content were increased at the highest CRF dose used.

3. ACTH infusion caused a progressive increase in adrenal weight and thymie involution which was marked at the higher doses; circulating corticosterone levels were not significantly altered by the lowest dose but were significantly raised by the higher doses. As expected, plasma ir‐β‐endorphin was suppressed to low levels with all doses. Adrenal DNA did not alter but there were progressive increases in adrenal protein and RNA.

4. There was a marked difference in gain between the two infusion regimens in terms of all parameters measured, suggesting that potent mechanisms exist to temper the pituitary‐adrenal response to markedly different levels of peripheral CRF input. The damped effect of CRF infusion compared with that of ACTH may represent desensitization of CRF receptors at the pituitary; alternatively, it may reflect binding and substantial inactivation of CRF in peripheral blood.
CARDIOVASCULAR RESPONSES TO ACUTE MYOCARDIAL ISCHAEMIA IN MORPHINE‐DEPENDENT RATS
Authors: Ko Wendy W‐W. , Dai Soter , Chan Mo‐Yin
Published: June 2007

1. The cardiovascular responses to acute myocardial ischaemia were studied in opiate‐dependent animals before and after 2 weeks morphine withdrawal.

2. Rats were treated with morphine sulphate in drinking water for 2, 3 or 5 weeks. The development of morphine tolerance and dependence was verified by the tailimmersion test for analgesia and the naloxone‐precipitated withdrawal syndrome, respectively.

3. Acute left coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate and ventricular tachycardia or fibrillation in anaesthetized naive rats.

4. Chronic morphine treatment did not alter the haemodynamic responses to coronary artery ligation. However, a significantly lowered incidence, and prolonged time of onset, of ventricular arrhythmias was found in 3 and 5 week morphine‐treated rats. This phenomenon did not occur in animals receiving morphine for 2 weeks and in a 3 week morphine‐treated group which was subsequently withdrawn for 2 weeks.

5. It is suggested that the decreased occurrence of early ventricular arrhythmias resulting from acute myocardial ischaemia in chronic morphine‐treated rats may be related to the degree of opiate tolerance and dependence.
RAPID HAEMODYNAMIC RESPONSES TO ATRIAL NATRIURETIC FACTOR (99–126) IN CONSCIOUS SHEEP
Authors: Parkes D. G. , Coghlan J. P. , McDougall J. G. , Scoggins B. A.
Published: June 2007

1. Haemodynamic effects of 20 μg and 100 μg injection of atrial natriuretic factor 99–126 (ANF) were studied in conscious sheep.

2. ANF injection rapidly decreased blood pressure associated with a fall in total peripheral resistance, increased heart rate and cardiac output. These parameters returned to normal within 5 min of injection.

3. This study shows that ANF has an initial vasodilatory action to decrease blood pressure, which is different from the hypotensive mechanism seen with short‐term infusion (60 min) of ANF in sheep.
INFLUENCE OF ACUTE MYOCARDIAL ISCHAEMIA ON VENTRICULAR CYCLIC AMP CONCENTRATIONS IN NAIVE AND MORPHINE‐TREATED RATS
Authors: Ko Wendy W. W. , Dai Soter , Chan Mo‐Yin
Published: June 2007

1. Ventricular cyclic AMP (cAMP) concentrations of naive and morphine‐treated rats subjected to acute myocardial ischaemia were examined.

2. In naive rats, ventricular cAMP levels were increased at 3 min but decreased 5 and 10 min after left coronary artery ligation. Statistically significant changes were observed in the right ventricle after 3 min and in the left ventricle after 10 min.

3. Acute morphine treatment did not significantly alter ventricular cAMP content in rats subjected to either sham operation or acute left coronary artery ligation.

4. Ventricular cAMP concentrations were significantly lower in sham‐operated rats after 5 weeks of chronic morphine treatment while after 3 weeks of chronic morphine treatment, this phenomenon was seen only after acute coronary ligation. The reductions were reversed by opiate withdrawal.

5. These observations support the theory that elevated cAMP levels may contribute to the production of early ventricular arrhythmias during acute myocardial ischaemia. It is suggested that the reduction in ventricular cAMP concentrations may partly account for the previously reported decreased occurrence of early ventricular arrhythmias in chronic morphine‐treated rats subjected to acute left coronary artery ligation.
RELATIONSHIP BETWEEN THE DOSE‐RESPONSE EFFECTS OF DIAZEPAM AND CLOBAZAM ON ELECTROENCEPHALOGRAPHIC PARAMETERS AND ON KINDLED AMYGDALOID SEIZURE ACTIVITY IN RATS
Authors: Harris Q. L. G. , Lewis S. J. , Young N. A. , Vajda F. J. E. , Jarrott B.
Published: June 2007

1. The possibility that the anticonvulsant activity of the benzodiazepines, diazepam and clobazam, is related to changes in EEG parameters, particularly β activity, was investigated in amygdaloid kindled rats.

2. The effects of diazepam (1, 2, 4, 8 and 16 μmol/kg), administered intraperitoneally (i.p.), clobazam (1, 2, 4, 8, 16 and 32 μmol/kg, i.p.) or vehicle (dimethyl sulfoxide) on the cortical EEG of amygdaloid kindled rats were quantitated for 15 min using computerized period amplitude analysis. Immediately afterwards, the amygdala was stimulated and the after‐discharge duration (AD) and the seizures stage (SS) were determined.

3. The equivalent percentage time (EPT) of the diazepam‐treated group was decreased in the θ band (4–8 Hz) and increased in the α (8–12 Hz) and first six β (12–36 Hz) bands. The mean peak amplitude (MPA) was increased in the α (8–12 Hz) and all seven β bands (12–40 Hz). Clobazam increased the EPT and MPA in the α (8–12 Hz) and all seven β (12–40 Hz) bands. The MPA was also increased by clobazam in the θ (4–8 Hz) band.

4. Diazepam reduced both the AD and SS of the kindled seizures at doses of 4, 8 and 16 μmol/kg, whereas clobazam was anticonvulsant at doses of 16 and 32 μmol/kg. The reduction in both AD and SS correlated with increases in the EPT and MPA in the first β (12–16 Hz) band in the diazepam‐treated group and in the first four β (12–28 Hz) bands in the clobazam‐treated group.
RILMENIDINE ACTS AS A PARTIAL AGONIST AT PREJUNCTIONAL α2‐ADRENOCEPTORS IN GUINEA‐PIG ATRIA
Authors: Li C. G. , Rand M. J.
Published: June 2007

1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on α2‐adrenoceptors, has partial agonist activity on prejunctional α2‐adrenoceptors in guinea‐pig atria.

2. Isolated preparations of guinea‐pig atria were incubated with [3H]‐noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as an index of release of transmitter noradrenaline.

3. Rilmenidine (1 μmol/1) inhibited noradrenaline release evoked by short trains (five, 20 and 50 pulses) of sympathetic nerve stimulation and this inhibitory effect of rilmenidine was antagonized by the α2‐adrenoceptor antagonists, idazoxan (0.1 and 0.3 umol/1) and rauwolscine (0.3 umol/1) whereas it was not affected by the α1‐adrenoceptor antagonist prazosin (0.1 μmol/1).

4. On the other hand, rilmenidine (1 μmol/1) enhanced noradrenaline release evoked by long trains (150 and 300 pulses) of stimulation and this effect was also abolished by idazoxan (0.1 μmol/1).

5. These findings suggest that the effects of rilmenidine on transmitter release depend on the degree of auto‐inhibition: when the concentration of noradrenaline in the biophase of the prejunctional α2‐adrenoceptors is low, rilmenidine acts as an agonist, but when the concentration is high it acts as an antagonist. Thus, rilmenidine, like clonidine, is a partial agonist on prejunctional α2‐adrenoceptors in guinea‐pig atria.
INVOLVEMENT OF HYPOTHALAMIC ADRENALINE IN THE CLONIDINE WITHDRAWAL SYNDROME IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Lewis Stephen J. , Rowe Peter , Jarrott Bevyn
Published: June 2007

1. The concentrations of adrenaline and other catecholamines (noradrenaline and its major metabolite DHPG, dopamine and its major metabolite DOPAC) were measured in the hypothalamus and medulla oblongata of normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR) which had received a continuous subcutaneous infusion of clonidine (10 μg/kg per h) for 10 days, and also in WKY and SHR rats which were killed 15–18 h after the cessation of the 10‐day infusion.

2. The concentrations of adrenaline in the hypothalamus and medulla oblongata/pons of the clonidine treated WKY and SHR rats were not different from their respective controls. However, the adrenaline concentrations in the hypothalamus (but not the medulla oblongata) were significantly decreased in the post‐infusion WKY and SHR.

3. These results suggest that hypothalamic adrenergic mechanisms may have a common involvement in the post‐clonidine infusion syndromes displayed by the WKY and SHR strains.
SHORT COMMUNICATION: LONG‐LASTING DEPOLARIZATION OF THE CENTRAL TERMINALS OF CUTANEOUS AFFERENTS IN L7 SEGMENT EVOKED BY VOLLEYS ASCENDING FROM THE SACRAL CORD IN THE CAT
Authors: Lupa K. , Wójcik G. , Tarnecki R. , Niechaj A.
Published: June 2007

1. In 72% of non‐anaesthetized spinal cats, single volleys ascending from the sacral cord evoke long‐lasting primary afferent depolarization in L7 segment. It occurs in the central terminals of cutaneous but not in Ia muscle afferents.

2. Volleys descending to L7 segment evoke only short‐lasting presynaptic depolarization.

3. It is concluded that presynaptic inhibition in L7 segment produced by ascending volleys is more effective than that evoked by descending volleys.
SHORT COMMUNICATION: EFFECT OF OESTRADIOL REPLACEMENT ON SWIM‐INDUCED ANTINOCICEPTION IN OVARIECTOMIZED MICE
Authors: Wong Chak‐Lam
Published: June 2007

1. A 30 s swim in water at 30°C reduced the number of abdominal constrictions produced in female mice by intraperitoneally administered acetic acid and this antinociceptive effect was antagonized by naloxone.

2. Oophorectomy abolished the development of antinociceptive activity in response to swim.

3. The development of antinociceptive activity and naloxone antagonism were restored in oophorectomized mice maintained on daily oestradiol injection.

4. The present study indicates that the increase in abdominal constriction response to acetic acid in oophorectomized mice was due to the removal of the source of female sex hormone.
INHIBITION OF α‐TOCOPHEROL AND CALCIUM CALMODULIN‐STIMULATED PHOSPHODIESTERASE ACTIVITY IN VITRO BY ANTHRACYCLINES
Authors: Nwankwoala Reginald N. P. , West William L.
Published: June 2007

b

1. The inhibition of α‐tocopherol and calmodulin‐stimulated phosphodiesterase activities was investigated in vitro.

2. Anthracyclines—doxorubicin, daunorubicin and aclacinomycin—inhibited calcium calmodulin‐stimulated cyclic 3′,5′‐AMP (cAMP) nucleotide phosphodiesterase (EC. 3.1.4–17) activity (IC50= 33.00 ± 3.50–36.50 ± 2.75 μmol/l). The stimulation of this enzyme by α‐tocopherol was also inhibited by doxorubicin (IC50= 18.50 ± 4.00 μmol/l).

3. The anthracycline‐induced inhibition of the calcium calmodulin and α‐tocopherol‐stimulated phosphodiesterase activity was competitive with calmodulin and α‐tocopherol respectively. Increasing the concentration of the substrate, cAMP or calcium ions did not attenuate the drug‐induced inhibition. The basal activity of the enzyme was not inhibited by concentration of doxorubicin up to 50 μmol/l.

4. In vivo, single dose drug distribution studies of the fluorescence of doxorubicin indicate that in the heart after a cardiotoxic dose (20 mg/kg), myocardial concentrations were achieved which could cause 70–80% inhibition of this phosphodiesterase enzyme.

5. Inhibition of calmodulin function by anthracyclines via direct interaction with calmodulin may contribute significantly to the effects of anthracyclines, such as disturbance in calcium homeostasis as well as acute and chronic deleterious effects on the myocardium. The action of α‐tocopherol to bind or complex anthracycline may in part contribute to its protection against anthracycline‐induced membrane damage and cardiotoxicity.
EFFECT OF ATRIAL PEPTIDE ON COLLECTING DUCT FUNCTION
Authors: Fitzgibbon Wayne , Morgan Trefor
Published: June 2007

b

1. The effects of synthetic rat atrial natriuretic peptides (ANP) on diffusional 22Na+, 36Cl− and tritiated water (THO) permeability of in vitro microperfused rat papillary collecting ducts and the effect in vivo of ANP on stop‐flow sodium concentrations in the terminal segment of rabbit nephrons were studied.

2. The addition of 4 ± 10−8 or 4 ± 10−7 mol/l ANP to the medium or perfusion solution did not alter diffusional 22Na+ or 36Cl− permeability of microperfused rat papillary collecting ducts.

3. The basal diffusional THO permeability of papillary collecting ducts was not altered when 4 ± 10−7 mol/l ANP was present in the medium and did not inhibit the increment in diffusional THO permeability induced by vasopressin or reduce the permeability to water in a duct previously stimulated by vasopressin.

4. The administration of ANP (2 μg/kg bodyweight) to rabbits in water diuresis did not alter systemic blood pressure but induced a marked natriuresis and increases in urine flow and potassium excretion. This natriuresis was not associated with alterations in stop‐flow sodium reabsorptive capacity or sodium permeability of the collecting tubules and ducts.

5. Previously reported in vivo clearance data suggest that ANP causes, at least in part, a natriuresis by altering sodium transport in the medullary collecting ducts. In this study, however, a direct effect could not be demonstrated and it is possible that the medulla needs to be functioning in its normal environment for such effects to be demonstrated.
EFFECT OF pH ON VASOPRESSIN‐INDUCED WATER PERMEABILITY IN COLLECTING DUCTS OF ISOLATED RAT PAPILLAE
Authors: Fitzgibbon Wayne , Morgan Trefor
Published: June 2007

b

1. The effects of basolateral and luminal pH on diffusional water permeability of microperfused collecting ducts of isolated rat papillae were examined in the presence and absence of vasopressin at two concentrations.

2. In the absence of vasopressin, collecting duct diffusional water permeabilities did not differ when the pH of the luminal fluid was varied. Similarly, in the absence of vasopressin, collecting duct diffusional water permeabilities did not differ when the bath pH was varied.

3. In the presence of 50 μU/ml vasopressin, increases in diffusional water permeability of collecting ducts perfused with solutions at pH 5.0, 7.4 or 9.0 did not differ significantly. Similarly, increases in diffusional water permeability induced by 200 μU/ml vasopressin were not different when collecting ducts were perfused with solutions at pH 5.0, 7.4 or 9.0.

4. The presence of vasopressin (50 μU/ml) in the bathing medium at pH 6.4, 7.4 and 8.4 induced increments in diffusional water permeability of 0.40 ± 0.21 (n= 14, P > 0.05), 1.56 ± 0.27 (n= 27, P < 0.001) and 1.67 ± 0.24 (n= 12, P < 0.001) μm/s, respectively. The increment in water permeability at pH 6.4 was significantly less than that at pH 7.4 (P < 0.001).

5. The presence of vasopressin (200 μU/ml) in the bathing medium at pH 6.4, 7.4 and 8.4 induced increments in diffusional water permeability of 2.16 ± 0.54 (n= 9, P < 0.01), 2.55 ± 0.51 (n= 17, P < 0.001) and 0.98 ± 0.34 (n= 11, P < 0.05) μm/s respectively. The increment in diffusional water permeability induced by 200 μU/ml vasopressin at pH 8.4 was significantly less than that at pH 7.4 (P < 0.025).

6. These findings indicate that vasopressin‐induced increases in diffusional water permeability across papillary collecting ducts are modified by changes in basolateral pH but not by changes in luminal pH. It is proposed that the interaction between vasopressin action and basolateral pH is due to alteration of different pre‐and post‐cAMP events by different basolateral pH.
MET‐ENKEPHALIN AND THE ENKEPHALIN ANALOGUE FK‐33824 CENTRALLY INHIBIT ADRENOCORTICOTROPHIC HORMONE SECRETION IN SHEEP
Authors: Wang Xiaoming , Tresham Janette J. , Scoggins Bruce A. , Coghlan John P.
Published: June 2007

b

1. The effects of central administration of met‐enkephalin, leu‐enkephalin, the enkephalin analogue FK‐33824 and the opiate antagonist naloxone on plasma concentration of adrenocorticotrophic hormone (ACTH) were examined in conscious sheep.

2. Intracerebroventricular infusion of met‐enkephalin and FK‐33824 significantly decreased the basal plasma concentration of ACTH.

3. Intracerebroventricular infusion of FK‐33824 inhibited the haemorrhage‐induced increase in plasma concentration of ACTH.

4. Intracerebroventricular infusion of naloxone attenuated the central inhibition of plasma concentration of ACTH induced by FK‐33824, but intravenous infusion of naloxone had no effect on the reduction in plasma concentration of ACTH induced by FK‐33824.

5. These studies suggest that in sheep met‐enkephalin may play a central inhibitory role in the control of ACTH secretion.
ENHANCEMENT OF RENAL BUT NOT HAEMODYNAMIC EFFECTS OF ATRIAL NATRIURETIC PEPTIDE (1–28) IN SHEEP TREATED WITH ACTH
Authors: Parkes David G. , Coghlan John P. , McDougall John G. , Scoggins Bruce A.
Published: June 2007

1. The haemodynamic and renal effects of short‐term infusion of human atrial natriuretic peptide (ANP) (1–28) were examined in sheep treated with ACTH and compared with the responses previously observed in normotensive sheep.

2. Infusion of ANP at 100 μg/h for 60 min in ACTH‐treated sheep (5 μg/kg per day for 5 days) decreased blood pressure and produced a fall in both cardiac output and stroke volume. No changes were seen in heart rate and total peripheral resistance.

3. ANP produced large increases in urine volume, urinary sodium and chloride excretion, and further decreased plasma potassium concentration in the ACTH‐treated sheep. Compared with normal sheep studied previously under the same conditions, the ACTH‐treated sheep showed a much greater diuretic and natriuretic response to ANP, although the blood pressure response to ANP was similar in both states.

4. The change in renal responsiveness to ANP in sheep may be related to the increased blood volume of the ACTH‐treated animals because volume expansion is known to enhance the renal effects of ANP.
PLASMA NEUROPEPTIDE Y AND ATRIAL NATRIURETIC PEPTIDE CONCENTRATIONS IN MAN
Authors: Russell A. E. , Aylward P. E. , Smith S. A. , Cain M. D. , McRitchie R. J. , Chalmers J. P.
Published: June 2007

1. In order to examine the concentration of neuropeptide Y‐like immuno‐reactivity (NPY‐LI) and atrial natriuretic peptide (ANP) in the circulation in man, blood was sampled from the iliac vein, the inferior vena cava, the superior vena cava, the pulmonary artery and the femoral artery in 13 patients undergoing cardiac catheterization.

2. Plasma NPY‐LI levels were similar at all points sampled and no arteriovenous differences were found. Plasma ANP concentration in the pulmonary artery was greater than in peripheral venous blood but there was a strong correlation between the two.

3. The concentration of NPY‐LI and ANP in peripheral venous blood reflects central venous and arterial concentrations.
CALCIUM ANTAGONISTS AND HYPERTENSION
Authors: Nayler W. G. , Dillon J. S. , Sturrock W. J.
Published: June 2007

1. Calcium antagonists, including verapamil, are now used widely in the management of patients with hypertension.

2. Six weeks of chronic therapy with verapamil (50 mg/kg per day, orally) to produce a plasma level of 80–100 ng/ml in Sprague‐Dawley rats depletes cardiac noradrenaline (NA) without apparently causing β1 adrenoceptor ‘up’ regulation.

3. The effect of verapamil on cardiac NA is rapidly reversed upon verapamil withdrawal.

4. Chronic therapy with nisoldipine (100 mg/kg per day, orally) had no effect on cardiac NA.

5. Verapamil (50 mg/kg per day, orally) and nisoldipine (100 mg/kg per day, orally) therapy for 6 weeks prevented the time‐dependent increase in systolic blood pressure in SHR rats.

6. Binding studies with (—)[3H]‐D888 (desmethoxyverapamil) indicated that the affinity of the phenylalkylamine binding sites is higher in hearts of SHR relative to hearts from age‐matched (25 weeks) WKY and SD, without any change in density.
N‐METHYL‐d‐ASPARTATE RECEPTORS IN THE SPINAL CORD MEDIATE PRESSOR RESPONSES TO STIMULATION OF THE ROSTRAL VENTROLATERAL MEDULLA IN THE RAT
Authors: Mills E. H. , Minson J. B. , Pilowsky P. M. , Chalmers J. P.
Published: June 2007

1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established.

2. Amino acid antagonists were introduced into the spinal subarachnoid space to investigate the role of spinal amino acid receptors in mediating this pressor response in the anaesthetized rat.

3. Intrathecal administration of the amino acid receptor antagonists 2‐aminophosphono valeric acid (2APV), γ‐glutamyl glycine, kynurenate or glutamic acid diethylester (GDEE) attenuated the pressor responses to stimulation of the Cl area. These compounds have been shown to antagonize N‐methyl‐d‐aspartate (NMDA) sensitive receptors.

4. Intrathecal administration of 2APV significantly attenuated the increase in blood pressure produced by injection of NMDA into the spinal subarachnoid space.

5. These results suggest that the pressor response produced by stimulation in the area of the Cl neurons in the rostral ventrolateral medulla of the rat is mediated at least in part by NMDA receptors in the spinal cord.
ALTERED LEVELS OF NEUROPEPTIDES IN THE MEDULLA AND SPINAL CORD OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Jarrott B. , Lewis S. J. , Maccarrone C. , Shulkes A.
Published: June 2007

1. Spontaneously hypertensive rats (SHR) are useful for investigating the possible pathophysiological and neurochemical basis of human essential hypertension.

2. The accepted pathogenic mechanism of hypertension in SHR is an increased central sympathetic drive which results in an increased peripheral resistance.

3. The neurochemical basis of the increased sympathetic drive is unknown. The observation that there are reduced levels of neuropeptides (vasoactive intestinal peptide, neuropeptide Y, cholecystokinin octapeptide, neurotensin and calcitonin gene related peptide) in the spinal cord in SHR rats compared with age and gender matched Wistar‐Kyoto normotensive rats could provide a basis for understanding the mechanism of hypertension in SHR.