bluuebunny/crossref_metadata_2025 huggingface dataset:
RAT MYOCARDIAL PROTEIN DEGRADATION
Authors: Steer J. H. , Hopkins B. E.
Published: June 2007

1. Myocardial protein degradation rates were determined by following tyrosine release from rat isolated left hemi‐atria in vitro.

2. After two 20 min preincubations the rate of tyrosine release from hemi‐atria was constant for 4 h.

3. Skeletal muscle protein degradation was determined by following tyrosine release from rat isolated hemi‐diaphragm (Fulks, Li & Goldberg, 1975).

4. Insulin (10‐7M) inhibited tyrosine release from hemi‐atria and hemi‐diaphragm to a similar extent. A 48 h fast increased tyrosine release rate from hemi‐diaphragm and decreased tyrosine release rate from hemi‐atria. Hemi‐diaphragm tyrosine release was inhibited by 15 mmol/1 D‐glucose but a variety of concentrations of D‐glucose (0, 5, 15 mmol/1) had no effect on tyrosine release from hemi‐atria. Five times the normal plasma levels of the branched‐chain amino acids leucine, isoleucine and valine had no effect on tyrosine release from either hemi‐atria or hemi‐diaphragm.
THE KETOTIC RATIO (KB/NEFA) IN MAN
Authors: Schade David S. , Eaton R. Philip
Published: June 2007

1. The ‘ketotic ratio’, which is defined as the plasma ketone‐body concentration divided by the plasma nonesterified fatty acid concentration, is potentially useful in predicting the magnitude of the ketone response to a given increment in plasma fatty acid concentration.

2. Two parameters of the ketotic ratio were studied. First, a comparison of the basal plasma ketotic ratio with the ketotic ratio following an acute heparin‐induced increase in nonesterified fatty acid concentration was made. Second, the effect upon the ketotic ratio of noradrenaline which has been reported to increase the plasma ketone‐body concentration independent of the change in plasma nonesterified fatty acid concentration, was determined.

3. The results suggest that the basal ketotic ratio has predictive value in estimating the rise in plasma ketone‐body concentration following an acute increase in plasma nonesterified fatty acid concentration. When noradrenaline was given to increase plasma nonesterified fatty acid concentration, this predictive value was still valid, although a steeper regression line was obtained. Thus, the ketotic ratio is a non‐invasive in vivo technique which provides insight into the direct ketotic activity of hormones independent of their lipolytic effects.
EFFECTS OF CHANGING HAEMATOCRIT, VENTRICULAR RATE AND MYOCARDIAL INOTROPY ON THE ACCURACY OF IMPEDANCE CARDIOGRAPHY
Authors: Quail A. W. , Traugott F. M.
Published: June 2007

1. The accuracy and limitations of the non‐invasive impedance cardiograph technique were examined in dogs with electromagnetic flow‐transducers mounted on the aortic root over a wide range of physiological conditions of anaemia, heart rate, stroke volume and myocardial inotropy.

2. The in vivo blood resistivity (ρ)‐haematocrit relationship is linear and slightly inverse, and is thus opposite to the curvilinear, direct relationship of the bench‐derived p‐haematocrit relationship. At haematocrit 41%, in vivoρ is 135 ohm. cm (s.e.m. = 1.0, n ‐ 134) and rises only to 143 ohm. cm (s.e.m. = 1.6, n= 134) as haematocrit falls to 26%.

3. When in vivoρ is used in the Kubicek formula for stroke volume (SV) calculation, the instrument is linear and accurate for heart rates over 38–156 min‐1. Thus 82% of all points fall within ±20% of the line of equal value over stroke volumes ranging from 8–46 ml (N = 3, n= 105). The standard error of the estimate for pooled data is ±2% of the mean impedance stroke volume value of 22.2 ml. The instrument tends to overread at heart rates lower than 60 min‐1.
INCREASED CONVERSION OF ARACHIDONIC ACID TO VASODILATOR PROSTANOIDS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Dusting G. J. , Davies W. , Drysdale T. , Doyle A. E.
Published: June 2007

1. Vasodepressor responses to intravenous injection of prostacyclin, arachidonic acid, and nitroprusside were examined in anaesthetized, spontaneously hypertensive rats (SHR) of the Okamoto strain, and in their normotensive Wistar– Kyoto (WKY) controls.

2. Depressor responses to prostacyclin and nitroprusside did not differ significantly between the two strains.

3. The vasodepressor effects of arachidonic acid were greater and much more prolonged in SHR than in WKY. In rats treated with indomethacin (2 mg/kg) arachidonic acid induced only transient depressor responses which did not differ significantly between these strains.

4. It is concluded that SHR do not differ from WKY in their sensitivity to prostacyclin but they have enhanced ability to transform exogenous arachidonic acid into vasodilator prostanoids.
IMMUNOREACTIVE β‐ENDORPHIN LEVELS IN PLASMA AND PITUITARY TISSUE FROM GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Hutchinson J. S. , Lim A. , DiNicolantonio R. , Clements J. A. , Funder J. W.
Published: June 2007

1. Levels of immunoreactive β‐endorphin were measured in neurointermediate lobes, anterior lobes and plasma from the Japanese and New Zealand strains of genetically hypertensive rats and their normotensive controls.

2. No significant differences were observed in β‐endorphin between the hypertensive and normotensive rats of the New Zealand strain.

3. The hypertensive rats of the Japanese strain showed significantly higher levels of β‐endorphin in neurointermediate lobe and lower levels in plasma than their normotensive controls.

4. These results suggest that the differences in β‐endorphin levels in the Japanese strain reflect a genetic difference not necessarily related to elevated blood pressure.
ON THE RELATIONSHIP BETWEEN CARDIAC OUTPUT AND PERIPHERAL ARTERIAL RESISTANCE
Authors: Boyd G.W. , Yong A.C.
Published: June 2007

The concept of ‘whole body auto‐regulation’ is a somewhat unsatisfactory explanation of the increased peripheral arterial resistance which follows a rise in cardiac output in ‘volume’ forms of hypertension. This analysis suggests that the resistance change may be due to the sodium retention and increased cardiac output having a direct effect to alter haemodynamics of flow through the arterioles in such a way as to damage their walls, and so lead to the gradual development of structural arteriolar narrowing. Studies are presented in the DOCA/salt hypertensive rat consistent with this proposal.
CENTRAL AMINERGIC MECHANISMS ASSOCIATED WITH THE CLONIDINE WITHDRAWAL SYNDROME
Authors: Lewis S.J. , Fennessy M. R. , Taylor D. A.
Published: June 2007

1.Rats were injected twice daily, at 12.00 and 24.00 hours, with clonidine hydrochloride (50 μg/kg, i‐P‐) until they had received seven injections. Two hours after the 7th injection, their blood pressures, heart rates and body temperatures were decreased (P<0.05) when compared to saline‐treated controls.

2. In rats which received six injections of clonidine hydrochloride (50 μg/kg, i.p.) and an injection of saline when the 7th injection of clonidine was due, the blood pressure, heart rate and body temperature were all significantly (P<0.05) increased 2 h after the saline injection, which was 14 h after the 6th injection of clonidine.

3. Chronic treatment with clonidine hydrochloride significantly (P<0.05) increased the concentrations of noradrenaline and decreased those of histamine in the medulla oblongata/pons. In the hypothalamus the concentrations of noradrenaline and serotonin were significantly (P<0.05) increased.

4. During the withdrawal phase the concentrations of dopamine and histamine were significantly (P<0.05) increased in the medulla oblongata/pons, while those of noradrenaline had returned to the control values. In the hypothalamus the concentrations of histamine and noradrenaline were significantly (P<0.05) increased while those of serotonin had returned to the control value.

5. Methysergide (2 mg/kg, i.p.) when injected during the withdrawal phase produced significant (P<0.05) reductions in the hypertension, tachycardia and hyperthermia which are displayed at this time.

6. It is concluded that chronic clonidine treatment may decrease the release of noradrenaline from the medulla oblongata/pons and that of serotonin from the hypothalamus. However, on cessation of treatment, increases in the release of these amines appear to be associated with the increases in blood pressure, heart rate and body temperature.
THE CARDIOVASCULAR EFFECTS OF INTRA VERTEBRAL ANGIOTENSIN II BEFORE AND AFTER TREATMENT WITH CLONIDINE
Authors: Lumbers Eugenie R. , Reid I. A.
Published: June 2007

1. In anaesthetized mongrel dogs it was shown that intravertebral infusions of angiotensin II (2–4 ng/kg per min) increased mean arterial pressure by causing an increase in cardiac output, while infusions of 10 ng/kg per min increased mean arterial pressure through an effect on peripheral resistance. After intravenous clonidine, intravertebral angiotensin no longer had any stimulatory effect on cardiac output, but arterial pressure still increased to the same extent.

2. It is concluded that intravertebral angiotensin can increase arterial pressure by increasing either cardiac output or peripheral resistance. The effects of intravertebral angiotensin on cardiac output can be reduced by concomitant stimulation of baroreflex pathways but its effects on peripheral resistance are not so readily antagonized.
β‐ADRENOCEPTORS IN THE HYPERTROPHIED RIGHT VENTRICLE OF THE DOG WITH PULMONARY STENOSIS
Authors: Sturm M. , Taylor R. R.
Published: June 2007

1.Right ventricular hypertrophy was produced in dogs by banding of the pulmonary artery for 28 days (n= 7) and results were compared with those in sham‐operated dogs (n= 5).

2. Myocardial noradrenaline and adrenaline levels were depressed in both the hypertrophied right ventricle and the non‐hypertrophied left ventricle and plasma levels were increased compared to the control dogs.

3. Myocardial β‐adrenoceptors were assessed in membrane preparations of both ventricles by 3H‐dihydroalprenolol binding. No change in binding site concentration (pmol/mg membrane protein) or in binding affinity was found in either the hypertrophied right ventricle or in the left ventricle.

4. Divergent results of studies on β‐adrenoceptors in ventricular hypertrophy are difficult to reconcile.
EFFECTS OF α‐ AND β‐ADRENOCEPTOR AGONISTS AND A PHOSPHODIESTERASE INHIBITOR (ICI 63 197) ON CYCLIC AMP AND GMP LEVELS IN BOVINE SPLENIC NERVE
Authors: Merican Zainuddin , Nott M. W.
Published: June 2007

1. Cyclic AMP and cyclic GMP levels were determined in bovine splenic nerve segments in the absence and presence of (±) ‐ isoprenaline, (‐)‐phenylephrine, clonidine and ICI 63 197 (a phosphodiesterase inhibitor). The chosen concentrations of adrenoceptor agonists were those which are known to affect stimulation‐induced overflow of noradrenaline from nerve terminals.

2. The mean levels of cyclic AMP ranged from 229 to 555 pmol/g of microwave irradiated tissue. Mean cyclic GMP levels ranged from 27.9 to 42.2 pmol/g.

3.Isoprenaline enhanced cyclic AMP levels but did not affect cyclic GMP levels. The effect was blocked with (±)‐propranolol. ICI 63 197 increased cyclic AMP levels but did not change cyclic GMP. Phenylephrine and clonidine caused no consistent changes in cyclic AMP or cyclic GMP levels or in the concentration ratio between these two nucleotides.

4.The results support the involvement of cyclic AMP in the enhancing effect of β‐adrenoceptor agonists and phosphodiesterase inhibitors on stimulation‐induced release of noradrenaline from sympathetic nerves.
KCL CONTRACTIONS IN THE RAT INTACT AND BISECTED VAS DEFERENS: CONTRIBUTION OF ENDOGENOUS NORADRENALINE RELEASE
Authors: Hay D. W. P. , Wadsworth R. M.
Published: June 2007

1 KCl produced a biphasic contraction in the intact rat vas deferens. Both components were larger and the initial rapid phasic component was faster in the prostatic portion than the epididymal portion. In some experiments the epididymal phasic response was a single slow contraction, while in others it had a mixture of fast and slow responses.

2 Phentolamine reduced the phasic response but not the tonic response of the intact vas deferens. This effect was not observed after denervation produced by chronic guanethidine treatment.

3 Both phases of the response to KC1 160 mmol/1 were substantially reduced by phentolamine in the epididymal portion. In the prostatic portion phentolamine produced only slight inhibition of the phasic component and had no effect on the tonic component.

4 Isoprenaline had no effect on the response to KC1160 mmol/1 but reduced both phases of the response to KC150 mmol/1. This effect was antagonized by propranolol.

5 It is concluded that part of the phasic component of the response to KC1 in the rat vas deferens is due to the release of noradrenaline from intramural nerves.
CEREBROVASCULAR AND METABOLIC EFFECTS OF BRADYKININ, ATP AND HYPERCAPNIA IN THE GOAT
Authors: Hoffman William E. , Miletich David J. , Volkman Paul H. , Albrecht Ronald F.
Published: June 2007

1. Cerebral blood flow (CBF) and cerebral O2 metabolism (CMRO2) changes were measured in these studies during treatment with three reputed cerebral vasodilators: bradykinin, adenosine triphosphate (ATP) and increased arterial Pco2.

2. Intracerebrovascular bradykinin infusions increased CMRO2 and CBF to a similar degree. Intramaxillary ATP infusions increased CBF to an extent greater than that required for increases seen in CMRO2. Hypercapnia increased CBF without a significant change in CMRO2.

3. Results suggest that increases in cerebral metabolism may mediate most, some and none of the cerebrovascular changes produced by bradykinin, ATP or hypercapnia, respectively.
MODIFICATION BY GABA‐ERGIC AGENTS AND CLONIDINE OF MORPHINE‐INDUCED CONVULSIONS AND TOXICITY IN RATS
Authors: Kulkarni S. K. , Nagrath Alka
Published: June 2007

1. Intracerebroventricular (i.c.v.) administration of morphine produced dose‐dependent behavioural changes in rats, the highest dose producing violent tonic convulsions.

2. Naloxone (up to 10 mg/kg i.p., or 100 μg i.c.v.) failed to reverse morphine‐induced toxicity.

3. The conventional anticonvulsant drugs also failed to offer protection to morphine‐induced seizures.

4. GABA‐ergic substances, GABA, piracetam and diazepam, on the other hand, protected the animals against morphine‐induced convulsions and toxicity. Similarly, clonidine pretreatment also had a protective action against morphine‐induced convulsions.
THE MECHANISM OF POLYURIA IN RATS PRETREATED WITH LITHIUM STUDIES BY IN VITRO MICROPERFUSION
Authors: Ray C. , Morgan T. , Carney S.
Published: June 2007

The collecting ducts in papillae taken from normal rats have a measurable increase in diffusional tritiated water (THO) permeability with ADH 5 μunit/ml and this increase is maximal with antidiuretic hormone (ADH) 100 μunit/ml added to the media.

2 The presence of plasma from rats pretreated with lithium to make them polyuric inhibited the response to ADH. The lowest concentration of ADH that caused a measurable increase in diffusional water permeability was 50 μunit/ml and the increase was maximal with ADH 2000 μunit/ml.

3 The maximum response to ADH did not differ whether plasma from control or lithium pretreated rats was used. However, the dose‐response curve to ADH was shifted to the right by the plasma from lithium‐pretreated rats.

4 Lithium added to the plasma from control rats did not alter the response to ADH.

5 It is proposed that lithium given to rats causes a circulatory factor to be produced that inhibits in a competitive fashion the response of the collecting duct to ADH. Such an effect would explain many features of the impairment of water excretion associated with lithium use.
GRADED EFFECTS OF SARALASIN ON PROSTAGLANDIN E, PLASMA RENIN ACTIVITY AND RENAL BLOOD FLOW IN ANAESTHETIZED DOGS
Authors: Wong Pancras C. , Zimmerman Ben G.
Published: June 2007

1. The objective of this study was to examine in anaesthetized dogs the graded effect of saralasin on renal prostaglandin E (PGE) release and to attempt to associate this change with its effects on plasma renin activity and renal blood flow.

2. Blood pressure and renal blood flow were monitored. Renal PGE concentration and plasma renin activity were measured by radioimmunoassay. Saralasin or saline vehicle was infused into the renal artery for 20 min.

3. Infusion of saralasin at the lowest dose of 0.25 m̈g/kg per min or saline vehicle did not alter either renal blood flow or plasma renin activity. Saralasin increased renal blood flow and caused a complete blockade of the renal vasoconstrictor response to exogenous angiotensin II at the two higher doses used (0.5 and 1 m̈g/kg per, min). Only the highest dose of saralasin increased plasma renin activity significantly.

4. Renal venous PGE concentration at the 5, 10 and 20 min periods of infusion was not changed significantly by any of these three doses of saralasin. We conclude therefore that the increases in renal blood flow and plasma renin activity caused by saralasin in the anaesthetized dog occur by mechanisms independent of changes in renal PGE.
ATTENUATION OF THE ANTIHYPERTENSIVE EFFECT OF CAPTOPRIL BY THE OPIOID RECEPTOR ANTAGONIST NALOXONE
Authors: Millar J. A. , Sturani A. , Rubin P. C. , Lawrie C. , Reid J. L.
Published: June 2007

1 To test a possible role of endogenous opioids in the blood pressure (BP) and heart rate (HR) responses to the converting enzyme inhibitor captopril in man, nine normal subjects were given captopril (50 mg) or placebo with and without the opioid antagonist naloxone (0.2 mg/kg i.v.).

2 Treatments were given in random order and under double‐blind conditions. BP and HR were measured supine and after a 5 min head‐up tilt to 60Â˚ before, 90, and 360 min after captopril. BP and HR responses to Valsalva's manoeuvre and isometric exercise (sustained hand grip) were also measured, as indirect tests of baroreceptor reflex function.

3 After captopril alone, there was a significant decrease in supine diastolic and tilt systolic and diastolic BP at 90 min (7.8, s.d. = 6; 15.4, s.d. = 13; and 7.0, s.d. = 12 mmHg, respectively). When naloxone was also given, corresponding changes were 0 (s.d. =9), 0 (s.d. = 15) and 3 (s.d. =7) mmHg.

4 The effect of naloxone on the changes in supine diastolic and tilt systolic BP were significant (P=0.017, P= 0.030 respectively; analysis of variance). No significant effects of treatment on supine or tilt HR were seen. BP and HR changes during Valsalva's manoeuvre and isometric exercise were not altered by active treatment.

5 These results suggest that the BP but not the HR responses to converting enzyme blockade are mediated by endogenous opioids.
ATTENUATION BY CAPTOPRIL OF PRESSOR RESPONSES TO PERIPHERAL SYMPATHETIC NERVE STIMULATION IN RATS IS ABOLISHED AFTER BILATERAL NEPHRECTOMY AND DURING MINERALOCORTICOID HYPERTENSION
Authors: Boura A. L. A. , Hui S‐C. G. , Ishac E. J. N. , Rechtman M. P. , Walters W. A. W.
Published: June 2007

1. Intravenous administration of captopril (0.1‐0.3 mg/kg) to normotensive pithed rats, with or without unilateral nephrectomy, was followed by a sustained fall in arterial blood pressure. Concomitantly pressor responses to electrical stimulation of the spinal sympathetic outflow (T11‐L3), ganglion stimulation with McNeil‐A‐343 (4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyl‐trimethylammonium chloride) or intravenous injection of noradrenaline were reduced. Attenuation by captopril (1 mg/kg) of pressor responses to McNeil‐A‐343 persisted after intravenous propranolol (1 mg/kg). Tachycardia caused by electrical stimulation of the spinal sympathetic nerves (C7‐T2) was unchanged after 3.0 mg/kg captopril.

2. After procedures reducing the activity of the renin angiotensin system, bilateral nephrectomy or induction of mineralocorticoid hypertension by unilateral nephrectomy and administration of desoxycorticosterone acetate, pressor responses to McNeil‐A‐343 or noradrenaline were unchanged after 1 mg/kg captopril.

3. It is concluded that in the pithed rat, basal arterial blood pressure and the height of pressor responses to either postganglionic sympathetic nerve activation or intravenous noradrenaline depend on converting enzyme activity maintaining circulating angiotensin II levels.
CARDIOVASCULAR EFFECTS OF STIMULATION OF NEURONES WITHIN THE ‘DEFENCE AREA’ OF THE HYPOTHALAMUS AND MIDBRAIN OF THE RABBIT
Authors: Tan Esther , Dampney R. A. L.
Published: June 2007

1. In anaesthetized rabbits, electrical stimulation applied at many sites within the medial hypothalamus and dorsal midbrain elicited a skeletal muscle vasodilatation.

2. Vasodilator responses were only elicited by microinjections of glutamate ions (which excite only cell bodies) into a much more restricted region: the periaqueductal grey (PAG) in the midbrain, and the ventromedial nucleus in the hypothalamus.

3. The results suggest that cell groups within the PAG and ventromedial nucleus are capable of generating skeletal muscle vasodilatation, which is characteristic of the ‘defence reaction’. At other sites within the ‘defence area’, the cardiovascular response to electrical stimulation arises from axons of passage.
EVIDENCE FOR A FUNCTIONAL CENTRAL DOPAMINERGIC INSUFFICIENCY IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Hutchinson J. S. , DiNicolantonio R. , Veroni M. , Cleverdon M.
Published: June 2007

1. Several neuroendocrine abnormalities reported in the spontaneously hypertensive rat (SHR) suggest that the function of the dopaminergic tuberoinfundibular tract is impaired in this strain.

2. SHR were pretreated with the peripheral acting inhibitor of dopa decarboxylase, carbidopa, or vehicle.

3. Intravenous injection of L‐dopa, the precursor of dopamine, lowered blood pressure only in the carbidopa treated SHR suggesting a central dopamine action.

4. Intracerebroventricular injection of dopamine in SHR lowered blood pressure towards normal.

5. The data are in agreement with the hypothesis that SHR have a functional central dopaminergic insufficiency.
THE QUANTITATION OF ARTERIAL ELASTICITY FROM DOPPLER FLOW MEASUREMENTS
Authors: Kenny Peter , Janod Francoise , Bellamy Greg R. , Mann Stewart , Hunyor Stephen N.
Published: June 2007

1. The pattern of phasic pressure and flow in an artery is related to the components of the impedance of that artery and hence to its compliance.

2. Phasic patterns of velocity in peripheral arteries have been recorded by using continuous wave ultrasound Doppler flowmeters coupled to high‐speed spectrum analysers; this has enabled display of the stored spectral ensembles as ‘sonograms’.

3. Simultaneous recordings at proximal and distal sites in each limb of a variety of subjects were made under standard resting conditions; characteristic patterns of change in the sonogram are recognized where gross abnormalities of arterial anatomy are present.

4. A technique is under development whereby the mean values of velocity for each 7.4 ms time slice are derived, smoothed, and the pulse described by standard Fourier transform analysis. The change of the waveform occurring during passage through the relevant arterial segment is then described by comparing the amplitude/frequency and time‐delay/frequency plots at proximal and distal sites.

5. Although results are at present preliminary, changes relating to age and known vascular abnormality are becoming apparent. Further development is in progress to determine the significance of these findings.
PERIPHERAL ADRENOCEPTORS AFTER SINO‐AORTIC DENERVATION
Authors: Morris Margaret J. , Woodcock Elizabeth A.
Published: June 2007

1. The effect of bilateral sino‐aortic denervation on cardiac and renal cortical α‐and β‐adrenoceptor concentrations was studied in rats by radioligand binding experiments using [3H]‐prazosin (α,), [3H]‐yohimbine (α2) and [125I]‐iodocyanopindolol (β).

2. Cardiac α‐ and β‐adrenoceptor concentrations were not altered by sino‐aortic denervation.

3. There was a significant increase in β‐adrenoceptor concentration in the renal cortex of sino‐aortic denervated rats compared to sham‐operated controls.
DIFFERENCES IN ARACHIDONIC ACID METABOLISM AND EFFECTS OF ASPIRIN BETWEEN ONE‐ AND TWO‐KIDNEY GOLDBLATT HYPERTENSIVE RATS
Authors: Dusting G. J. , Drysdale T. , Veroni M. , Doyle A. E.
Published: June 2007

1. Vasodepressor responses to prostacyclin, nitroprusside and arachidonic acid were compared in two groups of anaesthetized, two‐kidney, one‐clip Goldblatt rats. The groups were composed of rats which had high blood pressure (greater than 150 mmHg systolic) or normal blood pressure (less than 140 mmHg systolic).

2. The vasodepressor effects of prostacyclin and nitroprusside and arachidonic acid did not differ significantly between hypertensive and normotensive groups when measured as percentages of resting blood pressure.

3. Thus, in contrast to one‐kidney Goldblatt hypertensive rats, there is no evidence for increased vascular conversion of arachidonic acid to prostacyclin in the two‐kidney hypertensive model.

4. The effect of cyclo‐oxygenase inhibition on development of hypertension in one‐ and two‐kidney Goldblatt rats was also studied by treating them daily with aspirin (200 mg/kg orally) from 3 days before until 3 weeks after clipping the renal artery.

5. Aspirin‐treated two‐kidney rats developed significantly higher blood pressures than vehicle‐treated controls, but the blood pressures of aspirin‐treated one‐kidney rats increased less after clipping than those of vehicle‐treated controls.

6. It appears paradoxical that transformation of arachidonic acid to prostacyclin is increased, while aspirin has a blood pressure lowering effect in one‐kidney Goldblatt rats. It is suggested that there might be a more fundamental disturbance in arachidonate metabolism in hypertension which might contribute to increased vascular reactivity.
EFFECT OF SODIUM INTAKE ON INTRAERYTHROCYTE SODIUM CONCENTRATION IN NORMOTENSIVE SUBJECTS AND PATIENTS WITH UNTREATED MILD HYPERTENSION
Authors: Myers J. B. , Morgan T. O. , Edwards K.
Published: June 2007

1. The effect of changing sodium intake for 2 weeks was studied. Twelve nor‐motensive subjects and five patients with mild essential hypertension were given two different levels of sodium intake for 2 weeks.

2. Overall there was no significant rise in blood pressure but all patients with hypertension had a rise in blood pressure as they went from a low to a high sodium intake.

3. Plasma sodium was not altered but red cell sodium concentration was higher on the high sodium intake. This effect was observed in both normotensive and hypertensive people.

4. Alterations observed in cell sodium concentration provide support for the hypothesis that increased dietary intake of sodium may induce hypertension by causing changes in cellular transport systems.
PRESSOR EFFECT OF MODERATE ALCOHOL CONSUMPTION IN MAN: A PROPOSED MECHANISM
Authors: Ireland Mark , Vandongen Robert , Davidson Lisa , Beilin Lawrence , Rouse Ian
Published: June 2007

1. Ingestion of alcohol was associated with a highly significant increase in systolic blood pressure and heart rate which occurred before the blood alcohol reached its peak concentration of 16.9 (s.e.m. = 1.1) mol/1.

2. Drinking non‐alcoholic cold liquids caused a marked but transient fall in adrenaline and a rise in noradrenaline concentration.

3. Alcohol prevented this fall in adrenaline and led to a sustained increase in noradrenaline concentration.

4. These changes may be implicated in the elevation of blood pressure associated with alcohol consumption.
EFFECTS OF IMIPRAMINE ON THE ORTHOSTATIC CHANGES IN BLOOD PRESSURE, HEART RATE AND PLASMA CATECHOLAMINES
Authors: Nielsen Jens Rokkedal , Johansen Torben , Arentoft Anne , Gram Lars F.
Published: June 2007

2. Imipramine caused a moderate increase in supine systolic blood pressure, and a pronounced increase in the rise in heart rate, when the subjects assumed erect position.

3. The orthostatic drop in systolic blood pressure was in most cases only moderately increased after ingestion of imipramine, but in three subjects pronounced orthostatic hypotension developed when the sodium balance was low, whereas no clinical symptoms were seen in the same subjects when tested after imipramine ingestion on a high sodium balance.

4. The plasma catecholamine levels in supine and standing position were not influenced by imipramine or by the changes in sodium balance.

5. The data may suggest that inhibition of presynaptic reuptake of noradrenaline and/or α‐adrenoceptor blockade causes the moderate rise in supine blood pressure, whereas α,‐adrenoceptor blockade, mainly affecting the venous part of the vascular bed, may explain the orthostatic reactions.
ANTAGONISM BY MANGANESE OF ISOPRENALINE DILATATION OF THE GUINEA‐PIG ISOLATED TRACHEA
Authors: Jamieson Dana D. , Quinnf R. J. , le Coutier A.
Published: June 2007

1. Manganese (0.5‐100 μmol/1) was found to be a potent inhibitor of the dilator effect of isoprenaline on the isolated tracheal muscle of the guinea‐pig. Above these concentrations the inhibitory action of Mn2+ diminished and no inhibition occurred above 1000 μmol/I Mn2+. Thus a bell‐shaped dose‐response curve resulted for the inhibition of isoprenaline by Mn2+. The antagonism was surmountable but apparently noncompetitive.

2. Dilation of the isolated trachea caused by theophylline or nitroprusside was not inhibited by Mn2+ at concentrations of 12.5 to 750 μmol/1.

3. At the dose range which could be tested manganese did not antagonize isoprenaline bronchodilatation in vivo. However, manganese at doses between 0.5 and 2.0 μmol/kg inhibited increases in pulmonary resistance caused by acetylcholine, histamine or serotonin.

4. At concentrations above 250 μmol/1 Mn2+ inhibited constrictor responses to histamine, acetylcholine and serotonin in guinea‐pig isolated ileum and trachea, and inhibited serotonin and prostaglandin E2 contractions in rat fundus.

5. Co2+, Fe2+, Fe3+ and Zn2+ were also tested for their action against isoprenaline on the isolated trachea. Co2+ was similar in effect to Mn2+ but had only 1/50 of the potency. Up to the highest concentrations which could be tested, namely 1000 μmol/1, the other trace metals produced negligible effects.

6. Thus Mn2+ showed selective inhibition of the relaxant effect of isoprenaline on the guinea‐pig isolated trachea, at concentrations of Mn2+ well below those shown previously to inhibit constrictor responses by block of transmembrane Ca2+ entry. It is suggested that Mn2+ may interfere with intracellular Ca2+ fluxes in the isolated trachea.
PRESYNAPTIC INHIBITION BY SEROTONIN OF CARDIAC SYMPATHETIC TRANSMISSION IN DOGS
Authors: Kimura T. , Satoh S.
Published: June 2007

1. The effect of serotonin on cardiac sympathetic transmission was investigated in vagotomized and cardiac decentralized dogs.

2. Administration of serotonin in doses of 10‐100 μg/kg i.v., during the resting unstimulated state caused tachycardia and pressor responses which were inhibited by cyproheptadine but not by guanethidine. The tachycardia was reduced by a β‐adrenoceptor antagonist, bufetolol.

3. Serotonin in doses of 3‐100 μg/kg depressed the elevated heart rate during maintained electrical stimulation of the cardiac sympathetic nerves.

4. Cyproheptadine did not antagonize the serotonin‐induced depression of the stimulation‐elevated heart rate, while desipramine attenuated but did not abolish it.

5. Serotonin did not have a significant effect on the heart rate elevated by maintained infusion of noradrenaline.

6. The present results suggest that serotonin‐induced depression of heart rate during sympathetic nerve stimulation is due to presynaptic inhibition by serotonin of cardiac sympathetic transmission which is not mediated via‘classic’ tryptaminergic receptors.
INFLUENCE OF FLA‐63 ON PENTOBARBITONE SLEEP IN CHICKS AND RATS
Authors: Wambebe C. , Osuide G.
Published: June 2007

1. The influence of FLA‐63 on pentobarbitone‐induced sleep was studied in young chicks and adult rats.

2. FLA‐63 produced a time‐dependent biphasic effect on the gross behaviour of chicks and rats; an initial sedation followed by behavioural excitation.

3. The behavioural effects of FLA‐63 were associated with an initial EEG synchronization prior to an increased activity of the EMG of the neck muscle and desynchronization of the EEG of the hyperstriatum, optic tectum and pontine reticular formation of the chick. Similarly, in rats, the EEG of the frontal cortex, optic lobe and pontine reticular formation was desynchronized while the EMG activity of the neck muscle was enhanced by FLA‐63.

4. FLA‐63 delayed the onset and shortened the duration of pentobarbitone sleep.

5. Pentobarbitone‐induced EEG synchronization and decreased EMG activity in chicks was antagonized by FLA‐63.

6. Dopamine‐induced antagonism of pentobarbitone sleep was potentiated by FLA‐63 in chicks.

7. Levodopa antagonized pentobarbitone‐induced sleep in rats and this effect was potentiated by FLA‐63.

8. FLA‐63 potentiated levodopa‐induced desynchronization of the EEG of the frontal cortex, optic lobe and pontine reticular formation of the rat.

9. Haloperidol antagonized the effect of FLA‐63 on pentobarbitone‐induced sleep in both rats and chicks.

10. Noradrenaline induced behavioural sleep in young chicks dose‐dependently; this effect was antagonized by phentolamine. In the rat, phentolamine shortened pentobarbitone sleeping time but did not significantly influence the effects of FLA‐63 on pentobarbitone sleep.

11. Those results suggest that an increased dopamine neurotransmission may be associated with the mechanism of wakefulness in chicks and rats.
TRIFLUOPERAZINE ANTAGONIZES INHIBITION OF RENIN RELEASE BY ANGIOTENSIN II
Authors: Schwertschlag Ullrich , Hackenthal Eberhard
Published: June 2007

1. The influence of trifluoperazine (TFP) treatment on angiotensin H‐induced inhibition of renin release from the rat isolated perfused kidney was examined. Angiotensin II, 1 /imol/1, in the presence of 1 mmol/1 calcium, reduced basal renin secretion by 70%. When calcium was omitted from the perfusion medium, inhibition of renin release no longer occurred. Pretreatment of the rat isolated perfused kidney with the calmodulin inhibitor trifluoperazine (TFP), 10 μmol/1 for 6 min, interfered with the inhibitory action of angiotensin II on renin release as well as angiotensin II‐induced renal vasoconstriction. Our data suggest a role for calmodulin in mediating the effects of angiotensin II on both renin release and renal vascular resistance.
URINARY EXCRETION OF GLYCOSAMINOGLYCANS, HYDROXYPROLINE AND HYDROXYLYSINE IN RABBITS AFTER EXCESSIVE INGESTION OF FLUORIDE
Authors: Jha Mohan , Koacher Jasbeer , Susheela A. K.
Published: June 2007

1. Urinary levels of glycosaminoglycans (GAG) and hydroxyproline from normal and fluoride treated rabbits were estimated. The hydroxylysine content of serum and urine of rabbits after excessive ingestion of fluoride was also investigated.

2. There was a progressive decrease in GAG content, reduction in hydroxylysine, whereas the hydroxyproline content was increased after fluoride ingestion.

3. Enhanced hydroxyproline in urinary excretion is due to collagen breakdown after fluoride ingestion.

4. The reduction in hydroxylysine content is due to reduced collagen cross‐link formation.

5. The report suggests the possibility of using the urinary levels of GAG or hydroxyproline or hydroxylysine as an index of fluoride intoxication.
PHARMACOKINETICS OF AN OSMOTICALLY CONTROLLED DELIVERY INDOMETHACIN PREPARATION IN NORMAL VOLUNTEERS
Authors: Bertouch J. V. , Maycock S. , Harrington B. , Brooks P. M.
Published: June 2007

Indomethacin is still used commonly for the treatment of rheumatic diseases but is associated with side effects, particularly headache, in a number of patients. A controlled or sustained release formulation of indomethacin might provide lower peak plasma levels and thus reduce side effects while still maintaining adequate plasma levels to control pain and inflammation.

In this single dose crossover study, normal volunteers received the new formulation of indomethacin (Indocid GITS 6/85) fasting or with a standard meal, indomethacin 75 mg with a standard meal or indomethacin 25 mg three times daily with a standard meal.

Plasma concentration data showed that peak plasma levels were reduced but the area under the plasma concentration curve was not significantly different between the four treatments.
INFLUENCE OF SEASON AND ANAESTHETIC ON CUTANEOUS VASCULAR PERMEABILITY RESPONSES TO HISTAMINE, SEROTONIN AND MAST CELL‐RELEASING AGENTS IN RATS
Authors: Chahl Loris A.
Published: June 2007

The influences of season and anaesthetic on the cutaneous vascular permeability responses to histamine (2.5 × 10−8 mol), serotonin (5HT, 2.5 × 10−10 mol), and to the mast cell‐releasing agents adenosine 51‐triphosphate (2.5 × 10−7 mol), dextran (5 × 10−5 g) and compound 48/80 (1 × 10−7 g) were examined using an Evans blue dye leakage technique.

In rats anaesthetized with urethane (1 g/kg i.p.), responses to irritants were significantly less than in rats given ether for the period of administration of irritants and allowed to recover consciousness. The response to histamine was mediated by Hi‐receptors since it was abolished by mepyramine but not by metiamide.

The only seasonal variation observed was in responses to 5HT in urethane‐anaesthetized rats, which were significantly less in winter than in summer. It was concluded that dye leakage responses to irritants are affected more by anaesthetic than by seasonal variation.
LEAKAGE OF CATECHOLAMINES FROM RABBIT CEREBROSPINAL FLUID FOLLOWING INTRACEREBROVENTRICULAR INJECTION
Authors: Maccarrone C. , Malta E. , Raper C.
Published: June 2007

1. The intracerebroventricular (i.c.v.) injection of (‐)‐isoprenaline and the selective β1‐adrenoceptor agonist, RO363, elicited reproducible dose‐related increases in heart rate in unanaesthetized and anaesthetized rabbits. (‐)‐Isoprenaline produced vasodepressor effects in unanaesthetized animals, whereas both catecholamines decreased blood pressure in anaesthetized rabbits.

2. Pretreatment with guanethidine sulphate (5 mg/kg i.v.) reduced but did not abolish the tachycardia elicited by i.c.v. RO363, whereas heart rate responses to i.c.v. (‐)‐isoprenaline were unaffected.

3. Pretreatment of anaesthetized rabbits with hexamethonium bromide (10 mg/kg i.v.) did not markedly affect the tachycardia elicited by i.c.v. RO363 and reduced the response to i.c.v. (‐)‐isoprenaline in only one out of five experiments.

4. The results suggest that there is a marked leakage of centrally administered catecholamines into the peripheral circulation and that the rabbit may be unsuited for examining centrally mediated cardiovascular effects of catecholamines.
MUSCARINIC RECEPTOR INHIBITION AND OTHER EFFECTS OF PANCURONIUM IN THE RABBIT EAR ARTERY PREPARATION
Authors: Leung E. , Mitchelson F.
Published: June 2007

1. The effect of pancuronium in the rabbit ear artery was investigated in order to measure the inhibition it produces at the prejunctional muscarinic receptor on sympathetic nerve endings in this tissue.

2. Pancuronium (0.1–0.2 mmol/l) produced an enhancement of responses to transmural electrical stimulation but this effect was absent in experiments conducted in the presence of cocaine (10 μmol/l) suggesting that an inhibition of the uptake, mechanism occurs with pancuronium in this tissue.

3. Pancuronium (10 μmol/l) in the presence of cocaine (10 μmol/l) and yohimbine (1 μmol/l) caused a small transient increase in resting output of tritium from arteries preincubated with 3H‐noradrenaline but did not affect stimulated output of tritium nor the perfusion pressure in perfused preparations.

4. Pancuronium in the presence of cocaine or cocaine plus yohimbine caused a parallel shift of the concentration‐response curve for the inhibitory effect of carbachol (CCh) on the increase in perfusion pressure induced by nervous stimulation. An Arunlakshana‐Schild plot of the data was linear but the slopes of 0.92 and 0.95 respectively, were significantly different from unity (P<0.05).

5. The calculated pKB value suggests that pancuronium has a different affinity for prejunctional muscarinic receptors on sympathetic nerve endings in this tissue compared to that previously reported in cardiac or ileal smooth muscle.
ACTIONS OF INDORAMIN ON RABBIT AND HUMAN VASCULATURE IN VITRO
Authors: Black J. L. , Mylecharane E. J.
Published: June 2007

1. The antagonist effects of indoramin were investigated in rabbit perfused ear artery, common carotid artery, and human perfused temporal artery preparations.

2. Indoramin was a potent competitive antagonist of the constrictor effects of noradrenaline (NA) in all three preparations, pA2 values being 7.77 for the ear artery, 8.20 for the common carotid artery and 7.46 for the human temporal artery.

3. The constrictor actions of serotonin (5‐hydroxytryptamine, 5‐HT) were competitively antagonized by indoramin. The pA2 values obtained in the rabbit common carotid and human temporal artery (5.92 and 6.25, respectively), were lower than those for NA in the same preparations and lower than that obtained in the rabbit perfused ear artery (7.55).

4. Indoramin was a potent competitive antagonist (pA2:8.31) of histamine‐induced vasoconstriction in the rabbit perfused ear artery preparation.

5. These results can be explained on the basis of previous findings that the action of 5‐HT in the rabbit ear artery is mediated via an α‐adrenoceptor, and that the rabbit common carotid artery contains true 5‐HT receptors. The findings suggest that specific 5‐HT receptors may be present in the human temporal artery and that α‐adrenoceptor antagonism may be the pharmacological property of most relevance to the efficacy of indoramin in migraine prophylaxis.
IMPORTANCE OF CENTRAL SEROTONIN NEURONS IN THE HYPOTENSIVE ACTION OF METHYLDOPA IN THE RAT
Authors: Choy Vernon J. , Chalmers John
Published: June 2007

1. Normotensive (WKY) and stroke prone spontaneously hypertensive (SHR‐SP) rats were given methyldopa (200 mg/kg i.p.) daily for five days and their brains were then sectioned and processed with the Faglu method for catecholamine fluorescence.

2. This treatment with methyldopa induced a green fluorescence not seen in control animals, in cells coinciding with the B1–B9 groups of serotonin neurons in the brainstem.

3. Pretreatment with the neurotoxin 5,7‐dihydroxytryptamine (5,7‐DHT, i.c.v.), which is relatively specific for serotonin neurons, prevented the appearance of this green fluorescence in the serotonin cell groups of rats given methyldopa.

4. Pretreatment with 5,7‐DHT, i.c.v. approximately halved the magnitude of the hypotensive response to a single dose of methyldopa (80 mg/kg i.p.).

5. We suggest that central serotonin nerves contribute to the hypotensive action of methyldopa.

6. It is our hypothesis that methyldopa is taken up by these serotonin cells and that the green fluorescence reflects the production of α‐methyldopamine, as a result of decarboxylation by the ubiquitous enzyme, L‐aromatic amino acid decarboxylase.
EFFECTS OF HISTAMINE AND HISTAMINE ANTAGONISTS ON HEPATIC BILE FLOW IN THE CONSCIOUS SHEEP
Authors: Lee S. P.
Published: June 2007

1. The effects of histamine and histamine antagonists on bile flow have been studied using the cholecystectomized conscious sheep. Histamine stimulated bile flow in a dose‐dependent manner (D50= 15.7 μg/h per kg). Free water and HCO3− output were increased after intravenous histamine infusion. With histamine at 120 mg/h per kg, there was a 41.0 (s.d. = 4.6)% and 38.7 (s.d. = 4.2)% (n= 6) increase in bile volume and HCO3− output respectively. Bile salt concentration was decreased after intravenous histamine, but net bile salt secretory rate remained unchanged. There was no change observed in the molar ratios of bile salts:phospholipids:cholesterol. Total lipids were decreased from 2.2 (s.d. = 0.3) to 1.60 (s.d. = 0.4) g/dl (n=6). The corrected lithogenic index did not change significantly. 14C‐Erythritol clearance also increased during histamine infusion in a dose‐dependent manner but did not correspond to increments in bile flow.

2. The histamine H1‐receptor antagonist, diphenhydramine 0.05–1.0 mg/h per kg did not alter histamine stimulated bile flow. The H2‐receptor antagonists, cimetidine (0.5–4 mg/h per kg) and ranitidine (0.05–0.5 mg/h per kg) progressively reversed the histamine‐induced choleresis. Maximum inhibitory effect was attained at 2.0 and 0.25 mg/h per kg for cimetidine and ranitidine, respectively. At these levels, variation of intravenous infusion of histamine did not result in competitive displacement of the inhibitory response by either cimetidine or ranitidine. Moreover, concomitant infusion of diphenhydramine at 1.0 mg/h per kg potentiated the inhibitory effect of cimetidine or ranitidine on histamine‐induced choleresis.

3. Histamine increases the bile salt independent component of hepatic bile flow. This increase can be blocked by cimetidine or ranitidine by a non‐competitive inhibitory mechanism.
EFFECT OF ACTH ADMINISTRATION ON URINARY KALLIKREIN EXCRETION IN MAN
Authors: Whitworth Judith A. , van Leeuwen Barbara H. , Hannah Murray C. , Scoggins Bruce A. , Thatcher Robin
Published: June 2007

1. The effect of ACTH administration on urinary kallikrein excretion and its relationship to changes in plasma and urine electrolytes, renin concentration and steroids was examined in normotensive and mildly hypertensive subjects.

2. ACTH administration produced hypokalaemia, initial urinary sodium retention, a fall in active plasma renin concentration, a transient rise in plasma aldosterone concentration and sustained rises in plasma deoxycorticosterone concentration and urinary kallikrein activity.

3. Changes in patients with mild hypertension were similar in pattern to normotensives, but urinary kallikrein concentrations were lower.

4. The effects of ACTH on urinary kallikrein excretion appeared to be independent of aldosterone and correlated most closely with deoxycorticosterone concentrations.
PRESENCE OF CHOLINOCEPTORS IN MESENCEPHALIC RAPHE NUCLEI CONCERNED IN THERMOREGULATION IN RABBITS
Authors: Saxena A. K. , Tangri K. K. , Mishra Nisha , Vrat S. , Bhargava K. P.
Published: June 2007

1. The thermal effects of cholinomimetics and cholinoceptor blocking agents microinjected into mesencephalic nucleus raphe medianus (NRM) were investigated in rabbits to determine the nature and role of these cholinoceptors in thermoregulation.

2. Microinjection of cholinoceptor agonists, carbachol and pilocarpine, into NRM resulted in significant hyperthermia which could be blocked by local pretreatment with chlorisondamine (a nicotinic receptor blocker) as well as by ethybenztropine (a muscarinic receptor blocker).

3. Intracerebroventricular pretreatment with LM 5008 (serotonin reuptake blocker) significantly inhibited the carbachol‐induced hyperthermia.

4. Both nicotinic and muscarinic cholinoceptors are present in mesencephalic NRM which may be involved in thermoregulation in rabbits. Activation of these cholinoceptors in NRM results in hyperthermia which seems to be due to an inhibition of a serotonin sensitive hypothalamic heat loss mechanism.