摘要:

SUMMARY1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle.2. Ethionine does not cause changes in the blood parameters, including total plasma iron‐binding capacity and plasma iron clearance. Erythrocytes of rats injected with ethionine show altered responses to hypertonicity.3. Increased reticulo‐endothelial activity of the spleen, indicated by increased uptake of59Fe‐labelled erythrocytes by liver and spleen, apparently contributes to plasma iron elevation. Also the liver releases iron which further raises plasma

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01851.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Changes in heart rate were evoked by atrial pacing in anaesthetized dogs with no pretreatment and in dogs given reserpine or guanethidine for 72 h. The effect of alterations in heart rate were related to two indices of myocardial contractility: the maximal rate of change of left ventricular pressure (dp/dt), and an index which was independent of initial fibre length (dp/dt)/ITT, where IIT is integrated isometric tension.2. An increase in heart rate in control dogs was accompanied by a rise in both dp/dtand (dp/dt)/IIT confirming that the Bowditch staircase does exist in the intact ventricle. The regression line relating heart rate to (dp/dt)/IIT was significantly steeper than that relating heart rate to dp/dtbecause the reduction in left ventricular preload at high heart rate tends to attenuate the rise in dp/dt.3. Reserpine, but not guanethidine pretreatment was accompanied by either a slight decrease or no change in (dp/dt)/IIT during pacing.4. Acute elevation of (dp/dt)/IIT by either calcium or isoprenaline infusion in reserpine pretreated dogs did not restore the Bowditch effect.5. Acute depression of (dp/dt)/IIT by propranolol and pentobarbitone was accompanied by a greater rise in (dp/dt)/IIT with pacing in control dogs and a rise rather than a fall in reserpine‐pretreated dog

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01852.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The plasma half‐life and apparent volume of distribution of phenazone (antipyrine) was studied in twenty‐six normal adults (20–40 years of age) and twenty‐six geriatric patients.2. A wide range of values for plasma half‐life was recorded in both groups (young 7·7–19·9 h, elderly 9·5–30·1 h) but the mean plasma half‐life for the geriatric group (16·8 h; s.e.m. = 5·9) was significantly longer (P<0·01) than the normal adult group (12·5 h; s.e.m. = 3·2).3. No difference in plasma half‐life was noted between sexes in either the geriatric or control groups.4. Doubling the dose of phenazone from 10 to 20 mg/kg made no difference to the plasma half‐life in a subgroup of the geriatric patients.5. The volume of distribution of phenazone, representing total body water, was 0·59–0·63 l/kg in all groups except the elderly females, in whom it was 0·48 l/kg. This latter group showed a correspondingly higher plasma concentration extrapolated to time zero.6. The difference in plasma half‐life phenazone between normal adult and elderly groups is statistically significant, but the wide range of values in each group makes the biological significance less clear. Alteration of drug distribution with resultant higher plasma or tissue concentrations may contribute to adverse drug effects,

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01853.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Elimination rates of tritiated ouabain, digoxin and digitoxin after single intravenous administrations were investigated in guinea‐pigs, the total radioactivity in whole blood being traced for a period of up to 2 weeks.2. In the initial rapid phase of elimination between 2 and 30 min following intravenous glycoside administration, the concentration decline of radioactivity in the blood was found to be identical for the three glycosides investigated, this part of the elimination curve displaying a hyperbolic shape.3. During this early elimination phase, rapid metabolic degradation and excretion of digoxin had already taken place. The maximum concentration of radioactivity in the bile was reached 4 min following intravenous administration of3H‐digoxin. The positive inotropic response occurred in the cat heart‐lung preparation 1·5 min after intravenous injection of a therapeutic dose of digoxin, indicating a quick occupation of binding sites in the tissues.4. The biological half‐lives of tritiated ouabain, digoxin and digitoxin averaged 11 h, 2·5 days and 4·1 days, respectively, as determined by the terminal exponential elimination phase, in guinea‐pigs. This terminal phase was attained 6–12, 7–24, and 24–48 h after administration of ouabain, digoxin and digitoxin, respectively.5. The findings reveal that in the guinea‐pig, as has been demonstrated in man, the elimination rates of the three glycosides increase according to their hydrophobic properties.6. The biological half‐lives of tritiated ouabain, digoxin and digitoxin obtained in the guinea‐pig closely resemble th

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01854.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Conscious experimental hypertensive rats injected intraventricularly with 5,6‐dihydroxytryptamine (50 μg) responded with a rapid and long‐lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration.2. The acute actions of 5,6‐dihydroxytryptamine on the cardiovascular system were not modified by pretreatment with bromolysergide (0·5 mg/kg, i.p.), methysergide (2·5 mg/kg, i.p.) or intraventricular phentolamine (200 μg).3. The results suggest that central serotonergic neurones play an important role in the regulation of blood pressure. However, the site of action remains to be inv

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01855.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Vascular resistance was measured after acute surgical denervation in the blood‐perfused hind limbs of adult normal rats and rats which had been treated with 6‐hydroxydopamine in the first 2 weeks of postnatal life. Vascular resistance was significantly higher in the limbs of 6‐hydroxydopamine treated rats.2. No excess of vasoconstrictor materials was detected when blood from 6‐hydroxydopamine treated rats was used to perfuse the hind limbs of untreated rats or other 6‐hydroxydopamine treated rats.3. Hind limb blood vessels of 6‐hydroxydopamine treated rats showed increased sensitivity to normal amounts of circulating vasoconstrictors of adrenal origin and to intra‐arterial infusions of noradrenaline and angiotensin.4. Infusion of desipramine into the hindlimb blood vessels of 6‐hydroxydopamine treated rats did not increase vasoconstrictor responses to infused noradrenaline. Infusion of desipramine into the limbs of untreated rats increased responses to noradrenaline but these never attained the magnitude and duration of responses seen in limbs of 6‐hydroxydopamine treated rats.5. The increased sensitivity to noradrenaline of hindlimb vessels from 6‐hydroxydopamine treated rats could partly be accounted for by an absence of neuronal uptake sites and partly by the development of non‐specific post‐junc

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01856.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The effects of pentaerythritol trinitrate (pentrinitrol) and glyceryl trinitrate on myocardial oxygen consumption and myocardial and systemic haemodynamics were studied in anaesthetized open‐chest dogs. Anin vivooximeter in the coronary sinus permitted continuous determination of arteriovenous oxygen difference and myocardial oxygen consumption. All parameters were determined simultaneously at various intervals after drug administration.2. Myocardial oxygen consumption was diminished by both nitrates for more than 16 min. Changes in arteriovenous oxygen difference and coronary sinus oxygen content were variable between drugs. Following an initial transient increase, coronary blood flow was reduced by both nitrates. Aortic blood pressure, aortic blood flow, left ventricular end‐diastolic pressure and left ventricular dP/dtwere also reduced. Heart rate and contractile force were not appreciably altered by either nitrate.3. The decrease in myocardial oxygen consumption appears to be associated with the haemodynamic profile of these drugs. Both nitrates produced comparable reductions in preload (left ventricular end‐diastolic pressure) and afterload (aortic pressure) as well as

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01857.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The effect of intravenous pentaerythritol trinitrate and glyceryl trinitrate on left ventricular subepicardial (epi) and subendocardial (endo)Po2and perfusion were compared in anaesthetized open‐chest mongrel dogs. TissuePo2was determined simultaneously at a depth of 3 mm (epicardial) and 9 mm (endocardial) with small platinum electrodes by polarography. In a separate series of dogs tissue perfusion of those regions was measured by hydrogen (H2) clearance using similar electrodes.2. Both nitrates increased endocardialPo2while epicardialPo2was not altered. Perfusion was determined at the point of the maximal rise in endocardialPo2(4–7 min after injection of either nitrate). At that period average coronary artery inflow and epicardial perfusion were decreased but endocardial perfusion was not significantly altered.3. Using the data onPo2, hydrogen clearance and intercapillary distance, the effect of the nitrates on transmural metabolism (oxygen consumption) was estimated by Krogh analysis. Basal endocardial metabolism was 20–30% higher than epicardial metabolism. The nitrates reduced metabolism in each region. The absolute decrease in oxygen consumption was greater in the endocardium.4. The results show that both pentaerythritol trinitrate and glyceryl trinitrate improve endocardial oxygenation by producing a more favourable balance between perfusion and oxygen requirements in that r

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01858.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. A catecholamine β‐adrenoreceptor agonist, hexoprenaline, was examinedin vitroon five guinea‐pig tissues and its potency relative to isoprenaline (as 100) obtained.2. Hexoprenaline clearly delineated between those tissues classified as containing β2‐adrenoreceptors (trachea, hind limb blood vessels and uterus; relative potencies 219, 110 and 76 respectively) and those classified as containing β1‐adrenoreceptors (atria and ileum; relative potencies 3·3 and 1·0 respectively).3. Hexoprenaline differed from some previously studied noncatecholamine β‐adrenoreceptor agonists in being only two‐fold less potent, relative to isoprenaline, as a vasodilator in perfused hind limb than as a

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01859.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Incubation of parathyroid hormone with plasma membranes from rat kidney cortex resulted in rapid loss of all hormonal activity.2. Chick kidney membranes showed no ability to inactivate parathyroid hormone even with prolonged incubation.3. Biologically active, labelled parathyroid hormone was degraded to fragments by rat kidney membranes, but not by chick kidney.4. Hormone‐responsive adenylate cyclase activity in a mixture of rat and chick kidney membranes was additive.5. Parathyroid hormone bound specifically to chick kidney plasma membranes.6. It is concluded that hormone inactivation during incubation has little relevance to the effectiveness of parathyroid hormone in stimulating adenylate cyclase activity in kidney, and furthermore that failure of chick kidney to metabolize the hormone is not the explanation for the greater sensitivity of this species to the hormon

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01860.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY