摘要:

SUMMARY1. The haemodynamic and metabolic responses of four laboratory rabbits to horizontal treadmill exercise at 8, 12, 16 and 20 m/min were studied. The primary haemodynamic variables measured were heart rate, cardiac output and arterial pressure. The metabolic variables measured were arteriovenous oxygen difference, whole‐body oxygen consumption and central venous plasma lactate concentration.2. Only at 8 m/min did the haemodynamic and metabolic variables reach an approximate steady state. This was the greatest speed at whichaerobic exercise could be sustained for 4 min in all rabbits.3. As the speed of the treadmill was increased the rabbits showed signs of exhaustion after progressively shorter periods of exercise. Exhaustion was associated with steep rises in central venous plasma lactate concentration. Exhaustion was also usually associated with secondary rises in systemic vascular resistance and arterial pressure, especially at 20 m/min.4. The asymptotic (maximal) values for heart rate, cardiac index and O2consumption were 386 beats/min, 263 ml/kg per min and 21.7 ml/kg per min, respectively.heart do not permit it to run continuously at other than a slow rate. Exhaustion is associated with increasing oxygen debt and, especially at near‐maximal rates of exercise, with intense vasoconstriction in as yet unidentified vascular b

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02418.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. This study applied clearance methods of inulin, lithium, potassium, sodium and para‐aminohippuric acid (PAH) for investigation of the effects of cyclosporin A (CyA), furosemide and gentamicin on rat (n= 92) renal function. The drugs were dosed for 2 weeks; CyA 12.5 mg/kg per day, gentamicin 32 mg/kg per day and furosemide 5 mg/kg per day.2. The questions asked were: could these methods differentiate the effects of drugs with different sites of action, and would gentamicin or furosemide exaggerate the nephrotoxicity of CyA?3. Furosemide increased sodium clearance (CNa) 74% and fractional sodium clearance (FENa) 105%, while fractional sodium reabsorption in the distal nephron (FDNR) was reduced, compared with placebo‐treated controls.4. Gentamicin reduced CPAH29% and Cin37%, while FENaincreased 335%. Proximal fractional reabsorption (PFR) and absolute proximal reabsorption (APR) decreased.5. CyA depressed CPAH32% and lithium clearance (CLi) 56%, and increased PFR.6. The effects of CyA and furosemide in reducing renal function were not additive.7. CyA plus gentamicin reduced CPAHto 35% of the value in untreated controls, equal to 52% of the CPAHof CyA‐treated rats; Cinwas reduced to 46% of the Cinof CyA‐treated rats.8. Rats given CyA, furosemide and gentamicin had decreased Cin, CPAH and CLicompared with rats given either CyA plus furosemide or gentamicin plus furosemide.9. Thus, in this investigation of drugs known to have different sites of actions, the differences in renal and tubular function were discernible with the lithium clearance method.10. The nephrotoxicities of CyA and of gentamicin were additive, while furosemide did not aggravate CyA nephrot

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02419.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead‐space. Some chronically hypoxic rats, which have muscularized pulmonary arterioles similar to COAD patients, were also studied.2. In 18 chronically hypoxic (CH) rats and 17 littermate control rats (C), breathing air, doses of almitrine bismesylate caused greater increases in ventilation (VE) in C than in CH rats. FRC, which was initially greater in CH rats, increased significantly in both groups after almitrine.3. In C rats, breathing hypoxic or hypoxic/hypercapnic gas mixtures caused large increases in VE. Slow infusions of almitrine caused a further increase in VEusually via an increase in tidal volume (VT) but not frequency (f).4. In two series of rats (n= 9;n= 6) severe and moderate degrees of tracheal obstruction caused a fall inPaO2and a rise inPaCO2, a fall in VEdue to both VTand f and large changes in oesophageal pressure (Poes), which often became positive on expiration. Almitrine infusions usually caused a rise inPaO2, a rise in VTand no change in f; with moderate obstruction,Poesalso rose. The results were thought to depend on the balance between improved ventilation and increased O2demand of the respiratory muscles.5. Eleven ferrets were made hypoxic and hypercapnic by adding a large dead‐space to the trachea. A slow infusion of almitrine caused a significant rise inPaO2before any significant change in VEwas detected;PaCO2fell at some time during the infusion, but not significantly. The initial significant rise inPaO2, at 2.5 min, was not associated with significant changes in TI(time of inspiration) and VT/TI. At 5 min VT/TI, TIandPaO2were all significantly altered.6. Infusions of almitrine into hypoxic and hypercapnic animals caused improvements in the arterial oxygen tension which were associated with subtle changes in the breathing pattern; inspiratory time and inspiratory flow rate changed in the absence of an increase in total VE. Possible conclusions with respect to the action of almitrine in patients with COAD are discus

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02420.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. Coronary vasodilator effects of non‐ischaemic hypoxia (perfusion with non‐oxygenated Tyrode solution) and ischaemic hypoxia (coronary occlusion) were compared.2. The left anterior descending coronary artery (LAD) of sixin situcanine hearts was perfused selectively at controlled pressure with normal arterial blood or with non‐oxygenated Tyrode solution. LAD flow was measured continuously with an electromagnetic flowmeter. Reactive hyperaemic blood flow responses following 3 min Tyrode perfusion were compared with responses following 3 min complete coronary occlusion.3. Control LAD blood flow was 26.9 ± 4.6 ml/min. A 3 min period of Tyrode perfusion caused a peak reactive hyperaemic blood flow of 151 ± 31 ml/min, which was not significantly different from that caused by 3 min occlusion, 123 ± 17 ml/min. The duration and total volume of reactive hyperaemia flow following Tyrode perfusion were smaller than values following occlusion.4. The present findings demonstrate that myocardial hypoxiaper seis a sufficient vasodilatory stimulus to account for the peak reactive hyperaemic flow following 3 min occlusion, but that the prolonged reactive hyperaemic response depends on vasodilator metabolites which accumulate in ischaemic my

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02421.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. The use of the receptor stabilizing agent sodium molybdate, and of RU26988 to exclude [3H]‐aldosterone binding from Type II glucocorticoid receptors, has enabled the characterization of high affinity Type I aldosterone binding sites in rat atrial and ventricular cytosols.2. In adult male and female rats the affinity of binding (Kd4°C) is ∼ 1–2 nmol/l for both atria and ventricles; specificity of binding is similar to that for Type I sites in classical aldosterone target tissues (aldosterone = corticosterone≫dexamethasone).3. Levels of atrial Type I sites are higher than the corresponding levels in ventricle in both males and females, whereas for Type II (classical glucocorticoid) receptors the reverse is the case; levels of both Type I and Type II sites fall over the age range examined (40 days‐6 months).4. The physiological function(s) of cardiac Type I sites, and theirin vivomineralo‐corticoid or glucocorticoid selectivity, remain to

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02422.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. The diameter of, and blood flow in, the left circumflex coronary artery was measured in anaesthetized dogs and the carotid sinus reflex was stimulated by bilateral occlusion of the carotid arteries (BCO) for 2 min.2. The effect of BCO on coronary artery diameter and late diastolic coronary resistance was examined: (a) after bilateral vagotomy; (b) after vagotomy plus antagonism of β‐adrenoceptors with propranolol (1 mg/kg, i. v.); and (c) after vagotomy, antagonism of β‐adrenoceptors and antagonism of α‐adrenoceptors with phentolamine (0.5 mg/kg, i.v.).3. After vagotomy BCO increased mean arterial pressure (Δ= 72 ± 7 mmHg), heart rate (16 ± 3 beats/min), coronary blood flow (37 ± 11 ml/min) and coronary artery diameter (0.14 ± 0.04 mm). Late diastolic coronary resistance initially fell (‐0.26 ± 0.13 mmHg min/ml at 30s) but at the end of the 2 min occlusion it had returned to the baseline level (Δ= 0.04 ± 0.08 mmHg min/ml).4. In the presence of propranolol BCO increased arterial pressure (28 ± 12 mmHg), but did not alter heart rate (0.6 ± 0.4 beats/min) or coronary blood flow (2 ± 2 ml/min). There was a significant decrease in large artery diameter (‐0.24 ± 0.07 mm) and an increase in late diastolic coronary resistance (0.46 ± 0.12 mmHg min/ml). A mechanical increase in afterload did not affect large coronary artery diameter or coronary resistance5. Antagonism of α‐adrenoceptors abolished the reflex‐induced constriction of the large coronary artery (Δ= ‐0.02 ± 0.02 mm) and the coronary resistance vessels (ΔLDCR = ‐0.02 ± 0.03 mmHg min ml).6. In conclusion, in the anaesthetized, vagotomized dog BCO induces vasodilatation of the large coronary artery which is reversed to a vasoconstriction by antagonism of β‐adrenoceptors. Antagonism of α‐adrenoceptors abolishes the BCO‐induced constriction of the large coronary artery and the coronary resistance vessels. These findings suggest that the tone of the large coronary arteries, as well as the coronary resistanc

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02423.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. Noradrenaline plasma levels and cardiovascular function modifications with orthostatic challenge during therapy were studied in 59 female depressed inpatients treated with 100 mg amitriptyline daily by intramuscular route for 4 weeks.2. Therapy induced an increase in pulse rate in supine and upright positions, a decrease of noradrenaline levels and modified standing systolic and (partially) diastolic blood pressure, particularly in elderly subjects.3. No correlation between neurotransmitter or functional changes and drug plasma levels was noted.4. The supposed lower noradrenergic output together with blood pressure drop in both positions suggests a reduced sympathetic tone.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02424.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. After osmotic opening, the blood‐brain barrier (BBB) has been shown to reclose more rapidly to large than to small neutral, water‐soluble molecules. Quantitative analysis of these data supports the creation of interendothelial pores with radii of about 200 Å through which such molecules pass by both restricted diffusion and bulk flow (with solute drag) from blood to brain.2. The major reduction in BBB permeability from 6 to 35 min following osmotic opening seems to be due to a reduction in bulk flow by a factor of about 10, rather than marked decreases in pore densities or effective pore size. On this basis, quantitative predictions of brain uptake of neutral, water soluble substances are made for various times after osmotic opening of the BBB, as a function of molecular size.3. Implications of these results are discussed for enhancement of uptake of drugs, including enzymes and certain anti‐cancer agents, by the brain.4. The idea of a ‘therapeutic window’ as the period of time, following reversible osmotic opening, during which the permeability of the BBB is enhanced significantly for a particular compound, is introduced. Since the BBB is normally highly impermeable to plasma proteins, the effect of BBB opening on the uptake of highly protein‐bound drugs is discussed briefly.5. The effect of molecular charge on the passage of molecules through interendothelial pores into the brain is al

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02425.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. Clonidine (1–30 nmol/l) enhanced the vasoconstrictor responses to sympathetic nerve stimulation in isolated perfused artery preparations from the rat tail. Higher concentrations of clonidine produced vasoconstriction in most artery preparations and reduced the response to sympathetic nerve stimulation.2. The enhancing effect of clonidine was not affected by prazosin but was blocked by idazoxan, indicating that it was due to activation of α2‐adrenoceptors.3. The α2‐adrenoceptor agonists DPI and TL99, like clonidine, enhanced vasoconstrictor responses to sympathetic nerve stimulation.4. Vasoconstrictor responses to noradrenaline were enhanced by clonidine and TL99.5. The findings suggest that activation of postjunctional α2‐adrenoceptors results in facilitation of the contractile response elicited by activation of α1‐

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02426.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARY1. The effect of opioid receptor blockade by naloxonein vivoon hepatic venous plasma glucose concentration in rats was investigated.2. The plasma glucose levels in naloxone‐injected animals (10 mg/kg) were higher than in the control animals (P0.1).4. It is concluded that endogenous opioids may moderate the regulation of basal glucose levels in the ra

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1987.tb02427.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY