bluuebunny/crossref_metadata_2025 huggingface dataset:
ACCURACY OF THE TAKEDA TM‐2420 AMBULATORY BLOOD PRESSURE MONITOR
Authors: Russell A. E. , Tonkin A. L. , Wing L. M. H. , Hassam R. M. , McRitchie R. J. , Aylward P. E. , Minson R. B. , Bune A. J. C. , West M. J. , Chalmers J. P.
Published: June 2007

1. The accuracy of blood pressure measurement with the Takeda TM‐2420 ambulatory blood pressure monitor and the TM‐2020 data recorder have been assessed by comparison with simultaneous measurements taken using auscultation and direct femoral artery measurements.

2. Systolic blood pressure was underestimated by the TM‐2420 by a mean of 10 mmHg (s.d. = 6, 95% confidence interval (CI) =−13 to −7) over the range of pressures measured by auscultation. It was underestimated by 23 mmHg (s.d. = 12, 95% CI =−28 to −18) compared with direct femoral artery measurements.

3. Diastolic pressure measurements were similar to those obtained by auscultation. When compared with direct femoral artery recordings, diastolic pressure was overestimated by about 5 mmHg (s.d. = 4, 95% CI = 3.4–6.6), which is consistent with indirect readings, taken with a ‘standard’ cuff (inflatable bladder 23 cm × 12 cm).

4. The TM‐2420/2020 is thus suitable for ambulatory measurements of blood pressure when diastolic pressure is the criterion of interest.
RENAL ARTERY DUPLEX ULTRASONOGRAPHY: A RELIABLE NEW SCREENING TEST FOR FUNCTIONALLY SIGNIFICANT RENAL ARTERY STENOSIS
Authors: Hawkins Peter G. , McKnoulty Leanne M. , Gordon Richard D. , Klemm Shelley A. , Tunny Terry J.
Published: June 2007

1. Renal artery duplex ultrasonography (RADU) has recently become available as a rapid, relatively inexpensive, non‐invasive screening test for renal artery stenosis causing renovascular hypertension.

2. We compared the sensitivity of RADU with that of computerized nuclear renography (CNR) in 16 patients with renovascular hypertension. All had lateralizing renal venous renin ratio (RVRR) studies, 15 had renal artery stenosis (RAS) on angiography and one had unilateral chronic parenchymal renal disease (CPRD).

3. We found RADU to be at least as reliable as CNR with sensitivities of 100% and 93.7%, respectively. Neither RADU nor CNR was successful (sensitivity 25% and 0%, respectively) in detecting minor, functionally insignificant contralateral renal artery stenosis in four patients, two of whom had multiple small renal arteries — a recognized difficulty in the use of RADU.

4. After successful (RVRR became negative) therapeutic intervention in two patients with RAS (dilatation one, surgery one), RADU changed from positive to negative and may therefore be a useful alternative to repeat angiography in this setting.

5. Performed in conjunction with renal parenchymal B mode ultrasound, RADU correctly identified the presence of CPRD in one patient.
EXPERIMENTAL EVIDENCE FOR DIETARY PREVENTION OF CARDIOVASCULAR DISEASES
Authors: Yamori Y.
Published: June 2007

1. Since 100% stroke‐prone spontaneously hypertensive rats (SHRSP) develop cardiovascular diseases (CVD) spontaneously, they are the best models for experimental studies on CVD prevention. Previous studies have proven that stroke can be prevented by improving diets such as sodium (Na) restriction, potassium (K) supplementation and, feeding of animal or vegetable proteins, some amino acid and fatty acids and dietary fibres.

2. Recent studies in SHRSP have further confirmed the effectiveness of CVD prevention of the following dietary components.

3. Studies on SHRSP repeatedly demonstrated that the adverse effect of Na was counteracted by K, which reduced stroke incidence. Even a 1 min reduction in dietary Na/K ratios (from 0.93 to 0.61) delayed the development of stroke in SHRSP given 1% NaCl water for drinking.

4. Excess NaCl intake affected the development of stroke more adversely in SHRSP than Na citrate excess.

5. An increase in dietary Ca (from 0.6 to 1.2 or 1.6%) effectively attenuated the development of hypertension, prevented stroke and prolonged life‐span in salt‐loaded SHRSP, whereas additional dietary Mg (from 0.2 to 0.8%) did not affect BP levels.

6. The quality of protein is also important for stroke prevention. The protein content of 20% in regular laboratory diets was replaced with soy protein, which effectively prevented stroke. In contrast to short life‐span in salt‐loaded SHRSP (88 ± 1 days), this life prolongation effect was intensified with the addition of 1.0% Ca (344 ± 16) and became maximal with the further addition of 0.6% Mg (>416 ± 20).

7. In addition to the observed effect of palmitoleic acid (C16:1), undecylenic acid (C11:1), 1% in the diet effectively delayed the development of stroke and significantly prolonged life‐span in salt‐loaded SHRSP. Preventive effects were also confirmed with diets containing 23% lecithin from soy bean or krill.
ANGIOTENSIN CONVERTING ENZYME IN THE RAT HEART: STUDIES OF ITS INHIBITION IN VITRO AND EX VIVO
Authors: Fabris Bruno , Jackson Bruce , Cubela Rose , Mendelsohn Frederick A. O. , Johnston Colin I.
Published: June 2007

1. The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in rat heart and lung was evaluated in vitro and ex vivo.

2 Radioinhibitor [125I]‐351A binding displacement was used to assess the relative potency of six ACE‐inhibitors (CI906, CGS14831, S9780, 351A, MK521, SQ27519) in rat heart and lung homogenates, and estimate equilibrium association constant (Ka).

3. Following oral administration of 0.3 mg/kg of Quinapril (CI928) specific binding of [125I]‐351A to ACE was measured in rat heart.

4. Ka for binding to ACE of each inhibitor was significantly higher in right and left atrium than in lung (P < 0.05) or the right and left ventricle (P < 0.005). These differences did not affect the degree or time course of inhibition in vivo in the rat myocardial ACE following Quinapril treatment.

5. Rank order of potency of the ACE inhibitors tested was CI906 = CGS14831>S9780>351A>MK521>SQ27519
RENAL SYMPATHETIC NERVE ACTIVITY MEASURED BY NOREPINEPHRINE SPILLOVER RATE IN RESPONSE TO CHANGES IN BLOOD PRESSURE IN CONSCIOUS RABBITS
Authors: Sano Naoki , Way Diana , McGrath Barry P.
Published: June 2007

1. Renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) was examined by measuring renal norepinephrine (NE) spillover rate in conscious rabbits.

2. A chronic renal vein catheter was implanted for sampling renal venous blood without stress in conscious animals.

3. RSNA estimated by renal NE spillover rate significantly increased in response to moderate falls in MAP produced by sodium nitroprusside (SNP) infusion and decreased in response to moderate rises in MAP produced by phenylephrine (PE) infusion.

4. The NE spillover method is sufficiently sensitive to detect responses of RSNA to physiological stimuli in conscious rabbits.
hGK‐1: A KALLIKREIN GENE EXPRESSED IN HUMAN PROSTATE
Authors: Morris Brian J.
Published: June 2007

1. Humans have three kallikrein genes: hGK‐1, hRKALL (kinin‐generating) and a gene encoding prostate specific antigen (PSA).

2. Using a gene‐specific oligonucleotide, expression of hGK‐1 was demonstrated in human prostate, but not in 10 other tissues examined.

3. The similarity in tissue specificity of expression of hGK‐1 with that of the PSA gene led to an examination of putative regulatory DNA. Marked identity of >90% was seen (compared with 80% for hRKALL), thus supporting a role for the operation of similar tissue‐specific mechanisms for the control of hGK‐1 and the PSA gene.

4. Unique structural features were observed in the protein encoded by hGK‐1 suggestive of a capacity for interaction with substrate residues larger than those in kininogen. In particular it is predicted that a glycine at 186 would twist the polypeptide backbone in this crucial, highly conserved active site region and so profoundly influence interaction with substrate.
EFFECT OF FURAZOLIDONE AND NITROFURAZONE ON BRAIN GAMMA‐AMINO BUTYRIC ACID AND GLUTAMATE CONCENTRATIONS IN CHICKENS
Authors: Ali B. H.
Published: June 2007

1. The concentrations of gamma‐amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days.

2. At the end of the treatment, the birds lost about 9% of their bodyweight when on the small dose of FZ or NF and about 18% when on the high doses.

3. Both drugs produced dose‐dependent increases in the concentrations of GABA and glutamate which were statistically significant at doses of 25 and 50 mg/kg of NF, and 50 mg/kg of FZ.
ATRIAL NATRIURETIC PEPTIDE LEVELS IN CONGESTIVE HEART FAILURE IN MAN BEFORE AND DURING CONVERTING ENZYME INHIBITION
Authors: Crozier Ian G. , Nicholls M. Gary , Ikram Hamid , Espiner Eric A. , Yandle Tim G.
Published: June 2007

1. To determine the response of plasma atrial natriuretic peptide (ANP) to treatment with an angiotensin converting enzyme (ACE) inhibitor in heart failure, seven patients (NYHA Functional Class III‐IV) were studied before and after the addition of ramipril to maintenance digoxin and diuretic treatment.

2. Baseline arterial ANP levels were raised, but fell during ramipril treatment in parallel with changes in both haemodynamic recordings (arterial pressure, pulmonary artery diastolic pressure, and right atrial pressure) and hormone levels (antiotensin II and aldosterone).

3. Coronary sinus ANP, measured in three patients, was greater than concomitant arterial levels, and the coronary sinus ANP secretion rate was calculated to be between 15 and 119 pmol/min.

4. These results demonstrate that improvement in haemodynamic function during ACE inhibitor treatment is associated with a decline in elevated ANP levels, and support the concept that atrial stretch or pressure regulates the secretion of atrial peptides in man.
NORADRENALINE DIFFUSION, METABOLISM AND VASCULAR RESPONSE IN THE RABBIT EAR ARTERY
Authors: de la Lande I. S.
Published: June 2007

1. Effects of uptake1 and uptake2 inhibition on the vasoconstrictor activity of noradrenaline (NA) in the perfused artery of the rabbit ear are reviewed in the light of data on NA metabolism and diffusion.

2. The minor effect of uptake1 inhibition on the response to intraluminal NA is related to location of the sympathetic nerves at the medial‐adventitial border, and low diffusivity together with loss of amine by uptake2 in the media.

3. The minor effect of uptake2 inhibition on the vasoconstrictor activity of NA suggests that uptake2 has little effect on steady‐state amine concentration in the media. This suggestion is supported by analyses of patterns of normetanephrine efflux from the artery.

4. Attention is drawn to the ability of uptake inhibitors, and of constriction and distension, to influence entry of NA into the artery wall.
CHIRALITY: PHARMACOKINETICS AND PHARMACODYNAMICS IN 3 DIMENSIONS
Authors: Williams Kenneth M.
Published: June 2007

1. Biological macromolecules are able to distinguish between enantiomeric substrates. A three‐point interaction between the drug enantiomers and the macromolecule (Easson‐Stedman hypothesis) can frequently account for this selectivity.

2. Significant pharmacodynamic differences between enantiomers are more the rule than the exception.

3. Pharmacokinetic differences between enantiomers are, in general, not as great as the pharmacodynamic differences. However, stereoselective protein binding, metabolism and renal clearance are still very important aspects of understanding drug disposition and the time course of drug action.

4. There may be pharmacokinetic and pharmacodynamic enantiomer‐enantiomer interactions. Consequently, the activity and disposition of a racemic drug may not be the simple sum of the activities and disposition of the individual enantiomers.

5. Enantiomers have been used as sensitive 3‐dimensional probes to establish structure‐activity relationships, to provide insights into genetic polymorphism of drug metabolism, and to provide insights into other aspects of drug disposition.

6. A need for a 3‐dimensional understanding of pharmacodynamics and pharma‐cokinetics is implicit in the asymmetric nature of biological environments.
MUSCARINIC RECEPTOR DIFFERENTIATION
Authors: Mitchelson F. , Choo L. K. , Darroch S.
Published: June 2007

1. Several selective antagonists are available to differentiate between muscarinic receptors.

2. Further subdivision of M1 and M2 muscarinic receptors appears possible and is supported by studies with cloned receptors.

3. Reasons for differences between affinity constants determined in functional and binding studies and whether receptor subtypes couple exclusively with a particular cellular mechanism are still to be determined.
EFFECTS OF RESERPINE TREATMENT ON ARRHYTHMOGENESIS DURING ISCHAEMIA AND REPERFUSION IN THE ISOLATED RAT HEART
Authors: Zhan C. Y. , Tang F. , Lee A. Y. S. , Wong T. M.
Published: June 2007

1. The effects of reserpine treatment on the myocardial contents of catecholamines and enkephalins and the incidence of ventricular arrhythmias during ischaemia and reperfusion in the isolated rat heart were studied.

2. Reserpine treatment almost completely depleted the heart of noradrenaline (NA). It also significantly depleted the heart of adrenaline and dopamines. It did not, however, alter the myocardial contents of enkephalins.

3. Reserpine‐treatment attenuated significantly, but did not abolish, cardiac arrhythmias induced by ischaemia and reperfusion in the isolated heart preparation.

4. The results of the present study indicate that myocardial catecholamines especially NA are a contributing factor to arrhythmogenesis during ischaemia and reperfusion.
CENTRALLY MEDIATED INCREASED SYMPATHETIC ACTIVITY IS NOT IMPORTANT IN THE GENESIS OF ACTH‐INDUCED HYPERTENSION IN SHEEP
Authors: Spence Campbell D. , Mathai Michael , Mills Eric H. , Coghlan John P. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. Adrenocorticotrophin (ACTH) administration to sheep produces a rapid adrenally dependent hypertension which is maximal after 3 days and associated with increased cardiac output (CO) and heart rate (HR), while calculated total peripheral resistance remains unchanged.

2. This study investigated the proposal that a centrally mediated increase in sympathetic activity is important in the development of ACTH‐induced hypertension.

3. Concomitant intravenous infusions of either clonidine (60 μg/kg per day) or methyldopa (60 mg/kg per day) with ACTH (5 μg/kg per day) failed to inhibit the increase in mean arterial pressure (MAP) observed with ACTH.

4. In a separate experiment clonidine abolished the increase in CO and HR but not the pressor response associated with ACTH administration.

5. These results do not support a role for centrally mediated increase in sympathetic activity in the genesis of ACTH‐induced hypertension.
EFFECT OF CIGARETTE SMOKING ON THE FREQUENCY OF VENTRICULAR PREMATURE COMPLEXES IN NORMAL SUBJECTS
Authors: Pestell R. G. , Taylor R. R.
Published: June 2007

1. Ambulatory ECG monitoring was undertaken in healthy cigarette smokers (33) and non‐smokers (20) of similar age (21–66 years).

2. The frequency of ventricular premature complexes (VPC) was less in habitual smokers (P < 0,05; Mann‐Whitney rank test) and an average of more than 1 VPC per hour occurred in a higher proportion of non‐smokers than smokers: eight of 20 (40%) vs two of 33 (6%) (P < 0.01; Chi‐square test).
AMPLIFICATION BY SEROTONIN OF RESPONSES TO OTHER VASOCONSTRICTOR AGENTS IN THE RAT TAIL ARTERY
Authors: Xiao X‐H. , Rand M. J.
Published: June 2007

1. A low concentration of serotonin (3 nmol/L), which did not exert a direct vasoconstrictor action, amplified the responses to certain other vasoconstrictor agents (α1‐adrenoceptor agonists, KCl, ATP and vasopressin) in isolated perfused segments of the rat tail artery.

2. Low concentrations of serotonin (0.3 and 1 nmol/L) amplified vasoconstrictor responses to sympathetic nerve stimulation, but higher concentrations of serotonin (10 and 30 nmol/L) produced vasoconstriction and reduced responses to sympathetic nerve stimulation.

3. The calcium channel blocking drug diltiazem (1 and 10 μmol/L) produced concentration‐dependent reductions of vasoconstrictor responses to phenylephrine. The amplifying effect of serotonin on responses to phenylephrine was attenuated by 1 μmol/L and abolished by 10 μmol/L diltiazem, and was also abolished in a Ca2+‐free medium.

4. Ketanserin (10 nmol/L) antagonized the vasoconstrictor action of serotonin and, to a lesser extent, the vasoconstrictor actions of phenylephrine and noradrenaline. It abolished the amplifying effect of a low concentration of serotonin on responses to noradrenaline and phenylephrine.

5. The amplification of vasoconstrictor response in the rat tail artery by serotonin appears to be due to activation of receptors of the 5‐HT2 subtype which are coupled to an increase in Ca2+ influx into the vascular smooth muscle cells.
EDITORIAL REVIEW: MECHANISMS OF AMINOGLYCOSIDE NEPHROTOXICITY
Authors: Bennett William M.
Published: June 2007

Aminoglycosides continue to be widely used for the treatment of serious Gram‐negative infections. Ten to fifteen per cent of all courses of therapy are complicated by declines in renal function, despite close monitoring of serum drug levels. The proposed pathogenesis and biochemical mechanisms of renal dysfunction caused by these commonly used therapeutic agents are discussed.
HISTAMINE ENHANCES HYPOXIA‐INDUCED VENTRICULAR ARRHYTHMIAS IN ISOLATED RAT HEARTS
Authors: Dai Soter
Published: June 2007

1. The effects of hypoxia, histamine‐receptor agonist perfusion, and their combination on cardiac rhythm were studied in isolated rat hearts.

2. While hypoxia induced a high incidence of ventricular tachycardia or fibrillation, only a few preparations developed ventricular arrhythmias in response to perfusion with high concentration of histamine, 2‐pyridylethylamine or impro‐midine.

3. The times of onset of hypoxia‐induced ventricular arrhythmias were significantly shortened by perfusion with either histamine, 2‐pyridylethylamine or impro‐midine. The accelerated occurrence of hypoxia‐induced ventricular arrhythmias by histamine was significantly abolished by pretreatment with either diphenhydramine or cimetidine.

4. The results indicate that hypoxia and histamine can increase ventricular vulnerability of the rat heart to each other. It is also suggested that the arrhythmogenic actions of histamine in hypoxic rat hearts are mediated by both histamine H1‐ and H2‐receptors.
EFFECTS OF LOW DOSE INFUSION OF ATRIAL NATRIURETIC FACTOR ON ACUTE INHIBITION OF ANGIOTENSIN CONVERTING ENZYME IN NORMAL MAN
Authors: Nakamura Motoyuki , Arakawa Naoshi , Kawata Yukio , Kato Masataka
Published: June 2007

1. We have studied the effects of low dose infusions of atrial natriuretic factor (human ANF (99–126), 1.95 pmol/min per kg) on angiotensin converting enzyme (ACE) inhibitor‐induced haemodynamic and hormonal changes in healthy subjects.

2. ACE inhibitor (captopril 25 mg, administered orally) was given against a background infusion of physiological saline (placebo day) or ANF (experimental day).

3. Compared with the placebo observations, ANF enhanced the fall in plasma aldosterone concentrations induced by captopril (P<0.05).

4. The rise of plasma renin activity following administration of ACE inhibitor which was observed during placebo infusion was abolished by ANF (P<0.05).

5. The responses of systemic blood pressure and heart rate to the converting enzyme inhibition were not affected by the infusion of ANF.

6. These results suggest that variations in endogenous circulating ANF may influence, in part, the response of these hormonal levels during ACE inhibition.
VASOACTIVE INTESTINAL POLYPEPTIDE AND HUMAN VAGINAL BLOOD FLOW: COMPARISON BETWEEN TRANSVAGINAL AND INTRAVENOUS ADMINISTRATION
Authors: Palle Connie , Bredkjaer Helle E. , Ottesen Bent , Fahrenkrug Jan
Published: June 2007

1. The present study was performed to examine and compare the effect of increasing doses of vasoactive intestinal polypeptide (VIP) on vaginal blood flow following vaginal subepithelial and intravenous injection in normal women.

2. Local vaginal blood flow was measured by a heated oxygen electrode.

3. Peripheral blood samples were collected throughout the experiments for VIP analysis by radioimmunoassay.

4. Both subepithelial and intravenous injections induced a significant and dosedependent increase in vaginal blood flow (P<0.05), displaying the same efficacy, potency and sensitivity.

5. The vaginal flow values correlated with the corresponding plasma VIP concentrations after both routes of administration.

6. The systemic vascular side effects; that is, flushing, hypotension and tachycardia, were observed following both subepithelial and intravenous injection.

7. The findings indicate that the effect of VIP on vaginal blood flow irrespective of route of administration is part of a systemic vasodilatory effect rather than a local response.
VASCULAR ACTIONS OF ENDOTHELIN IN THE RABBIT KIDNEY
Authors: Denton K. M. , Anderson W. P.
Published: June 2007

1. The effect of two doses of endothelin, 10 and 50 ng/kg per min, i.v., on glomerular filtration rate (GFR), tubular stop flow pressure and pre‐ and postglomerular vascular resistance have been studied in anaesthetized rabbits.

2. Blood pressure did not change significantly in response to 10 ng/kg per min endothelin or vehicle infusion, but rose steadily during infusion of 50 ng/kg per min endothelin, increasing 11.8±2.7 mmHg by 90 min of infusion.

3. Glomerular filtration fraction (3H‐inulin extraction ratio) rose and remained elevated throughout the endothelin infusion at 50 ng/kg per min. GFR did not change significantly until 70–90 min of the infusion (50 ng/kg per min) when it decreased by about 35%. No significant changes were seen at 10 ng/kg per min endothelin.

4. Sodium excretion rate rose in response to the lower dose, due to an increase in fractional sodium excretion. No changes in sodium excretion were seen at the higher dose of endothelin.

5. Glomerular capillary pressure rose significantly in response to endothelin infusion (50 ng/kg per min).

6. Renal blood flow fell progressively in response to endothelin (50 ng/kg per min), to about one‐third of the pre‐infusion value.

7. Renal vascular resistance increased progressively with both doses of endothelin, by about 35% at 10 ng/kg per min and about 400% at 50 ng/kg per min after 70–90 min. Preglomerular resistance increased from 1.0±0.1 to 5.0±1.9 mmHg/mL per min in response to endothelin 50 ng/kg per min. Postglomerular resistance rose from 1.0±0.1 to 5.6±2.17 mmHg/mL per min.

8. Thus endothelin infusion caused progressive renal vasoconstriction with similar magnitude increases in both pre‐ and postglomerular vessels. The vasoconstriction of the kidney caused by endothelin occurred at a dose which did not effect systemic blood pressure.
EFFECT OF CGS 9896 ON STRESS‐INDUCED GASTRIC ULCER IN RAT
Authors: Najim Rafid A. , Karim Kassim H.
Published: June 2007

1. The effects of CGS 9896, a partial benzodiazepine agonist, and chlordiazepoxide, a full benzodiazepine agonist, on stress‐induced gastric ulcers as well as blood glucose were compared.

2. Ulceration in the glandular stomach was induced by 2 h restraint at 4°C.

3. CGS 9896 reduced significantly the ulcer parameters but did not affect blood glucose. The effect of CGS 9896 was dose‐dependently blocked by the benzodiazepine antagonist flumazepil.

4. Chlordiazepoxide reduced the ulcer parameters but increased blood glucose.

5. Since CGS 9896 lacks sedative effects but reduced ulcer parameters, the antiulcer and sedative effects of drugs acting at benzodiazepine receptors are disassociated.

6. Benzodiazepine‐induced hyperglycaemia does not play a major role in the antiulcer effects.
A ‘HYPERTENSINOGENIC’ CLASS OF STEROID HORMONE ACTIVITY IN MAN?
Authors: Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. Studies in sheep have led to the concept of a ‘hypertensinogenic’ (HT) steroid hormone activity, whereby the blood pressure (BP) raising effects of adrenocortical steroids can be separated from their in vivo glucocorticoid (GC) or mineralocorticoid (MC) activities.

2. The three main lines of evidence are as follows: (i) BP raising effects of ACTH cannot be reproduced by appropriate rates of infusion of steroids with GC and MC activities; (ii) certain steroids e.g. 9α‐fluorocortisol can increase BP at rates of infusion below threshold for in vivo GC or MC actions and for many steroids there is no correlation between GC, MC and HT effects; (iii) demonstration of differential antagonism of HT, MC and GC effects.

3. Studies in man show that the BP effects of ACTH are due to cortisol (F) at levels which have both MC and GC activity. However, BP effects of ACTH cannot be blocked by MC and GC antagonists.

4. Although complete separation of in vivo GC, MC and HT activities has not been possible in man, our own studies show a degree of dissociation. Taken together, these data suggest that steroids may raise BP by a HT mechanism distinct from classical in vivo MC or GC activities in man as well as sheep.
HAEMODYNAMIC EFFECTS OF LONG‐TERM ENDOTHELIN INFUSION IN CONSCIOUS SHEEP
Authors: Reid Amanda F. , Parkes David G. , Coghlan John P. , Scoggins Bruce A. , Whitworth Judith A.
Published: June 2007

1. Synthetic human endothelin‐1 was infused intravenously at 15 μg/h for 24 h to examine its cardiovascular actions in five conscious sheep.

2. Endothelin produced a maximum increase in mean arterial pressure (MAP) of + 8 mmHg at 8 h, with an increase in calculated total peripheral resistance (CTPR) of +2.6 mmHg/L per min, whilst cardiac output (CO) was unchanged. At 24 h MAP was not significantly elevated, however CTPR had increased by +2.8 mmHg/L per min and CO had decreased by 0.9 L/min.

3. This study shows that long‐term administration of endothelin produces sustained arterial vasoconstriction in sheep.
CONTROLLED COMPARISON OF EFFECTS OF EXERCISE AND ALCOHOL ON BLOOD PRESSURE AND SERUM HIGH DENSITY LIPOPROTEIN CHOLESTEROL IN SEDENTARY MALES
Authors: Cox K. L. , Puddey I. B. , Morton A.R. , Masarei J. R. L. , Vandongen R. , Beilin L. J.
Published: June 2007

1. Seventy‐two sedentary male drinkers, aged 20–45 years, and with mean blood pressure (BP) at entry of 132±1.2/73±0.9 mmHg, completed a 4 week study during which they were assigned randomly to either drink a low alcohol beer (effectively reducing their weekly alcohol intake from 481±47 mL to 52±5 mL) or to continue their normal drinking habits.

2. Within these two groups subjects were further assigned to either a moderate exercise programme of three 30 min sessions per week of stationary cycling at 60–70% maximum workload or to a control light exercise programme where they pedalled against zero or minimal resistance.

3. Both alcohol restriction and moderate exercise were associated with mean falls in bodyweight of 0.5 kg. After adjustment for bodyweight a significant main effect of alcohol restriction on systolic BP (‐4.1±1.7 mmHg, P<0.05) and diastolic BP (‐1.6±0.8 mmHg, P= 0.05) was demonstrated. There was no significant main effect of moderate exercise on systolic or diastolic blood pressure despite a significant improvement in physical fitness (maximal oxygen uptake increasing from 33.2±0.08 mL/kg per min to 35.5±0.1 mL/kg per min).

4. Significant falls in high density lipoprotein cholesterol (HDLC) and triglyceride levels seen with alcohol restriction were unaffected by the increase in fitness, the magnitude of the fall being similar in both the moderate and light exercise groups.

5. We conclude that in male drinkers 4 weeks of moderate exercise has no influence on serum HDLC levels and when combined with alcohol restriction does not lead to a greater fall in BP than that seen with a reduction of alcohol intake alone.
MECHANISMS INVOLVED IN THE STIMULATION OF ALDOSTERONE PRODUCTION BY ANGIOTENSIN II, VASOPRESSIN AND ENDOTHELIN
Authors: Woodcock Elizabeth A. , Tanner Jennifer K. , Caroccia Lucy M. , Little Peter J.
Published: June 2007

SUMMAY

1. Endothelin (ET), vasopressin (VP) and angiotensin II (AII) all stimulate aldosterone production in adrenal glomerulosa cells but the response to AII is greater than that to either ET or VP.

2. Total inositol phosphate responses to AII and ET were similar but the response to VP was lower.

3. Cytosolic free Ca2+ responses to AII were higher than to either of the other peptides.

4. Metabolism of 145IP3 was different under stimulation by the three different peptides.

5. Adrenal glomerulosa cells can distinguish between three different agonists which stimulate phosphatidylinositol turnover and produce a selective response to each peptide.
ENDOTHELIN STIMULATES INOSITOL PHOSPHATE ACCUMULATION IN RAT RIGHT AND LEFT ATRIA: A COMPARISON WITH NORADRENALINE
Authors: Kuraja Ivana J. , Woodcock Elizabeth A.
Published: June 2007

1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H]‐inositol labelling.

2. In the presence of 10 mmol/L LiCl, endothelin caused dose‐dependent increases in the accumulation of inositol mono, bis and trisphosphates which were maximal at 10‐6 mol/L endothelin. The dose–response relationship was similar in right and left atria, but right atria showed a higher maximal inositol phosphate response.

3. Endothelin produced a rapid and transient stimulation of inositol tris‐phosphate accumulation, which peaked at 15 s followed by a slower increase which continued linearly past 20 min.

4. The time course of inositol trisphosphate release under noradrenaline stimulation showed a similar profile but the maximum stimulation was smaller than endothelin.

5. As with endothelin, responses to noradrenaline also were higher in right atria compared with left atria.

6. These data demonstrate that endothelin receptors in rat atria are coupled to the stimulation of the phosphatidylinositol turnover pathway in an essentially similar manner to α1‐adrenoceptors. The phosphatidylinositol pathway may be important in mediating the reported cardiac actions of endothelin.
INCREASED CARDIAC ANGIOTENSIN‐CONVERTING ENZYME IN RATS WITH CHRONIC HEART FAILURE
Authors: Fabris B. , Jackson B. , Kohzuki M. , Perich R. , Johnston C. I.
Published: June 2007

XUMMARY

1. Chronic heart failure was induced in rats by ligation of the left coronary artery to produce a left ventricular myocardial infarct.

2. Cardiac angiotensin‐converting enzyme (ACE) was estimated by radioligand binding in myocardial homogenates and by autoradiography studies of radioligand binding to ACE in heart sections.

3. Radioligand binding studies demonstrated an increase in binding sites in animals with myocardial infarction, compared with sham operated animals. Mean increases were 457% in right atrium, 295% in left atrium, 326% in right ventricle, 187% in left ventricle and 530% in the region of the left ventricular infarct, compared with the sham left ventricle.

4. Autoradiography studies confirmed tissue homogenate binding studies, demonstrating (i) a marked increase in ligand binding in the infarct area and (ii) an increase in binding density in the hypertrophied myocardium of right and left atrium, and right and left ventricle.

5. The induction of cardiac ACE in the myocardium of rats with chronic heart failure may participate in the pathophysiology of cardiac hypertrophy.
DOPAMINE INFUSION IN HEALTHY SUBJECTS AND CRITICALLY ILL PATIENTS
Authors: Ratge D. , Steegmüller U. , Mikus G. , Kohse K. P. , Wisser H.
Published: June 2007

1. Little is known about the metabolism and the pharmacokinetics of dopamine (DA) in critically ill patients. To study the influence of the total administered DA dose on the disposition of free (i.e. unconjugated) and sulfoconjugated DA, plasma levels of free and sulfoconjugated DA were measured following infusion of 5 μg DA/kg per min for 0.5 and 3 h in six healthy volunteers and in eight critically ill patients receiving DA at the same infusion rate for 6.5 to 329 h.

2. In patients and volunteers steady state concentrations of free DA showing fairly large inter‐individual variations (12.4–73.4 μg/L) were reached within 10 min of the beginning of the infusion.

3. DA sulfate was generated immediately. In volunteers peak values of the sulfoconjugate were observed 15–60 min after the termination of the DA infusion. In patients steady state concentrations of conjugated DA (63–80 μg/L) were reached within 5–10 h of DA infusion.

4. The initial half‐life (t1/2α), the terminal elimination half life (t1/2) and the distribution volume of free DA in the volunteers were significantly higher after 3 h of the DA infusion as compared to the shorter infusion. These parameters as well as the total plasma clearance of free DA were independent of the length of the DA infusion period in patients. The large distribution volumes of 19.8–75 L/kg indicate that DA has been taken up by peripheral tissues.

5. Substantial inter‐individual variations in the patients' clearance of free DA (3.9–16.5 L/kg per h) may partly explain the variability in haemodynamic responses to DA infusion reported in clinical studies. No effects of DA on the systolic and diastolic blood pressures or the plasma concentrations of norepinephrine were found in the healthy subjects. The physiological significance of sulfated DA as a potential reserve pool for free DA has to be further clarified.
EFFECT OF DIMETHYLSULPHOXIDE ON CYSTEAMINE‐INDUCED DUODENAL ULCERATION IN RATS
Authors: Ali B. H.
Published: June 2007

1. Rats were pretreated with dimethylsulphoxide (DMSO) at concentrations of 2, 4 and 6% v/v in the drinking water for 7 days, then injected with a single subcutaneous dose of cysteamine (28 mg/100 g bodyweight) to induce duodenal ulceration.

2. DMSO reduced, in a dose‐dependent manner, the incidence and extent of the ulceration.

3. Mucus duodenal content was not significantly affected by either DMSO or cysteamine treatments.
A LACK OF POTENCY FOR THE δ‐OPIOID ANTAGONIST NALTRINDOLE AFTER MICROINJECTION INTO THE ROSTRAL VENTROLATERAL MEDULLA OF RABBITS
Authors: Morilak David , Drolet Guy , Chalmers John
Published: June 2007

1. Naltrindole is a novel δ‐opioid antagonist which is highly potent in vitro. We examined the effects on arterial pressure of naltrindole (0.3–300 pmol) after microinjection into the pressor area of the rostral ventrolateral medulla of chloralose‐anaesthetized rabbits.

2. Naltrindole itself had no significant effects on arterial pressure, and only slightly attenuated the hypotensive effect of an exogenous agonist ([d‐Ala2, d‐Leu5]‐enkephalin). This is in contrast to previous demonstration of a marked pressor effect following another δ‐antagonist, ICI 174,864.

3. Thus, naltrindole, tested in vivo against endogenous opioid effects, does not appear to be as potent as it is in vitro, and in this case was virtually ineffective.
INFLUENCE OF CARDIAC AFFERENTS ON TIME‐DEPENDENT CHANGES IN THE RENAL SYMPATHETIC BAROREFLEX OF CONSCIOUS RABBITS
Authors: Bell Leonard B. , Dorward Patricia K. , Rudd Carl D.
Published: June 2007

1. The stability of the renal sympathetic baroreflex and nasopharyngeal reflex, and the role of cardiac sensory receptors, was studied in conscious rabbits over a 5 h experimental period.

2. Renal sympathetic nerve activity (SNA) was recorded during (i) slow ramp changes in mean arterial pressure (MAP) of 1–2 mmHg/s induced by inflating perivascular balloon cuffs, and (ii) the inhalation of cigarette smoke. Experiments were repeated in other rabbits after blocking cardiac afferents with 5% intrapericardial procaine.

3. Baroreflex responses to the first two caval cuff inflations of the day were significantly greater than subsequent responses. After this, triplicate sets of reflex curves were relatively stable during a 2 h period in the morning. When the experiment was repeated in the afternoon, there was a significant attenuation of baroreflex range and a small fall in resting renal SNA which were abolished by pericardial procaine.

4. Changes in baroreflex properties were minimal when the reflex was assessed only twice, at the beginning and end of a 5 h period. No change was seen in the nasopharyngeal reflex whether the rabbits had been subjected to few or to many cuff inflations.

5. We conclude that time dependent changes can occur in the renal sympathetic baroreflex of conscious rabbits which must be allowed for by appropriate protocol design. These include increasing inhibitory influences from cardiac sensory receptors in experimental situations requiring multiple reflex estimations.
EVIDENCE FOR THE INHIBITORY EFFECT OF 5‐HYDROXYTRYPTAMINE AT CENTRAL AND PERIPHERAL SITES ON OVULATION IN RABBITS
Authors: Mishra N. , Tangri K. K. , Bhargava K. P. , Gupta M. L.
Published: June 2007

1. The effect of 5‐hydroxytryptamine (5‐HT) has been investigated on ovulation per se as well as on induced ovulation in rabbits.

2. 5‐HT administered intracerebroventricularly (i.c.v.) did not induce ovulation per se.

3. The ovulation was induced by coitus, subcutaneous administration of progesterone and intravenous administration of cupric acetate.

4. Postcoital and progesterone induced ovulation was found to be blocked by i.c.v. administered 5‐HT.

5. Cupric acetate induced ovulation was, however, not found to be blocked by i.c.v. administered 5‐HT.

6. Intraperitoneal administration of 5‐HT was found to block cupric acetate induced ovulation.

7. It is concluded that 5‐HT exerts an inhibitory control over ovulation by acting at central as well as at peripheral sites in rabbits.
CHARACTERISTICS OF CARDIOVASCULAR REFLEXES ORIGINATING FROM 5‐HT3 RECEPTORS IN THE HEART AND LUNGS OF UNANAESTHETIZED RABBITS
Authors: Evans Roger G. , Ludbrook John , Michalicek Jan
Published: June 2007

1. When phenylbiguanide (1‐PBG) (6.25–400 μg) was injected into the left atrium, right atrium or pulmonary artery of unanaesthetized rabbits it caused dose‐dependent falls of heart rate and arterial pressure, and short‐lived hypopnoea or apnoea. The threshold dose was 50–100 μg. Maximal falls of heart rate (86–108 beats/min) and arterial pressure (33–35 mmHg) occurred at a dose of 200 μg. The latency between injection and onset of the bradycardia was 2.2–2.6 s and did not depend on the route. Cardiac output fell transiently with heart rate, but at the time of the maximal fall of arterial pressure it had returned to normal. All effects were abolished by intrapericardial procaine. The haemodynamic effects were exaggerated by sino‐aortic barodenervation. Intrapericardial 1‐PBG (200–400 μg) was without effect. Injection of 1‐PBG (>50–100 μg) into the aortic arch caused a variable increase in heart rate and arterial pressure.

2. When both cervical vagus nerves were crushed the depressor effects of atrial 1‐PBG were reduced by only 76–84%.

3. The dose–response curves for left atrial and pulmonary artery injection of 1‐PBG were shifted successively to the right by intravenous infusion of the 5‐HT3 antagonist MDL72222 (0.1 and 1.0 mg/kg).

4. We conclude that in unanaesthetized rabbits left atrial 1‐PBG selectively excites myocardial afferents, whereas right atrial or pulmonary artery 1‐PBG excites afferents that originate close to the pulmonary vasculature. In each case 1‐PBG acts through pharmacologically specific 5‐HT3 receptors. The afferents run mainly, but not exclusively, in the vagus nerves. The reflex fall of arterial pressure is accounted for almost entirely by a decrease in peripheral resistance.
HYPERTENSION AND COMPONENTS OF VASCULAR RESISTANCE
Authors: West Malcolm J.
Published: June 2007

1. In renal wrap hypertension in the rabbit and in essential hypertension in humans, non‐autonomic components of resistance are the major factors contributing to elevated blood pressure.

2. The central nervous system plays an important role in moment to moment blood pressure control but is not responsible for maintenance of elevated pressure in essential hypertension.

3. Specific regions of the brain‐stem maintain vascular tone through the effects of bulbospinal neurones which are organized both topographically and by chemical content.

4. Structural wall thickening in resistance vessels in hypertension is a manifestation of an abnormality of a growth controlling process.

5. Although several structural muscle growth factors have been identified, it is likely that only a few regulatory processes are critical.

6. Future studies in hypertension should examine associations between genetic markers of medial thickening and environmental influences.
ACUTE EFFECTS OF EXERCISE ON PLASMA LIPIDS, NORADRENALINE LEVELS AND PLASMA VOLUME
Authors: Krum H. , Conway E. L. , Howes L. G.
Published: June 2007

1. Total plasma cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low density lipoprotein cholesterol (LDL‐C), noradrenaline, haematocrit, haemoglobin and heart rate were measured in blood sampled from an antecubital vein in nine volunteers after 1 min standing and at intervals up to 1 h following 5 min of vigorous bicycle exercise.

2. Heart rates and plasma noradrenaline levels rose substantially immediately following exercise and gradually returned toward baseline levels 60 min post‐exercise.

3. Total plasma cholesterol levels rose by 24% immediately post‐exercise and slowly returned to baseline levels 60 min post‐exercise. Similar changes were observed for LDL‐C (20.2%) and HDL‐C (27.7%). As a result, LDL:HDL ratios did not alter.

4. These changes in total plasma cholesterol, HDL‐C and LDL‐C were explained by changes in plasma volume that occurred as a consequence of vigorous exercise.

5. Changes in plasma volume may be a mechanism by which some environmental factors such as stress are associated with elevated plasma cholesterol levels.
EFFECTS OF CLONIDINE ON BLOOD PRESSURE AND HEART RATE RESPONSES TO AN EMOTIONAL STRESS IN THE RAT: A SPECTRAL STUDY
Authors: Blanc Jocelyne , Grichois Marie‐Laure , Elghozi Jean‐Luc
Published: June 2007

1. The fluctuations that underlie the spontaneous variability of blood pressure (BP) and heart rate (HR) were investigated in conscious normotensive rats using power spectral analysis.

2. Air jet stimulation determined a significant BP rise associated with a tachycardia. This environmental mild stressor amplified the 195–605 mHz oscillations of HR which are under autonomic control. No habituation to this stressor was observed since a second stimulation determined similar responses.

3. Clonidine (10 μg/kg, i.v.) prevented the BP rise normally associated with air jet stimulation. In addition, clonidine dramatically reduced the amplitude of BP and HR oscillations in the frequency region of 195–605 mHz.

4. It is concluded that a mild emotional stressor elicits in normotensive rats a rise in BP and HR associated with modified spectral profiles reflecting sympathetic hyperactivity. Clonidine minored the effects of stress on BP and HR variability and also prevented BP elevation.
DIFFERENTIAL ACTIONS OF THE MEDIAL REGION OF CAUDAL MEDULLA ON AUTONOMIC NERVE ACTIVITIES
Authors: Yen C. T. , Hwang J. C. , Su C. K. , Lin Y. F. , Yang J. M. , Chai C. Y.
Published: June 2007

1. The inhibitory effects produced by activation of the medial region of caudal medulla on activities of the left and right cardiac sympathetic, vagus and greater splanchnic nerves were studied in chloralose‐urethane anaesthetized cats.

2. Electrical stimulation of the medial region produced an 80–92% inhibition of the sympathetic nerve activities, and a 45% and 58% inhibition of the left and right cardiac vagal nerve activities, respectively. There were no significant differences between effects elicited in the left and right autonomic nerves. Similar but smaller inhibitory effects were produced by micro‐injection of sodium glutamate (0.5 mol/L) or DL‐homocysteic acid (50 mmol/L) to the same medullary sites.

3. These data suggest that neurons residing in the medial medullary region exert strong inhibitory effects on autonomic nerve activities. Since the vasculature is principally innervated by sympathetic nerves, inhibition of sympathetic nerve activities might be the principal factor responsible for the depressor effects caused by activation of the medial region of caudal medulla. The heart is innervated both by sympathetic and parasympathetic nerves. Thus, their simultaneous inhibition during activation of the medial region elicits only a weak and variable inhibition of the heart.
ALTERED RESPONSES OF AORTIC SMOOTH MUSCLE FROM SPRAGUE‐DAWLEY RATS WITH SALT‐INDUCED HYPERTENSION
Authors: Obiefuna Peter C. M. , Ebeigbe Anthony B. , Sofola Olusoga A. , Aloamaka C. Peter
Published: June 2007

1. The contractile responses of aortic ring preparations from Sprague‐Dawley rats made hypertensive by 6‐week dietary salt loading were studied. The test and control diet contained 8.0 and 0.3% NaCl, respectively. Aortic rings from salt‐loaded rats showed enhanced sensitivity to nor‐adrenaline (NA) but not to serotonin. Contractile responses to CaCl2 in Ca‐free NA‐containing medium was significantly enhanced in salt‐loaded rats, but was unchanged in K+‐depolarised medium. K+induced relaxation (a functional indicator of Na‐K adenosine triphosphatase activity) was sensitive to 10 μmol/L ouabain and was significantly attenuated in aortic rings from salt‐loaded rats. The results suggest that hypertension induced by salt‐loading is associated with enhanced sensitivity to NA, increased Ca2+ entry through receptor‐operated channels, and impairment of Na‐K ATPase enzyme activity.
ROLE OF NON‐ESTERIFIED FATTY ACIDS IN REGULATING PLASMA CHOLESTEROL TRANSPORT
Authors: Barter Philip J.
Published: June 2007

1. The cholesteryl ester transfer protein (CETP) promotes an equimolar exchange of cholesteryl esters between the high density lipoproteins (HDL) and low density lipoproteins (LDL) in human plasma.

2. Sodium oleate converts this CETP‐mediated process of exchange into one of net mass transfer of cholesteryl esters from HDL to LDL.

3. Thus, conditions which increase the concentration of non‐esterified fatty acids in plasma may favour the redistribution of cholesterol from the non‐atherogenic HDL to the atherogenic LDL fraction.
ANGIOTENSIN II RECEPTOR SUBTYPES IN RAT BRAIN
Authors: Song Keifu , Allen Andrew M. , Paxinos George , Mendelsohn Frederick A. O.
Published: June 2007

1. Angiotensin II (AII) receptor binding was localized in the rat brain by in vitro autoradiography using the antagonist analogue, 125I‐[Sar1, Ile8] AII. AII receptor binding was then differentiated into type I and type II subtypes by displacement with unlabelled non‐peptide antagonists specific for AII subtypes.

2. Type I binding was determined as that inhibited by Dup753 (10 μmol/L) and type II binding as that inhibited by XD329‐1 (10 μmol/L). The reducing agent dithiothreitol (DTT) decreased the binding to type I receptors and enhanced the binding to type II receptors.

3. Structures such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, which are known to be related to some central actions of AII, contain exclusively type I AII receptors.

4. In contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus, subthalamic nucleus, some nuclei of the thalamus, and the nuclei of the inferior olive contain predominantly type II AII receptors.

5. These results reveal important pharmacological heterogeneity of brain AII receptors which suggest different regional functions and are relevant to the central actions of emerging classes of new non‐peptide AII receptor antagonists.