摘要:

SUMMARY1. It was observed that the effectiveness of diazepam in causing sleep, as denned by the loss of righting reflex, was significantly decreased after a single exposure to either diazepam or lorazepam.2. RO 15‐1788, a benzodiazepine antagonist, in contrast did not induce tolerance to diazepam. The mechanism for this acute tolerance is unclear. The rapidity in its development may exclude metabolic tolerance while alterations in brain sensitivity to diazepam remain a possibilit

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00309.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. This paper reports the effects of lowering (bath) temperature upon contractile responses of prostatic and epididymal ends of the rat isolated vas deferens to electrical field stimulation.2. Responses to field stimulation with single pulses at 60 s intervals were potentiated by lowering the bath temperature. This effect was maximal at temperatures of 25‐27°C and was reduced in preparations treated with phentolamine (5 μmol/l).3. Field stimulation with trains of 50 pulses at 5 Hz every 5 min produced biphasic contractions of preparations.The initial, twitch‐like component, prominent at the prostatic end and resistant to blockade by phentolamine (5μmol/1) was little affected by lowering the bath temperature from 37.5°C to 19°C. In contrast, the second, more prolonged, component of the response to pulse trains, which was prominent at the epididymal end of the tissue was decreased by lowering the bath temperature and by phentolamine.4. In the epididymal segment, responses to exogenous noradrenaline were enhanced by lowering the bath temperature.5. It is concluded that lowering the bath temperature enhances the contractility of the vas deferens in response to the release of neurotransmitters and to the application of exogenous noradrenaline via a postsynaptic action. In addition, via a presynaptic action, lowering the bath temperature depresses or delays the release of the noradrenergic transmitter from the sympathetic nerve t

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00310.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive.2. The effects of the angiotensin converting enzyme inhibitor enalapril (10‐40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80‐160 mg/day, p.o.) for 4 more weeks during a randomized double‐blind parallel study in 14 essential hypertensives.3. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids.4. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P<0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values.5. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal.6. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodil

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00311.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. These experiments were designed to confirm that at the onset of treadmill exercise in rabbits the tonic reflex depressor effects of input to the central nervous system from arterial baroreceptors is abolished, thus contributing to the rise of systemic arterial pressure (SAP) and heart rate (HR).2. An inflatable cuff was placed around one common carotid artery after the remaining arterial baroreceptors had been surgically denervated. Transient inflation of the cuff caused reflex rises of SAP and HR, which were much reduced during the first minute of exercise. Deflation of the cuff caused a brisk fall of HR, which was completely abolished by exercise.3. A snare was placed around one carotid sinus nerve after the remaining arterial baroreceptors had been surgically denervated. Where the snare was tightened all arterial baroreceptor reflexes were immediately and permanently abolished. This allowed the reflex effects of baroreceptor input to be calculated by difference. The magnitude of these calculated effects, at rest and during exercise, diminished according to how long after barodenervation the observations were made.4. We conclude from the above experiments that the resting tonic reflex depression of SAP and HR caused by baroreceptor input is much reduced, rather than completely abolished, at the onset of exercise.5. We also conclude, from the effects of partial surgical barodenervation, and of unloading the carotid baroreceptors prior to exercise by inflating the carotid cuff, that resting input from the arterial baroreceptors must be near zero before the cardiovascular response to exercise is grossly altered.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00312.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. The effect of cyclic GMP was investigated using guinea‐pig tracheal smooth muscle.2. 8‐Bromo‐cyclic GMP showed a dose‐dependent relaxation of spontaneous tension of tracheal smooth muscle.3. Administration of sodium nitroprusside induced dose‐dependent relaxation of tracheal smooth muscle as well as an increase in tissue levels of cyclic GMP.4. Nicorandil,N‐(2‐hydroxyethyl) nicotinamide nitrate showed dose‐dependent relaxation of tracheal smooth muscle and an increase in cyclic GMP levels in the tissue.5.N‐(2‐aminoethyl) nicotinamide dihydrochloride, which is a nicorandil derivative and differs minimally in its molecular structure (‐NH2vs ‐NO2), had neither a relaxant effect on tracheal smooth muscle nor did it increase the level of cyclic GMP in the tissue.6. The rise in cyclic GMP levels preceded the relaxation of tracheal smooth muscle induced by sodium nitroprusside.7. These results suggest that cyclic GMP is one of the relaxant factors and that nitro‐derivatives exhibit their relaxant effect on the smooth muscle mediated by an inc

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00313.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. Utilizing a mono‐specific antiserum produced in rabbits to hog kidney aromaticl‐amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining.2. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts.3. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney.4. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading.5. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium load

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00314.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. The effects of pre‐ and post‐treatment with naloxone on the cardiotoxicity of ouabain in the guinea‐pig were studied.2. After pretreatment with naloxone, the dose of ouabain required to induce ventricular arrhythmias and cardiac arrest were significantly increased, in a dose‐dependent manner, compared with the control, indicating a protective effect of naloxone against digitalis intoxication.3. Administration of naloxone at the onset of cardiac arrhythmias induced by a lethal dose of ouabain restored the cardiac rhythm and consequently saved life in seven out of eight animals, indicating an antiarrhythmic effect of naloxone in digitalis‐intoxicated guinea‐pigs.4. The protective and antiarrhythmic effects of naloxone against digitalis intoxication have clinical i

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00315.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. Experiments were performed in anaesthetized rats to investigate the vasodilator actions of the β‐adrenoceptor antagonist bucindolol. Bucindolol (3 mg/kg) lowered blood pressure significantly in rats pretreated with (i) prazosin (0.4 mg/kg) (ii) prazosin (0.4 mg/kg) plus propranolol (0.5 mg/kg) or (iii) labetalol (0.5 mg/kg). Thus, a portion of the hypotensive effect of bucindolol was independent of effects on α‐ or β‐adrenoceptors. This was attributed to direct vasodilatation.2. In reserpinized anaesthetized rats bucindolol increased heart rate and thus had an intrinsic sympathomimetic action (ISA). The ISA was equipotent with that of isoprenaline at the 0.25 nmol/kg dose level, but declined with increasing bucindolol doses, probably due to the onset of β‐adrenoceptor blockade.3. In isolated perfused rat tail arteries constricted by perfusing with a high‐K+Krebs solution, bucindolol (10−5mol/l, 10−4mol/l) caused a significant reduction in perfusion pressure indicative of vasodilatation. Since the perfusate contained 10−6mol/l propranolol, the vasodilatation was not due to β‐adrenoceptor stimulation.4. These results are consistent with a direct vasodilator action of bucindolol. We suggest bucindolol lowers blood pressure by a complex mechanism involving β‐adrenoceptor blockade, α‐adrenoceptor blockade, vasodilatation and perhaps

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00316.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. Changes in plasma active and inactive renin concentration (ARC and IRC) after captopril administration and angiotensin II (AII) infusion were studied in six patients with Bartter's syndrome.2. A single oral dose of captopril (8‐25 mg) lowered the blood pressure and increased both ARC and IRC. AII infusion elevated blood pressure, suppressed ARC and increased IRC.3. In this syndrome of high renin levels, infused AII appeared to increase inactive renin secretion by reducing its conversion to active renin. On the other hand, an acute fall in AII levels and/or renal perfusion pressure by captopril increased both active and inactive renin. This indicates that the increase in the secretion of inactive renin, stimulated by captopril, might exceed any increase in its conversion to active renin in patients with Bartter's syndrome, in whom the production of renin is accelerated, and conversion of inactive renin to active renin probably already operates near its maximu

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00317.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARY1. In Inactin‐anaesthetized rats inhibition of angiotensin converting enzyme by captopril resulted in a small decrease in mean arterial blood pressure accompanied by increases in the rates of glomerular filtration, water and electrolyte excretion.2. Infusion (100 pmol/min) of sar1‐leu8‐angiotensin II (sar1‐leu8‐AII) during continuing converting enzyme blockade reversed these changes in renal function but had no effect on arterial blood pressure.3. The data indicate that sar1‐leu8‐AII has partial agonist activity in the kidney although it acts as an antagonist of AII in the systemic circulation. This supports the proposai that angiotensin receptors within the kidney differ from those in the periphera

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1986.tb00318.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY