bluuebunny/crossref_metadata_2025 huggingface dataset:
RELATIVE CONTRIBUTIONS OF VAGAL AND CARDIAC SYMPATHETIC NERVES TO THE REFLEX BRADYCARDIA INDUCED BY A PRESSOR STIMULUS IN THE CONSCIOUS RABBIT: COMPARISON OF ‘STEADY STATE’ AND ‘RAMP’ METHODS
Authors: Weinstock Marta , Rosin A. J.
Published: June 2007

1. The bradycardic response to a pressor stimulus, phenylephrine, was studied simultaneously in conscious rabbits by two different methods.

2. The ‘steady state’ method, in which bradycardia was measured at the peak of each pressor stimulus, demonstrated the existence of two groups of animals, in which the maximal heart periods were 867 (s.e.m. =49) and 563 (s.e.m. =34) ms and the slopes of the MAP‐HP relationship were 24.6 (s.e.m. =1.6) and 8.1 (s.e.m. =0.7) ms/mmHg, respectively.

3. The difference in baroreflex sensitivity in the two groups was abolished by sympathetic nerve blockade with guanethidine (10 mg/kg) but not by vagal blockade.

4. The ‘ramp method’ which measures bradycardia during the rapid phase of MAP rise after phenylephrine did not detect any difference in response of the two groups of rabbits.

5. Guanethidine did not alter the slope of the MAP‐HP relationship in either group of rabbits when this was assessed by the ‘ramp’ method.

6. These findings demonstrate that the ‘steady state’ method can detect changes in both vagal and sympathetic activity, while the ‘ramp’ method measures only vagally induced bradycardia.

7. It is concluded that some rabbits may have a genetic ability to activate baroreflex pathways mediating cardiac sympathetic inhibition in addition to vagal stimulation in response to a pressor stimulus.
INFLUENCE OF VARIATION IN DIETARY SODIUM INTAKE ON BIOCHEMICAL INDICES OF SYMPATHETIC ACTIVITY IN NORMAL MAN
Authors: Watson R. D. S. , Esler M. D. , Leonard P. , Korner P. I.
Published: June 2007

1. The effects of variation in dietary sodium intake on biochemical indices of sympathetic activity were investigated in normal subjects.

2. Sodium restriction for 7 days (mean urinary sodium excretion 21 mmol/day, s.e.m. =4) increased supine plasma noradrenaline concentration significantly (1.78 nmol/l, s.e.m. =0.23) compared to levels during medium sodium intake (1.31 nmol/l, s.e.m. =0.14) and high sodium intake (1.35 nmol/l, s.e.m. =0.25), when urinary sodium excretion averaged 186 (s.e.m. =24) and 310 (s.e.m. =43) mmol/l respectively. Plasma adrenaline concentrations did not vary significantly.

3. During sodium restriction, the apparent release rate of noradrenaline increased significantly; noradrenaline clearance remained unchanged.

4. No changes were observed in the heart rate response after β‐adrenoceptor stimulation with isoprenaline, suggesting that increased sympathetic activity during sodium restriction did not necessarily alter cardiac β‐receptor sensitivity.

5. The responses to cardiac autonomic blockade with propranolol and atropine did not vary with sodium intake.

6. These observations suggest that the sympathetic response to sodium restriction may not be generalized, excluding, in particular, the sympathetic nerves to the heart.
CARDIOVASCULAR EFFECTS OF NEUROMUSCULAR BLOCKADE DURING INDUCED HYPOTHERMIA
Authors: Wyse Richard K. H. , Silove Eric D. , Godley Margaret L. , Welham Kenneth C.
Published: June 2007

1. Young lambs were used to study the effects of progressive cooling and rewarming on cardiovascular function during neuromuscular blockade induced by gallamine.

2. Initially, it was shown that gallamine exerted no immediate, direct haemodynamic effect in normothermic or hypothermic lambs (cooled by 10°C).

3. By comparison with hypothermic controls, neuromuscular blockade was associated with increases in left ventricular (LV) max dP/dt (153%; P<0.02) as cooling progressed, and even greater increases (232%; P<0.001) during rewarming. It was concluded that these changes seem likely to represent enhanced myocardial contractility since preload did not closely follow LV max dP/dt (heart rate and mean aortic pressure fell gradually during cooling but values were restored in the rewarming phase).

4. LV max dP/dt in lambs given gallamine only after cooling also showed a similar response during rewarming.

5. Results of this study may have clinical relevance relating to the mechanical recovery of the hypothermic heart in patients receiving neuromuscular blockade during cardiac surgery, and they argue against using gallamine as such an agent.
A SIMPLE HPLC ASSAY FOR URINARY PARACETAMOL METABOLITES AND ITS USE TO CHARACTERIZE THE C3H MOUSE AS A MODEL FOR PARACETAMOL METABOLISM STUDIES
Authors: Miners John , Adams John F. , Birkett Donald J.
Published: June 2007

1. A high performance liquid chromatographic (HPLC) assay for unchanged paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates in the urine of man, mouse and rat is described. The method is simple, rapid and reproducible.

2. The metabolite assay has been used to characterize the male C3H mouse, which shows sensitivity to paracetamol toxicity similar to man, as a model for paracetamol metabolism studies.

3. In male C3H mice there was no evidence to suggest saturability of the glucuronidation pathway on increasing the paracetamol dose from 50 to 300 mg/kg. By contrast, the metabolic ratio and fractional excretion of both the sulphate and glutathione‐derived conjugates decreased with increasing paracetamol dose.

4. For animals administered a 200 mg/kg dose of paracetamol, pretreatment with phenobarbitone or 3‐methylcholanthrene increased the fractional excretion and metabolic ratio of the glutathione‐derived and glucuronic acid conjugates. Piperonyl butoxide pretreatment of animals administered the same dose of paracetamol inhibited glutathione and glucuronic acid conjugation.
EFFECT OF INCREASED BILE FLOW AND BILE ACID SECRETION ON THE HEPATIC ELIMINATION OF SODIUM VALPROATE IN THE CAT
Authors: Marshall A. W. , Mihaly G. W. , Smallwood R. A. , Hanson R. G. , Vajda F. J. E. , Phillips J. , Baldas J.
Published: June 2007

1. The effect of increased bile flow and hepatic bile acid flux on the systemic clearance and hepatic elimination of intravenously administered sodium valproate was studied in the bile fistula cat. Taurochenodeoxycholic acid (TCDC), tauro‐3α, 7β‐dihydroxy‐12‐keto‐5β‐cholanoic acid (T12K), SC‐2644, and secretin were infused intravenously to vary bile flow and biliary bile acid secretion. Control animals were infused with 0.15 mol/l NaCl.

2. Less than 1% of the drug administered to controls appeared as unchanged valproate in the bile over 6 h. Although SC‐2644, T12K, and secretin significantly increased biliary excretion of valproate, it did not exceed 2% of the intravenous dose. Biliary clearance was directly related to the rate of bile flow, but not to the bile acid flux.

3. By contrast, 18–19% of the dose appeared in bile as metabolite in controls, and none of the choleretic agents significantly increased this percentage. As a result, systemic clearance of valproate was unaltered.

4. We conclude that the movement of unchanged valproate into bile is consistent with a process of simple diffusion. The fact that choleretic agents do not increase metabolite excretion into bile suggests that metabolite formation may be the rate‐limiting step in the hepatic elimination of valproate, rather than transport and excretion of metabolites into bile.
ERYTHROCYTE CATION TRANSPORT DISTURBANCES IN PATIENTS WITH ENDOGENOUS DEPRESSION
Authors: Rybakowski Janusz , Potok Elżzbieta , Strzyżewski Włlodzimierz , Nowakowska Cecylia
Published: June 2007

1. The active cation transport mechanisms (ouabain‐dependent fluxes of sodium; ODS) and potassium (ODK), sodium‐potassium adenosine triphosphatase ([Na+‐K+]‐ATPase) activity as well as lithium‐sodium countertransport (LSC) reflecting sodium exchange diffusion, were studied in erythrocytes of forty‐four patients with endogenous depression both in acute episode and in remission, and compared with thirty healthy control subjects.

2. During depressive episodes, the activities of all mechanisms studied were significantly lower than those of control subjects. In female depressives the values of ODS and LSC were lower than in males.

3. In remission, the activity of all mechanisms rose, reaching in most patients the values of control subjects. In female patients, activities of ODS and LSC were still lower than in male patients and female controls.

4. The activities of ODS and LSC had the highest discriminating power between depressive patients and control subjects.

5. It appears that membrane pathology may be an aetiologic factor in endogenous depression. A disturbance in erythrocyte transport presents most conspicuously during depressive episodes and in some patients may also persist to the normothymic period.
SODIUM DETECTION THRESHOLD AND PREFERENCE FOR SODIUM CHLORIDE IN HUMANS ON HIGH AND LOW SODIUM DIETS
Authors: DiNicolantonio R. , Teow B. H. , Morgan T. O.
Published: June 2007

1. Sodium detection threshold and preference for sodium chloride was examined in human volunteers on 2 week periods of high and low salt diets.

2. There was no significant difference in salivary electrolytes or sodium detection threshold between the high and low salt diet periods.

3. Sodium preference, defined as the final sodium concentration of unsalted tomato juice following the ad libitum addition of NaCl, was significantly less on the low salt diet when compared to the high salt period.

4. These results suggest that short periods of dietary salt modification can result in marked shifts in preference for NaCl in the absence of changes in the physiological parameters measured.
SEROTONIN ENHANCES SYMPATHETIC VASOCONSTRICTOR RESPONSES IN RAT ISOLATED PERFUSED TAIL ARTERY BY ACTIVATION OF POSTJUNCTIONAL SEROTONIN‐2 RECEPTORS
Authors: Medgett Iain C. , Fearn Herbert J. , Rand Michael J.
Published: June 2007

1. The effects of serotonin and the selective serotonin‐2 receptor antagonist ketanserin have been investigated on sympathetic vasoconstrictor responses in rat isolated perfused/superfused proximal tail artery segments.

2. Serotonin (6 nmol/l) markedly enhanced responses to low frequency, short duration electrical stimulation (0.1 ms pulses at 1 Hz for 10 s).

3. Serotonin (6 nmol/1) had a very slight (<10 mmHg) direct vasconstrictor effect.

4. Both the enhancing effect of serotonin on responses to electrical stimulation and the slight direct vasoconstrictor effect were blocked by ketanserin (3 nmol/l).

5. Ketanserin (3 nmol/l) had no significant effect on resting tone or on responses to electrical stimulation.

6. It is concluded that serotonin enhances sympathetic vasoconstrictor responses in rat tail artery by activation of postjunctional serotonin‐2 receptors. Blockade of this effect by ketanserin is entirely consistent with its antihypertensive effect in vivo.
MODERATE SODIUM RESTRICTION AND POTASSIUM SUPPLEMENTATION IN ESSENTIAL HYPERTENSION
Authors: Richards A. Mark , Nicholls M. Gary , Espiner Eric A. , Ikram Hamid , Maslowski Andrew H. , Hamilton Eric J. , Wells J. Elisabeth
Published: June 2007

1. Continuous 24 h arterial blood pressure and vasoactive hormones were measured in twelve patients with essential hypertension after 4 weeks on a control sodium intake (180 mmol/day) and after similar periods of sodium restriction (80 mmol/day) and potassium supplementation (200 mmol/day).

2. Sodium restriction was associated with variable blood pressure changes in individual patients and a small reduction in 24 h mean pressure of 4/3 mmHg.

3. The greatest fall in blood pressure with sodium restriction was seen in those patients with the least rise in renin.

4. Potassium supplementation was associated with variable individual blood pressure changes and a trivial reduction in mean 24 h pressures (0.1/0.8 mmHg).

5. Mean 24 h plasma aldosterone concentration was significantly higher during sodium restricted and potassium‐supplemented diets, compared to control levels, but other vasoactive hormones were unchanged.
CONCERN ABOUT GAIN: IS THIS THE BEST MEASURE OF PERFORMANCE OF CARDIOVASCULAR REFLEXES?
Authors: Ludbrook John
Published: June 2007

1. Open‐loop gain is commonly used as a measure of the effectiveness of cardiovascular reflex control systems.

2. There is no evidence that directly measured baroreflex gain for heart rate gives useful information about blood pressure control in human or experimental hypertension.

3. Calculation of open‐loop gain for blood pressure from closed‐loop observations requires many assumptions to be made.

4. Calculation of the independent and interactive effects of reflex inputs by factorial analysis may be more versatile, and give a more useful expression of the actions and interactions of cardiovascular reflexes in response to physiological disturbances, than does the calculation of gain.
ADJUNCTIVE EFFECT OF SALT RESTRICTION ON ANTIHYPERTENSIVE EFFICACY
Authors: Gillies A. H. B. , Carney S. L. , Smith A. J. , Waga S. M.
Published: June 2007

1. The effect of dietary salt restriction on blood pressure was measured in patients with moderate hypertension receiving antihypertensive medication. Patients were studied during a randomly allocated 6 week period of moderate dietary salt restriction and during a 6 week period of normal diet.

2. Twenty‐four of twenty‐eight patients achieved a reduction of salt excretion exceeding 20%. In these patients mean urinary sodium excretion fell from 169 (s.e.m. = 13) mmol/24 h to 92 (s.e.m. = 7) mmol/24 h. Potassium excretion and body weight did not change, and with the exception of the erect systolic pressure, there was no overall change in blood pressure.

3. When the data were grouped according to the patient medication, mean supine systolic pressure fell from 148.9 (s.e.m. = 4.4) to 140.3 (s.e.m. = 5.0) mmHg (n= 14, P>0.05) and mean supine diastolic pressure fell from 100.8 (s.e.m. = 2.9) to 97.0 (s.e.m. = 2.8) mmHg (n= 14, P>0.05) in patients taking diuretics. Blood pressure did not change in patients whose medication did not include diuretics.

4. Moderate dietary salt restriction may be therapeutically useful in patients with moderate hypertension treated with diuretics but is of little value in those not receiving diuretics.
DEMONSTRATION OF PROXIMAL TUBULAR α‐ADRENOCEPTORS IN VIVO
Authors: Woodcock Elizabeth A. , McLeod Jennifer K. , Johnston Colin I.
Published: June 2007

1. Receptors for parathyroid hormone (PTH) in the renal tubule are coupled to adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from cells of the proximal convoluted tubule.

2. The effects of α‐adrenergic agonists and antagonists on the urinary cAMP response to PTH were investigated in anaesthetized rats in vivo. Injection of PTH (15 u/kg i.v.) produced an increase in urinary cAMP from 1.7 (s.e.m. = 0.3, n= 6) to 7.47 (s.e.m. =0.7, n=6) nmol cAMP/μmol creatinine in 30 min urine samples. Infusion of the α2‐adrenoceptor agonist clonidine at 1 μg/kg per min caused a decrease in the cAMP response to PTH to 3.6 (s.e.m. =0.5, n= 12) nmol cAMP/μmol creatinine. Infusion of the α2‐selective catecholamine α‐methylnoradrenaline (1 μg/kg per min) caused a similar reduction in urinary cAMP response to that observed with clonidine.

3. The α‐adrenoceptor antagonist phentolamine (100 μg/kg per min) enhanced the cAMP response to PTH and reversed the decreased response caused by clonidine.

4. These results demonstrate the presence of α‐receptors in the rat proximal convoluted tubule which oppose the actions of PTH in vivo.
RENAL VENOUS RENIN RATIO AS A PREDICTOR OF IMPROVEMENT IN HYPERTENSION FOLLOWING NEPHRECTOMY FOR UNILATERAL RENAL DISEASE
Authors: Gordon R. D. , Tunny T. J. , Evans E. B. , Fisher P. M. , Jackson R. V.
Published: June 2007

1. Renal venous renin ratio (RVRR) was measured in twenty hypertensive patients before removal of a kidney for unilateral, parenchymal renal disease. They were then followed for 1.3–9 y.

2. Hypertension was cured or improved in six of eight patients with positive unstimulated and stimulated ratios, in none of five whose ratios became positive only on stimulation, and in one of seven with all ratios negative.

3. Patients improved or cured by surgery had a significantly shorter duration of hypertension and a significantly lower serum creatinine after nephrectomy.

4. Unstimulated RVRR was a reliable predictor of the effect of unilateral nephrectomy on blood pressure level.
THE USE OF A RAT ISOLATED ILEAL PREPARATION TO INVESTIGATE THE RELEASE OF NEUROTENSIN
Authors: Gill S. S. , Lee Y. C. , Ghatei M. A. , Ghiglione M. , Uttenthal L. O. , Bloom S. R.
Published: June 2007

1. An isolated and perfused preparation of rat ileum was used to investigate the effects of cholinergic, adrenergic and bombesin stimuli on neurotensin release into the vascular compartment.

2. A vigorous release of neurotensin like immunoreactivity (NTLI) to 200% above basal values in response to intraluminal infusions of emulsified soybean oil (Intralipid) demonstrated the physiological responsiveness of the preparation.

3. Carbachol significantly stimulated the release of both NTLI and bombesin like immunoreactivity (BLI), with maximal responses at 5 times 10‐9 mol/l carbachol of 100% and 400% above basal values for NTLI and BLI, respectively.

4. Noradrenaline at 10‐6 and 10‐4 mol/l caused no significant release of NTLI but markedly inhibited spontaneous BLI release.

5. Synthetic amphibian bombesin caused a marked release of NTLI to 81% and 100% above basal at infusion concentrations of 5 times 10‐11 and 5 times 10‐10 mol/l respectively.

6. These results suggest that there is either a direct effect of cholinergic agents on the N cells bringing about NTLI release, or an indirect effect via the release of bombesin like peptides from intrinsic gut neurones. This preparation provides a useful model to study the complex neural, paracrine and endocrine interactions in the gastrointestinal tract.
THE EFFECT OF QUATERNARY NALOXONE ON THE INCREASED NALOXONE POTENCY INDUCED BY MORPHINE
Authors: Wong Chak‐Lam , Wai Man‐Keung
Published: June 2007

1. Using the abdominal constriction test in mice it was shown that the antinociceptive effect of morphine was inhibited by naloxone hydrochloride and its quaternary derivative naloxone methylbromide which presumably only acts peripherally.

2. Pretreatment with a single dose of morphine 2.0 mg/kg s.c. did not alter the antinociceptive effect of a second dose of morphine given 3 h later. However, the antagonistic effect of naloxone against morphine was enhanced at this time.

3. The development of increased naloxone potency was inhibited when naloxone hydrochloride was given together with morphine in the pretreatment.

4. A similar inhibitory effect was observed when the quarternary derivative naloxone methylbromide was used instead of naloxone hydrochloride in the pretreatment regime.

5. As there was no difference between the effects of naloxone hydrochloride and naloxone methylbromide in suppressing the development of increased naloxone potency induced by morphine pretreatment, it was concluded that this phenomenon may be mediated mainly through peripheral opiate receptors.
DIURETIC AND HAEMODYNAMIC EFFECTS OF MK 447 IN NORMOTENSIVE AND HYPERTENSIVE SHEEP
Authors: Humphery T. J. , Coghlan J. P. , Denton D. A. , Fei D. W. T. , Graham W. F. , Scoggins B. A. , Whitworth J. A.
Published: June 2007

1. The short term effects of the novel diuretic MK 447 were examined in both normotensive and hypertensive (ACTH treated) conscious sheep.

2. The drug had profound diuretic, natriuretic and kaliuretic effects in both groups. Plasma sodium was unchanged but plasma potassium fell and haematocrit increased. Plasma renin concentration increased with MK 447 in the normotensive but not the hypertensive sheep.

3. In the normotensive sheep cardiac output fell, peripheral resistance increased and blood pressure was unchanged. In the hypertensive ACTH treated sheep cardiac output and blood pressure fell but resistance was unchanged.
EFFECTS OF THYROXINE TREATMENT ON CONTRACTIONS OF SOLEUS MUSCLES OF ANAESTHETIZED CATS
Authors: Merican Zainuddin , Morat Paden
Published: June 2007

1. The effects of chronic thyroxine treatment on cat soleus muscle contractions were studied.

2. Maximum twitch tension, contraction time, half relaxation time and tensiontime integral of maximal twitches of the soleus muscles of thyroxine treated cats were significantly decreased. Consequently, there was a decrease in tension and degree of fusion of incomplete tetanic contractions of the soleus muscle. The maximum tetanic tension was not statistically significantly changed, suggesting that the effects may be due to a decrease in the duration of the active state of the muscle.

3. Isoprenaline given intravenously during incomplete tetanic contractions of the soleus muscle caused a statistically significant depression of tension in the control group but not in the thyroxine treated group. This further suggests reduction in the duration of the active state of soleus muscles of thyroxine treated cats.

4. Propranolol injected chronically with thyroxine reversed or prevented the depression of tension caused by thyroxine treatment, suggesting the involvement of β‐adrenoceptors in these effects.

5. The decrease in tension and degree of fusion during incomplete tetanic contractions of the thyroxine treated soleus could be responsible, at least partly, for the muscle weakness and tremor of thyrotoxicosis. Cyclic AMP may possibly be the mediator of these effects.
EFFECT OF DIETARY UREA ON BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Wang Hong , Ikeda Katsumi , Kihara Masahiro , Nara Yasuo , Horie Ryoichi , Yamori Yukio
Published: June 2007

1. The feeding of a normal diet containing 13.5% urea (in place of protein in a high protein diet) attenuated the development of severe hypertension and decreased the incidence of stroke in spontaneously hypertensive rats (SHR), when 1% NaCl solution was given to them.

2. The urea not only increased urine volume, but also increased urinary sodium excretion in SHR given 1% NaCl for drinking.

3. Although there was no obvious difference in erythrocyte size between the urea and the control groups, there was a significant inverse correlation between plasma urea level and erythrocyte size.

4. These results suggest that a high protein diet reduced blood pressure partly through the diuretic effect of urea, the common metabolite of various proteins.
EFFECTS OF β‐ADRENOCEPTOR BLOCKADE ON PROSTACYCLIN MEDIATED RENIN RELEASE IN SHEEP
Authors: Mason R. T. , Coghlan J. P. , Denton D. A. , Fei D. W. T. , Whitworth J. A. , Scoggins B. A.
Published: June 2007

1. The effect of prostacyclin (PGI2) infusion on plasma renin concentration (PRC) was examined before and after propranolol treatment in sheep.

2. Increasing doses of prostacyclin (0.05, 0.1 or 0.3 μg/kg per min) produced dose dependent increases in PRC.

3. There was a significantly lower PRC response after propranolol at 0.3 μg/kg per min only.
CANINE NONRESPONDERS TO ALVEOLAR HYPOXIC VASOCONSTRICTION AND QUANTITATIVE RESTORATION OF THE RESPONSE BY ASPIRIN I‐3
Authors: Siefkin Allan D. , Parsons Gibbe H.
Published: June 2007

1. Hypoxic pulmonary vasoconstriction is characterized by considerable variability in rate of response (pulmonary vascular resistance [PVR] as a function of time under hypoxia). To further define this response, forty‐five closed chest dogs were anaesthetized (pentobarbitone sodium), intubated, and mechanically ventilated. Constant left lower lobar pulmonary artery flow was maintained through a balloon tipped 14F catheter via an extracorporeal pump at a rate to achieve lobar pulmonary artery pressure (Plobar) equal to main pulmonary artery pressure (Ppa) and thereafter held constant. Left ventricular end diastolic pressure (Plved) was measured by left ventricular catheter and lobar pulmonary artery flow rate (Q) by flow meter. Lobar PVR (mmHg/min per 1) was calculated every 15 min.

2. Ventilation with 10% oxygen (O2) separated two groups based on the increase in PVR over time: twenty‐two rapid hypoxic responders [HR] (slope =ΔPVR/Δmin>0.3) and twenty‐three slow or nonresponders [NR] (slope < 0.1). The twenty‐three NR were divided into two groups. Ten NR dogs (NR control) had no change in mean PVR (23.9, s.d. = 8.2, to 24.1, s.d. = 9.6) over a mean of 78 min and were used as controls. Thirteen NR dogs (NR ASA) had no change in mean PVR (32.9, s.d. = 9.5, to 32.3, s.d. = 9.8) over 75 min and were given aspirin (ASA), 10–15 mg/kg intra‐arterially. The NR ASA group mean PVR then increased from 32.3 (s.d. = 9.8) to 59.1 (s.d. = 23.9, 82.9% increase, P < 0.01) over a mean of 54 min. The mean PVR for the twenty‐two HR rose from 39.8 (s.d. = 34.0) to 64.5 (s.d. = 36.6, 62.1% increase, P<0.01) over a mean of 72 min. The slopes of rate of response for HR (0.66) and for NR ASA (0.88) were not significantly different. The absolute values of PVR reached after plateau for HR and for NR ASA (after ASA) were also not different.

3. Aspirin restored the NR capability to develop pulmonary vasoconstriction in response to alveolar hypoxia. The rate of response and the absolute level of response reached were also restored by aspirin.
PARTICIPATION OF PROSTANOIDS IN CHEMICAL ACTIVATION OF THE PERICARDIAL PRESSOR REFLEX IN DOGS
Authors: Nolan Peter N. , Luk Denise E. , Staszewska‐Woolley Janina
Published: June 2007

1. Experiments were performed on anaesthetized, open‐chest dogs to determine the reflex effects on systemic blood pressure and heart rate produced by stimulation of the parietal pericardium with bradykinin, prostacyclin, prostaglandin E2 (PGE2), prostaglandin D2 (PGD2) and arachidonic acid.

2. Pericardial application of bradykinin (1 μg) consistently elicited reflex increases in blood pressure and heart rate, whereas application of prostanoids or arachidonic acid in doses up to 10 μg failed to produce any cardiovascular responses.

3. Indomethacin, applied either directly to the parietal pericardium (1 μg/ml) or given intravenously (5 mg/kg) caused a long lasting reduction of the reflex responses to bradykinin. The reflex effects of bradykinin could be temporarily restored by treatment of the pericardium with either prostacyclin (0.1 μg/min) or PGE2 (0.1 μg/min). PGD2 (0.1‐1 μg/min) did not influence the bradykinin induced pericardial reflex.

4. Superfusion of arachidonic acid (3 μg/min) over the pericardium amplified the reflex effects of bradykinin when given before, but not when given after indomethacin treatment.

5. The results indicate that locally formed prostanoids, specifically prostacyclin and PGE2, can facilitate activation of the pericardial pressor reflex by bradykinin. The findings may be relevant to the changes in cardiovascular activity occurring during pericardial inflammation.
THE EFFECT OF DOPAMINE ON TRACHEAL SMOOTH MUSCLE
Authors: Michoud M. C. , Amyot R. , St‐Jean S. , Vaillancourt R.
Published: June 2007

1. Dose‐response curves to dopamine were obtained on guinea‐pig, dog and human tracheal smooth muscle.

2. Dopamine produced a relaxation of the guinea‐pig tracheal chain, and this relaxation was completely blocked by propranolol. The potency of dopamine as a β‐agonist was 1/10 000 that of isoprenaline, 1/250 that of adrenaline and 1/50 that of noradrenaline.

3. In human and dog tracheal smooth muscle, dopamine induced a contraction which could be entirely abolished by α‐adrenoceptor antagonists. As an α‐agonist, the potency of dopamine was 1/20 that of adrenaline and noradrenaline.

4. Our data also show that a dopamine induced contraction is greatly potentiated if the smooth muscle specimen has been previously slightly contracted with histamine.

5. We conclude that there are few, if any, specific dopaminergic receptors in the airways. Dopamine acts on both α‐ and β‐adrenoceptors, but in humans and dogs, its effect is predominantly on α‐adrenoceptors.
EFFECT OF SECRETAGOCUES ON PANCREATIC EXOCRINE SECRETION IN THE MONKEY AND THE DOG
Authors: Iwatsuki K. , Iijima F. , Yamagishi F. , Chiba S.
Published: June 2007

1. The effects of secretin, cholecystokinin, dopamine, histamine and acetylcholine on the secretion of pancreatic juice were investigated in the monkey and the dog.

2. In the resting state, bicarbonate concentration and the volume of pancreatic juice in the monkey were greater than those in the dog. However, the protein concentration of pancreatic juice in the monkey was less than that in the dog.

3. Intravenous administration of secretin, cholecystokinin, histamine and acetylcholine caused a dose dependent increase in pancreatic secretion in both species. The responses in the monkey were greater than those in the dog. Dopamine caused pancreatic secretion only in the dog.

4. The increase in bicarbonate concentrations of pancreatic juice induced by secretin and histamine in the monkey were greater than that in the dog. Increase in protein concentrations of the juice induced by cholecystokinin and acetylcholine in the monkey were less than that in the dog. However, pancreatic juice pH in both species was the same and was not affected by the secretagogues in the resting state or during the stimulation by secretogogues.

5. From these results, it is concluded that there is a species difference in the secretory actions of the secretagogues in the monkey and the dog.
CORRELATION OF PLASMA ANGIOTENSIN II CONCENTRATION AND PLASMA RENIN ACTIVITY DURING ACUTE HYPOXIA IN DOGS
Authors: Raff Hershel , Maselli Judy , Reid Ian A.
Published: June 2007

1. The effects of isocapnic hypoxia on plasma renin activity (PRA) and angiotensin II (AH) concentration were studied in anaesthetized, artificially ventilated dogs. Regression analysis of plasma All concentration vs PRA, both measured by radio‐immunoassay (RIA), was used as an index of converting enzyme activity in vivo.

2. PaO2 decreased from 82 to 30 mmHg but regression analysis did not reveal any inhibition of All production within the limits of detection of this method (<20% inhibition).

3. We conclude that systemic converting enzyme activity, assessed by in vivo measurement and correlation of PRA and AII, is not inhibited by severe hypoxia.
COMPARISON OF THE AFFINITY OF SECOVERINE FOR SOME MUSCARINIC RECEPTORS
Authors: Choo L. K. , Mitchelson F.
Published: June 2007

1. The selective muscarinic receptor antagonist secoverine was found to have a similar affinity for muscarinic receptors in the guinea‐pig left atrium and ileal longitudinal muscle as well as in the rat urinary bladder and ileum.
NALOXONE DOES NOT REVERSE ETHANOL ANALGESIA IN MAN
Authors: Saddler J. M. , James M. F. M. , Harington A. P.
Published: June 2007

1. The effects of intravenously administered ethanol and morphine on pain threshold, reaction time, motor skills and short‐term memory were investigated, and the ability of naloxone to reverse any changes was studied.

2. Morphine (loading dose 0.2 mg/kg with an infusion of 0.004 mg/kg per min) and ethanol (loading dose 0.75 ml/kg with an infusion of 0.0025 ml/kg per min) produced a similar increase in pain threshold of 6.3 (s.e.m. = 1.5, n= 8) pain units and 7.7 (s.e.m. = 1.9, n= 8) pain units, respectively. Naloxone 0.015 mg/kg produced a significant reduction in pain threshold in the morphine group, but not in the ethanol group, and there was a significant difference between the groups following naloxone (P<0.05, t‐test, 7 d.f.).

3. Ethanol produced a significantly greater deterioration in motor skills than did morphine (P<0.05, t‐test, 7 d.f.) and performance in both groups was improved following naloxone (P<0.05, t‐test, 7 d.f.).

4. There was no significant change in the other modalities studied.

5. It is concluded that the reversal of ethanol effects by naloxone is probably due to a non‐specific analeptic action rather than blockade of opioid receptors.
NALOXONE BLOCKS THE CARDIAC EFFECTS OF MYOCARDIAL ISCHAEMIA AND REPERFUSION IN THE RAT ISOLATED HEART
Authors: Zhan Z. Y. , Lee A. Y. S. , Wong T. M.
Published: June 2007

1. The effects of naloxone on contractility and cardiac rhythm were studied in the rat isolated perfused heart during myocardial ischaemia and reperfusion.

2. Pretreatment of the rat isolated perfused heart with naloxone abolished the reduction in left ventricular pressures and attenuated greatly the arrhythmias due to myocardial ischaemia and reperfusion.

3. Administration of naloxone into the fibrillating rat isolated heart induced by myocardial ischaemia and reperfusion also attenuated the arrhythmias in a dose‐dependent manner.

4. The results indicate a possible involvement of the endogenous opioid peptides in the cardiac effects due to myocardial ischaemia and reperfusion. The anti‐arrhythmic effect of naloxone has great clinical implications.
CARDIAC ANTIARRHYTHMIC EVALUATION OF NALOXONE WITH OR WITHOUT PROPRANOLOL USING A MODIFIED CHLOROFORM‐HYPOXIA SCREENING TEST IN THE RAT
Authors: Wong T. M. , Lee A. Y. S.
Published: June 2007

1. The effects of naloxone and propranolol on cardiac arrhythmias and durations from respiratory arrest to ventricular asystole and cardiac standstill were studied in unanaesthetized young rats induced to suffer respiratory arrest and exhibit ventricular fibrillation (VF) by a modified chloroform hypoxia technique.

2. Both naloxone and propranolol reduced the incidence of VF dose dependently, indicating that they have antiarrhythmic effects. Addition of naloxone to propranolol shifted the dose‐response curve of propranolol to the left significantly, indicating an additive effect of the two drugs in their antiarrhythmic activity.

3. Both naloxone and propranolol prolonged the duration from respiratory arrest to ventricular asystole. However, joint administration of both did not further prolong this duration indicating an absence of additive effects.

4. Naloxone prolonged the duration from respiratory arrest to cardiac standstill, indicating that naloxone prolonged the survival time. In contrast, propranolol did not produce the same effect.

5. That naloxone both produced antiarrhythmic effect and prolonged the survival time whereas propranolol only corrected cardiac arrhythmias suggests that the antiarrhythmic effect of naloxone may not result in prolongation of survival time and that different mechanisms may be involved in the antiarrhythmic effect.
PLASMA NORADRENALINE AND ITS RELATIONSHIP TO PLASMA OESTRADIOL IN NORMAL WOMEN DURING THE MENSTRUAL CYCLE
Authors: Davidson Lisa , Rouse Ian L. , Vandongen Robert , Beilin Lawrence J.
Published: June 2007

1. In order to investigate a possible relationship beween sympatho‐adrenal neuronal activity and the endocrine changes during the menstrual cycle, free and sulphate‐conjugated plasma catecholamines and oestradiol were measured under carefully controlled conditions in 26 normal menstruating women.

2. Plasma oestradiol levels were generally higher during the luteal compared with the follicular phase which corresponded to the self‐reported day of the cycle.

3. Free plasma noradrenaline concentration was higher during the luteal phase (P= 0.02) and was positively correlated with plasma oestradiol concentration (r= 0.40, P= 0.023). These relationships were not present for plasma adrenaline.

4. It is conceivable that the higher luteal phase noradrenaline is causally related to the higher oestradiol levels, leading to incomplete inactivation by reducing tissue uptake or competitive inhibition of catechol‐O‐methyl transferase.

5. As sulphated noradrenaline was not significantly different between the follicular and luteal phases, competitive inhibition of phenolsulphotransferase by oestradiol was considered unlikely.
FURTHER INVESTIGATIONS ON THE α1‐ADRENOCEPTOR BLOCKING PROPERTIES OF AR‐C 239 IN RATS
Authors: Huchet Anne‐Marie , Andréjak Michel , Lucet Bernadette , Gautret Bruno , Doursout Marie‐Françoise , Ostermann† Gérard , Schmitt Henri
Published: June 2007

1. AR‐C 239, a new α‐adrenoceptor blocking drug, appears to act selectively on α1 sites in rats. At peripheral sites, this drug did not change the tachycardia induced by spinal sympathetic outflow stimulation in pithed rats, and did not antagonize the inhibitory effects of clonidine on this preparation. In addition, AR‐C 239 showed predominant α1‐adrenoceptor blocking properties in the bisected rat vas deferens preparation. AR‐C 239 did not prevent or reverse the centrally mediated hypotensive and bradycardic actions induced by clonidine, in intact animals.

2. In conclusion, AR‐C 239 seems to be a very useful tool for the characterization of peripheral and central α1‐adrenoceptors, in this animal species.
THE ANTICHOLINESTERASE ACTIVITY OF MEFLOQUINE
Authors: Lim L. Y. , Go M. L.
Published: June 2007

1. The characteristics of the inhibition of electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by the antimalarial agents mefloquine, chloroquine, amodiaquine and amopyroquine were determined.

2. The antimalarials were found to be non‐competitive inhibitors of both AChE and BChE. In both enzyme systems, inhibitory potencies were in the order amodiaquine > amopyroquine > chloroquine > mefloquine.

3. The low inhibitory potency of mefloquine may account in part for the appearance of gastrointestinal and central nervous system disturbances only at high doses of the drug.
THE EFFECT OF AGING ON α‐ADRENOCEPTORS AND THEIR RESPONSES IN RABBITS
Authors: Hamilton C. A. , Dalrymple H. W. , Jones C. R. , Reid J. L.
Published: June 2007

1. The effects of age on α‐adrenoceptor responses, sensitivity and number were studied in rabbits aged from 1 to 36 months.

2. Three types of investigation were carried out: conscious animal studies, isolated tissue studies and radioligand binding studies.

3. Specific [3H]‐prazosin binding decreased with age in both spleen and heart suggesting that the number of α1‐receptors declined at least in the tissues studied. The specific binding of [3H]‐clonidine to spleen membranes and [3H]‐yohimbine to platelets was not affected by age.

4. In vitro responsiveness to α‐adrenoceptor agonists decreased with age in abdominal aorta and renal artery, while the affinity of adrenoceptors for prazosin (pA2) was not altered. The decrease may be non‐specific as responses to potassium were also altered. No change in α2‐adrenoceptor mediated platelet aggregation was observed.

5. No change in pressor or depressor responses to full adrenoceptor agonists or to antagonists was observed in vivo. However, responses to clonidine, which is a partial agonist at α1‐adrenoceptors, were decreased.

6. While aging influenced α‐adrenoceptor subtypes differently, there was no direct relation between functional changes and number of receptors.
EFFECTS OF D‐PENICILLAMINE ON COLLAGEN BIOSYNTHESIS BY FIBROBLAST CELL CULTURES
Authors: Chamson Annette , Frey Jacques
Published: June 2007

1. The effects of d‐penicillamine on collagen and total protein synthesis by fibroblast cell cultures were studied.

2. High concentration of d‐penicillamine (10 mmol/1) produced a toxic effect consisting of inhibition of growth and a non‐specific increase in protein synthesis.

3. A low concentration of d‐penicillamine (100 μmol/1) decreased the biosynthesis of both type I and type III collagens.
DIGITALIS RECEPTORS AND DIGOXIN SENSITIVITY IN RENAL FAILURE
Authors: Malini Pier Luigi , Strocchi Enrico , Feliciangeli Giorgio , Buscaroli Andrea , Bonomini Vittorio , Ambrosioni Ettore
Published: June 2007

1. The number and the in vitro and in vivo affinity of digitalis receptors for digoxin were measured in patients with normal renal function and in uraemics.

2. In uraemic patients the number of receptors was decreased. Although their in vitro affinity for digoxin was unchanged the in vivo affinity was decreased, probably due to hyperkalaemia.

3. These findings provide a possible pharmacodynamic explanation for decreased activity of cardiac glycosides in chronic renal failure.
CARDIOVASCULAR EFFECTS OF BROVINCAMINE AND POSSIBLE MECHANISMS INVOLVED
Authors: Kushiku K. , Katsuragi T. , Mori R. , Morishita H. , Furukawa T.
Published: June 2007

1. Cardiovascular effects of brovincamine (BV) and possible modes of action were studied in dogs, rabbits and guinea‐pigs.

2. In pentobarbitone‐anaesthetized dogs, intravenous administration of BV (1.6–12.8 mg/kg) induced a dose‐dependent decrease of blood pressure and heart rate, a slight and transient stimulation of respiration, and a prolongation of the R‐R interval in ECG without changes of wave pattern.

3. In the isolated atria of guinea‐pigs, BV showed no effect at 10−7 and 10−6 g/ml, but dose‐dependently inhibited both myocardial contractile force and heart rate at the higher concentrations of 10−5 and 10−4 g/ml.

4. In pentobarbitone‐anaesthetized dogs, BV (0.1–1.6 mg/kg) administered to the vertebral or carotid artery dose‐dependently increased the blood flow in the respective artery.

5. Intravenous administration of BV (0.8–12.8 mg/kg) also exhibited a dose‐dependent increase of the vertebral and carotid blood flow, but the increase was a little reduced at the higher dose of 12.8 mg/kg, probably resulting from marked hypotension and negative chronotropism. Intravenous administration of BV at 6.4 mg/kg induced a marked increase of the coronary flow, a slight increase of the renal flow and a slight decrease of the femoral flow.

6. 11–Bromovincaminic acid (BVA, 0.1, 0.2 mg/kg), a major metabolite of BV, given intravenously or to the internal carotid artery, did not exert actions on the blood pressure, heart rate and carotid blood flow, implying that it is an inactive metabolite.

7. In rabbit pulmonary arterial strips, BV showed no influence on effects of noradrenaline and adenosine but inhibited KC1‐induced contracture. This inhibitory effect of BV, but not papaverine, was antagonized by an increase of external Ca2+ concentration.

8. In conclusion, BV rather selectively increases the cranial and coronary blood flow. The vasodilative effects of BV seem to involve an inhibition of depolarization dependent Ca2+ slow channel. A major metabolite of BV, BVA, is inactive.
KETANSERIN DOES NOT PREVENT ACTH‐INDUCED HYPERTENSION IN SHEEP
Authors: Nelson Mark A. , Coghlan John P. , Denton Derek A. , Whitworth Judith A. , Scoggins Bruce A.
Published: June 2007

1. The role of serotonin (5HT) in the pathogenesis of ACTH‐induced hypertension in sheep has been examined.

2. The pressor responses to injections of 5HT (0.1–30 μg/kg) were similar in normotensive and hypertensive sheep.

3. Prior treatment with the 5HT2 receptor antagonist ketanserin had no effect on the development of hypertension produced by ACTH administration.
LACK OF EFFECT OF CHLORAMPHENICOL ON MONOAMINE, DIAMINE AND PLASMA AMINE OXIDASE ACTIVITIES
Authors: Ali B. H.
Published: June 2007

1. Chloramphenicol treatment in rabbits (60 mg/kg i.m. for 5 days) did not affect significantly (P > 0.1) the activities of monoamine oxidase (MAO) or diamine oxidase (DAO) in liver, heart or brain.

2. Plasma amine oxidase (PAO) was not significantly inhibited (P>0.1) in goats treated with chloramphenicol (60 mg/kg i.m. for 5 days).

3. Chloramphenicol (2×10−3 mol/l) preincubated with rabbit hepatic MAO had no significant effect (P>0.1) on the enzyme activity.
IMPORTANCE OF ENDOGENOUS VASOPRESSIN IN THE HYPERTENSIVE AND BRADYCARDIC RESPONSE TO CENTRAL α1‐ADRENERGIC STIMULATION
Authors: Hiwatari Masao , Johnston Colin I.
Published: June 2007

1. To determine the interaction between α1‐adrenergic and vasopressinergic mechanisms in the central regulation of cardiovascular functions, the effects of intracerebroventricular (i.c.v.) administration of the α1‐agonists, methoxamine and phenylephrine, were examined in conscious Long‐Evans (LE) rats and Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI).

2. In LE rats, i.c.v. methoxamine and phenylephrine (3–30 μg/kg) increased blood pressure and decreased heart rate in a dose‐related manner, while they had no detectable cardiovascular effects in DI rats.

3. Neither i.c.v. (0.5 ng/kg per min, 1 h) nor intravenous (i.v., 2 ng/kg per min, 2 h) infusion of vasopressin (AVP) restored the cardiovascular response to i.c.v. phenylephrine in DI rats.

4. In LE rats, however, i.v. pretreatment with the specific antagonist to the pressor effect of AVP, d(CH2)5Tyr(Me)AVP (10 μg/kg), attenuated the hypertensive and bradycardic effects of i.c.v. phenylephrine, while i.c.v. pretreatment with AVP antagonist (300 ng/kg) did not alter the cardiovascular response to i.c.v. α1‐agonist.

5. The cardiovascular response to i.c.v. phenylephrine was blocked by i.c.v. pretreatment with the α1‐antagonist, prazosin (2 μg/kg).

6. Intracerebroventricular phenylephrine increased plasma AVP levels 14‐fold without affecting plasma angiotensin II levels.

7. The present study clearly demonstrated that endogenous AVP plays a significant role in the cardiovascular response to i.c.v. α1‐agonist.
POTENTIATION OF ACTH HYPERTENSION IN MAN WITH SALT LOADING
Authors: Whitworth Judith A. , Saines Dianne , Scoggins Bruce A.
Published: June 2007

1. ACTH 1 mg/day for 5 days raises systolic blood pressure (SBP) in normotensive and hypertensive subjects on a fixed electrolyte intake of 100 mmol/day sodium (Na) and potassium (K) (Whitworth et al. 1983).

2. The present study examined the effect of Na intake in the high normal range on the haemodynamic and metabolic responses to ACTH.

3. ACTH administration on a 200–300 mmol Na intake increased SBP by 35 mmHg (s.e.m. = 11, n= 5) compared with the 22 mmHg (s.e.m. = 4, n= 12) rise seen on a 100 mmol Na intake in our previous study.

4. These studies suggest that the effects of adrenocortical steroids on blood pressure in man may be magnified by increasing dietary Na intake.
A RANDOMIZED CONTROLLED TRIAL OF THE EFFECT OF ALCOHOL CONSUMPTION ON BLOOD PRESSURE
Authors: Puddey I. B. , Beilin L. J. , Vandongen R. , Rouse I. L.
Published: June 2007

1. Forty‐six healthy normotensive male drinkers participated in a randomized, controlled, crossover trial to study the effects of varying alcohol intake on blood pressure.

2. Alcohol consumption (calculated from weekly diaries) was reduced from 336.3 (s.e.m. = 20.2) to 64.5 (s.e.m. = 5.6) ml ethanol/week by drinking low alcohol content beer alone.

3. Systolic blood pressure fell significantly during reduction of alcohol intake and rose again when normal drinking habits were resumed, the mean difference during the last 2 weeks of normal or low alcohol intake being 3.8 mmHg.

4. This effect of alcohol on blood pressure was independent of a small but significant decrease in weight following reduction of alcohol intake.

5. The change in blood pressure correlated with change in alcohol consumption (r= 0.53, P<0.001) with a 1 mmHg fall predicted for each 100 ml of reduction in ethanol intake/week.

6. We conclude that regular moderate alcohol consumption has a direct (but reversible) pressor effect in normotensive men.
A RANDOMIZED CONTROLLED TRIAL OF WEIGHT REDUCTION AND METOPROLOL IN THE TREATMENT OF HYPERTENSION IN YOUNG OVERWEIGHT PATIENTS
Authors: MacMahon S. W. , Macdonald G. J. , Bernstein L. , Andrews G. , Blacket R. B.
Published: June 2007

1. The effects of weight reduction and metoprolol (100 mg, b.d.) in the treatment of hypertension (diastolic blood pressure 90–109 mmHg) in 56 young, overweight patients were investigated in a randomized placebo controlled trial. After a 4‐week baseline, subjects were followed up for 21 weeks.

2. In the weight reduction group, the fall in systolic and diastolic blood pressure (13/10 mmHg), associated with a mean group weight loss of 7.4 kg, was greater (P<0.001) than that in the placebo group (7/3 mmHg); the fall in diastolic pressure but not systolic pressure was also greater than that in the metoprolol group (10/6 mmHg). At the end of follow‐up, 50% of the weight reduction group, 39% of the metoprolol group and 17% of the placebo group had a diastolic blood pressure of less than 90 mmHg.

3. In the weight reduction group there was a fall in total cholesterol and the ratio of total to HDL‐cholesterol (P<0.001); in the metoprolol group there was a fall in HDL‐cholesterol and an increase in the ratio of total to HDL‐cholesterol (P<0.001).

4. It was concluded that a vegetarian diet may have an adjunctive role in control of mild hypertension, but that in view of likely problems with acceptability those dietary components responsible for the blood pressure differences need to be identified.