摘要:

SUMMARY2. Imipramine caused a moderate increase in supine systolic blood pressure, and a pronounced increase in the rise in heart rate, when the subjects assumed erect position.3. The orthostatic drop in systolic blood pressure was in most cases only moderately increased after ingestion of imipramine, but in three subjects pronounced orthostatic hypotension developed when the sodium balance was low, whereas no clinical symptoms were seen in the same subjects when tested after imipramine ingestion on a high sodium balance.4. The plasma catecholamine levels in supine and standing position were not influenced by imipramine or by the changes in sodium balance.5. The data may suggest that inhibition of presynaptic reuptake of noradrenaline and/or α‐adrenoceptor blockade causes the moderate rise in supine blood pressure, whereas α,‐adrenoceptor blockade, mainly affecting the venous part of the vascular bed, may explain the orthostatic reac

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00217.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. The ability of verapamil to induce a contractile response in skeletal muscle was investigated using the canine isolated, blood‐perfused diaphragm preparation.2. Verapamil‐induced contracture was characterized by a biphasic increase in muscle tension consisting of an initial phasic and subsequent tonic contracture.3. The second tonic component of the verapamil‐induced contracture was inhibited by procaine, but procaine had no effect on the initial phasic contracture.4. Verapamil potentiated both KCl‐ and caffeine‐induced contractures during the second tonic stage. This action might be explained by enhancement by the drug of availability, or by an increased sensitivity of the contractile machinery to calcium liberated by membrane depolarization or by the calcium‐induced calcium release mechanism.5. The second tonic component of verapamil‐induced contracture was much less than the initial phasic component. It seems, therefore, that the calcium release induced by the procaine‐resistant process is the principal action of verapamil in inducing contracture in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00218.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. Manganese (0.5‐100 μmol/1) was found to be a potent inhibitor of the dilator effect of isoprenaline on the isolated tracheal muscle of the guinea‐pig. Above these concentrations the inhibitory action of Mn2+diminished and no inhibition occurred above 1000 μmol/I Mn2+. Thus a bell‐shaped dose‐response curve resulted for the inhibition of isoprenaline by Mn2+. The antagonism was surmountable but apparently noncompetitive.2. Dilation of the isolated trachea caused by theophylline or nitroprusside was not inhibited by Mn2+at concentrations of 12.5 to 750 μmol/1.3. At the dose range which could be tested manganese did not antagonize isoprenaline bronchodilatationin vivo.However, manganese at doses between 0.5 and 2.0 μmol/kg inhibited increases in pulmonary resistance caused by acetylcholine, histamine or serotonin.4. At concentrations above 250 μmol/1 Mn2+inhibited constrictor responses to histamine, acetylcholine and serotonin in guinea‐pig isolated ileum and trachea, and inhibited serotonin and prostaglandin E2contractions in rat fundus.5. Co2+, Fe2+, Fe3+and Zn2+were also tested for their action against isoprenaline on the isolated trachea. Co2+was similar in effect to Mn2+but had only 1/50 of the potency. Up to the highest concentrations which could be tested, namely 1000 μmol/1, the other trace metals produced negligible effects.6. Thus Mn2+showed selective inhibition of the relaxant effect of isoprenaline on the guinea‐pig isolated trachea, at concentrations of Mn2+well below those shown previously to inhibit constrictor responses by block of transmembrane Ca2+entry. It is suggested that Mn2+may interfere with intracellular Ca2+fluxes in the

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00219.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. Reducing the cerebrospinal fluid concentration of NaCl by infusion into a lateral cerebral ventricle of isotonic solutions of 0.3 mol/1 mannitol or sucrose at 1 ml/h for 2 h caused a large reduction in renal Na excretion in conscious sheep deprived of water for 24 or 48 h.2. Infusion of 0.3 mol/1 mannitol into the lateral ventricle of water‐replete sheep did not alter renal Na excretion but induced a water diuresis.3. These data indicate that during dehydration, renal Na excretion may be under the control of the brain. The pathway(s) from brain to kidney mediating this antinatriuretic effect are not know

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00220.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. Thein vitroeffects of the major non‐benzodiazepine anticonvulsants were studied upon potassium‐stimulated release of radiolabelled GABA and D‐aspartate from minislices of rat cerebral cortex.2. At 100 μmol/1, some anticonvulsants effective ingrand malseizures (phenytoin, phenobarbitone, mephobarbitone and beclamide) selectively inhibited K+‐evoked release of the excitant amino acid D‐aspartate, consistent with an anticonvulsant action.3. In contrast, several other anticonvulsants, namely ethosuximide, methsuximide, carbamazepine, sulthiame and dipropylacetate failed to alter potassium‐evoked release of either amino acid.4. The ionic basis of phenytoin action on release was further studied; interactions with both neuronal calcium and sodium ion channels appear necessary for the drug's inhib

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00221.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. The effect of serotonin on cardiac sympathetic transmission was investigated in vagotomized and cardiac decentralized dogs.2. Administration of serotonin in doses of 10‐100 μg/kg i.v., during the resting unstimulated state caused tachycardia and pressor responses which were inhibited by cyproheptadine but not by guanethidine. The tachycardia was reduced by a β‐adrenoceptor antagonist, bufetolol.3. Serotonin in doses of 3‐100 μg/kg depressed the elevated heart rate during maintained electrical stimulation of the cardiac sympathetic nerves.4. Cyproheptadine did not antagonize the serotonin‐induced depression of the stimulation‐elevated heart rate, while desipramine attenuated but did not abolish it.5. Serotonin did not have a significant effect on the heart rate elevated by maintained infusion of noradrenaline.6. The present results suggest that serotonin‐induced depression of heart rate during sympathetic nerve stimulation is due to presynaptic inhibition by serotonin of cardiac sympathetic transmission which is not mediatedvia‘classic’ trypta

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00222.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. In the rat kidney catecholaminergic nerve elements were identified by fluorescence histochemistry in perivascular plexuses around corticula arteries and juxtaglomerular arterioles and in medullary vascular bundles. Fluorescence was abolished in all areas 24 h after treatment with 6‐hydroxydopamine (6‐OHDA; 150 mg/kg i.v.). Protection of noradrenergic endings from destruction by 6‐OHDA was afforded by pretreatment with desipramine (DMI; 25 mg/kg i.p.) which restored fluorescence towards control levels. By semiquantitative analysis fluorescence was identical in juxtaglomerular regions but slightly reduced around larger vessels in (DMI + 6‐OHDA)‐treated rats when compared to controls.2. Changes in tissue noradrenaline content, but not dopamine content, paralleled the changes in nerve fluorescence. Noradrenaline content was 4.10 pmol/mg protein (s.e.m. =0.22,n= 32) in controls and was reduced by 90% to 0.40 pmol/mg (s.e.m. =0.05,n= 23) in 6‐OHDA‐treated and by 26% to 3.01 pmol/mg (s.e.m. = 0.21,n= 23) in (DMI + 6‐OHDA)‐treated rats. Kidney dopamine content was 0.38 pmol/mg protein (s.e.m. =0.05,n= 32) in controls and was reduced by 55% to 0.18 pmol/mg (s.e.m. =0.02,n=17) in 6‐OHDA‐treated and by 53% to 0.17 pmol/mg (s.e.m. =0.02,n= 23) in (DMI +6‐OHDA)‐treated rats.3. The renin response to haemorrhage was examined in pentobarbitone sodium‐anaesthetized rats as a test of functional integrity of renal nerves in the three groups. Progressive 1 ml haemorrhages (to total blood loss of 4 ml, 1.3% body weight) resulted in similar increases in plasma renin activity in controls and (DMI + 6‐OHDA)‐treated animals but the response was significantly attenuated in 6‐OHDA‐treated rats.4. Renal catecholaminergic nerves appear to be predominantly noradrenergic. It is doubtful if a significant intrarenal do

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00223.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. The influence of FLA‐63 on pentobarbitone‐induced sleep was studied in young chicks and adult rats.2. FLA‐63 produced a time‐dependent biphasic effect on the gross behaviour of chicks and rats; an initial sedation followed by behavioural excitation.3. The behavioural effects of FLA‐63 were associated with an initial EEG synchronization prior to an increased activity of the EMG of the neck muscle and desynchronization of the EEG of the hyperstriatum, optic tectum and pontine reticular formation of the chick. Similarly, in rats, the EEG of the frontal cortex, optic lobe and pontine reticular formation was desynchronized while the EMG activity of the neck muscle was enhanced by FLA‐63.4. FLA‐63 delayed the onset and shortened the duration of pentobarbitone sleep.5. Pentobarbitone‐induced EEG synchronization and decreased EMG activity in chicks was antagonized by FLA‐63.6. Dopamine‐induced antagonism of pentobarbitone sleep was potentiated by FLA‐63 in chicks.7. Levodopa antagonized pentobarbitone‐induced sleep in rats and this effect was potentiated by FLA‐63.8. FLA‐63 potentiated levodopa‐induced desynchronization of the EEG of the frontal cortex, optic lobe and pontine reticular formation of the rat.9. Haloperidol antagonized the effect of FLA‐63 on pentobarbitone‐induced sleep in both rats and chicks.10. Noradrenaline induced behavioural sleep in young chicks dose‐dependently; this effect was antagonized by phentolamine. In the rat, phentolamine shortened pentobarbitone sleeping time but did not significantly influence the effects of FLA‐63 on pentobarbitone sleep.11. Those results suggest that an increased dopamine neurotransmission may be associated with the mechan

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00224.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. 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 10‐6mol/1 (6.6 nmol per 109platelets).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 vivoplatelet activation by immune complexes may be releasing sufficient concentrations of serotonin to constrict peripheral blood vessels and contribute to the hype

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00225.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

SUMMARY1. 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 thes

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00226.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY