摘要:

SUMMARY1. The actions of histamine on pulmonary vascular smooth muscle have been studied in isolated cat and rat lungs perfused with blood, lobes of cat lung perfusedin vivoand isolated strips of rat, cat and rabbit pulmonary artery.2. In all the lung preparations histamine caused both dilatation and constriction. In the rat strips it caused both contraction and relaxation. Dilatation was only well shown when the vessels were in a prior constricted state. In any one lung dilatation occurred with smaller doses than constriction.3. Histamine caused both increases and decreases in pulmonary artery pressure in collapsed lungs. In this condition these effects are unlikely to have been a consequence of changes in airway pressure.4. From forward and reverse perfusions of lungs in the waterfall state, where changes in postalveolar vessels do not affect pulmonary artery pressure, it appeared that histamine caused both dilatation and constriction on both sides of the point of collapse caused by alveolar pressure.5. Plots of the relationship between left atrial and pulmonary artery pressure (at constant alveolar pressure and blood flow) showed that histamine caused both increases and decreases in pulmonary vascular resistance and sometimes also increased the ‘Starling resistor’ properties of lung vessels.6. In plethysmograph experiments histamine caused moderate dilatation and constriction without affecting lung volume but strong vasoconstriction was accompanied by increases in lung vol

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00618.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. Preparations of isolated bladder‐urethral junction from cats and guinea‐pigs were suspended in Krebs solution (37°C) which was bubbled with carbogen. The urethral lumen was perfused at a very low rate (1–3 ml/h) with Krebs solution. Resistance to flow and changes in longitudinal tension (initial setting 0.5 g) were recorded. In additional experiments, tension changes in urethral circular muscle preparations were registered.2. The urethral preparations had a basal resistance to flow within the range 5–20 cm H2O. They had a spontaneous contractile activity that was unaffected by atropine 0·1 μg/ml, phenoxybenzamine 0·1 μg/ml, and tetrodotoxin 0·1–0·5 μg/ml, suggesting it was of myogenic origin.3. The basal characteristics and the drug‐induced changes in the perfused urethras were independent of whether the longitudinal tension was recorded iso‐metrically or isotonically, or whether the perfusion was made retrograde or ante‐grade. Passive changes in longitudinal tension between 0·5 and 2·0 g did not affect the resistance to flow through the urethra.4. Adrenaline and noradrenaline, 0·01–1 μg/ml, increased longitudinal tension and resistance to flow in the perfused preparations. The effects, which were sustained and concentration‐related, were blocked or reversed into inhibition in the presence of phenoxybenzamine, 0·1 μg/ml. This finding suggests that the stimulatory effects were mediated via a‐receptors.5. Isoprenaline, 0·001–0·005 μg/ml, relaxed and inhibited the activity in the cat urethral smooth muscle and decreased the resistance to flow both under basal conditions and when the urethra was contracted by noradrenaline or acetylcholine. The inhibitory effects were blocked by propranolol, 0·1 μg/ml, suggesting that they were mediated via β‐receptors. In guinea‐pig preparations, no effect of isoprenaline was observed.6. Acetylcholine, 0·02–0·5 μg/ml, increased the longitudinal tension and the resistance to flow through the urethras. The latter effect was less pronounced than that produced by noradrenaline, especially in the guinea‐pig preparations. Nor‐adrenaline was also more effective than acetylcholine in contracting the circular muscle of the urethra. The effect of acetylcholine was blocked by atropine, 0·1 μg/ml, suggesting that the con

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00619.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The effects on the coronary and systemic haemodynamics of intravenous and intracoronary injections of two benzfuran derivatives, amiodarone and its brominated analogue (L8040), were studied in open‐chest anaesthetized dogs. The effects of L8040 on cardiac intracellular potentials after 6 weeks of 20 mg/kg intraperitoneal injections in rabbits were also investigated.2. Both compounds produced dose‐related and quantitatively similar decreases in coronary vascular resistance following their intracoronary administration; threshold effects occurred with about 0.25 mg of each drug and maximal effects with 4 mg. Larger intracoronary doses produced measurable systemic effects.3. Intravenous injections of amiodarone and L8040 (2·5·10 mg/kg) produced dose‐related decreases in heart rate and aortic pressure with a fall in total peripheral resistance. The left ventricular output was either unaffected or increased with a consistent augmentation in stroke volume.4. The bradycardia produced by both drugs was associated with prolongation of the P–R interval of the electrocardiogram with no significant effect on the QRS duration or the Q–T interval.5. Each drug produced a decrease in the total peripheral vascular resistance with no change in left ventricular end diastolic pressure except after 10 mg/kg doses which led to an increase in this parameter.6. Cardiac contractile force and peak LVdp/dt were reduced by both drugs in a dose‐related manner.7. Chronic intraperitoneal administration of L8040 in rabbits caused a prolongation of the duration of the atrial and ventricular intracellular potential without an effect on the maximal rate of depolarization.8. The effects of amiodarone or L8040 on the coronary circulation and arterial pressure may be attributed to their vasodilator properties but their depressant actions on cardiac contractile force and peak LVdp/dt with an increase in left ventricular end diastolic pressure at high doses, also suggest intrinsic negative inotropic propensity for both compounds.9. It is concluded that the overall effects on coronary and systemic haemodynamics of amiodarone and its brominated analogue are likely to permit a favourable influence on the balance of oxygen supply and demand in myocardial ischaemia; in addition, their actions on sinoatrial and atrio‐ventricular conduction as well as those on cardiac repolarization suggest potential antiarrhythmic properties which meri

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00620.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The central depressant effects of bromvaletone, carbromal and six non‐bromo analogues were compared in mice.2. The chloro analogues of bromvaletone and carbromal were slightly less potent as central depressant agents than the bromo compounds.3. The chloro analogue of bromvaletone had the greatest margin between central depressant and lethal doses.4. Lipophilicity (octanol‐water partition coefficient) did not provide a unifying relationship for potency within this group of eight acylureas. However, within each of the two subsets of compounds, a linear relationship was found between relative potency and lipophilic

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00621.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The cardiovascular changes of conscious cold‐acclimated (CA) and warm‐acclimated (WA) rats during exposure to 5°C or 28°C were studied.2. The cardiac output, heart rate and stroke volume of CA rats exposed to 5°C and of WA rats during cold stress were significantly greater, and their calculated total peripheral resistance significantly less than those of WA rats exposed to 28°C. These results show that circulatory changes participate in cold acclimation and cold stress. The circulatory changes in the two conditions were compared and the mechanism of the observed differences were discussed.3. CA rats exposed to 28°C showed a striking decrease of oxygen consumption and arterio‐venous O2difference, but significant circulatory changes were decreased heart rate and cardiac index only, indicating that the response was mainly

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00622.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The urinary excretion pattern of ethotoin and five metabolites were examined in three patients receiving continuous treatment with ethotoin at two dose levels, in order to investigate the mechanism behind the dose‐dependent kinetics of this anticonvulsant drug.2. The results suggest a partial saturation in the dealkylation process at high dose levels in three patients.3. A rough approximation of the Michaelis‐Menten constants for different enzymatic processes was attempted. On the basis of the results obtained, thep‐hydroxylation may be a saturable process.4. The dose‐dependent kinetics of ethotoin in man seem to be explicable by the existence of partly saturable enzymatic p

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00623.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The distribution of intrarenal blood flow has been measured using the133Xe‐washout technique in thirteen baboons 2 weeks after ligation of the common bile duct.2. In comparison with eight sham‐operated baboons, there was a significant decrease in the percentage distribution of blood flow to the cortex, although the rate of flow was unchanged. These changes were accompanied by a significantly increased flow rate and percentage distribution of flow through the juxtamedullary circulation.3. In a further five baboons treated in the same way, various doses of noradrena‐line were infused into the renal artery. In these animals there was an enhanced pressor response to noradrenaline, and this effect was completely abolished by an α‐adrenoreceptor blocking agent (phenoxybenzamine). The β‐adrenoceptor blocking drug (propranolol) had no such effect.4. This enhanced response was not seen when noradrenaline was infused into three sham‐operated baboons.5. These observations suggest that the alterations in renal perfusion in obstructive jaundice may be due to an increased renovascular sensitivity to circulating catecholamines and an enhanced α‐dren

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00624.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The effects of single oral doses of propranolol, practolol and a new cardio‐selective β‐adrenoceptor blocking drug, metoprolol, on exercise‐induced tachycardia in relation to plasma levels were studied in six normal volunteers.2. Exercise undertaken on treadmill was submaximal which, under control conditions, increased the heart rate from 74·3 (s.e.m. = 6·8) to 153·8 (s.e.m. = 9·8) beats/min.3. Plasma concentrations of propranolol and practolol were assayed fluoro‐metrically and of metoprolol by electron‐capture gas liquid chromatography, the details of which are described.4. Between 1·5 and 2 h after drug ingestion 80 mg of propranolol associated with plasma level of 50–60 ng/ml (half‐life 2·75 h), reduced the exercise‐induced tachycardia by 27%, 250 mg of practolol with plasma levels of 1050–1100 ng/ml reduced it by 28% and 100 mg of metoprolol with plasma concentrations of 140–150 ng/ml (half‐life 1·7 h), reduced it by 30%.5. The resting heart rates were reduced significantly by propranolol and metoprolol but not by practolol.6. Metoprolol is a potent short‐acting β‐adrenoceptor antagonist; its advantages as a cardioselective agent over practolo

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00625.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. The interaction between the reversible cholinesterase inhibitors, physostigmine and neostigmine and reserpine was studied.2. A combination of reserpine plus a cholinesterase inhibitor significantly increased lethality in adult male Swiss‐Webster mice above that caused by either neostigmine, physostigmine, or reserpine alone.3. Methscopolamine completely reversed this effect.4. It would appear that the presence of the antiadrenergic agent, reserpine, increases the toxicity of cholinomimetic agents.5. The above results may have clinical significance, since reserpine and cholinesterase inhibitors are used in the practice of medicin

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00626.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARY1. Circulating catecholamines and dopamine‐β‐hydroxylase (DPH) have been studied in a child with bilateral phaeochromocytoma.2. Venous catheterization showed a great increase in catecholamine efflux from the left adrenal vein while DPH activity in the latter was only slightly elevated.3. Circulating catecholamines fluctuated greatly while DBH activity decreased gradually during the removal of the tumours.4. Post‐operatively, circulating catecholamines declined to normal values while DβH activity returned to pre‐operative levels.5. It is concluded that these tumours released circulating catecholamines independent of an exocytotic secretion of DβH and that the circulating DβH reflected the activity of the sympathetic ner

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1976.tb00627.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY