bluuebunny/crossref_metadata_2025 huggingface dataset:
RESPONSES OF HUMAN ARTERIAL MUSCLE TO STABLE VASOACTIVE SUBSTANCES RELEASED FROM HUMAN PLATELETS BY COLLAGEN AND HEAT AGGREGATED IgG
Authors: Medcalf R. L. , Iwanov V. , Moulds R. F. W.
Published: June 2007

1. The supernatant solutions obtained after aggregation or sonication of washed human platelets were superfused over preparations of human isolated digital arteries using a small volume bioassay method. The agents released from the platelets caused strong contractions of the artery strips.

2. Platelet aggregation induced by 10 μg/ml collagen or by 100 μg/ml heat aggregated IgG, released 31.5% and 38.5% respectively, of the contractile activity produced by sonication of the platelets.

3. The quantitative contractile effect of supernatants from platelets aggregated by 50 μg/ml IgG was significantly less than that for 100 μg/ml HA IgG. Similarly, the maximum contractile effect of supernatants from platelets aggregated by 300 ng/ml collagen was significantly less than that for 1 μg/ml collagen. This suggests that the concentration of contractile agents released from platelets depends on the concentration of aggregating stimulus.

4. Comparison with concentration‐effect curves for exogenous serotonin suggests that if the contractility of the platelet supernatant occurring after sonication of platelets is solely due to serotonin, then it is present in a concentration of approximately 3.3 times 10‐6 mol/1 (6.6 nmol per 109 platelets).

5. It is suggested from this study that in certain clinical situations characterized by hypertension, and in which circulating immune complexes have been found, in vivo platelet activation by immune complexes may be releasing sufficient concentrations of serotonin to constrict peripheral blood vessels and contribute to the hypertension.
ADRENERGIC FACTORS INVOLVED IN THE CONTROL OF CRYPT CELL PROLIFERATION IN JEJUNUM AND DESCENDING COLON OF MOUSE
Authors: Kennedy M. F. G. , Tutton P. J. M. , Barkla D. H.
Published: June 2007

1. The mitotic rates in the crypts of Lieberkühn of the proximal jejunum and descending colon of mouse, following different treatments, were measured using a stathmokinetic technique. Regression coefficients, representing mitotic rates, were then calculated by the method of least squares.

2. Treatment with adrenaline, isoprenaline, phenylephrine, phentolamine, and yohimbine all resulted in decreased mitotic rate of jejunal and colonic crypt cells. Chemical sympathectomy and cryosympathectomy had a similar effect, and chemical sympathectomy was followed by a supersensitivity to clonidine.

3. Intraperitoneal injection of metaraminol, clonidine, propranolol, prazosin, labetolol and simultaneous injection of propranolol and adrenaline all resulted in an increased rate of crypt cell proliferation in both jejunum and colon.

4. A significant increase in mitotic rate was observed in both tissues at night. The amplitude of this diurnal variation was decreased in both jejunum and colon following chemical sympathectomy. In addition, the amplitude of this variation in jejunum was decreased after treatment with yohimbine or phentolamine.

5. The results of the study suggest that the sympathetic nervous system stimulates epithelial cell proliferation in both the small and large intestine and that this effect is mediated by an α2‐adrenoceptor. By contrast, stimulation of α1‐ and β‐adrenoceptors is inhibitory to cell proliferation in these tissues.
EVALUATION OF THE CO2 REBREATHING METHOD FOR THE NONINVASIVE MEASUREMENT OF RESTING CARDIAC OUTPUT IN MAN
Authors: Hargreaves M. , Jennings G.
Published: June 2007

1. We have compared the indirect Fick, a non‐invasive CO2 rebreathing method for measuring resting cardiac output, with the thermodilution method in eleven subjects including some with cardiac and pulmonary disease. Three alternative methods for calculating veno‐arterial CO2 content difference were used: (i) from end‐tidal and rebreathing bag equilibrium Pco2 modified from the equations developed for use during exercise by Jones et al. (1975); (ii) by using the uncorrected difference between end‐tidal and equilibrium Pco2 and the standard CO2 dissociation curve; (iii) by direct measurement of arterial Pco2.

2. Each method was satisfactory in that reproducibility was similar to thermodilution (5‐10%) and the equations relating thermodilution to indirect Fick cardiac output were linear with slope and intercept, close to 1 and 0, respectively. End‐tidal Pco2 accurately predicted arterial Pco2 except in five patients with liver disease. Direct measurement of arterial Pco2 is recommended in such patients. In other subjects there was no advantage in either correcting non‐invasive measurements of alveolar gas to obtain veno‐arterial CO2 content difference, or in direct measurement.

3. The indirect Fick is an accurate method for measuring cardiac output at rest in normal subjects and those with cardiovascular disease. Its use can be extended to other groups by a single arterial blood sample.
CARDIOVASCULAR RESPONSES ELICITED BY MICROINJECTION OF CHOLINERGIC AGENTS INTO NUCLEUS DORSALIS RAPHE IN CATS
Authors: Saxena A. K. , Pant K. K. , Saksena A. K. , Tangri K. K. , Vrat S. , Bhargava K. P.
Published: June 2007

1. The effect of cholinomimetics and cholinoceptor blocking agents microinjected into nucleus dorsalis raphe (NDR) has been studied on heart rate and blood pressure to identify the nature and role of these cholinoceptors in cardiovascular regulation.

2. Microinjection of the cholinoceptor agonists, pilocarpine and carbachol into NDR elicited bradycardia and hypotension accompanied by salivation which could be blocked by local pretreatment with ethybenztropine (a muscarinic réceptor blocker), but not by chlorisondamine (a nicotinic receptor blocker).

3. Pretreatment with atropine methylnitrate (i.v.), which blocks only peripheral muscarinic receptors, did not prevent these cardiovascular responses evoked by carbachol microinjection.

4. These cholinergic receptors seem to be localized in NDR since, microinjection of carbachol into neural structures adjoining NDR, failed to induce any cardiovascular responses.

5. Muscarinic cholinoceptors are present in NDR which modulate cardiovascular activity by influencing sympathetic preganglionic neurons in the intermediolateral columns of the spinal cord.
HAEMODYNAMIC EFFECTS OF A SINGLE LOW DOSE OF PRAZOSIN IN PATIENTS WITH CHRONIC CONGESTIVE CARDIAC FAILURE CORRELATIONS WITH PHARMACOKINETICS
Authors: Horowitz J. D. , Dynon M. K. , Jarrott B. , Brennan J. B. , Oliver L. E. , Goble A. J. , Louis W. J.
Published: June 2007

1. The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m.=4.5 to 19.4, s.e.m.=5.1 mmHg; P<0.001), mean arterial blood pressure (from 94.5, s.e.m.=6.0 to 85.4, s.e.m.=5.0 mmHg; P<0.01), and systemic vascular resistance (from 1690, s.e.m.=360 to 1420, s.e.m.=200 dyn. s/cm5; P<0.05) and a rise in cardiac index from 1.98 (s.e.m.=0.07) to 2.28 (s.e.m.=0.16) litres/min per m2 (P<0.05). There was a non‐significant fall in heart rate.

2. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m.=1.4) ng/ml, occurring 2.1 (s.e.m.=0.4) h after drug ingestion. The mean elimination half‐life was 5.1 (s.e.m.=0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half‐life and area under the concentration‐time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters.

3. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral doses of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.
ELIMINATION OF HYALURONIC ACID FROM THE BLOOD STREAM IN THE HUMAN
Authors: Fraser J. R. E. , Laurent T. C. , Engström‐Laurent A. , Laurent U. G. B.
Published: June 2007

1. The removal of hyaluronic acid (HA) from the blood‐stream was studied in four normal human subjects after injection of high molecular weight preparations labelled with 3H in the acetyl position. The plasma half‐life of the injected material ranged between 2.5 and 5.5 min.

2. The daily turnover of HA in the circulation was estimated to be at least 150 mg. Its elimination was predominantly extrarenal, the upper molecular weight limit for renal excretion being 25 000.

3. Evidence for rapid degradation was provided by the identification of 3H2O in urine. Calculations from the specific activity of urinary 3H2O indicated that approximately 55% of the acetyl content of the injected HA was completely oxidized within 3 h, and 85% within the first day.

4. It is concluded that hyaluronic acid in the amounts currently used for therapeutic purposes should not accumulate significantly in the circulation.
PRESENCE AND STABILITY OF GASTRIN IN THE GASTRIC JUICE OF THE FETAL SHEEP
Authors: Shulkes Arthur , Chick Patricia , Hardy Kenneth J.
Published: June 2007

1. Although gastrin is found in adult gastric juice, rapid enzymatic destruction by pepsin in the acid environment makes a physiological role in the adult unlikely.

2. Gastric pH in the fetal sheep is neutral so that gastric juice gastrin could be present, and if present, have a physiological function.

3. The aim of this study was to determine the presence, molecular forms and metabolism of gastrin in gastric juice.

4. Gastrin was present in fetal gastric juice at significantly higher concentrations than in fetal plasma.

5. The majority of gastric juice gastrin was present as the biologically active gastrin‐17.

6. Gastrin was stable in normal fetal gastric juice, but was rapidly metabolized to smaller C‐terminal fragments when the gastric juice was acidified.

7. With the known growth promoting effect of gastrin on gastrointestinal mucosa, gastrin in fetal juice could have a unique role in the in utero development of the gastrointestinal tract.
PROSTAGLANDINS AND THE RENAL RESPONSES TO HAEMORRHAGE, ANGIOTENSIN II AND METHOXAMINE IN CONSCIOUS RABBITS
Authors: Bartley P. J. , Anderson W. P.
Published: June 2007

1. The responses to 20% haemorrhage were examined in conscious rabbits with or without inhibition of prostaglandin production by indomethacin (5 mg/kg +0.5 mg/kg per h i.v.). In rabbits not pretreated with indomethacin, haemorrhage lowered mean arterial pressure by 6.3 (s.e.m. = 1.6) mmHg, renal blood flow by 22.8 (s.e.m. = 3.4) ml/min and glomerular filtration rate (GFR) by 3.4 (s.e.m. = 0.6) ml/min, and raised plasma renin activity by 5.2 (s.e.m. = 1.0) ng/ml per h. Pretreatment of the rabbits with indomethacin did not significantly alter the responses to haemorrhage. Mean arterial pressure fell by 10.9 (s.e.m. = 1.8) mmHg, renal blood flow by 24.9 (s.e.m. = 3.9) ml/min and GFR by 4.2 (s.e.m. = 1.8) ml/min and plasma renin activity rose by 3.2 (s.e.m. = 0.5) ng/ml per h.

2. In a separate group of 5 rabbits, angiotensin II was infused at 10, 25 and 50 ng/kg per min i.v. or methoxamine was infused at 10 and 25 μg/kg per min i.v. After indomethacin pretreatment, angiotensin II caused a significantly greater rise in mean arterial pressure and greater fall in renal vascular conductance, but there was no effect on the GFR response. In contrast, methoxamine caused significantly smaller falls in GFR, renal blood flow and renal vascular conductance after indomethacin pretreatment.

3. Indomethacin significantly lowered resting GFR but not renal blood flow or arterial pressure.

4. Thus, indomethacin pretreatment accentuated the renal vasoconstriction to angiotensin II, reduced the renal vasoconstriction to methoxamine and had no effect on the responses to haemorrhage.

5. The results therefore suggest that prostaglandins do not act to lessen the renal effects of all vasoconstrictor stimuli, but that the prostaglandin response depends on the nature of the ischaemic stimulus.
EFFECT OF POSTASSIUM, ANGIOTENSIN II AND ACTH ON BLOOD ALDOSTERONE AND CORTISOL IN SHEEP ON DIFFERENT DIETARY POTASSIUM AND SODIUM INTAKES
Authors: Humphery T. J. , Coghlan J. P. , Denton D. A. , Fan J. S. K. , Scoggins B. A. , Stewart K. W. , Whitworth Judith A.
Published: June 2007

1. The short term aldosterone response to manipulations of potassium (K), angiotensin II (AII) and ACTH were examined in sheep on a variety of chronic electrolyte regimes.

2. Reduction in Na intake increased blood aldosterone to a greater extent on 100 mmol/day K than a K‐free diet.

3. Aldosterone increased in response to AII under conditions of chronic dietary Na restriction, in contrast to acute Na depletion.

4. The effects of K, AII, and ACTH on aldosterone concentrations in sheep on varying intakes of Na and K are similar to that reported for other species.
TRANSIENT PRESSURE‐FLOW RESPONSES IN THE RESTING CANINE HINDLIMB ‐ ANALYSIS AS RESPONSES TO RAPID STRETCHING OF THE RESISTANCE MICROVESSELS
Authors: Goodman A. H. , Einstein Rosemarie
Published: June 2007

1. The transient hyperaemia caused by sudden elevation of arterial pressure and reactive hyperaemia after interruption of arterial pressure for 3, 5, 10, 20 and 40 s were studied in the perfused resting hindlimb of anaesthetized areflexic dogs. Experiments were performed using steady‐state pressures ranging from 50–150 mmHg.

2. The component of the hyperaemia response (ΔQ) that was attributable to resistance vessel distension by a sudden rise in pressure (ΔP), was measured as the difference between peak hyperaemic flow change and the flow change predicted for that ΔP in a system having constant resistance.

3. Over the range of steady‐state pressures used, vascular conductance was approximately constant, indicating that steady‐state flow autoregulation was weak.

4. ΔQ was a linear function of ΔP for both the hyperaemia of sudden pressure elevation and reactive hyperaemia, and the ΔQ/ΔP relationships were independent of steady‐state perfusion pressure.

5. The ΔQ/ΔP relationships for sudden pressure elevation and reactive hyperaemia after 40 s occlusion did not differ significantly. For a given ΔP, however, ΔQ decreased with decreasing occlusion time.

6. The magnitude of reactive hyperaemia after brief occlusion depended not only on the degree of resistance vessel relaxation achieved during occlusion but also on the pressure step resulting from restoration of pressure.

7. Using data from these experiments in a simple mathematical model of an idealized resistance vessel, a series of distensibility curves were constructed that showed that as active wall tension increased with increasing steady‐state pressure, resistance vessel distensibility decreased.
STRESS, DOPAMINERGIC BLOCKADE AND MEDIAN EMINENCE‐NEUROINTERMEDIATE LOBE CATECHOLAMINE DEPLETION: EFFECTS ON HYPOTHALAMIC, PITUITARY AND PLASMA IMMUNOREACTIVE β‐ENDORPHIN
Authors: Lim Alan T. , Smith Graeme C. , Clements Judith A. , Funder John W.
Published: June 2007

1. We have compared immunoreactive β‐endorphin (ir‐βEP) levels in plasma, hypothalamus, anterior pituitary and neurointermediate lobe of adult female Sprague‐Dawley rats, in studies in which levels of catecholamines were manipulated.

2. Whole‐brain catecholamines were manipulated by intraperitoneal haloperidol and/or bromocriptine; median eminence and neurointermediate lobe catecholamines were manipulated specifically and differentially by intravenous 6‐hydroxydopamine (6‐OHDA), with and without pretreatment with intraperitoneal desipramine; changes in amine neurons were assessed by fluorescence histochemistry.

3. Haloperidol and 6‐OHDA administration produced a selective reduction of neurointermediate lobe ir‐βEP, to levels equivalent to those seen with prolonged stress; the haloperidol effect was blocked by bromocriptine and the 6‐OHDA effect by desipramine.

4. Specific depletion of catecholamine nerve terminals in the median eminence and the neurointermediate lobe was associated with elevated plasma ir‐βEP, with no changes in pituitary or hypothalamic levels.

5. These studies confirm and extend previous reports documenting that ir‐βEP levels in different tissues are modulated by different neural stimuli.
EFFECT OF CAPTOPRIL ON BRAIN CONVERTING ENZYME IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Nicolantonio R. Di , Mendelsohn F. A. O. , Hutchinson J. S. , Doyle A. E.
Published: June 2007

1. The effect of oral captopril (30 mg/kg per day) on the blood pressure, plasma aldosterone concentration, urinary electrolytes and brain angiotensin‐converting enzyme activity of spontaneously hypertensive rats of the Okamoto strain was examined.

2. Over a seven day period, captopril caused a progressive fall in blood pressure with increased sodium excretion and urine volume and a significant fall in plasma aldosterone concentration.

3. Following captopril, angiotensin converting enzyme activity increased significantly in the midbrain and medulla oblongata; the pituitary level of angiotensin converting enzyme activity was significantly decreased.

4. The hypotensive action of captopril in the spontaneously hypertensive rat is associated with changes in body sodium, water and plasma aldosterone concentration. The alterations in brain angiotensin‐converting enzyme activity following captopril treatment suggest that, with chronic administration, captopril can alter the activity of the brain renin‐angiotensin system.
REVERSAL OF ADRENALINE‐INDUCED CONTRACTION IN THE RABBIT PULMONARY ARTERY BY CLONIDINE
Authors: Katsuragi T. , Mori R. , Su C. , Furukawa T.
Published: June 2007

1. Characterization of clonidine which reversed the adrenaline‐induced contractions was assessed using the rabbit pulmonary arterial segment.

2. Clonidine in high concentrations (10−5‐10−4 mol/l) contracted this vascular tissue. Nevertheless, an adrenaline (3 × 10−6mol/l)‐induced contraction, which can be markedly depressed by phentolamine, was reversed to relaxation by pre‐addition of 3 × 10−5mol/l clonidine. This reversal was abolished by mol/l propranolol, a β‐adrenoceptor antagonist.

3. The cumulative concentration‐contraction curve for adrenaline was shifted to the right by 10−5 mol/l clonidine without further alteration at 10−4 mol/l, suggesting a partial agonistic feature of clonidine for α‐adrenoceptors.

4. Contractions evoked by 5 × 10−5 mol/l clonidine alone were effectively reduced by prazosin (IC50= 1.7 × 10−7 mol/l) or yohimbine, (IC50= 3.3 × 10−5 mol/l) and those by phenylephrine (10−5 mol/l) were suppressed as well (prazosin, IC50= 3.4 × 10−8 mol/l; yohimbine, IC50= 5.0 × 10−6 mol/l). However, the depolarization‐induced contractions with 30 mmol/l KCl were virtually unaltered by both antagonists.

5. These results suggest that the reversal action of clonidine on the adrenaline‐induced contraction is primarily mediated by a partial agonistic property for postsynaptic α1‐adrenoceptors.
DIGITALIS ‘RECEPTORS’ DURING CHRONIC DIGOXIN TREATMENT
Authors: Malini Pier Luigi , Strocchi Enrico , Marata Anna Maria , Ambrosioni Ettore
Published: June 2007

1. The effect of digoxin treatment on Mg‐dependent [Na+‐K+]‐ATPase (the receptor for cardiac glycosides) was assessed by comparison of intracellular Na+‐K+, 86Rb uptake and number of digoxin binding sites in the erythrocytes of 138 patients on long term digoxin and of 133 control subjects. The parameters were also assessed in thirty‐two patients followed longitudinally for 1 y.

2. The results indicate that the cells adapt to chronic exposure to ‘therapeutic’ dosage of digoxin with an overcompensatory synthesis of new receptors, a possible mechanism through which the normal intraerythrocytic ionic equilibrium is re‐established.

3. The process of synthesis of new receptors appears to be completed in erythrocytes in a period of 4 months after the start of digoxin treatment.
INCREASED NALOXONE POTENCY INDUCED BY PRETREATMENT WITH MORPHINE AND NALBUPHINE IN MICE
Authors: Wong Chak‐Lam , Wai Man‐Keung
Published: June 2007

1. Both morphine and nalbuphine were effective in suppressing the abdominal constriction response induced by intraperitoneal injection of acetic acid in mice. On a weight to weight basis, nalbuphine was more potent than morphine in this test. However, the effect of nalbuphine was more effectively blocked by naloxone.

2. Pretreatment with morphine 2.0 mg/kg subcutaneously did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later. However, naloxone was about 1.4‐fold more effective in antagonizing the antinociceptive effect of both drugs in morphine‐pretreated mice than in saline‐pretreated animals.

3. Pretreatment with nalbuphine (1.0–2.0 mg/kg s.c.) did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later, while naloxone was more effective in antagonizing the antinociceptive actions of morphine and nalbuphine.

4. The increases in naloxone potency in antagonizing morphine after nalbuphine pretreatment were not dose‐dependent on the amount of nalbuphine in the pretreatment and they were only marginally significant. In addition, these increases were much lower than that induced by morphine pretreatment.

5. On the other hand, the naloxone effectiveness against nalbuphine itself was enhanced to a greater extent than that induced by morphine pretreatment. Furthermore, these increases in naloxone potency showed a dose‐dependent relationship to the amount of nalbuphine used in the pretreatment.

6. Based on these results, it was concluded that nalbuphine is an analgesic drug with properties in between those of the full agonist morphine and the partial agonist pentazocine.
PROTEIN‐ENERGY MALNUTRITION ALTERS THEOPHYLLINE EFFECT ON DNA SYNTHESIS IN NEONATAL RAT BRAIN IN VITRO
Authors: Quinby Griffith E. , Nakamoto T.
Published: June 2007

1. The rate of incorporation of [3H]‐thymidine into DNA in whole brain in response to various concentrations of theophylline was studied in normal and malnourished neonatal rats in vitro. Malnutrition appeared to produce an increased sensitivity to theophylline.

2. [3H]‐Thymidine uptake was significantly increased in normally nourished animals at a concentration of 2 × 10−4 mol/l (36 μg/ml), while malnourished animals showed a similar effect at 1 × 10−4 mol/l (18 μg/ml).

3. These data suggest that the nutritional status of a growing organ could be important in determining the cellular effects of conventionally dosed theophylline under clinical conditions.
EFFECT OF ANTIHYPERTENSIVE DRUGS ON NEONATAL BLOOD PRESSURE
Authors: Henderson‐Smart D. J. , Horvath J. S. , Phippard A. , Korda A. , Child A. , Duggin G. G. , Hall B. M. , Storey B. , Tiller D. J.
Published: June 2007

1. This study evaluates the perinatal outcome of infants born to ninety‐five mothers with hypertension in pregnancy whose blood pressure was treated in a double blind trial comparing clonidine hydrochloride (C) and α‐methyldopa (A).

2. There were no fetal deaths and two neonatal deaths, giving a perinatal mortality of 2%. There was no significant difference between Groups C and A with regard to the gestation or weight at birth, incidence of intrauterine growth retardation, or condition at birth as judged by Apgar scores and acid‐base status. No infant in either group developed significant hypotension or rebound hypertension. The blood pressure was not significantly different between Groups C and A, and controls. In each of these three groups there was a similar significant rise in systolic blood pressure with age.
THRESHOLD FOR THE EFFECTS OF ACTH ON BLOOD PRESSURE IN SHEEP
Authors: Scoggins B. A. , Allen K. J. , Coghlan J. P. , Denton D. A. , Tresham J. J. , Wang X‐M. , Whitworth J. A.
Published: June 2007

1. The time of onset and dose threshold for ACTH induced hypertension was examined in conscious sheep.

2. ACTH 1 μg/kg per day significantly raised blood pressure. The maximum rise occurred at 2 μg/kg per day.

3. The rise in pressure was significant after 8 h of ACTH infusion.
INTRACEREBROVENTRICULAR INFUSIONS OF CORTICOTROPHIN RELEASING FACTOR (CRF) AND ACTH RAISE BLOOD PRESSURE IN SHEEP
Authors: Scoggins Bruce A. , Coghlan John P. , Denton Derek A. , Fei David W. , Nelson Mark A. , Tregear Geoffrey W. , Tresham Janette , Wang Xiao‐Ming
Published: June 2007

1. Infusion of synthetic ovine CRF (10 or 100 μg/h) into the lateral cerebral ventricle for 24 h increased mean arterial blood pressure of conscious sheep.

2. CRF infusion also increased urine output and sodium excretion.

3. Intravenous infusion of CRF (100 μg/h) or intraventricular infusion of artificial CSF had no effect on blood pressure.

4. Intraventricular infusion of ACTH (1–24) at 0.5 μg/kg per day, a rate of infusion which has no systemic effect on blood pressure, also raised mean arterial pressure.

5. These studies suggest that two peptides involved in the physiological response to ‘stress’ may influence blood pressure by mechanisms which do not involve stimulation of adrenocortical steroid production.
PHARMACOLOGICAL ACTIVITIES OF THE ANTIHYPERTENSIVE DRUG URAPIDIL IN THE RAT
Authors: Verberne A. J. M. , Rand M. J.
Published: June 2007

1. Urapidil had blocking activity on α1‐adrenoceptors in the rat isolated caudal artery (pA2≏ 7) and in the anaesthetized rat.

2. Urapidil had no clonidine like agonistic activity on α2‐adrenoceptors in preparations of the guinea‐pig ileum (prejunctional) or dog saphenous vein (postjunctional).

3. Urapidil (0.01–0.1 mg/kg i.v.) had a hypotensive effect in the anaesthetized rat. In a dose of 0.1 mg/kg, the depressor response was accompanied by bradycardia. Vagotomy abolished the bradycardia and attenuated the depressor response.

4. The results indicate that the antihypertensive effect of urapidil may be due partly to blockade of postjunctional α1‐adrenoceptors, but in addition there is a central component of action.
FACILITATION OF NORADRENERGIC TRANSMISSION BY LOCALLY GENERATED ANGIOTENSIN II IN GUINEA‐PIG ISOLATED ATRIA AND IN THE PERFUSED CAUDAL ARTERY OF THE RAT
Authors: Ziogas J. , Story D. F. , Rand M. J.
Published: June 2007

1. In guinea‐pig isolated atria, angiotensin I and angiotensin II produced concentration dependent increases in the rate of spontaneous beating and in the release of noradrenaline produced by field stimulation of sympathetic nerves.

2. In rat isolated caudal artery preparations, both angiotensin I and angiotensin II had direct vasoconstrictor actions and also produced concentration dependent increases in constrictor responses to periarterial sympathetic stimulation.

3. All the above effects of angiotensin I and angiotensin II were blocked by the receptor antagonist saralasin, but only those of angiotensin I were blocked by the converting enzyme inhibitor enalaprilat (MK‐422).

4. The findings confirm that angiotensin II generated locally from precursor angiotensin I within cardiac and vascular tissues may modulate noradrenergic transmitter release.
THE RENIN‐ANGIOTENSIN SYSTEM AND HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY IN THE RAT
Authors: Newling R. , Fletcher P. J. , Duggin G. G.
Published: June 2007

1. The relationship between left ventricle‐to‐body weight ratio (LV/BW), mean arterial pressure (MAP, the average of 12 h of intra‐arterial monitoring in conscious animals) and plasma renin activity (PRA) was assessed at 12 weeks after unilateral clipping or sham operation in twenty‐four one‐kidney rats and twenty‐six two‐kidney rats.

2. The degree of hypertension and left ventricular hypertrophy were similar in one‐kidney and two‐kidney groups. There was a close linear relationship between LV/BW and MAP which was similar in one‐kidney and two‐kidney rats.

3. PRA was significantly elevated only in two‐kidney rats and was not related to the degree of hypertrophy after accounting for the effect of PRA on MAP.

4. These data suggest that activation of the renin‐angiotensin system does not contribute directly to myocardial hypertrophy in rats with renal‐clip hypertension.
SEROTONIN (5HT) AND ITS ANTAGONISTS: INVOLVEMENT IN THE CARDIOV ASCULAR SYSTEM
Authors: Marwood John F. , Stokes Gordon S.
Published: June 2007

The cardiovascular actions of serotonin and its antagonists are reviewed with a view to clarifying whether serotonin has a role in blood pressure control through actions on the peripheral vasculature. Serotonin has complex actions in the heart and vasculature but none of these actions is completely understood. There is no doubt, however, that serotonin has extensive interactions with the sympathetic nervous system. The nature of the serotonin receptor is also discussed. There is extensive evidence that more than one type of serotonin receptor exists. Biochemical studies in brain homogenates have delineated two sub‐populations of serotonin receptors, named 5HT1 and 5HT2. It is not clear whether the same receptor types exist in the vasculature but various actions of serotonin on the vasculature have tentatively been ascribed to actions on 5HT1‐ and 5HT2‐type receptors. It is clear that there is some functional overlap between serotonin‐receptors and α‐adrenoceptors. The mechanism by which this overlap could occur is unknown although we suggest it may result from a physical overlap of serotonin receptors and α‐adrenoceptors. Compounds which antagonize serotonin have provided the means for investigating serotonin receptors but have not clarified the role of serotonin in blood pressure control; certainly they have comparatively little effect on blood pressure and this may simply reflect the lack of free circulating serotonin. In animal studies the new serotonin antagonist ketanserin appears to lower blood pressure via α‐adrenoceptor blockade.
PERITONEAL DIALYSIS SOLUTIONS AND FELINE SPLANCHNIC BLOOD FLOW
Authors: Granger D. Neil , Ulrich Michele , Perry Michael A. , Kvietys Peter R.
Published: June 2007

1. Splanchnic blood flow is generally considered to be one of the major factors governing the efficiency of peritoneal dialysis; however, few direct measurements of blood flow have been made during peritoneal dialysis.

2. The radioactive microsphere technique was used to assess the effects of 1.5 and 4.25 g/100 ml dextrose‐Dianeal solutions on blood flow to various tissues in the abdominal cavity. The effects of dialysis solution on blood flow through the superior mesenteric and coeliac arteries were measured by electromagnetic flowmetry.

3. The results indicate that the commercial peritoneal dialysis solutions dramatically increase blood flow to the mesentery, omentum, intestinal serosa and parietal peritoneum. These changes are not accompanied by significant alterations in blood perfusion in the major abdominal organs (liver, stomach, intestine, pancreas, spleen). Peritoneal dialysis solutions do not significantly alter blood flow through the coeliac and superior mesenteric arteries.

4. These findings indicate that commercial dialysis solutions improve perfusion to the peritoneum without significantly altering splanchnic blood flow.
THE EFFECT OF VASOPRESSIN ON HEPATIC ARTERY FLOW IN THE RAT
Authors: Jenkins S. A. , Mooney B. , Devitt P. , Taylor I. , Shields R.
Published: June 2007

1. The effects of vasopressin infusion on hepatic artery flow was studied in rats.

2. Hepatic artery ligation followed by the infusion of vasopressin (0.08 μU/g body weight per min) decreases portal venous flow and liver blood flow.

3. Vasopressin infusion results in an increase in hepatic artery flow and liver blood flow both of which are abolished by subsequent hepatic artery ligation.

4. The increase in hepatic artery flow and the decrease in portal venous flow following the infusion of vasopressin is discussed in relation to the management of patients presenting with bleeding oesophageal varices.
EFFECTS OF METRONIDAZOLE ON INTESTINAL TRANSIT TIME AND FAECAL WEIGHTS OF HUMAN SUBJECTS
Authors: Kurpad A. V. , Shetty P. S.
Published: June 2007

1. The combined administration of metronidazole and ampicillin increased faecal weights by 198% in normal male subjects on controlled diets with constant energy, protein and dietary fibre content.

2. Intestinal transit times were unaltered despite marked increase in faecal weights.
POTENTIATION OF DEPRESSOR RESPONSES TO ARACHIDONIC ACID BY ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN THE RAT
Authors: Hui S‐C. G. , Dai S. , Ogle C. W.
Published: June 2007

1. In chloralose anaesthetized rats, intravenous administration of captopril, SQ 20881, SA 446 or MK 421 (0.5 mg/kg) potentiated the depressor responses to arachidonic acid 3 mg/kg given intravenously.

2. Same doses of the above angiotensin converting enzyme inhibitors caused an approximately 100‐fold decrease in sensitivity to the pressor effects of angiotensin I, with a concomitant similar increase in sensitivity to the depressor effects of bradykinin.

3. Depressor responses to arachidonic acid, both before and after administering the converting enzyme inhibitors, were abolished by intravenous indomethacin (5 mg/kg).

4. These results suggest that increased synthesis of prostaglandins in the circulation may contribute to the hypotensive effect of the angiotensin converting enzyme inhibitors, a group of newly developed antihypertensive agents.
FAILURE OF NEOMYCIN TO MODIFY ACTH INDUCED HYPERTENSION IN SHEEP
Authors: Tresham Janette , Coghlan John P. , Denton Derek A. , Scoggins Bruce A. , Whitworth Judith A.
Published: June 2007

1. Studies in rats have shown that neomycin administration attenuates certain types of adrenocortical steroid dependent hypertension, including ACTH hypertension.

2. The effects of oral neomycin on ACTH induced hypertension were examined in conscious sheep.

3. Neomycin has no effect on the blood pressure or metabolic responses to ACTH in sheep.
SEROTONIN IN TOXAEMIA OF PREGNANCY
Authors: Gujrati V. R. , Shanker K. , Parmar S. S. , Chandrawati S. Vrat , Bhargava K. P.
Published: June 2007

1. Serotonin (5‐hydroxytryptamine) contents of maternal blood, fetal cord blood, and placenta from thirty‐five patients with toxaemia of pregnancy and forty normal pregnant subjects were estimated. Placental monoamine oxidase activity from ten normal and ten toxaemic cases were also estimated.

2. An increased content and uptake of serotonin by platelets in maternal blood from toxaemic patients were observed and there was a concomitant reduction in platelet count.

3. Raised levels of serotonin and a decrease in monoamine oxidase levels were observed in placentas of the toxaemic group.

4. The levels of serotonin in fetal cord blood were significantly higher than those in normal maternal blood. It is suggested that the fetus could be the source of increased serotonin in this syndrome, due to the decrease in monoamine oxidase activity in the toxaemic placenta.

5. An abnormality in indole amine metabolism may contribute to the pathology associated with toxaemia of pregnancy.
INFLUENCE OF PROSTAGLANDIN INHIBITION ON DIHYDRALAZINE INDUCED ACUTE EFFECTS IN PATIENTS WITH ESSENTIAL HYPERTENSION*
Authors: Heimann Ingrid W. , Ratge Dieter , Wisser Hermann , Frölich Jürgen C.
Published: June 2007

1. In order to determine whether vasodilator prostaglandins (PG) contribute to the acute vascular and endocrine responses to intravenously administered dihydralazine, we examined its effects on systolic and diastolic blood pressure (BP), heart rate (HR), plasma renin activity (PRA) and the plasma catecholamines (CA) noradrenaline (NA), adrenaline (A) and dopamine (DA) as well as on sodium, potassium and creatinine clearance (CNa, CKand CCrrespectively), urinary flow rate, urinary catecholamines (NA, A, DA) and iPGE2and i6‐keto‐PGF1αexcretion rate in six patients (three females, three males) with essential hypertension before and after PG synthesis inhibition by the nonsteroidal, anti‐inflammatory agent diclofenac.

2. Diclofenac, which reduced urinary iPGE2and i6‐keto‐PGF1α, excretion by 62% (P= 0.026) and 45% (P= 0.037), respectively, antagonized dihydralazine induced diastolic BP reduction (P= 0.0009), HR increase (P= 0.01), noradrenaline and adrenaline increase in plasma (P= 0.02 andP= 0.05, respectively), increase in urine flow rate (P= 0.03), sodium clearance (P= 0.01) and tended to reduce PRA.

3. We conclude that dihydralazine‐mediated changes can be reduced by cyclooxygenase inhibition, most likely on the basis of a reduction of its effect on peripheral resistance, thereby leading to less reflex activation of the sympathetic nervous and renin‐angiotensin systems.
EFFECTS OF DOPAMINE ON RENAL FUNCTION IN THE RAT ISOLATED PERFUSED KIDNEY
Authors: McGrath Barry , Bode Karin , Luxford Ann , Howden Brian , Jablonski Paula
Published: June 2007

1. The renal effects of dopamine, the dopamine antagonist spiperone and the combination of dopamine and spiperone were examined in the isolated perfused rat kidney preparation. Studies were carried out at constant perfusion pressure and the following were measured at 10 min intervals for 1 h: perfusate flow; GFR (3H‐inulin); urine flow rate; sodium, potassium and kallikrein excretion; perfusate renin concentration; perfusate and urinary‐dopamine levels.

2. Low‐dose dopamine infusion (6 × 10‐10 mol/min) resulted in significant diuresis, natriuresis and kaluresis but little change in GFR. These effects were blocked by spiperone (10‐10 mol/min) which had no significant effects when infused alone.

3. At a higher dose (10‐8 mol/min) dopamine significantly increased urine flow alone; this too was reversed by spiperone.

4. Dopamine had no significant effects on perfusate flow, renin release or kallikrein excretion.

5. Perfused control kidneys excreted amounts of dopamine (328 pmol/h, s.e.m. = 57, n= 6) far in excess of kidney dopamine content (49 pmol/g, s.e.m. = 6, n= 32). Renal handling of infused dopamine was dose‐related; the fraction of the administered dose taken up and/or metabolized by the kidney on the higher dose infusion was considerably less than on the lower dose (40%, s.e.m. = 3 vs. 82%, s.e.m. = 6) while more was excreted (13%, s.e.m. = 3 vs. 2%, s.e.m. = 1).

6. These studies indicate that dopamine at low doses can produce diuresis, natriuresis and kaluresis independently of extrarenal or haemodynamic influences and not mediated by renal renin or kallikrein systems. The kidney also exhibits a saturable capacity for dopamine uptake and/or metabolism.
ANTICHOLINESTERASE ACTIVITY OF AND POSSIBLE ION‐CHANNEL BLOCK BY CIMETIDINE, RANITIDINE AND OXMETIDINE IN THE TOAD ISOLATED RECTUS ABDOMINIS MUSCLE
Authors: Cheah L. S. , Lee H. S. , Gwee M. C. E.
Published: June 2007

1. Responses of the toad isolated rectus abdominis muscle to cumulative doses of acetylcholine were recorded in the absence or presence of varying concentrations of cimetidine, ranitidine or oxmetidine. The corresponding cumulative log concentration‐response curves for acetylcholine were then plotted for each antagonist studied.

2. Cimetidine (5 mmol/1), ranitidine (1 mmol/1) and oxmetidine (0.02 mmol/1) potentiated the effect of acetylcholine by 4‐fold, 2.6‐fold and 1.3‐fold, respectively.

3. At higher concentrations all three histamine H2‐receptor antagonists produced a concentration‐dependent and non‐parallel shift of the acetylcholine curve to the right of the corresponding control curve accompanied by a depression of the maximal response.

4. The results provide further evidence that the H2‐antagonists studied possess anticholinesterase activity and also suggest that the H2‐antagonists may produce neuromuscular blockade by ion‐channel block. The clinical implications of the results obtained are also discussed.
CONTINUOUS 24‐HOUR INTRA‐ARTERIAL BLOOD PRESSURE RECORDING IN THE CONSCIOUS UNRESTRAINED RABBIT
Authors: Sneek J. H. J. , Eijzenbach V. , Ligtenberg A. C. M. , Borst C.
Published: June 2007

1. A measuring system is described for the long‐term continuous beat‐to‐beat measurement of mean aortic pressure and heart period (interval between beats) in the conscious unrestrained rabbit. Pressures and heart periods were collected in hourly histograms. The histograms were summed into day (0800–2000 h), night (2000–0800 h) and 24‐hour histograms. Separate histograms were formed for resting and active periods. From each histogram the mean value, standard deviation, fifth percentile, 50th percentile and 95th percentile were calculated and stored on a floppy disc together with the histograms. Off‐line, histograms and their descriptive parameters were plotted and sent to a HP 1000 computer for bulk storage and further analysis.

2. The measuring system is capable of handling up to eight animals simultaneously for an indefinite period.

3. The design functioned properly in the long‐term measurement (more than 4 weeks) of mean level and variability of arterial pressure and heart period. The measuring system is useful in the study of arterial blood pressure behaviour after sino‐aortic denervation and in the evaluation of drug effects in conscious animals.
EFFECTS OF NEUROTOXIN‐INDUCED BRAINSTEM LESIONS ON THE RESPIRATORY RESPONSES OF CONSCIOUS RATS
Authors: Martin‐Body R. L. , Grundy H. R.
Published: June 2007

1. Respiration was recorded in unanaesthetized rats breathing air, or CO2 in air, 4–8 days after injection into the rostral brainstem at the level of the dorsal raphe nucleus of either a catecholaminergic neurotoxin, a serotoninergic neurotoxin, or the vehicle (0.5% ascorbic acid) of these drugs. Some rats were pretreated with the noradrenergic neurone protecting agent, desmethylimipramine (DMI).

2. Vehicle injection resulted in an increase in the frequency (f) sensitivity to CO2. In two of four cases, injection of 6‐hydroxydopamine caused a similar response but in the remaining cases injections caused increases in inspiratory duration (TI), expiratory duration (TE) and tidal volume (VT) during air‐breathing.

3. The serotonergic neurotoxin, 5,7‐dihydroxytryptamine, reduced the frequency sensitivity to CO2 significantly. This reduction was not sustained. In all cases air‐breathing f was decreased due to a prolongation of TI; in most cases air‐breathing VT was increased. The characteristic effect of midline 5,7‐dihydroxytryptamine lesions was an increase in the VT sensitivity to CO2.

4. On the basis of the results, it is proposed that noradrenaline is essential to the processes determining basic respiratory rhythm, whereas dopamine and serotonin are important inhibitors in chemoreflex ventilatory patterns.
THE INTERACTION OF EPHEDRINE WITH β‐ADRENOCEPTORS IN TRACHEAL, CARDIAC AND SKELETAL MUSCLES
Authors: Waldeck Bertil , Widmark Erik
Published: June 2007

1. Three β‐adrenoceptor mediated effects were measured in vitro on tissues from guinea‐pig: (a) relaxation of the trachea (mainly β2), (b) increase in the force of contraction of the papillary muscle (β1), and (c) depression of the subtetanic contractions of the soleus muscle (β2).

2. The relaxant effect of ephedrine on the trachea was weak but was resistant to reserpine pretreatment. There was no appreciable agonistic effect of ephedrine on the soleus muscle.

3. Ephedrine per se had a marked positive inotropic effect on the papillary muscle with a pD2 of about 6.0. This effect disappeared completely after pretreatment with reserpine.

4. Ephedrine inhibited the response to isoprenaline. The apparent pA2 was about 4.8 in all tissues studied.
GANGLION BLOCKING ACTIVITY OF CIMETIDINE IN THE ANAESTHETIZED CAT
Authors: Gwee M. C. E. , Cheah L. S. , Lee H. S.
Published: June 2007

1. Cimetidine produced a dose‐dependent and reversible inhibition of contractions of the nictitating membrane elicited through stimulation of the preganglionic nerve supplying the superior cervical ganglion in the anaesthetized cat. Postganglionic nerve stimulation resulted in only a slight and variable inhibition of the contractions. Both hexamethonium and cimetidine also produced a dose‐dependent and reversible fall in arterial blood pressure.

2. The ganglion blocking activity of cimetidine was much weaker than that of hexamethonium; the ED50 ratio (cimetidine:hexamethonium) calculated from the cumulative log dose‐response curves for the two drugs was 64.

3. The possible mechanism(s) of ganglion blockade produced by cimetidine is discussed including a possible action at nicotinic receptors, either directly or indirectly (via its anticholinesterase activity), and ion channel blockade.

4. The clinical implications of cimetidine‐induced ganglionic blockade are also discussed, especially with respect to sexual impotence associated with the use of cimetidine.
METOCLOPRAMIDE ENHANCES BETHANECHOL‐INDUCED PANCREATIC EXOCRINE SECRETION OF THE DOG
Authors: Yamagishi F. , Haruta K. , Homma N. , Iwatsuki K. , Chiba S.
Published: June 2007

1. The effects of metoclopramide on pancreatic exocrine secretion were investigated in the pentobarbitone‐anaesthetized dog. All drugs were injected into the femoral vein.

2. Metoclopramide (10–1000 μg/kg) did not change the resting rate of pancreatic secretion.

3. Pancreatic secretion, induced by bethanechol (3 μg/kg), was dose‐dependently enhanced by simultaneous injections of metoclopramide (10 and 30 μg/kg), but the protein and bicarbonate concentrations of the pancreatic juice were not affected. Secretions induced by secretin (0.1 units/kg) and dopamine (3 μg/kg) were not modified by metoclopramide at up to 30 μg/kg.

4. A larger dose of metoclopramide (1000 μg/kg) suppressed dopamine‐induced secretion to a lesser extent than the same dose of sulpiride.

5. From these results, it is concluded that metoclopramide enhances secretory responses to cholinergic stimulations by peripherally sensitizing the muscarinic receptor‐mediated exocrine process and this drug is a weaker antagonist of the dopamine D2 receptors than sulpiride.
EFFECTS OF ENERGY AND PROTEIN RESTRICTION ON ACETYLCHOLINE SENSITIVITY OF RAT ISOLATED PERFUSED HEART
Authors: Venkataraman B. V. , Shetty P. S. , Joseph Thangam , Arifullah H. Mohamed , Stephen P. M.
Published: June 2007

1. Responses to acetylcholine of isolated perfused hearts obtained from rats which were acutely starved, chronically half‐starved or protein‐restricted were compared with those of paired control groups.

2. Isolated hearts of totally starved rats showed no significant change in the responses elicited by 10 and 20 μg doses of acetylcholine as compared with paired controls. With 40 μg acetylcholine a significantly greater reduction (P < 0.001) in heart rate and coronary flow was seen and the duration of the negative chronotropic action was significantly increased (P < 0.05), as compared with controls.

3. Isolated hearts of half‐starved and protein‐restricted rats responded to 10, 20 and 40 μg doses of acetylcholine with significantly greater reduction (P < 0.001) in heart rate, coronary flow and increase in duration of negative chronotropic action (P < 0.001) as compared to controls.
EFFECTS OF THE INTRAPERITONEAL ADMINISTRATION OF DIAZEPAM ON RAT SERUM LIPOPROTEINS SEPARATED BY POLYACRYLAMIDE GEL ELECTROPHORESIS
Authors: Cuparencu B. , Tomus C. , Horák J. , Nan A. , Cordos M. , Puia L. , A M. , Marino E.
Published: June 2007

1. In normolipidaemic young rats the intraperitoneal administration of diazepam (10 mg/kg) induced a marked fall of the total serum lipids and total cholesterol. A dose of 5 mg/kg brought about an increase of HDL2 lipoprotein fraction and an elevation of the HDL2/HDL2.HDL3 ratio.

2. Margarine administration elicited a significant augmentation of the total serum lipids and a reduction of the HDL2/HDL2.HDL3 ratio. The intraperitoneal injection of diazepam in margarine‐treated rats brought about a decrease of total serum lipids and total cholesterol, (when compared to the margarine values), an obvious elevation of the HDL2 fraction and of HDL2/HDL2.HDL3 ratio. The LDL, (β) fraction was decreased.

3. These data confirm our earlier findings which show that diazepam improves the HDL cholesterol/total cholesterol ratio.